Sample records for variant prn3 strains
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Nairismägi, M -L; Gerritsen, M E; Li, Z M; Wijaya, G C; Chia, B K H; Laurensia, Y; Lim, J Q; Yeoh, K W; Yao, X S; Pang, W L; Bisconte, A; Hill, R J; Bradshaw, J M; Huang, D; Song, T L L; Ng, C C Y; Rajasegaran, V; Tang, T; Tang, Q Q; Xia, X J; Kang, T B; Teh, B T; Lim, S T; Ong, C K; Tan, J
2018-05-01
Aberrant activation of the JAK3-STAT signaling pathway is a characteristic feature of many hematological malignancies. In particular, hyperactivity of this cascade has been observed in natural killer/T-cell lymphoma (NKTL) cases. Although the first-in-class JAK3 inhibitor tofacitinib blocks JAK3 activity in NKTL both in vitro and in vivo, its clinical utilization in cancer therapy has been limited by the pan-JAK inhibition activity. To improve the therapeutic efficacy of JAK3 inhibition in NKTL, we have developed a highly selective and durable JAK3 inhibitor PRN371 that potently inhibits JAK3 activity over the other JAK family members JAK1, JAK2, and TYK2. PRN371 effectively suppresses NKTL cell proliferation and induces apoptosis through abrogation of the JAK3-STAT signaling. Moreover, the activity of PRN371 has a more durable inhibition on JAK3 compared to tofacitinib in vitro, leading to significant tumor growth inhibition in a NKTL xenograft model harboring JAK3 activating mutation. These findings provide a novel therapeutic approach for the treatment of NKTL.
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Directory of Open Access Journals (Sweden)
Maciej Polak
2017-05-01
Full Text Available Bordetella pertussis strains, which have lost the ability to produce antigens, such as pertactin - Prn, pertussis toxin - Ptx, filamentous haemagglutinin - FHA, fimbriae type 2 and 3 - Fim 2 and 3, tracheal colonization factor - TcfA, have recently been isolated in countries with a high vaccination coverage. The emergence of such isolates might have resulted from B. pertussis natural evolution course or adaptive mechanisms, allowing increased circulation of the pathogen in vaccinated populations. So far, the majority of described mutants were deficient in the Prn production. Prn deficient isolates were found in countries which use acellular pertussis vaccines (aP in routine immunization programmes. The increase of frequency of Prn¯ strains isolation was correlated with the period of routine vaccination with aP vaccines. In most countries, the spread of these isolates has resulted from independent mutations rather than from the expansion of a single clone. Prn¯ isolates were collected from patients showing typical clinical symptoms of pertussis found for Prn+ strains. Results of in vitro and in vivo studies have shown that Prn¯, Ptx¯ and FHA¯ isolates retain cytotoxic properties, and besides Ptx¯ isolates, were lethal in intranasally infected mice. Further explanation of the impact of antigen deficiencies on virulence and transmission of B. pertussis in the context of the continuous increase of pertussis incidence is necessary to develop a new, optimized strategy of pertussis prevention.
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An effective method of handling PRN orders to reduce labor and improve efficiency.
McCollum, G K; Poe, W D
1990-11-01
Rex Hospital, Raleigh, NC, found its method of PRN (unit dose) medication delivery to be time consuming, labor intensive, and repetitive. Thus, it was decided to evaluate this system and to find a more efficient method of PRN delivery. A 24 hour supply of unit dose medication is delivered daily using a cart exchange system at this hospital. Three approaches were used to reduce the handling of PRN medications: (1) Removing all PRN orders of Milk of Magnesia, cascara, and mineral oil from the patient drawer. These three medications are now floor stock items at each nursing station; (2) Removing all PRN orders of 325 mg aspirin and acetaminophen tablets, 600 mg aspirin, and 650 mg acetaminophen suppositories. These items are now kept at the nurses station as a "no charge" floor stock item; and (3) Using zip-lock bags for all other non-controlled PRN medication orders. A 48 hour supply of medication is sent upon receipt of the original order, and not filled again until the empty bag is returned to the pharmacy. The plastic bag is identified by a computer generated label containing the patient's name, room number, and medication identification. The patient medication drawer is divided into two areas, one for storing standing medication orders and one for PRN orders. A time study showed a 40% improvement in cart filling time. The 48 hour supply of PRN medications rarely need refilling. Milk of Magnesia, cascara, and mineral oil PRN orders are often ordered, but seldom used. Thus, floor stocking these items has not been a problem. Floor stocking aspirin and acetaminophen as no charge items has been very successful. All medication orders, including aspirin, acetaminophen, Milk of Magnesia, and so forth are entered onto the patient's medication profile even though they are not sent from the pharmacy. Drug allergies or drug-drug interactions can be detected by reviewing the patient profile when the original order is entered onto the profile. Nursing is very pleased with the
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Souza, J.T.; Raaijmakers, J.M.
2003-01-01
Pyrrolnitrin (PRN) and pyoluteorin (PLT) are broad-spectrum antibiotics produced by several strains of Pseudomonas and Burkholderia species. Both antibiotics play an important role in the suppression of multiple plant pathogenic fungi. Primers were developed from conserved sequences and amplified
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Hayes, Ariel; Russ, Mark J
2016-03-01
This study examined the impact of eliminating intramuscular PRN medication for agitation on patient and staff safety in an acute psychiatric inpatient setting. The current retrospective chart review investigated the use of PRN medications (oral and intramuscular) to treat acute agitation, including aggression, and related outcomes before and after a mandated change in PRN practice that required real time physician input before administration of intramuscular medications. The use of both oral and intramuscular PRN medications dramatically decreased following implementation of the mandated change in practice. In particular, the use of intramuscular PRNs for agitation decreased by about half. Despite this decrease, the assault rate in the hospital was unchanged, and the utilization of restraint and seclusion continued to decrease. It is possible to reduce the utilization of PRN medications for agitation without broadly compromising safety on acute care psychiatric inpatient units.
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Barr, Lesley; Wynaden, Dianne; Heslop, Karen
2018-02-01
Many countries now have national mental health policies and guidelines to decrease or eliminate the use of seclusion and restraint yet the use of Pro Re Nata (PRN) medications has received less practice evaluation. This research aimed to identify mental health nurses' attitudes towards the use of PRN medications with mental health consumers. Participants were working in forensic mental health and non-forensic acute mental health settings. The "Attitudes towards PRN medication use survey" was used and data were collected online. Data were analysed using the Statistical Package Social Sciences, Version 22.0. Practice differences between forensic and other acute mental health settings were identified related to the use of PRN medications to manage symptoms from nicotine, alcohol and other drug withdrawal. Differences related to the useage of comfort rooms and conducting comprehensive assessments of consumers' psychiatric symptoms were also detected. Qualitative findings highlighted the need for increased accountability for the prescribing and administration of PRN medications along with more nursing education/training to use alternative first line interventions. Nurses administering PRN medications should be vigilant regarding the indications for this practice to ensure they are facilitating the consumer's recovery by reducing the use of all forms of potentially restrictive practices in the hospital setting. The reasons for using PRN medications and PRN administration rates must be continually monitored to avoid practices such as high dose antipsychotics use and antipsychotic polypharmacy to ensure the efficacy of the consumers' management plans on their health care outcomes. © 2017 Australian College of Mental Health Nurses Inc.
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Baker, J A; Lovell, K; Harris, N
2008-10-01
As required or pro re nata (PRN) psychotropic medicines are frequently used in acute mental health wards. PRN is known to contribute to polypharmacy and high doses of antipsychotic medication. Few studies have attempted to improve clinician's use of these potentially harmful drugs. The objectives of the study were to determine the impact and acceptability of a good practice manual on prescribing and administration practices of PRN psychotropic medication in acute mental health wards. The study used a pre-post exploratory design with two acute mental health wards in the NW of England. Over the total trial period of 10 weeks, 28 of 35 patients received 484 doses of PRN. Patients had a mean of 3.6 prescriptions of 14 different PRN medications in 34 different dose combinations prescribed. Medication errors beyond poor quality of prescribing occurred in 23 of the 35 patients (65.7%). Prescription quality improved following the introduction of the intervention but quality of nursing notes reduced. Acceptability of the manual to both nursing and medical staff was high. The introduction of the manual appeared to influence some of the practices associated with the prescribing and administration of PRN psychotropic medications. Further, larger, more robust studies are required in this area. In particular research is required to identify the reasons why professionals continue to rely so heavily on using PRN medication.
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Functional characterization of the origin of replication of pRN1 from Sulfolobus islandicus REN1H1.
Directory of Open Access Journals (Sweden)
Chijioke J Joshua
Full Text Available Plasmid pRN1 from Sulfolobus islandicus REN1H1 is believed to replicate by a rolling circle mechanism but its origin and mechanism of replication are not well understood. We sought to create minimal expression vectors based on pRN1 that would be useful for heterologous gene expression in S. acidocaldarius, and in the process improve our understanding of the mechanism of replication. We constructed and transformed shuttle vectors that harbored different contiguous stretches of DNA from pRN1 into S. acidocaldarius E4-39, a uracil auxotroph. A 232-bp region 3' of orf904 was found to be critical for pRN1 replication and is therefore proposed to be the putative origin of replication. This 232-bp region contains a 100-bp stem-loop structure believed to be the double-strand origin of replication. The loop of the 100-bp structure contains a GTG tri-nucleotide motif, a feature that was previously reported to be important for the primase activity of Orf904. This putative origin and the associated orf56 and orf904 were identified as the minimal replicon of pRN1 because transformants of plasmids lacking any of these three features were not recovered. Plasmids lacking orf904 and orf56 but harboring the putative origin were transformable when orf904 and orf56 were provided in-trans; a 75-bp region 5' of the orf904 start codon was found to be essential for this complementation. Detailed knowledge of the pRN1 origin of replication will broaden the application of the plasmid as a genetic tool for Sulfolobus species.
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Xu, Jun; Wang, Fang; Zhao, Desheng; Liu, Jiang; Su, Hong; Wang, Baolong
2018-03-30
Enterovirus 71 (EV71) is the main pathogen of hand-foot-mouth disease (HFMD) and causes several neurological complications. As new strains of EV71 are constantly discovered, it is important to understand the genomic characteristics of the viruses and the mechanism of virulence. Herein, we isolated five strains of EV71 from HFMD patients with or without neurovirulence and sequenced their whole genomes. We then performed whole genome sequence analysis of totally 36 EV71 strains. The phylogenetic analysis of the VP1 region revealed all five isolated strains are clustered into C4a of C4 subgenotype. In addition, by comparing the complete genome sequences of 36 strains, 253 variable amino acid positions were found, 14 of which were identified to be associated with neurovirulence (P < 0.05). Moreover, a similar pattern of amino acid variants combination was identified in four strains without neurovirulence, indicating this type of variant pattern might be associated with avirulence. The strains with neurovirulence appeared to be distinguished from those without neurovirulence by the variants in VP1 and P2 regions, implying VP1 and P2 are the important regions associated with neurovirulence. Indeed, 3-D modeling of VP1 and P2 regions of non-neurovirulent and neurovirulent strains revealed that the different variants resulted in different protein structures and amino acid composition of ligand binding site, which might account for their difference in neurovirulence. In summary, our study reveals 14 variable amino acid positions of VP1, P2 and P3 regions are related to the virulence and that mutations in the capsid proteins of EV71 might contribute to neurovirulence. © 2018 Wiley Periodicals, Inc.
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Martin, Krystle; Ham, Elke; Hilton, N Zoe
2018-05-31
Most psychiatric inpatients will receive psychotropic PRN medication during their hospital stay for agitation, anxiety, and/or insomnia. While helpful in some cases, caution is warranted with regard to PRN use due to inherent risks of additional medication; therefore, experts advise that non-pharmacological interventions should be attempted first where indicated. However, research to date highlights that, in practice, non-pharmaceutical approaches are attempted in a minority of cases. While some information is known about the practice of PRN administration and the use of and barriers to implementing non-pharmacological interventions for treating acute psychiatric symptoms, full understanding of this practice is hampered by poor or altogether missing documentation of the process. This study used interviews with patients and staff from two psychiatric hospitals to collect first-person accounts of administering PRN medication for anxiety, thereby addressing the limitations of relying on documented notation found in previous research. Our results indicate that nurses are engaging in non-pharmacological interventions more often than had previously been captured in research. However, the types of strategies suggested are not typically evidence based and further, only happening approximately half the time. The barriers to providing such care are centred on two main beliefs about client choice and efficacy of these non-medical strategies. Implications for research and practice are discussed. © 2018 Australian College of Mental Health Nurses Inc.
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Martin, Krystle; Ham, Elke; Hilton, Zoe
2018-05-12
To describe the documentation of pro re nata (PRN) medication for anxiety, and to compare documentation at two hospitals providing similar psychiatric services, one that used paper charts and another that used an electronic health record (EHR). We also assessed congruence between nursing documentation and verbal reports from staff about the PRN administration process. The ability to accurately document patients' symptoms and the care given is considered a core competency of the nursing profession (Wilkinson, 2007); however, researchers have found poor concordance between nursing notes and verbal reports or observations of events (e.g., De Marinis, Piredda, Pascarella et al., 2009) and considerable information missing (e.g., Marinis et al., 2010). Additionally, the administration of PRN medication has consistently been noted to be poorly documented (e.g., Baker, Lovell, & Harris, 2008). The project was a mixed method, two-phase study that collected data from two sites. In phase 1, nursing documentation of PRN medication administrations was reviewed in patient charts; phase 2 included verbal reports from staff about this practice. Nurses using EHR documented more information than those using paper charts, including the reason for PRN administration, who initiated the administration, and effectiveness. There were some differences between written and verbal reports, including whether potential side effects were explained to patients prior to PRN administration. We continue the calls for attention to be paid to improving the quality of nursing documentation. Our results support the shift to using EHR, yet not relying on this method completely to ensure comprehensiveness of documentation. Efforts to address the quality of documentation, particularly for PRN administration, are needed. This could be done through training, using structured report templates, and switching to electronic databases. This article is protected by copyright. All rights reserved. This article is
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Carlow virus, a 2002 GII.4 variant Norovirus strain from Ireland.
LENUS (Irish Health Repository)
Kearney, Karen
2007-01-01
BACKGROUND: Noroviruses are the leading cause of infectious non-bacterial gastroenteritis in Ireland (population 4 million). Due to the number of outbreaks, its massive impact on the Irish health service and its seasonality, Norovirus has gained public notoriety as The Winter Vomiting Bug. The increase in cases in Ireland in the 2002-2003 season coincided with the emergence of two new Genogroup II genotype 4 variant clusters of Norovirus worldwide. RESULTS: Little research has been done on the epidemiology or molecular biology of Norovirus strains in Ireland. In an effort to combat this discrepancy, we cloned a full length human norovirus genome as a cDNA clone (J3) which can produce full length transcripts in vitro. A polymerase mutant cDNA clone (X1), in addition to a sub genomic cDNA clone (1A) were produced for use in future work. Carlow virus (Hu\\/NoV\\/GII\\/Carlow\\/2002\\/Ire) genome is 7559 nts in length, excluding the 3-end poly A tail and represents the first Norovirus strain from Ireland to be sequenced. CONCLUSION: Carlow virus is a member of the Farmington Hills variant cluster of Genogroup II genotype 4 noroviruses.
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Gerritsen, L.J.M.; Smits, P.H.
1997-01-01
The preference of nematodes for feeding on, and retention of strains and form variants of symbionts was tested. Heterorhabditis megidis strains DH-SH1 (= HSH) and NLH-E87.3 (= HE) could multiply on the primary forms of both symbionts. Photorhabdus luminescens strains PSH/1 and PE/1, respectively,
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Toxin Gene Analysis of a Variant Strain of Clostridium difficile That Causes Human Clinical Disease
Sambol, Susan P.; Merrigan, Michelle M.; Lyerly, David; Gerding, Dale N.; Johnson, Stuart
2000-01-01
A toxin variant strain of Clostridium difficile was isolated from two patients with C. difficile-associated disease (CDAD), one of whom died from extensive pseudomembranous colitis. This strain, identified by restriction endonuclease analysis (REA) as type CF2, was not detected by an immunoassay for C. difficile toxin A. Culture supernatants of CF2 failed to elicit significant enterotoxic activity in the rabbit ileal loop assay but did produce atypical cytopathic effects in cell culture assay. Southern hybridization, PCR amplification, and DNA sequence analyses were performed on the toxin A (tcdA) and toxin B (tcdB) genes of type CF2 isolate 5340. Type CF2 5340 tcdA exhibited a 1,821-bp truncation, due to three deletions in the 3′ end of the gene, and a point mutation in the 5′ end of the gene, resulting in a premature stop codon at tcdA position 139. Type CF2 5340 tcdB exhibited multiple nucleotide base substitutions in the 5′ end of the gene compared to tcdB of the standard toxigenic strain VPI 10463. Type CF2 5340 toxin gene nucleotide sequences and deduced amino acid sequences showed a strong resemblance to those of the previously described variant C. difficile strain 1470, a strain reported to have reduced pathogenicity and no association with clinical illness in humans. REA of strain 1470 identified this strain as a distinct type (CF1) within the same REA group as the closely related type CF2. A review of our clinical-isolate collection identified five additional patients infected with type CF2, three of whom had documented CDAD. PCR amplification of the 3′ end of tcdA demonstrated identical 1.8-kb deletions in all seven type CF2 isolates. REA type CF2 is a toxin variant strain of C. difficile that retains the ability to cause disease in humans but is not detected in clinical immunoassays for toxin A. PMID:10992443
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Reversion in variants from a duplication strain of Aspergillus nidulans
International Nuclear Information System (INIS)
Menezes, E.M.; Azevedo, J.L.
1978-01-01
Strains of Aspergillus nidulans with a chromosome segment in duplicate, one in normal position and one translocated to another chromosome, are unstable at mitosis. In addition to variants which result from deletions in either of the duplicate segments, which usually have improved morphology, they produce variants with deteriorated morphology. Three deteriorated variants reverted frequently to parental type morphology, both spontaneously and after ultra-violet treatment. Of six reversions analysed genetically, five were due to suppressors and one was probably due to back mutation. The suppressors segregated as single genes and were not linked to the mutation which they suppress. The instability of these so-called 'deteriorated' variants is discussed in relation to mitotic instability phenomena in A. nidulans. (orig.) [de
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2012-12-12
... Bacillus subtilis Strain QST 713 To Include Residues of Bacillus subtilis Strain QST 713 Variant Soil... existing exemption from the requirement of a tolerance for residues of the Bacillus subtilis strain QST 713 in or on all food commodities by including residues of Bacillus subtilis strain QST 713 variant soil...
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Measles in Italy: Co-circulation of B3 variants during 2014.
Magurano, Fabio; Baggieri, Melissa; Bordi, Licia; Lalle, Eleonora; Chironna, Maria; Lazzarotto, Tiziana; Amendola, Antonella; Baldanti, Fausto; Ansaldi, Filippo; Filia, Antonietta; Declich, Silvia; Iannazzo, Stefania; Pompa, Maria Grazia; Bucci, Paola; Marchi, Antonella; Nicoletti, Loredana
2016-06-01
In 2013, the majority of the WHO/EUR countries reported an annual incidence of >1 case per one million population indicating that the elimination target is far from being met. Thus, there is the urgent need to uncover and analyze chains of measles virus (MV) transmission with the objective to identify vulnerable groups and avoid possible routes of introduction of MV variants in the European population. The analysis of molecular epidemiology of MV B3 strains identified in 2014 has shown that four different variants co-circulated in Italy, including the strain that caused a cruise-line ship outbreak at the beginning of the year. © 2015 Wiley Periodicals, Inc.
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Richard, Léa; Rua, Réjane; Betsem, Edouard; Mouinga-Ondémé, Augustin; Kazanji, Mirdad; Leroy, Eric; Njouom, Richard; Buseyne, Florence; Afonso, Philippe V; Gessain, Antoine
2015-12-01
Simian foamy virus (SFV) is a ubiquitous retrovirus in nonhuman primates (NHPs) that can be transmitted to humans, mostly through severe bites. In the past few years, our laboratory has identified more than 50 hunters from central Africa infected with zoonotic SFVs. Analysis of the complete sequences of five SFVs obtained from these individuals revealed that env was the most variable gene. Furthermore, recombinant SFV strains, some of which involve sequences in the env gene, were recently identified. Here, we investigated the variability of the env genes of zoonotic SFV strains and searched for possible recombinants. We sequenced the complete env gene or its surface glycoprotein region (SU) from DNA amplified from the blood of (i) a series of 40 individuals from Cameroon or Gabon infected with a gorilla or chimpanzee foamy virus (FV) strain and (ii) 1 gorilla and 3 infected chimpanzees living in the same areas as these hunters. Phylogenetic analyses revealed the existence of two env variants among both the gorilla and chimpanzee FV strains that were present in zoonotic and NHP strains. These variants differ greatly (>30% variability) in a 753-bp-long region located in the receptor-binding domain of SU, whereas the rest of the gene is very conserved. Although the organizations of the Env protein sequences are similar, the potential glycosylation patterns differ between variants. Analysis of recombination suggests that the variants emerged through recombination between different strains, although all parental strains could not be identified. SFV infection in humans is a great example of a zoonotic retroviral infection that has not spread among human populations, in contrast to human immunodeficiency viruses (HIVs) and human T-lymphotropic viruses (HTLVs). Recombination was a major mechanism leading to the emergence of HIV. Here, we show that two SFV molecular envelope gene variants circulate among ape populations in Central Africa and that both can be transmitted to
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Directory of Open Access Journals (Sweden)
Suvi Niemi
2011-01-01
Full Text Available Our aims were to genotype Chlamydia trachomatis strains present in urogenital samples and to investigate the occurrence of the Swedish new variant of C. trachomatis in Finland. We genotyped 160 C. trachomatis positive samples with ompA real-time PCR and analyzed 495 samples for the new variant. The three most prevalent genotypes were E (40%, F (28%, and G (13%. Only two specimens containing bacteria with the variant plasmid were detected. It seems that in Finland the percentage of infections due to genotypes F and G has slightly increased during the last 20 years. Genotypes E and G appear to be more common, and genotypes J/Ja and I/Ia appear to be less common in Europe than in the USA. Although the genotype E was the most common genotype among C. trachomatis strains, the new variant was rarely found in Finland.
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Mesquita, Leonardo Pereira; Gamon, Thais Helena Martins; Cuevas, Silvia Elena Campusano; Asano, Karen Miyuki; Fahl, Willian de Oliveira; Iamamoto, Keila; Scheffer, Karin Correa; Achkar, Samira Maria; Zanatto, Dennis Albert; Mori, Cláudia Madalena Cabrera; Maiorka, Paulo César; Mori, Enio
2017-12-01
Rabies is one of the most important zoonotic diseases and is caused by several rabies virus (RABV) variants. These variants can exhibit differences in neurovirulence, and few studies have attempted to evaluate the neuroinvasiveness of variants derived from vampire bats and wild carnivores. The aim of this study was to evaluate the neuropathogenesis of infection with two Brazilian RABV street variants (variant 3 and crab-eating fox) in mice. BALB/c mice were inoculated with RABV through the footpad, with the 50% mouse lethal dose (LD 50 ) determined by intracranial inoculation. The morbidity of rabies in mice infected with variant 3 and the crab-eating fox strain was 100% and 50%, respectively, with an incubation period of 7 and 6 days post-inoculation (dpi), respectively. The clinical disease in mice was similar with both strains, and it was characterized initially by weight loss, ruffled fur, hunched posture, and hind limb paralysis progressing to quadriplegia and recumbency at 9 to 12 dpi. Histological lesions within the central nervous system (CNS) characterized by nonsuppurative encephalomyelitis with neuronal degeneration and necrosis were observed in mice infected with variant 3 and those infected with the crab-eating fox variant. However, lesions and the presence of RABV antigen, were more widespread within the CNS of variant-3-infected mice, whereas in crab-eating fox-variant-infected mice, RABV antigens were more restricted to caudal areas of the CNS, such as the spinal cord and brainstem. In conclusion, the results shown here demonstrate that the RABV vampire bat strain (variant 3) has a higher potential for neuroinvasiveness than the carnivore variant.
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Hovingh, Elise Sofie; Mariman, Rob; Solans, Luis; Hijdra, Daniëlle; Hamstra, Hendrik-Jan; Jongerius, Ilse; van Gent, Marjolein; Mooi, Frits; Locht, Camille; Pinelli, Elena
2018-01-01
Whooping cough, caused by Bordetella pertussis, has resurged and presents a global health burden worldwide. B. pertussis strains unable to produce the acellular pertussis vaccine component pertactin (Prn), have been emerging and in some countries represent up to 95% of recent clinical isolates.
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Chen, Qi; Gauger, Phillip C; Stafne, Molly R; Thomas, Joseph T; Madson, Darin M; Huang, Haiyan; Zheng, Ying; Li, Ganwu; Zhang, Jianqiang
2016-05-01
At least two genetically different porcine epidemic diarrhoea virus (PEDV) strains have been identified in the USA: US PEDV prototype and S-INDEL-variant strains. The objective of this study was to compare the pathogenicity differences of the US PEDV prototype and S-INDEL-variant strains in conventional neonatal piglets under experimental infections. Fifty PEDV-negative 5-day-old pigs were divided into five groups of ten pigs each and were inoculated orogastrically with three US PEDV prototype isolates (IN19338/2013, NC35140/2013 and NC49469/2013), an S-INDEL-variant isolate (IL20697/2014), and virus-negative culture medium, respectively, with virus titres of 104 TCID50 ml- 1, 10 ml per pig. All three PEDV prototype isolates tested in this study, regardless of their phylogenetic clades, had similar pathogenicity and caused severe enteric disease in 5-day-old pigs as evidenced by clinical signs, faecal virus shedding, and gross and histopathological lesions. Compared with pigs inoculated with the three US PEDV prototype isolates, pigs inoculated with the S-INDEL-variant isolate had significantly diminished clinical signs, virus shedding in faeces, gross lesions in small intestines, caeca and colons, histopathological lesions in small intestines, and immunohistochemistry staining in ileum. However, the US PEDV prototype and the S-INDEL-variant strains induced similar viraemia levels in inoculated pigs. Whole genome sequences of the PEDV prototype and S-INDEL-variant strains were determined, but the molecular basis of virulence differences between these PEDV strains remains to be elucidated using a reverse genetics approach.
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Genetic heterogeneity of L-Zagreb mumps virus vaccine strain.
Kosutic-Gulija, Tanja; Forcic, Dubravko; Santak, Maja; Ramljak, Ana; Mateljak-Lukacevic, Sanja; Mazuran, Renata
2008-07-10
The most often used mumps vaccine strains Jeryl Lynn (JL), RIT4385, Urabe-AM9, L-Zagreb and L-3 differ in immunogenicity and reactogenicity. Previous analyses showed that JL, Urabe-AM9 and L-3 are genetically heterogeneous. We identified the heterogeneity of L-Zagreb throughout the entire genome. Two major variants were defined: variant A being identical to the consensus sequence of viral seeds and vaccine(s) and variant B which differs from variant A in three nucleotide positions. The difference between viral variants in L-Zagreb strain is insufficient for distinct viral strains to be defined. We demonstrated that proportion of variants in L-Zagreb viral population depends on cell substrate used for viral replication in vitro and in vivo. L-Zagreb strain should be considered as a single strain composed of at least two variant viral genomes.
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Womack, J E; Cramer, D V
1980-10-01
Starch gel electrophoresis and histochemical staining with L-leucyl-L-tyrosine have revealed genetic variation for dipeptidase in Rattus norvegicus. The tissue distribution, substrate specificity, and heterozygous expression as a monmeric protein suggest homology of the variant peptidase to human PEP-C and mouse Pep-3 (Dip-1). We propose Peptidase-3 (Pep-3) as a name for this autosomal locus in the rat. The allele responsible for slower (less anodal) electrophoretic migration is designated Pep-3a and is characteristic of strain ACI/Pit. A faster (more anodal) electrophoretic mobility is the product of the Pep-3b allele in strain F344/Pit. Twenty-five additional inbred strains carry Pep-3a and 16 others carry Pep-3b. Wild rats trapped in Pittsburgh were polymorphic for this locus. Alleles at Pep-3 segregated independently of c (linkage group I), a (linkage group IV), RT2 and Es-1 (linkage group V), h (linkage group VI), and RTI (linkage group VIII).
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Genetic heterogeneity of L-Zagreb mumps virus vaccine strain
Directory of Open Access Journals (Sweden)
Mateljak-Lukacevic Sanja
2008-07-01
Full Text Available Abstract Background The most often used mumps vaccine strains Jeryl Lynn (JL, RIT4385, Urabe-AM9, L-Zagreb and L-3 differ in immunogenicity and reactogenicity. Previous analyses showed that JL, Urabe-AM9 and L-3 are genetically heterogeneous. Results We identified the heterogeneity of L-Zagreb throughout the entire genome. Two major variants were defined: variant A being identical to the consensus sequence of viral seeds and vaccine(s and variant B which differs from variant A in three nucleotide positions. The difference between viral variants in L-Zagreb strain is insufficient for distinct viral strains to be defined. We demonstrated that proportion of variants in L-Zagreb viral population depends on cell substrate used for viral replication in vitro and in vivo. Conclusion L-Zagreb strain should be considered as a single strain composed of at least two variant viral genomes.
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Genetic heterogeneity of L-Zagreb mumps virus vaccine strain
Kosutic-Gulija, Tanja; Forcic, Dubravko; Šantak, Maja; Ramljak, Ana; Mateljak-Lukacevic, Sanja; Mazuran, Renata
2008-01-01
Background The most often used mumps vaccine strains Jeryl Lynn (JL), RIT4385, Urabe-AM9, L-Zagreb and L-3 differ in immunogenicity and reactogenicity. Previous analyses showed that JL, Urabe-AM9 and L-3 are genetically heterogeneous. Results We identified the heterogeneity of L-Zagreb throughout the entire genome. Two major variants were defined: variant A being identical to the consensus sequence of viral seeds and vaccine(s) and variant B which differs from variant A in three nucleotide positions. The difference between viral variants in L-Zagreb strain is insufficient for distinct viral strains to be defined. We demonstrated that proportion of variants in L-Zagreb viral population depends on cell substrate used for viral replication in vitro and in vivo. Conclusion L-Zagreb strain should be considered as a single strain composed of at least two variant viral genomes. PMID:18616793
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International Nuclear Information System (INIS)
Ueshima, N.; Yasuda, H.; Yoshiya, M.; Fukuda, T.; Kakeshita, T.
2014-01-01
Variant selection of L1 0 -type ferromagnetic alloys has been numerically investigated using the phase-field modeling, to clarify the phenomena at greater temporal and spatial resolution and to reveal the underlying mechanism. The duration for which the external magnetic field is effective is found to be very short, and variant selection is significantly affected by not only direct response to the external magnetic field but also their interplay between the field, intrinsic transformation strain, and various thermodynamic energy components involved in the course of microstructure evolution. The detailed mechanism of the interplay was quantitatively analyzed in terms of the driving force for the variant selection, by partitioning it into the various energy components. Careful examination of the variant selection at the very early stage revealed that the slight difference in size and configuration of variants during disorder-to-order transition realized by the interplay between transformation strain and external field is essentially needed before proceeding to the latter stage of the variant selection driven by interface energy
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Epstein-Barr virus strains and variations: Geographic or disease-specific variants?
Neves, Marco; Marinho-Dias, Joana; Ribeiro, Joana; Sousa, Hugo
2017-03-01
The Epstein-Barr Virus (EBV) is associated with the development of several diseases, including infectious mononucleosis (IM), Burkitt's Lymphoma (BL), Nasopharyngeal Carcinoma, and other neoplasias. The publication of EBV genome 1984 led to several studies regarding the identification of different viral strains. Currently, EBV is divided into EBV type 1 (B95-8 strain) and EBV type 2 (AG876 strain), also known as type A and type B, which have been distinguished based upon genetic differences in the Epstein-Barr nuclear antigens (EBNAs) sequence. Several other EBV strains have been described in the past 10 years considering variations on EBV genome, and many have attempted to clarify if these variations are ethnic or geographically correlated, or if they are disease related. Indeed, there is an increasing interest to describe possible specific disease associations, with emphasis on different malignancies. These studies aim to clarify if these variations are ethnic or geographically correlated, or if they are disease related, thus being important to characterize the epidemiologic genetic distribution of EBV strains on our population. Here, we review the current knowledge on the different EBV strains and variants and its association with different diseases. J. Med. Virol. 89:373-387, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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Diack, Abigail B; Boyle, Aileen; Ritchie, Diane; Plinston, Chris; Kisielewski, Dorothy; de Pedro-Cuesta, Jesús; Rábano, Alberto; Will, Robert G; Manson, Jean C
2017-09-01
We investigated transmission characteristics of variant Creutzfeldt-Jakob disease in a mother and son from Spain. Despite differences in patient age and disease manifestations, we found the same strain properties in these patients as in UK vCJD cases. A single strain of agent appears to be responsible for all vCJD cases to date.
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Livingstone, Morag; Wheelhouse, Nicholas; Ensor, Hannah; Rocchi, Mara; Maley, Stephen; Aitchison, Kevin; Wattegedera, Sean; Wilson, Kim; Sait, Michelle; Siarkou, Victoria; Vretou, Evangelia; Entrican, Gary; Dagleish, Mark; Longbottom, David
2017-01-01
This study investigated the pathogenesis of two variant strains (LLG and POS) of Chlamydia abortus, in comparison to a typical wild-type strain (S26/3) which is known to be responsible for late term abortion in small ruminants. Challenge with the three strains at mid-gestation resulted in similar pregnancy outcomes, with abortion occurring in approximately 50-60% of ewes with the mean gestational lengths also being similar. However, differences were observed in the severity of placental pathology, with infection appearing milder for strain LLG, which was reflected in the lower number of organisms shed in vaginal swabs post-partum and less gross pathology and organisms present in placental smears. Results for strain POS were somewhat different than LLG with a more focal restriction of infection observed. Post-abortion antibody responses revealed prominent differences in seropositivity to the major outer membrane protein (MOMP) present in elementary body (EB) preparations under denaturing conditions, most notably with anti-LLG and anti-POS convalescent sera where there was no or reduced detection of MOMP present in EBs derived from the three strains. These results and additional analysis of whole EB and chlamydial outer membrane complex preparations suggest that there are conformational differences in MOMP for the three strains. Overall, the results suggest that gross placental pathology and clinical outcome is not indicative of bacterial colonization and the severity of infection. The results also highlight potential conformational differences in MOMP epitopes that perhaps impact on disease diagnosis and the development of new vaccines.
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Directory of Open Access Journals (Sweden)
Morag Livingstone
Full Text Available This study investigated the pathogenesis of two variant strains (LLG and POS of Chlamydia abortus, in comparison to a typical wild-type strain (S26/3 which is known to be responsible for late term abortion in small ruminants. Challenge with the three strains at mid-gestation resulted in similar pregnancy outcomes, with abortion occurring in approximately 50-60% of ewes with the mean gestational lengths also being similar. However, differences were observed in the severity of placental pathology, with infection appearing milder for strain LLG, which was reflected in the lower number of organisms shed in vaginal swabs post-partum and less gross pathology and organisms present in placental smears. Results for strain POS were somewhat different than LLG with a more focal restriction of infection observed. Post-abortion antibody responses revealed prominent differences in seropositivity to the major outer membrane protein (MOMP present in elementary body (EB preparations under denaturing conditions, most notably with anti-LLG and anti-POS convalescent sera where there was no or reduced detection of MOMP present in EBs derived from the three strains. These results and additional analysis of whole EB and chlamydial outer membrane complex preparations suggest that there are conformational differences in MOMP for the three strains. Overall, the results suggest that gross placental pathology and clinical outcome is not indicative of bacterial colonization and the severity of infection. The results also highlight potential conformational differences in MOMP epitopes that perhaps impact on disease diagnosis and the development of new vaccines.
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Directory of Open Access Journals (Sweden)
Skilton Rachel J
2009-05-01
Full Text Available Abstract Background Chlamydia trachomatis is the most common cause of sexually transmitted infections globally and the leading cause of preventable blindness in the developing world. There are two biovariants of C. trachomatis: 'trachoma', causing ocular and genital tract infections, and the invasive 'lymphogranuloma venereum' strains. Recently, a new variant of the genital tract C. trachomatis emerged in Sweden. This variant escaped routine diagnostic tests because it carries a plasmid with a deletion. Failure to detect this strain has meant it has spread rapidly across the country provoking a worldwide alert. In addition to being a key diagnostic target, the plasmid has been linked to chlamydial virulence. Analysis of chlamydial plasmids and their cognate chromosomes was undertaken to provide insights into the evolutionary relationship between chromosome and plasmid. This is essential knowledge if the plasmid is to be continued to be relied on as a key diagnostic marker, and for an understanding of the evolution of Chlamydia trachomatis. Results The genomes of two new C. trachomatis strains were sequenced, together with plasmids from six C. trachomatis isolates, including the new variant strain from Sweden. The plasmid from the new Swedish variant has a 377 bp deletion in the first predicted coding sequence, abolishing the site used for PCR detection, resulting in negative diagnosis. In addition, the variant plasmid has a 44 bp duplication downstream of the deletion. The region containing the second predicted coding sequence is the most highly conserved region of the plasmids investigated. Phylogenetic analysis of the plasmids and chromosomes are fully congruent. Moreover this analysis also shows that ocular and genital strains diverged from a common C. trachomatis progenitor. Conclusion The evolutionary pathways of the chlamydial genome and plasmid imply that inheritance of the plasmid is tightly linked with its cognate chromosome. These data
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Directory of Open Access Journals (Sweden)
Weerayuth Kittichotirat
2017-12-01
Full Text Available Pythium insidiosum is a unique oomycete microorganism, capable of infecting humans and animals. The organism can be phylogenetically categorized into three distinct clades: Clade-I (strains from the Americas; Clade-II (strains from Asia and Australia, and CladeâIII (strains from Thailand and the United States. Two draft genomes of the P. insidiosum Clade-I strain CDC-B5653 and Clade-II strain Pi-S are available in the public domain. The genome of P. insidiosum from the distinct Clade-III, which is distantly-related to the other two clades, is lacking. Here, we report the draft genome sequence of the P. insidiosum strain Pi45 (also known as MCC13; isolated from a Thai patient with pythiosis; accession numbers BCFM01000001-BCFM01017277 as a representative strain of the phylogenetically-distinct Clade-III. We also report a genome-scale data set of sequence variants (i.e., SNPs and INDELs found in P. insidiosum (accessible online at the Mendeley database: http://dx.doi.org/10.17632/r75799jy6c.1. Keywords: Pythium insidiosum, Pythiosis, Draft genome, Sequence variant
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Calderon, Marina Gallo; Mattion, Nora; Bucafusco, Danilo; Fogel, Fernando; Remorini, Patricia; La Torre, Jose
2009-08-01
PCR amplification with sequence-specific primers was used to detect canine parvovirus (CPV) DNA in 38 rectal swabs from Argentine domestic dogs with symptoms compatible with parvovirus disease. Twenty-seven out of 38 samples analyzed were CPV positive. The classical CPV2 strain was not detected in any of the samples, but nine samples were identified as CPV2a variant and 18 samples as CPV2b variant. Further sequence analysis revealed a mutation at amino acid 426 of the VP2 gene (Asp426Glu), characteristic of the CPV2c variant, in 14 out of 18 of the samples identified initially by PCR as CPV2b. The appearance of CPV2c variant in Argentina might be dated at least to the year 2003. Three different pathogenic CPV variants circulating currently in the Argentine domestic dog population were identified, with CPV2c being the only variant affecting vaccinated and unvaccinated dogs during the year 2008.
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Terasaki, Hidenori; Moriguchi, Koji; Tomio, Yusaku; Yamagishi, Hideki; Morito, Shigekazu
2017-12-01
The effect of carbon content on the density of variant-pair boundaries was investigated in 9Ni steel using an electron backscatter diffraction patterns method. The changes in the density of variant-pair boundaries were correlated with the nondestructive measured values of shear modulus of the austenite phase at the phase transformation point. Furthermore, the effective grain size was correlated with the shear modulus and the density of variant-pair boundaries. These relations are discussed from the viewpoint of self-accommodation of elastic strain energy and the nucleation event in the bainite and martensitic transformations.
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Directory of Open Access Journals (Sweden)
Munmun Nandi
Full Text Available Pseudomonas chlororaphis strain PA23 is a biocontrol agent able to suppress growth of the fungal pathogen Sclerotinia sclerotiorum. This bacterium produces an arsenal of exometabolites including pyrrolnitrin (PRN, phenazine (PHZ, hydrogen cyanide (HCN, and degradative enzymes. Production of these compounds is controlled at both the transcriptional and posttranscriptional levels by the Gac-Rsm system, RpoS, PsrA, and the Phz quorum-sensing system. Beyond pathogen-suppression, the success of a biocontrol agent is dependent upon its ability to establish itself in the environment where predation by bacterivorous organisms, including nematodes, may threaten persistence. The focus of this study was to investigate whether PA23 is able to resist grazing by Caenorhabditis elegans and to define the role played by exoproducts in the bacterial-nematode interaction. We discovered that both PRN and HCN contribute to fast- and slow-killing of C. elegans. HCN is well-established as having lethal effects on C. elegans; however, PRN has not been reported to be nematicidal. Exposure of L4 stage nematodes to purified PRN reduced nematode viability in a dose-dependent fashion and led to reduced hatching of eggs laid by gravid adults. Because bacterial metabolites can act as chemoattractants or repellents, we analyzed whether PA23 exhibited attractant or repulsive properties towards C. elegans. Both PRN and HCN were found to be potent repellents. Next we investigated whether the presence of C. elegans would elicit changes in PA23 gene activity. Co-culturing the two organisms increased expression of a number of genes associated with biocontrol, including phzA, hcnA, phzR, phzI, rpoS and gacS. Exoproduct analysis showed that PHZ and autoinducer signals were upregulated, consistent with the gene expression profiles. Collectively, these findings indicate that PA23 is able to sense the presence of C. elegans and it is able to both repel and kill the nematodes, which
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GERBER, P; LOOSLI, C G; HAMBRE, D
1955-06-01
Antigenically different strains of mouse-adapted PR8 influenza A virus have been produced by 17 serial passages of the virus in the lungs of mice immunized with the homologous agent. Comparative serological tests show that the variant strains share antigenic components with the parent strain but the dominant antigen is different. By means of antibody absorption it was shown that the "new" antigenic component of the variant was already present in minor amounts up to the eighth passage and thereafter gained prominence with continued passage in vaccinated mice. Groups of mice vaccinated with either the PR8-S or T(21) virus and having comparable antibody titers showed no growth of virus in the lungs following aid-borne challenge with homologous strains. On the other hand, following heterologous air-borne challenge no deaths occurred, but virus grew in the lungs of both groups of vaccinated mice. Almost unrestricted virus multiplication took place in the lungs of mice vaccinated with the parent strain and challenged with the PR8-T(21) virus which resulted in extensive consolidation. Less virus grew in the lungs of the mice vaccinated with the variant strains and challenged with the PR8-S virus. In these animals only microscopic evidence of changes due to virus growth in the lungs was observed. The successful serial passage of PR8 influenza A virus in immunized animals was dependent on the initial selection of mice with uniformly low H.I. antibody titers as determined on tail blood, and the intranasal instillation of sufficient virus to favor the survival of those virus particles least related to the antibodies present. The epidemiological implications of these observations are discussed briefly.
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Cui, Haibo; Wei, Xiaomei; Huang, Yu; Hu, Bin; Fang, Yaping; Wang, Jia
2014-01-01
Among human influenza viruses, strain A/H3N2 accounts for over a quarter of a million deaths annually. Antigenic variants of these viruses often render current vaccinations ineffective and lead to repeated infections. In this study, a computational model was developed to predict antigenic variants of the A/H3N2 strain. First, 18 critical antigenic amino acids in the hemagglutinin (HA) protein were recognized using a scoring method combining phi (ϕ) coefficient and information entropy. Next, a prediction model was developed by integrating multiple linear regression method with eight types of physicochemical changes in critical amino acid positions. When compared to other three known models, our prediction model achieved the best performance not only on the training dataset but also on the commonly-used testing dataset composed of 31878 antigenic relationships of the H3N2 influenza virus.
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Influence of population diversity on neurovirulence potential of plaque purified L-Zagreb variants.
Ivancic-Jelecki, Jelena; Forcic, Dubravko; Jagusic, Maja; Kosutic-Gulija, Tanja; Mazuran, Renata; Balija, Maja Lang; Isakov, Ofer; Shomron, Noam
2016-04-29
Despite continuing research efforts, determinants of mumps virus virulence are still largely unknown. One of consequences of this is difficulty in striking a balance between efficacy and safety of live attenuated mumps vaccines. Among mumps vaccine strains associated with occurrence of postvaccinal aseptic meningitis is L-Zagreb, developed by further attenuation of vaccine strain L-3. Starting from an archived L-Zagreb sample with suboptimal neuroattenuation score, we isolated different viral variants and compared their genetic and phenotypic properties, in investigation of neurovirulence markers. Six different L-Zagreb variants were isolated by plaque purification. Their neurovirulent status was determined by rat-based neurovirulence test; population structure was determined by deep sequencing. We isolated one well neuroattenuated viral variant, two marginally neuroattenuated, and three insufficiently neuroattenuated. No genetic markers of neurovirulence could be identified. None of variants had detectable amounts of defective interfering particles. Two characteristics set insufficiently neuroattenuated variants apart from less-neurovirulent ones: elevated variability level in regions 1293-3314, 5363-7773 and 9382-11657, and/or elevated number of mutations present in frequencies ≥ 1%. The most neurovirulent variants possessed both of these features. Distinctive heterogeneity profiles were obtained for insufficiently neuroattenuated L-Zagreb variants. No markers that would discriminate between marginally and well neuroattenuated variants were identified. The findings of this study may serve as a guideline during development of an improved L3/L-Zagreb vaccine strain. Copyright © 2016 Elsevier Ltd. All rights reserved.
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APOBEC3G Variants and Protection against HIV-1 Infection in Burkina Faso.
Compaore, Tegwinde Rebeca; Soubeiga, Serge Theophile; Ouattara, Abdoul Karim; Obiri-Yeboah, Dorcas; Tchelougou, Damehan; Maiga, Mamoudou; Assih, Maleki; Bisseye, Cyrille; Bakouan, Didier; Compaore, Issaka Pierre; Dembele, Augustine; Martinson, Jeremy; Simpore, Jacques
2016-01-01
Studies on host factors, particularly the APOBEC3G gene, have previously found an association with AIDS progression in some populations and against some HIV-1 strains but not others. Our study had two main objectives: firstly, to screen a population from Burkina Faso for three variants of APOBEC3G previously described, and secondly to analyze the effect of these three variants and their haplotypes on HIV-1 infection with Circulating Recombinant Forms (CRFs) present in Burkina Faso. This case control study involved 708 seropositive and seronegative individuals. Genotyping was done by the TaqMan allelic discrimination method. Minor allele frequencies of rs6001417 (p<0.05), rs8177832 (P<0.05), and rs35228531 (P<0.001) were higher in seronegative subjects. The rs6001417 and rs8177832 SNPs were associated with HIV-1 infection in an additive model (P<0.01). Furthermore the SNP rs35228531 was also associated with HIV-1 infection in a dominant model (P<0.001). Odds ratio analysis of genotypes and alleles of the different APOBEC3G variants showed that there is a strong association between the minor genetic variants, genotype of the three SNPs, and HIV-1 status. Haplotype analysis demonstrated that rs6001417, rs8177832, and rs35228531 are in linkage disequilibrium. The haplotype GGT from the rs6001417, rs8177832 and rs35228531 respectively has a protective effect OR = 0.54 [0.43-0.68] with P<0.001. There was also associations between the haplotypes GGC OR = 1.6 [1.1;-2.3] P<0.05, and CGC OR = 5.21 [2.4-11.3] P<0.001, which increase the risk of infection by HIV-1 from almost two (2) to five (5) fold. This study demonstrates an association of rs6001417, rs8177832, and rs35228531 of APOBEC3G with HIV-1 infection in a population from Burkina Faso.
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APOBEC3G Variants and Protection against HIV-1 Infection in Burkina Faso.
Directory of Open Access Journals (Sweden)
Tegwinde Rebeca Compaore
Full Text Available Studies on host factors, particularly the APOBEC3G gene, have previously found an association with AIDS progression in some populations and against some HIV-1 strains but not others. Our study had two main objectives: firstly, to screen a population from Burkina Faso for three variants of APOBEC3G previously described, and secondly to analyze the effect of these three variants and their haplotypes on HIV-1 infection with Circulating Recombinant Forms (CRFs present in Burkina Faso. This case control study involved 708 seropositive and seronegative individuals. Genotyping was done by the TaqMan allelic discrimination method. Minor allele frequencies of rs6001417 (p<0.05, rs8177832 (P<0.05, and rs35228531 (P<0.001 were higher in seronegative subjects. The rs6001417 and rs8177832 SNPs were associated with HIV-1 infection in an additive model (P<0.01. Furthermore the SNP rs35228531 was also associated with HIV-1 infection in a dominant model (P<0.001. Odds ratio analysis of genotypes and alleles of the different APOBEC3G variants showed that there is a strong association between the minor genetic variants, genotype of the three SNPs, and HIV-1 status. Haplotype analysis demonstrated that rs6001417, rs8177832, and rs35228531 are in linkage disequilibrium. The haplotype GGT from the rs6001417, rs8177832 and rs35228531 respectively has a protective effect OR = 0.54 [0.43-0.68] with P<0.001. There was also associations between the haplotypes GGC OR = 1.6 [1.1;-2.3] P<0.05, and CGC OR = 5.21 [2.4-11.3] P<0.001, which increase the risk of infection by HIV-1 from almost two (2 to five (5 fold. This study demonstrates an association of rs6001417, rs8177832, and rs35228531 of APOBEC3G with HIV-1 infection in a population from Burkina Faso.
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Energy Technology Data Exchange (ETDEWEB)
Rong, Libin [Los Alamos National Laboratory; Ribeiro, Ruy M [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory
2008-01-01
Telaprevir (VX-950), a novel hepatitis C virus (HCV) NS3-4A serine protease inhibitor, has demonstrated substantial antiviral activity in patients infected with HCV genotype 1. Some patients experience viral breakthrough, which has been shown to be associated with emergence of telaprevir-resistant HCV variants during treatment. The exact mechanisms underlying the rapid selection of drug resistant viral variants during dosing are not fully understood. In this paper, we develop a two-strain model to study the pre-treatment prevalence of the mutant virus and derive an analytical solution of the mutant frequency after administration of the protease inhibitor. Our analysis suggests that the rapid increase of the mutant frequency during therapy is not due to mutant growth but rather due to the rapid and profound loss of wild-type virus, which uncovers the pre-existing mutant variants. We examine the effects of backward mutation and hepatocyte proliferation on the pre-existence of the mutant virus and the competition between wild-type and drug resistant virus during therapy. We then extend the simple model to a general model with multiple viral strains. Mutations during therapy do not play a significant role in the dynamics of various viral strains, although they are capable of generating low levels of HCV variants that would otherwise be completely suppressed because of fitness disadvantages. Hepatocyte proliferation may not affect the pretreatment frequency of mutant variants, but is able to influence the quasispecies dynamics during therapy. It is the relative fitness of each mutant strain compared with wild-type that determines which strain(s) will dominate the virus population. The study provides a theoretical framework for exploring the prevalence of pre-existing mutant variants and the evolution of drug resistance during treatment with other protease inhibitors or HCV polymerase inhibitors.
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Influenza A (H3N2) Variant Virus
... Swine Variant Pandemic Other Influenza A (H3N2) Variant Virus Language: English (US) Español Recommend on Facebook Tweet Share Compartir Influenza viruses that normally circulate in pigs are called “variant” ...
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Complete Nucleotide Sequence Analysis of the Norovirus GII.4 Sydney Variant in South Korea
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Ji-Sun Park
2015-01-01
Full Text Available Norovirus is the primary cause of acute gastroenteritis in individuals of all ages. In Australia, a new strain of norovirus (GII.4 was identified in March 2012, and this strain has spread rapidly around the world. In August 2012, this new GII.4 strain was identified in patients in South Korea. Therefore, to examine the characteristics of the epidemic norovirus GII.4 2012 variant in South Korea, we conducted KM272334 full-length genomic analysis. The genome of the gg-12-08-04 strain consisted of 7,558 bp and contained three open reading frame (ORF composites throughout the whole genome: ORF1 (5,100 bp, ORF2 (1,623 bp, and ORF3 (807 bp. Phylogenetic analyses showed that gg-12-08-04 belonged to the GII.4 Sydney 2012 variant, sharing 98.92% nucleotide similarity with this variant strain. According to SimPlot analysis, the gg-12-08-04 strain was a recombinant strain with breakpoint at the ORF1/2 junction between Osaka 2007 and Apeldoorn 2008 strains. This study is the first report of the complete sequence of the GII.4 Sydney 2012 strain in South Korea. Therefore, this may represent the standard sequence of the norovirus GII.4 2012 variant in South Korea and could therefore be useful for the development of norovirus vaccines.
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Characterization of form variants of Xenorhabdus luminescens.
Gerritsen, L J; de Raay, G; Smits, P H
1992-01-01
From Xenorhabdus luminescens XE-87.3 four variants were isolated. One, which produced a red pigment and antibiotics, was luminescent, and could take up dye from culture media, was considered the primary form (XE-red). A pink-pigmented variant (XE-pink) differed from the primary form only in pigmentation and uptake of dye. Of the two other variants, one produced a yellow pigment and fewer antibiotics (XE-yellow), while the other did not produce a pigment or antibiotics (XE-white). Both were less luminescent, did not take up dye, and had small cell and colony sizes. These two variants were very unstable and shifted to the primary form after 3 to 5 days. It was not possible to separate the primary form and the white variant completely; subcultures of one colony always contained a few colonies of the other variant. The white variant was also found in several other X. luminescens strains. DNA fingerprints showed that all four variants are genetically identical and are therefore derivatives of the same parent. Protein patterns revealed a few differences among the four variants. None of the variants could be considered the secondary form. The pathogenicity of the variants decreased in the following order: XE-red, XE-pink, XE-yellow, and XE-white. The mechanism and function of this variability are discussed. Images PMID:1622273
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Sánchez, Sergio; Díaz-Sánchez, Sandra; Martínez, Remigio; Llorente, María Teresa; Herrera-León, Silvia; Vidal, Dolors
2013-10-25
Subtilase cytotoxin (SubAB) is an AB5 toxin produced by Shiga toxin (Stx)-producing Escherichia coli (STEC) strains usually lacking the eae gene product intimin. Two allelic variants of SubAB encoding genes have been described: subAB1, located on a plasmid, and subAB2, located on a pathogenicity island (PAI) together with tia gene. While subAB1 has been reported to be more frequent among bovine strains, subAB2 has been mainly associated with strains from small ruminants. We investigated the presence of the two variants of subAB among 59 eae-negative STEC from large game animals (deer and wild boar) and their meat and meat products in order to assess the role of other species in the epidemiology of subAB-positive, eae-negative STEC. For this approach, the strains were PCR-screened for the presence of subAB, including the specific detection of both allelic variants, for the presence of saa, tia and sab, and for stx subtyping. Overall, subAB genes were detected in 71.2% of the strains: 84.1% of the strains from deer and 33.3% of the strains from wild boar. Most of them (97.6%) possessed subAB2 and most of these subAB2-positive strains (92.7%) were also positive for tia and negative for saa, suggesting the presence of the subAB2-harbouring PAI. Subtype stx2b was present in most of the strains (67.8%) and a statistically significant association could be established between subAB2 and stx2b. Our results suggest that large game animals, mainly deer, may represent an important animal reservoir of subAB2-positive, eae-negative STEC, and also highlight the risk of human infection posed by the consumption of large game meat and meat products. Copyright © 2013 Elsevier B.V. All rights reserved.
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Genomic constitution of an H-2:Tla variant leukemia.
Shen, F W; Chaganti, R S; Doucette, L A; Litman, G W; Steinmetz, M; Hood, L; Boyse, E A
1984-10-01
A TL+ leukemia of a (B6 X A)F1 hybrid mouse (H-2b/H-2a) was previously subjected to immunoselection against H-2a by passage in (B6 X A.SW)F1 mice (H-2b/H-2s). A variant leukemia line was obtained that serologically lacked not only the H-2a phenotype but also the TL phenotype determined by the linked cis Tlaa allele of strain A. The H-2b phenotype and the TL phenotype of the Tlab allele of the B6 strain, which is expressed only by leukemia cells, were retained by the variant. Southern blotting with an H-2 cDNA probe that identifies restriction fragment polymorphisms distinguishing alleles of the H-2 and Tla regions of the B6 and A strains indicates that both the H-2a and Tlaa alleles are missing from the genome of this H-2a:Tlaa negative variant. Since the variant has two apparently unaltered chromosomes 17, where the H-2:Tla complex is situated, and since the intensity of bands in Southern blotting is suggestive of H-2b homozygosity, it is considered that loss of the H-2a:Tlaa haplotype by the variant was accompanied by duplication of the H-2b:Tlab haplotype. The implied change from heterozygosity to homozygosity that the variant has undergone with respect to H-2:Tla was not paralleled by a similar change at the three other loci tested, since the variant retained heterozygosity for Pep-3 (chromosome 1), Gpi-1 (chromosome 7), and Es-1 (chromosome 8).
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Lizárraga-Partida, Marcial Leonardo; Quilici, Marie-Laure
2009-05-01
We studied the evolution of Vibrio cholerae O1 during the 1991 to 2000 cholera epidemic in Mexico by biochemical, serological, and molecular characterization of strains collected during this period. Strains were divided into toxigenic and nontoxigenic groups according to the presence or absence of genes encoding cholera toxin. As previously reported, we characterized two populations among toxigenic strains, which were present from the first year of the epidemic. BglI rRNA analysis revealed that these strains had ribotype profiles, denoted M5 and M6 in our study, that were identical to those previously designated Koblavi B5 or Popovic 5 and Popovic 6a or Tamayo B21a, respectively. Ribotype M5 was isolated between 1991 and 1993. This ribotype had a low level of genetic variation as detected by pulsed-field gel electrophoresis (PFGE). Ribotype M6 persisted from 1991 to 2000. However, PFGE profiles suggested that two epidemiologically unrelated strains coexisted within this single ribotype from 1995 until the end of the epidemic. We identified three new BglI ribotypes, Mx1, Mx2, and Mx3, from nontoxigenic V. cholerae O1 strains isolated between 1998 and 2000; one of them grouped strains positive for the toxin-coregulated pilus island. They differed from nontoxigenic clones isolated in Latin America and on the U.S. Gulf Coast and are probably autochthonous Mexican V. cholerae O1 variants. Most of these new variants were isolated from states surrounding the Gulf of Mexico, where the highest incidence of cholera in the country was recorded. Thus, the Mexican Gulf Coast, like the U.S. Gulf Coast, may act as an environmental reservoir of V. cholerae O1.
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Zhang, Dong-Yan; Feng, Yan; Zhong, Shu-Ling; Lu, Yi-Yu; Zhuang, Fang-Cheng; Xu, Chang-Ping
2012-03-01
To compare the differences in the complete genome sequence between mumps epidemic strain and mumps vaccine strain S79 isolated in Zhejiang province. A total of 4 mumps epidemic strains, which were separated from Zhejiang province during 2005 to 2010, named as ZJ05-1, ZJ06-3, ZJ08-1 and ZJ10-1 were selected in the study. The complete genome sequences were amplified using RT-PCR. The genetic differences between vaccine strain S79 and other genotype strains were compared; while the genetic-distance was calculated and the evolution was analyzed. The biggest difference between the 4 epidemic strains and the vaccine strain S79 was found on the membrane associated protein gene; whose average nucleotide differential number was 42.5 +/- 3.0 and the average variant ratio was 13.6%; while the mean amino acid differential number was 12.8 +/- 1.5 and the average variant ratio was 22.4%. The smallest difference among the 4 epidemic strains and the vaccine strain was found in stromatin genes, whose average nucleotide differential number was 73.8 +/- 2.5 and the average variant ratio was 5.9%; while the mean amino acid differential number was 3.0 +/- 0.8 and the average variant ratio was 0.8%. The dn/ds value of the stromatin genes of the 4 epidemic strains reached the highest, as 0.6526; but without any positive pressure (dn/ds 0.05). There were mutations happened on the known antigen epitope, as 8th amino acid of membrane associated protein genes and on the 336th and 356th amino acid of hemagglutinin/neuraminidase proteins. Compared with the vaccine strain, the glycosylation sites of ZJ05-1, ZJ06-3, ZJ08-1 and ZJ10-1 increased 1, 1, 2 and 2 respectively. The complete amino acid sequence of all strains showed that there were 17 characteristic sites found on the genotype-F mumps strain. Within the complete genome, the genetic-distance between epidemic strains and vaccine strains in Zhejiang province (0.071) was significantly larger than the genetic-distance between strains in
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Isolation of a variant of Candida albicans.
Buckley, H R; Price, M R; Daneo-Moore, L
1982-01-01
During the course of Candida albicans antigen production, a variant of this organism was encountered which did not produce hyphae at 37 degrees C. Presented here are some of the characteristics of this variant. It produces hyphae at 25 degrees C on cornmeal agar and synthetic medium plus N-acetylglucosamine and Tween 80. At 37 degrees C, it does not produce hyphae on these media, although C. albicans normally does produce hyphae under these circumstances. In liquid synthetic medium, this variant does not produce hyphae at 37 degrees C. The variant strain was analyzed for DNA, RNA, protein content, and particle size. After 50 to 70 h in balanced exponential-phase growth, particle size distribution was narrow, and there were no differences in the DNA, RNA, or protein content per particle in the two strains. When balanced exponential-phase cultures were brought into stationary phase, both strains contained the same amount of DNA per cell. Images PMID:6752021
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Isolation of a variant of Candida albicans.
Buckley, H R; Price, M R; Daneo-Moore, L
1982-09-01
During the course of Candida albicans antigen production, a variant of this organism was encountered which did not produce hyphae at 37 degrees C. Presented here are some of the characteristics of this variant. It produces hyphae at 25 degrees C on cornmeal agar and synthetic medium plus N-acetylglucosamine and Tween 80. At 37 degrees C, it does not produce hyphae on these media, although C. albicans normally does produce hyphae under these circumstances. In liquid synthetic medium, this variant does not produce hyphae at 37 degrees C. The variant strain was analyzed for DNA, RNA, protein content, and particle size. After 50 to 70 h in balanced exponential-phase growth, particle size distribution was narrow, and there were no differences in the DNA, RNA, or protein content per particle in the two strains. When balanced exponential-phase cultures were brought into stationary phase, both strains contained the same amount of DNA per cell.
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Directory of Open Access Journals (Sweden)
Ruben Pérez
Full Text Available Canine parvovirus (CPV, a fast-evolving single-stranded DNA virus, comprises three antigenic variants (2a, 2b, and 2c with different frequencies and genetic variability among countries. The contribution of co-infection and recombination to the genetic variability of CPV is far from being fully elucidated. Here we took advantage of a natural CPV population, recently formed by the convergence of divergent CPV-2c and CPV-2a strains, to study co-infection and recombination. Complete sequences of the viral coding region of CPV-2a and CPV-2c strains from 40 samples were generated and analyzed using phylogenetic tools. Two samples showed co-infection and were further analyzed by deep sequencing. The sequence profile of one of the samples revealed the presence of CPV-2c and CPV-2a strains that differed at 29 nucleotides. The other sample included a minor CPV-2a strain (13.3% of the viral population and a major recombinant strain (86.7%. The recombinant strain arose from inter-genotypic recombination between CPV-2c and CPV-2a strains within the VP1/VP2 gene boundary. Our findings highlight the importance of deep-sequencing analysis to provide a better understanding of CPV molecular diversity.
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Pérez, Ruben; Calleros, Lucía; Marandino, Ana; Sarute, Nicolás; Iraola, Gregorio; Grecco, Sofia; Blanc, Hervé; Vignuzzi, Marco; Isakov, Ofer; Shomron, Noam; Carrau, Lucía; Hernández, Martín; Francia, Lourdes; Sosa, Katia; Tomás, Gonzalo; Panzera, Yanina
2014-01-01
Canine parvovirus (CPV), a fast-evolving single-stranded DNA virus, comprises three antigenic variants (2a, 2b, and 2c) with different frequencies and genetic variability among countries. The contribution of co-infection and recombination to the genetic variability of CPV is far from being fully elucidated. Here we took advantage of a natural CPV population, recently formed by the convergence of divergent CPV-2c and CPV-2a strains, to study co-infection and recombination. Complete sequences of the viral coding region of CPV-2a and CPV-2c strains from 40 samples were generated and analyzed using phylogenetic tools. Two samples showed co-infection and were further analyzed by deep sequencing. The sequence profile of one of the samples revealed the presence of CPV-2c and CPV-2a strains that differed at 29 nucleotides. The other sample included a minor CPV-2a strain (13.3% of the viral population) and a major recombinant strain (86.7%). The recombinant strain arose from inter-genotypic recombination between CPV-2c and CPV-2a strains within the VP1/VP2 gene boundary. Our findings highlight the importance of deep-sequencing analysis to provide a better understanding of CPV molecular diversity. PMID:25365348
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Lizárraga-Partida, Marcial Leonardo; Quilici, Marie-Laure
2009-01-01
We studied the evolution of Vibrio cholerae O1 during the 1991 to 2000 cholera epidemic in Mexico by biochemical, serological, and molecular characterization of strains collected during this period. Strains were divided into toxigenic and nontoxigenic groups according to the presence or absence of genes encoding cholera toxin. As previously reported, we characterized two populations among toxigenic strains, which were present from the first year of the epidemic. BglI rRNA analysis revealed that these strains had ribotype profiles, denoted M5 and M6 in our study, that were identical to those previously designated Koblavi B5 or Popovic 5 and Popovic 6a or Tamayo B21a, respectively. Ribotype M5 was isolated between 1991 and 1993. This ribotype had a low level of genetic variation as detected by pulsed-field gel electrophoresis (PFGE). Ribotype M6 persisted from 1991 to 2000. However, PFGE profiles suggested that two epidemiologically unrelated strains coexisted within this single ribotype from 1995 until the end of the epidemic. We identified three new BglI ribotypes, Mx1, Mx2, and Mx3, from nontoxigenic V. cholerae O1 strains isolated between 1998 and 2000; one of them grouped strains positive for the toxin-coregulated pilus island. They differed from nontoxigenic clones isolated in Latin America and on the U.S. Gulf Coast and are probably autochthonous Mexican V. cholerae O1 variants. Most of these new variants were isolated from states surrounding the Gulf of Mexico, where the highest incidence of cholera in the country was recorded. Thus, the Mexican Gulf Coast, like the U.S. Gulf Coast, may act as an environmental reservoir of V. cholerae O1. PMID:19213700
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Directory of Open Access Journals (Sweden)
YaoXia eKang
2015-12-01
Full Text Available A newly isolated smooth colony morphology phage-resistant (SPR strain 8416 isolated from a 45-year-old cattle farm cleaner with clinical features of brucellosis in China was reported. The most unusual phenotype was its resistance to two Brucella phages Tbilisi and Weybridge, but sensitive to Berkeley 2, a pattern similar to that of B. melitensis biovar 1. VITEK 2 biochemical identification system found that both strain 8416 and B. melitensis strains shared positive ILATk, but negative in other B. abortus strains. However, routine biochemical and phenotypic characteristics of strain 8416 were most similar to that of B. abortus biovar 9 except CO2 requirement. In addition, multiple PCR molecular typing assays including AMOS-PCR, B. abortus special PCR (B-ab PCR and a novel sub-biovar typing PCR, indicated that strain 8416 may belong to either biovar 3b or 9 of B. abortus. Surprisingly, further MLVA typing results showed that strain 8416 was most closely related to B. abortus biovar 3 in the Brucella MLVA database, primarily differing in 4 out of 16 screened loci. Therefore, due to the unusual discrepancy between phenotypic (biochemical reactions and particular phage lysis profile and molecular typing characteristics, strain 8416 couldn’t be exactly classified to any of the existing B. abortus biovars and might be a new variant of B. abortus biovar 9. The present study also indicates that the present phage typing scheme for Brucella spp. is subject to variation and the routine Brucella biovar typing needs further studies.
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Kang, Yao-Xia; Li, Xu-Ming; Piao, Dong-Ri; Tian, Guo-Zhong; Jiang, Hai; Jia, En-Hou; Lin, Liang; Cui, Bu-Yun; Chang, Yung-Fu; Guo, Xiao-Kui; Zhu, Yong-Zhang
2015-01-01
A newly isolated smooth colony morphology phage-resistant strain 8416 isolated from a 45-year-old cattle farm cleaner with clinical features of brucellosis in China was reported. The most unusual phenotype was its resistance to two Brucella phages Tbilisi and Weybridge, but sensitive to Berkeley 2, a pattern similar to that of Brucella melitensis biovar 1. VITEK 2 biochemical identification system found that both strain 8416 and B. melitensis strains shared positive ILATk, but negative in other B. abortus strains. However, routine biochemical and phenotypic characteristics of strain 8416 were most similar to that of B. abortus biovar 9 except CO2 requirement. In addition, multiple PCR molecular typing assays including AMOS-PCR, B. abortus special PCR (B-ab PCR) and a novel sub-biovar typing PCR, indicated that strain 8416 may belong to either biovar 3b or 9 of B. abortus. Surprisingly, further MLVA typing results showed that strain 8416 was most closely related to B. abortus biovar 3 in the Brucella MLVA database, primarily differing in 4 out of 16 screened loci. Therefore, due to the unusual discrepancy between phenotypic (biochemical reactions and particular phage lysis profile) and molecular typing characteristics, strain 8416 could not be exactly classified to any of the existing B. abortus biovars and might be a new variant of B. abortus biovar 9. The present study also indicates that the present phage typing scheme for Brucella sp. is subject to variation and the routine Brucella biovar typing needs further studies.
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Joffré , Enrique; von Mentzer, Astrid; Abd El Ghany, Moataz; Oezguen, Numan; Savidge, Tor; Dougan, Gordon; Svennerholm, Ann-Mari; Sjö ling, Å sa
2015-01-01
Enterotoxigenic Escherichia coli (ETEC) is a significant cause of morbidity and mortality in the developing world. ETEC-mediated diarrhea is orchestrated by heat-labile toxin (LT) and heat-stable toxins (STp and STh), acting in concert with a repertoire of more than 25 colonization factors (CFs). LT, the major virulence factor, induces fluid secretion after delivery of a monomeric ADP-ribosylase (LTA) and its pentameric carrier B subunit (LTB). A study of ETEC isolates from humans in Brazil reported the existence of natural LT variants. In the present study, analysis of predicted amino acid sequences showed that the LT amino acid polymorphisms are associated with a geographically and temporally diverse set of 192 clinical ETEC strains and identified 12 novel LT variants. Twenty distinct LT amino acid variants were observed in the globally distributed strains, and phylogenetic analysis showed these to be associated with different CF profiles. Notably, the most prevalent LT1 allele variants were correlated with major ETEC lineages expressing CS1 + CS3 or CS2 + CS3, and the most prevalent LT2 allele variants were correlated with major ETEC lineages expressing CS5 + CS6 or CFA/I. LTB allele variants generally exhibited more-stringent amino acid sequence conservation (2 substitutions identified) than LTA allele variants (22 substitutions identified). The functional impact of LT1 and LT2 polymorphisms on virulence was investigated by measuring total-toxin production, secretion, and stability using GM1-enzyme-linked immunosorbent assays (GM1-ELISA) and in silico protein modeling. Our data show that LT2 strains produce 5-fold more toxin than LT1 strains (P < 0.001), which may suggest greater virulence potential for this genetic variant. Our data suggest that functionally distinct LT-CF variants with increased fitness have persisted during the evolution of ETEC and have spread globally.
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Joffré, Enrique
2015-01-15
Enterotoxigenic Escherichia coli (ETEC) is a significant cause of morbidity and mortality in the developing world. ETEC-mediated diarrhea is orchestrated by heat-labile toxin (LT) and heat-stable toxins (STp and STh), acting in concert with a repertoire of more than 25 colonization factors (CFs). LT, the major virulence factor, induces fluid secretion after delivery of a monomeric ADP-ribosylase (LTA) and its pentameric carrier B subunit (LTB). A study of ETEC isolates from humans in Brazil reported the existence of natural LT variants. In the present study, analysis of predicted amino acid sequences showed that the LT amino acid polymorphisms are associated with a geographically and temporally diverse set of 192 clinical ETEC strains and identified 12 novel LT variants. Twenty distinct LT amino acid variants were observed in the globally distributed strains, and phylogenetic analysis showed these to be associated with different CF profiles. Notably, the most prevalent LT1 allele variants were correlated with major ETEC lineages expressing CS1 + CS3 or CS2 + CS3, and the most prevalent LT2 allele variants were correlated with major ETEC lineages expressing CS5 + CS6 or CFA/I. LTB allele variants generally exhibited more-stringent amino acid sequence conservation (2 substitutions identified) than LTA allele variants (22 substitutions identified). The functional impact of LT1 and LT2 polymorphisms on virulence was investigated by measuring total-toxin production, secretion, and stability using GM1-enzyme-linked immunosorbent assays (GM1-ELISA) and in silico protein modeling. Our data show that LT2 strains produce 5-fold more toxin than LT1 strains (P < 0.001), which may suggest greater virulence potential for this genetic variant. Our data suggest that functionally distinct LT-CF variants with increased fitness have persisted during the evolution of ETEC and have spread globally.
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International Nuclear Information System (INIS)
Ueshima, N; Yoshiya, M; Yasuda, H; Fukuda, T; Kakeshita, T
2015-01-01
Through three-dimensional (3D) simulations of microstructure evolution by phase-field modeling (PFM), microstructures have been quantified during their time evolution by an image processing technique with particular attention to the shape of variants in the course of variant selection. It is found that the emerging variants exhibit planar shapes rather than 3D shapes due to the elastic field around the variants arising upon disorder-to-order transition to the L1 0 phase. The two-dimensionality is more pronounced as variant selection proceeds. Although three equivalent variants compete for dominance under an external field, one of the three variants vanishes before final competition occurs between the remaining variants, which can be explained by the elastic strain energy. These numerical analyses provide better understanding of the microstructure evolution in a more quantitative manner, including the small influence of the third variant, and the results obtained confirm that the understanding of variant selection obtained from two-dimensional (2D) simulations by PFM is valid. (paper)
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Radtke, Andreas; Bruheim, Torkjel; Afset, Jan Egil; Bergh, Kåre
2012-06-15
Group B streptococci (GBS) were considered a major cause of mastitis in cattle until preventive measures succeeded in controlling the disease in the 1970s and 1980s. During the last 5-6 years an increasing number of cases have been observed in some Scandinavian countries. A total of 187 GBS isolates from mastitis cases were collected from 119 animals in 34 Norwegian farms in the period from April 2007 to November 2010. 133 (71%) of the isolates were from farms with automated milking systems. The strains underwent typing of capsular polysaccharides (CPS) and surface proteins, and were analyzed by multi-locus variable repeat assay (MLVA) to investigate the epidemiological relationship of strains within and between farms. The GBS strains were differentiated into 12 types by CPS and surface protein analysis, with CPS types V (54%) and IV (34%) predominating. MLVA was superior to CPS and protein typing for strain differentiation, resolving the 187 strains into 37 types. In 29 of 34 farms all GBS strains had identical MLVA profiles specific for each farm. However, in one farm represented with 48 isolates, four MLVA variants with differences in one repeat locus were observed during the almost 3-year long collection period. Similar variations were observed at four other farms. This might reflect the stability of repeat loci under in vivo conditions. Farms with automated milking systems were overrepresented in this material. In conclusion, the five-loci MLVA allowed rapid high-resolution genotyping of the bovine GBS strains within and between farms. Copyright © 2012 Elsevier B.V. All rights reserved.
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Shakibaie, Mohammad Reza; Azizi, Omid; Shahcheraghi, Fereshteh
2017-07-01
Metallo-β-lactamases (MBLs) such as IMPs are broad-spectrum β-lactamases that inactivate virtually all β-lactam antibiotics including carbapenems. In this study, we investigated the hydrolytic activity, phylogenetic relationship, three dimensional (3D) structure including zinc binding motif of a new IMP variant (IMP-55) identified in a clinical strain of Acinetobacter baumannii (AB). AB strain 56 was isolated from an adult ICU of a teaching hospital in Kerman, Iran. It exhibited MIC 32μg/ml to imipenem and showed MBL activity. Hydrolytic property of the MBL enzyme was measured phenotypically. Presence of bla IMP gene encoded by class 1 integrons was detected by PCR-sequencing. Phylogenetic tree of IMP protein was constructed using the Unweighted Pair Group Method with Arithmetic Mean (UPGMA) and 3D model including zinc binding motif was predicted by bioinformatics softwares. Analysis of IMP sequence led to the identification of a novel IMP-type designated as IMP-55 (GenBank: KU299753.1; UniprotKB: A0A0S2MTX2). Impact in term of hydrolytic activity compared to the closest variants suggested efficient imipenem hydrolysis by this enzyme. Evolutionary distance matrix assessment indicated that IMP-55 protein is not closely related to other A. baumannii IMPs, however, shared 98% homology with Escherichia coli IMP-30 (UniprotKB: A0A0C5PJR0) and Pseudomonas aeruginosa IMP-1 (UniprotKB: Q19KT1). It consisted of five α-helices, ten β-sheets and six loops. A monovalent zinc ion attached to core of enzyme via His95, His97, His157 and Cys176. Multiple amino acid sequence alignments and mutational trajectory with reported IMPs showed 4 amino acid substitutions at positions 12(Phe→Ile), 31(Asp→Glu), 172(Leu→Phe) and 185(Asn→Lys). We suggest that the pleiotropic effect of mutations due to frequent administration of imipenem is responsible for emergence of new IMP variant in our hospitals. Copyright © 2017 Elsevier B.V. All rights reserved.
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Silvério, D; Lopes, A M; Melo-Ferreira, J; Magalhães, M J; Monterroso, P; Serronha, A; Maio, E; Alves, P C; Esteves, P J; Abrantes, J
2018-02-11
Rabbit haemorrhagic disease (RHD) is a viral disease that affects the European rabbit. RHD was detected in 1984 in China and rapidly disseminated worldwide causing a severe decline in wild rabbit populations. The aetiological agent, rabbit haemorrhagic disease virus (RHDV), is an RNA virus of the family Caliciviridae, genus Lagovirus. Pathogenic (G1-G6 or variants GI.1a-GI.1d) and non-pathogenic strains (GI.4) have been characterized. In 2010, a new variant of RHDV, RHDV2/RHDVb/GI.2, was detected in France. GI.2 arrived to the Iberian Peninsula in 2011, and several recombination events were reported. Here, we sequenced full genomes of 19 samples collected in Portugal between 2014 and 2016. New GI.2 recombinant strains were detected, including triple recombinants. These recombinants possess a non-structural protein p16 related to a non-pathogenic strain. Evolutionary analyses were conducted on GI.2 VP60 sequences. Estimated time to the most recent common ancestor (tMRCA) suggests an emergence of GI.2 in July 2008, not distant from its first detection in 2010. This is the first study on GI.2 evolution and highlights the need of continued monitoring and characterization of complete genome sequences when studying lagoviruses' evolution. © 2018 Blackwell Verlag GmbH.
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Balendra, Rubika; Uphill, James; Collinson, Claire; Druyeh, Ronald; Adamson, Gary; Hummerich, Holger; Zerr, Inga; Gambetti, Pierluigi; Collinge, John; Mead, Simon
2016-04-07
Human prion diseases are relentlessly progressive neurodegenerative disorders which include sporadic Creutzfeldt-Jakob disease (sCJD) and variant CJD (vCJD). Aside from variants of the prion protein gene (PRNP) replicated association at genome-wide levels of significance has proven elusive. A recent association study identified variants in or near to the PLCXD3 gene locus as strong disease risk factors in multiple human prion diseases. This study claimed the first non-PRNP locus to be highly significantly associated with prion disease in genomic studies. A sub-study of a genome-wide association study with imputation aiming to replicate the finding at PLCXD3 including 129 vCJD and 2500 sCJD samples. Whole exome sequencing to identify rare coding variants of PLCXD3. Imputation of relevant polymorphisms was accurate based on wet genotyping of a sample. We found no supportive evidence that PLCXD3 variants are associated with disease. The marked discordance in vCJD genotype frequencies between studies, despite extensive overlap in vCJD cases, and the finding of Hardy-Weinberg disequilibrium in the original study, suggests possible reasons for the discrepancies between studies.
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DIF3D-VARIANT 11.0: A Decade of Updates
Energy Technology Data Exchange (ETDEWEB)
Smith, M. A. [Argonne National Lab. (ANL), Argonne, IL (United States); Lewis, E. E. [Argonne National Lab. (ANL), Argonne, IL (United States); Shemon, E. R. [Argonne National Lab. (ANL), Argonne, IL (United States)
2014-04-09
The DIF3D code has been a workhorse of fast reactor analysis work at Argonne National Laboratory for over 30 years. In 1995, a transport option called VARIANT was added to DIF3D to improve the flux solutions for fast reactor problems. VARIANT performs nodal neutron transport calculations using PN or SPN theory in Cartesian and hexagonal two- and threedimensional geometries. Because of the computing capabilities at that time, VARIANT was restricted to 33 group P3 flux approximations with P1 scattering. Clearly computer memory capabilities have increased since then and thus large space-angle-energy approximations are possible. This manuscript serves as an update to the theory section of the original manual and details more than a decade worth of changes made to DIF3D to make DIF3D 11.0.
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Deoxyribonucleic acid-deficient strains of Candida albicans.
Olaiya, A F; Steed, J R; Sogin, S J
1980-03-01
We analyzed a series of germ tube-negative variants isolated from Candida albicans 3153A for deoxyribonucleic acid content. As analyzed by flow microfluorometry, the deoxyribonucleic acid level in these variant strains was 50% of that of the parental strain and equivalent to that of haploid Saccharomyces cerevisiae. This finding was confirmed by comparison of survival rates when exposed to the mutagens ultraviolet light, ethyl methane sulfonate, and methyl methane sulfonate. The diameter of the variant cells as compared to the diameter of the parental 3153A strain showed a relationship similar to that of the diameters of haploid versus diploid S. cerevisiae. These results indicate that those strains may be representative of the imperfect stage of C. albicans.
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Characterization of Canine parvovirus 2 variants circulating in Greece.
Ntafis, Vasileios; Xylouri, Eftychia; Kalli, Iris; Desario, Costantina; Mari, Viviana; Decaro, Nicola; Buonavoglia, Canio
2010-09-01
The aim of the present study was to characterize Canine parvovirus 2 (CPV-2) variants currently circulating in Greece. Between March 2008 and March 2009, 167 fecal samples were collected from diarrheic dogs from different regions of Greece. Canine parvovirus 2 was detected by standard polymerase chain reaction, whereas minor groove binder probe assays were used to distinguish genetic variants and discriminate between vaccine and field strains. Of 84 CPV-2-positive samples, 81 CPV-2a, 1 CPV-2b, and 2 CPV-2c were detected. Vaccine strains were not detected in any sample. Sequence analysis of the VP2 gene of the 2 CPV-2c viruses revealed up to 100% amino acid identity with the CPV-2c strains previously detected in Europe. The results indicated that, unlike other European countries, CPV-2a remains the most common variant in Greece, and that the CPV-2c variant found in Europe is also present in Greece.
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Molecular Evolution of the VP1 Gene in Human Norovirus GII.4 Variants in 1974–2015
Directory of Open Access Journals (Sweden)
Takumi Motoya
2017-12-01
Full Text Available Human norovirus (HuNoV is a leading cause of viral gastroenteritis worldwide, of which GII.4 is the most predominant genotype. Unlike other genotypes, GII.4 has created various variants that escaped from previously acquired immunity of the host and caused repeated epidemics. However, the molecular evolutionary differences among all GII.4 variants, including recently discovered strains, have not been elucidated. Thus, we conducted a series of bioinformatic analyses using numerous, globally collected, full-length GII.4 major capsid (VP1 gene sequences (466 strains to compare the evolutionary patterns among GII.4 variants. The time-scaled phylogenetic tree constructed using the Bayesian Markov chain Monte Carlo (MCMC method showed that the common ancestor of the GII.4 VP1 gene diverged from GII.20 in 1840. The GII.4 genotype emerged in 1932, and then formed seven clusters including 14 known variants after 1980. The evolutionary rate of GII.4 strains was estimated to be 7.68 × 10−3 substitutions/site/year. The evolutionary rates probably differed among variants as well as domains [protruding 1 (P1, shell, and P2 domains]. The Osaka 2007 variant strains probably contained more nucleotide substitutions than any other variant. Few conformational epitopes were located in the shell and P1 domains, although most were contained in the P2 domain, which, as previously established, is associated with attachment to host factors and antigenicity. We found that positive selection sites for the whole GII.4 genotype existed in the shell and P1 domains, while Den Haag 2006b, New Orleans 2009, and Sydney 2012 variants were under positive selection in the P2 domain. Amino acid substitutions overlapped with putative epitopes or were located around the epitopes in the P2 domain. The effective population sizes of the present strains increased stepwise for Den Haag 2006b, New Orleans 2009, and Sydney 2012 variants. These results suggest that HuNoV GII.4 rapidly
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Singh, R S; Saini, G K
2008-06-01
The studies were carried out for the isolation of efficient pullulan producing strains of Aureobasidium pullulans. Five strains were isolated from phylloplane of different plants. Amongst these, three were producing black pigment melanin, while the remaining two produced pink pigment. These two color variant isolates of A. pullulans were designated as FB-1 and FG-1, and obtained from phylloplane of Ficus benjamina and Ficus glometa, respectively. The parameters employed for the identification of the isolates included morphology, nutritional assimilation patterns and exopolysaccharide (EPS) production. Isolates were compared with standard cultures for EPS production. A. pullulans FB-1 was the best producer of pullulan giving up to 1.9, 1.4 and 1.7 times more pullulan than the control of A. pullulans NCIM 976, NCIM 1048 and NCIM 1049, respectively. The IR spectra of the isolates and standard strains revealed that the polysaccharide was pullulan, but not aubasidan. The study also supported the fact that A. pullulans is a ubiquitous organism and phylloplane being the important niche of the organism.
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Dean, Melissa A; Olsen, Randall J; Long, S Wesley; Rosato, Adriana E; Musser, James M
2014-04-01
Staphylococcus aureus small-colony variants (SCVs) are implicated in chronic and relapsing infections that are difficult to diagnose and treat. Despite many years of study, the underlying molecular mechanisms and virulence effect of the small-colony phenotype remain incompletely understood. We sequenced the genomes of five S. aureus SCV strains recovered from human patients and discovered previously unidentified nonsynonymous point mutations in three genes encoding proteins in the menadione biosynthesis pathway. Analysis of genetic revertants and complementation with wild-type alleles confirmed that these mutations caused the SCV phenotype and decreased virulence for mice.
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Ryschkewitsch, C F; Friedlaender, J S; Mgone, C S; Jobes, D V; Agostini, H T; Chima, S C; Alpers, M P; Koki, G; Yanagihara, R; Stoner, G L
2000-07-01
The peopling of the Pacific was a complex sequence of events that is best reconstructed by reconciling insights from various disciplines. Here we analyze the human polyomavirus JC (JCV) in Highlanders of Papua New Guinea (PNG), in Austronesian-speaking Tolai people on the island of New Britain, and in nearby non-Austronesian-speaking Baining people. We also characterize JCV from the Chamorro of Guam, a Micronesian population. All JCV strains from PNG and Guam fall within the broad Asian group previously defined in the VP1 gene as Type 2 or Type 7, but the PNG strains were distinct from both genotypes. Among the Chamorro JCV samples, 8 strains (Guam-1) were like the Type 7 strains found in Southeast Asia, while nine strains (Guam-2) were distinct from both the mainland strains and most PNG strains. We identified three JCV variants within Papua New Guinea (PNG-1, PNG-2 and PNG-3), but none of the Southeast Asian (Type 7) strains. PNG-1 strains were present in all three populations (Highlanders and the Baining and Tolai of New Britain), but PNG-2 strains were restricted to the Highlanders. Their relative lack of DNA sequence variation suggests that they arose comparatively recently. The single PNG-3 strain, identified in an Austronesian-speaking Tolai individual, was closely related to the Chamorro variants (Guam-2), consistent with a common Austronesian ancestor. In PNG-2 variants a complex regulatory region mutation inserts a duplication into a nearby deletion, a change reminiscent of those seen in the brains of progressive multifocal leukoencephalopathy patients. This is the first instance of a complex JCV rearrangement circulating in a human population.
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Rare novel variants in the ZIC3 gene cause X-linked heterotaxy
DEFF Research Database (Denmark)
Paulussen, Aimee D C; Steyls, Anja; Vanoevelen, Jo
2016-01-01
male deaths due to heterotaxy in the family (n=1). All variants were located within the zinc-finger domains or leading to a truncation before these domains. Truncating variants showed abnormal trafficking of mutated ZIC3 proteins, whereas the missense variant showed normal trafficking. Overexpression...
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Suárez, Viviana B; Maciel, Natalia; Guglielmotti, Daniela; Zago, Miriam; Giraffa, Giorgio; Reinheimer, Jorge
2008-12-10
The aim of this work was to study the relationship between the cell morphological heterogeneity and the phage-resistance in the commercial strain Lactobacillus delbrueckii subsp. lactis Ab1. Two morphological variants (named C and T) were isolated from this strain. Phage-resistant derivatives were isolated from them and the percentage of occurrence of confirmed phage-resistant cells was 0.001% of the total cellular population. Within these phage-resistant cell derivatives there were T (3 out of 4 total isolates) and C (1 out of 4 total isolates) variants. The study of some technological properties (e.g. proteolytic and acidifying activities) demonstrated that most of phage-resistant derivatives were not as good as the parental strain. However, for one derivative (a T variant), the technological properties were better than those of the parental strain. On the other hand, it was possible to determinate that the system of phage-resistance in the T variants was interference in adsorption step, with adsorption rates M.
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Epidemiological dynamics of norovirus GII.4 variant New Orleans 2009.
Medici, Maria Cristina; Tummolo, Fabio; De Grazia, Simona; Calderaro, Adriana; De Conto, Flora; Terio, Valentina; Chironna, Maria; Bonura, Floriana; Pucci, Marzia; Bányai, Kristián; Martella, Vito; Giammanco, Giovanni Maurizio
2015-09-01
Norovirus (NoV) is one of the major causes of diarrhoeal disease with epidemic, outbreak and sporadic patterns in humans of all ages worldwide. NoVs of genotype GII.4 cause nearly 80-90 % of all NoV infections in humans. Periodically, some GII.4 strains become predominant, generating major pandemic variants. Retrospective analysis of the GII.4 NoV strains detected in Italy between 2007 and 2013 indicated that the pandemic variant New Orleans 2009 emerged in Italy in the late 2009, became predominant in 2010-2011 and continued to circulate in a sporadic fashion until April 2013. Upon phylogenetic analysis based on the small diagnostic regions A and C, the late New Orleans 2009 NoVs circulating during 2011-2013 appeared to be genetically different from the early New Orleans 2009 strains that circulated in 2010. For a selection of strains, a 3.2 kb genome portion at the 3' end was sequenced. In the partial ORF1 and in the full-length ORF2 and ORF3, the 2011-2013 New Orleans NoVs comprised at least three distinct genetic subclusters. By comparison with sequences retrieved from the databases, these subclusters were also found to circulate globally, suggesting that the local circulation reflected repeated introductions of different strains, rather than local selection of novel viruses. Phylogenetic subclustering did not correlate with changes in residues located in predicted putative capsid epitopes, although several changes affected the P2 domain in epitopes A, C, D and E.
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Biologico-clinical significance of DNMT3A variants expression in acute myeloid leukemia.
Lin, Na; Fu, Wei; Zhao, Chen; Li, Bixin; Yan, Xiaojing; Li, Yan
2017-12-09
DNA methyltransferase 3A (DNMT3A) catalyzes de novo DNA methylation and plays important roles in the pathogenesis of acute myeloid leukemia. However, the expression status of DNMT3A variants in acute myeloid leukemia remains obscure. This study aimed to assess the expression levels of alternative splicing of DNMT3A variants and explore their roles in acute myeloid leukemia (AML). DNMT3A variants gene expression were assessed, measuring their effects on cell proliferation. In addition, the expression of DNMT3A variants were evaluated in acute myeloid leukemia patients. Four DNMT3A variants were identified, with DNMT3A1 and DNMT3A2V found to be dominant in acute myeloid leukemia cell lines. Moreover, DNMT3A2V overexpression delayed cell proliferation; while, DNMT3A2V R882H mutation promoted cell proliferation. Further, DNMT3A1 and DNMT3A2V were detected in newly diagnosed acute myeloid leukemia (AML) patients and controls with non-malignant hematological disease, with DNMT3A2V significantly up-regulated in AML patients. The main transcript switched from DNMT3A1 to DNMT3A2V in some patients, especially the low risk group based on the NCCN 2016 guidelines. These findings suggest that DNMT3A1 and DNMT3A2V are the main variants in acute myeloid leukemia with different clinical association, and might play important roles in the pathophysiology of acute myeloid leukemia. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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Carlisle, G E; Falkinham, J O
1989-01-01
A nonmucoid colonial variant of a mucoid Bacillus subtilis strain produced less amylase activity and a transparent colonial variant of a B. licheniformis strain produced less protease activity compared with their parents. Antibiotic susceptibility patterns of the colonial variants differed, and increased resistance to beta-lactam antibiotics was correlated with increased production of extracellular beta-lactamase.
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Energy Technology Data Exchange (ETDEWEB)
Zhou, Ting; Ren, Xiaoming; Adams, Rebecca L.; Pyle, Anna Marie; Ou, J. -H. James
2017-10-25
Hepatitis C viruses (HCV) encode a helicase enzyme that is essential for viral replication and assembly (nonstructural protein 3 [NS3]). This helicase has become the focus of extensive basic research on the general helicase mechanism, and it is also of interest as a novel drug target. Despite the importance of this protein, mechanistic work on NS3 has been conducted almost exclusively on variants from HCV genotype 1. Our understanding of NS3 from the highly active HCV strains that are used to study HCV genetics and mechanism in cell culture (such as JFH-1) is lacking. We therefore set out to determine whether NS3 from the replicatively efficient genotype 2a strain JFH-1 displays novel functional or structural properties. Using biochemical assays for RNA binding and duplex unwinding, we show that JFH-1 NS3 binds RNA much more rapidly than the previously studied NS3 variants from genotype 1b. Unlike NS3 variants from other genotypes, JFH-1 NS3 binds RNA with high affinity in a functionally active form that is capable of immediately unwinding RNA duplexes without undergoing rate-limiting conformational changes that precede activation. Unlike other superfamily 2 (SF2) helicases, JFH-1 NS3 does not require long 3' overhangs, and it unwinds duplexes that are flanked by only a few nucleotides, as in the folded HCV genome. To understand the physical basis for this, we solved the crystal structure of JFH-1 NS3, revealing a novel conformation that contains an open, positively charged RNA binding cleft that is primed for productive interaction with RNA targets, potentially explaining robust replication by HCV JFH-1.
IMPORTANCE Genotypes of HCV are as divergent as different types of flavivirus, and yet mechanistic features of HCV variants are presumed to be held in common. One of the most well-studied components of the HCV replication complex is a helicase known as nonstructural protein 3 (NS3). We set out to determine whether this important -
Equestre, M; Genovese, D; Cavalieri, F; Fiore, L; Santoro, R; Perez Bercoff, R
1991-01-01
Complete nucleotide sequencing of the RNAs of two unrelated neurovirulent isolates of Sabin-related poliovirus type 2 revealed that two nucleotides and one amino acid (amino acid 143 in the major capsid protein VP1) consistently departed from the sequences of the nonneurovirulent poliovirus type 2 712 and Sabin vaccine strains. This pattern of mutation appeared to be a feature common to all neurovirulent variants of poliovirus type 2.
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International Nuclear Information System (INIS)
Bai, M.; Guo, Q.; Li, S.
2013-01-01
Aim: To report the prevalence and characteristic features of persistent trigeminal artery (PTA), PTA variant (PTAV), and other variants of the head and neck vessels, identified using magnetic resonance angiography (MRA). Materials and methods: The three-dimensional (3D) time of flight (TOF) MRA and 3D contrast-enhanced (CE) MRA images of 6095 consecutive patients who underwent 3 T MRA at Liaocheng People's Hospital from 1 September 2008 through 31 May 2012 were retrospectively reviewed and analysed. Thirty-two patients were excluded because of suboptimal image quality or internal carotid artery (ICA) occlusion. Results: The prevalence of both PTA and PTAV was 0.63% (PTA, 26 cases; PTAV, 12 cases). The prevalence of coexisting variants of the head and neck vessels in cases of PTA/PTAV was 52.6% (20 of 38 cases). The vascular variants that coexisted with cases of PTA/PTAV were as follows: the intracranial arteries varied in 10 cases, the origin of the supra-aortic arteries varied in nine cases, the vertebral artery (VA) varied in 14 cases, and six cases displayed fenestrations. Fifteen of the 20 cases contained more than two types of variants. Conclusion: The prevalence of both PTA and PTAV was 0.63%. Although PTA and PTAV are rare vascular variants, they frequently coexist with other variants of the head and neck vessels. Multiple vascular variations can coexist in a single patient. Recognizing PTA, PTAV, and other variants of the head and neck vessels is crucial when planning a neuroradiological intervention or surgery. Recognizing the medial PTA is very important in clinical practice when performing trans-sphenoidal surgery on the pituitary as failure to do so could result in massive haemorrhage
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Tong, Wu; Li, Guoxin; Liang, Chao; Liu, Fei; Tian, Qing; Cao, Yanyun; Li, Lin; Zheng, Xuchen; Zheng, Hao; Tong, Guangzhi
2016-06-01
Emerging pseudorabies virus (PRV) variant have led to pseudorabies outbreaks in Chinese pig farms. The commercially available PRV vaccine provides poor protection against the PRV variant. In this study, a gE/gI deleted PRV strain JS-2012-△gE/gI was generated from a PRV variant strain using homologous DNA recombination. Compared to the parental strain JS-2012, JS-2012-△gE/gI grew slowly and showed small plaque morphology on Vero cells. The safety and immunological efficacy of JS-2012-△gE/gI was evaluated as a vaccine candidate. JS-2012-△gE/gI was avirulent to suckling piglets, but was able to provide full protection for young piglets against challenge with both the classical virulent PRV and the emerging PRV variant. After sows were vaccinated with the gE/gI-deleted strain, their suckling offspring were resistant to an otherwise lethal challenge with the classical and the variant PRVs. Piglets inoculated with JS-2012-△gE/gI did not develop PRV-specific gE-ELISA antibodies. Thus, JS-2012-△gE/gI appears to be a promising marker vaccine candidate to control PRV variant circulating in pig farms in China. Copyright © 2016 Elsevier B.V. All rights reserved.
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Molecular models of NS3 protease variants of the Hepatitis C virus
Directory of Open Access Journals (Sweden)
Mello Isabel MVGC
2005-01-01
Full Text Available Abstract Background Hepatitis C virus (HCV currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed. Results The atomic coordinates of crystallographic structure 1CU1 and 1DY9 were used as starting model for modeling of the NS3 protease variant structures. The NS3 protease variant structures are composed of six subdomains, which occur in sequence along the polypeptide chain. The protease domain exhibits the dual beta-barrel fold that is common among members of the chymotrypsin serine protease family. The helicase domain contains two structurally related beta-alpha-beta subdomains and a third subdomain of seven helices and three short beta strands. The latter domain is usually referred to as the helicase alpha-helical subdomain. The rmsd value of bond lengths and bond angles, the average G-factor and Verify 3D values are presented for NS3 protease variant structures. Conclusions This project increases the certainty that homology modeling is an useful tool in structural biology and that it can be very valuable in annotating genome sequence information and contributing to structural and functional genomics from virus. The structural models will be used to guide future efforts in the structure
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Extension twin variant selection during uniaxial compression of a magnesium alloy
DEFF Research Database (Denmark)
Pei, Y.; Godfrey, A.; Jiang, J.
2012-01-01
is also observed in that smaller grains are less likely to contain lower ranked twin variants. For both 5% and 10% compression no clear relationship exists between the volume fraction of each twin variant in a given grain population and the Schmid factor for the twin variant. A positive linear......Samples of the magnesium alloy AZ31 have been deformed by compression to strains of 5% and 10% and microstructural observations made to investigate the activation of specific {1 0 1¯ 2} extension twin variants. The twinning has been analyzed on a grain-by-grain basis for more than 260 grains...... to determine both the number of extension twin variants in each grain, and the volume fraction of each. At 5% strain approx. 30% of the grains contain twins corresponding to variants with the third or lower ranked Schmid factor, with the fraction increasing to 40% after 10% compression. A grain size effect...
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Allelic variants of melanocortin 3 receptor gene (MC3R) and weight loss in obesity
DEFF Research Database (Denmark)
L. Santos, José; De la Cruz, Rolando; Holst, Claus
2011-01-01
receptor gene (MC3R) have been associated with childhood obesity, higher BMI Z-score and elevated body fat percentage compared to non-carriers. The aim of this study is to assess the association in adults between allelic variants of MC3R with weight loss induced by energy-restricted diets.......The melanocortin system plays an important role in energy homeostasis. Mice genetically deficient in the melanocortin-3 receptor gene have a normal body weight with increased body fat, mild hypophagia compared to wild-type mice. In humans, Thr6Lys and Val81Ile variants of the melanocortin-3...
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Zahid, M Shamim Hasan; Awasthi, Sharda Prasad; Hinenoya, Atsushi; Yamasaki, Shinji
2015-05-01
To search natural compounds having inhibitory effect on bacterial growth is important, particularly in view of growing multidrug resistant (MDR) strains of bacterial pathogens. Like other bacterial pathogens, MDR Vibrio cholerae, the causative agent of diarrheal disease cholera, is becoming a great concern. As an approach of searching new antimicrobial agents, here, we show that anethole, a well-studied natural component of sweet fennel and star anise seeds, could potentially inhibit the growth of MDR O1 El Tor biotype, the ongoing 7th cholera pandemic variant strains of toxigenic V. cholerae. The minimum inhibitory concentration (MIC) of anethole against diverse O1 El Tor biotype strains is evaluated as 200 µg/ml. Moreover, the effect of anethole is bactericidal and exerts rapid-killing action on V. cholerae cells. This study is the first report which demonstrates that anethole, purified from natural compound, is a potent inhibitor of growth of toxigenic V. cholerae. Our data suggest that anethole could be a potential antimicrobial drug candidate, particularly against MDR V. cholerae mediated infections.
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Variants in SLC18A3, vesicular acetylcholine transporter, cause congenital myasthenic syndrome
O'Grady, Gina L.; Verschuuren, Corien; Yuen, Michaela; Webster, Richard; Menezes, Manoj; Fock, Johanna M.; Pride, Natalie; Best, Heather A.; Damm, Tatiana Benavides; Turner, Christian; Lek, Monkol; Engel, Andrew G.; North, Kathryn N.; Clarke, Nigel F.; MacArthur, Daniel G.; Kamsteeg, Erik-Jan; Cooper, Sandra T.
2016-01-01
Objective: To describe the clinical and genetic characteristics of presynaptic congenital myasthenic syndrome secondary to biallelic variants in SLC18A3. Methods: Individuals from 2 families were identified with biallelic variants in SLC18A3, the gene encoding the vesicular acetylcholine transporter
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Ivanova, V T; Trushakova, S V; Oskerko, T A; Shevchenko, E S; Kolobukhina, L V; Vartanian, R V; Beliakova, N V; Iatsyshina, S B; Feodoritova, E L; Zueva, N D; Burtseva, E I
2009-01-01
In 2007-2008 in Russia, the epidemic upsurge of influenza morbidity was caused by the active circulation of influenza A(H1N1, A(H3N2), and B viruses. The center for Ecology and Epidemiology of Influenza studied 334 epidemic strains. The results of a comparative study of the svirus specificity of commercial test systems (AmpliSens Influenza virus A/B and AmpliSens Influenza virus A/H5N1) for the polymerase chain reaction diagnosis and virological assays, including virus isolation, revealed their high correlation, which confirms that they may be expensively used to monitor the circulation of influenza viruses in the Russian Federation. All the strains were isolated in the MDCK cell culture. Influenza A(H1N1) viruses (n = 127) were antigenic variants of the reference strains A/Solomon Islands/3/06 and A/Brisbane/59107. Influenza A(H3N2) viruses (n = 49) were antigenic variants of the reference strains A/Wisconsin/67/05 and A/Brisbane/10/08. One hundred and fifty seven Influenza B strains were drift variants of the reference strains B/Florida/4/06 and B/Shanghai/361/02 of lineage B/Yamagata/16/88 and one strain, a variant of Malaysia/2506/04 related to lineage B/victoria/2/87. The isolates interacted actively with human 0(I) blood group erythrocytes and much more weakly with chicken ones. All study influenza A(H1N1) viruses (n = 74) preserved their sensitivity to rimantadine while 24 (77%) of the 31 study influenza A(H3N2) virus strains were resistant. A study of the time course of changes in the generation of antibodies in the donor sera obtained in Moscow and the Moscow Region in different periods of the epidemic process revealed an increase in antibodies to the reference influenza A and B virus strains circulating in this period.
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Variant selection of primary, secondary and tertiary twins in a deformed Mg alloy
International Nuclear Information System (INIS)
Mu, Sijia; Jonas, John J.; Gottstein, Günter
2012-01-01
Samples of magnesium alloy AZ31 were deformed in plane strain compression in a channel die at 100 °C and a strain rate of 5 × 10 −3 s −1 . The initial texture was favorably oriented for extension twinning. At a true strain of ε = −0.11, many primary extension twins were observed to consume their parent grains completely. Furthermore, numerous secondary contraction twins formed within the primary extension twins and some tertiary extension twins grew within the secondary contraction twins. The orientations of the parent grains and all three generations of twins were measured. The twin variants selected during each of the three stages of twinning were determined by electron backscatter diffraction techniques and the absent potential twin variants were also identified. The way in which the selected primary extension twins grow so as to consume the parent grains and contact all the neighboring grains is explained in terms of the accommodation strains imposed on the neighboring grains. The analysis shows that the primary twin selected is not necessarily the variant with the highest Schmid factor but the one that requires the least accommodation work in most of the neighboring grains. The same principle was found to hold for the secondary and tertiary twins. By contrast, potential high Schmid factor twins that required the consumption of appreciable accommodation energy did not form. A Taylor simulation produced similar results and indicates that the accommodation strain concept is consistent with the principle of the minimization of plastic work.
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Identification and characterization of two functional variants in the human longevity gene FOXO3
DEFF Research Database (Denmark)
Flachsbart, Friederike; Dose, Janina; Gentschew, Liljana
2017-01-01
FOXO3 is consistently annotated as a human longevity gene. However, functional variants and underlying mechanisms for the association remain unknown. Here, we perform resequencing of the FOXO3 locus and single-nucleotide variant (SNV) genotyping in three European populations. We find two FOXO3 SN...
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Deoxyribonucleic acid-deficient strains of Candida albicans.
Olaiya, A F; Steed, J R; Sogin, S J
1980-01-01
We analyzed a series of germ tube-negative variants isolated from Candida albicans 3153A for deoxyribonucleic acid content. As analyzed by flow microfluorometry, the deoxyribonucleic acid level in these variant strains was 50% of that of the parental strain and equivalent to that of haploid Saccharomyces cerevisiae. This finding was confirmed by comparison of survival rates when exposed to the mutagens ultraviolet light, ethyl methane sulfonate, and methyl methane sulfonate. The diameter of t...
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Genetic variants in CHI3L1 influencing YKL-40 levels
DEFF Research Database (Denmark)
Kjaergaard, Alisa D; Johansen, Julia S; Nordestgaard, Børge G
2013-01-01
Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population.......Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population....
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Moriuchi, Takumi; Vichit, Ork; Vutthikol, Yong; Hossain, Md Shafiqul; Samnang, Chham; Toda, Kohei; Grabovac, Varja; Hiramatsu, Yukihiro; Otsuka, Nao; Shibayama, Keigo; Kamachi, Kazunari
2017-09-01
This study sought to determine the genotypes of circulating Bordetella pertussis, the causative agent of pertussis, in Cambodia by direct molecular typing of clinical specimens. DNA extracts from nasopharyngeal swabs obtained from 82 pertussis patients in 2008-2016 were analyzed by multilocus variable-number tandem repeat analysis (MLVA). B. pertussis virulence-associated allelic genes (ptxA, prn, and fim3) and the pertussis toxin promoter ptxP were also investigated by DNA sequence-based typing. Forty-four DNA extracts (54%) yielded a complete MLVA profile, and these were sorted into 8 MLVA types (MT18, MT26, MT27, MT29, MT43, MT72, MT95, and MT200). MT27 and MT29, which are common in developed countries, were the predominant strain types (total 73%). The predominant profile of virulence-associated allelic genes was the combination of ptxP3/ptxA1/prn2/fim3A (48%). MT27 strains were detected during the entire study period, whereas MT29 strains were only found in 2014-2016. The B. pertussis population in Cambodia, where a whole-cell pertussis vaccine (WCV) has been continuously used, resembled those observed previously in developed countries where acellular pertussis vaccines are used. Circulating B. pertussis strains in Cambodia were distinct from those in other countries using WCVs. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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Mouse ribosomal RNA genes contain multiple differentially regulated variants.
Directory of Open Access Journals (Sweden)
Hung Tseng
2008-03-01
Full Text Available Previous cytogenetic studies suggest that various rDNA chromosomal loci are not equally active in different cell types. Consistent with this variability, rDNA polymorphism is well documented in human and mouse. However, attempts to identify molecularly rDNA variant types, which are regulated individually (i.e., independent of other rDNA variants and tissue-specifically, have not been successful. We report here the molecular cloning and characterization of seven mouse rDNA variants (v-rDNA. The identification of these v-rDNAs was based on restriction fragment length polymorphisms (RFLPs, which are conserved among individuals and mouse strains. The total copy number of the identified variants is less than 100 and the copy number of each individual variant ranges from 4 to 15. Sequence analysis of the cloned v-rDNA identified variant-specific single nucleotide polymorphisms (SNPs in the transcribed region. These SNPs were used to develop a set of variant-specific PCR assays, which permitted analysis of the v-rDNAs' expression profiles in various tissues. These profiles show that three v-rDNAs are expressed in all tissues (constitutively active, two are expressed in some tissues (selectively active, and two are not expressed (silent. These expression profiles were observed in six individuals from three mouse strains, suggesting the pattern is not randomly determined. Thus, the mouse rDNA array likely consists of genetically distinct variants, and some are regulated tissue-specifically. Our results provide the first molecular evidence for cell-type-specific regulation of a subset of rDNA.
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Characterisation of canine parvovirus strains isolated from cats with feline panleukopenia.
Decaro, Nicola; Buonavoglia, Domenico; Desario, Costantina; Amorisco, Francesca; Colaianni, Maria Loredana; Parisi, Antonio; Terio, Valentina; Elia, Gabriella; Lucente, Maria Stella; Cavalli, Alessandra; Martella, Vito; Buonavoglia, Canio
2010-10-01
Unlike the original canine parvovirus type 2 (CPV-2), CPV-2 variants have gained the ability to replicate in vivo in cats but there is limited information on the disease patterns induced by these variants in the feline host. During 2008, two distinct cases of parvoviral infection were diagnosed in our laboratories. A CPV-2a variant was identified in a 3-month-old Persian kitten displaying clinical sign of feline panleukopenia (FPL) (acute gastroenteritis and marked leukopenia) and oral ulcerations, that died eight days after the onset of the disease. Two pups living in the same pet shop as the cat were found to shed a CPV-2a strain genetically identical to the feline virus and were likely the source of infection. Also, non-fatal infection by a CPV-2c strain occurred in a 2.5-month-old European shorthair kitten displaying non-haemorrhagic diarrhoea and normal white blood cell counts. By sequence analysis of the major capsid protein (VP2) gene, the feline CPV-2c strain showed 100% identity to a recent canine type-2c isolate. Both kittens had been administered multivalent vaccines against common feline pathogens including FPL virus. Whether and to which extent the FPL vaccines can protect cats adequately from the antigenic variants of CPV-2 should be assessed. 2010 Elsevier Ltd. All rights reserved.
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Directory of Open Access Journals (Sweden)
Krzysztof Lepek
2015-01-01
Full Text Available Monitoring and control of infections are key parts of surveillance systems and epidemiological risk prevention. In the case of influenza A viruses (IAVs, which show high variability, a wide range of hosts, and a potential of reassortment between different strains, it is essential to study not only people, but also animals living in the immediate surroundings. If understated, the animals might become a source of newly formed infectious strains with a pandemic potential. Special attention should be focused on pigs, because of the receptors specific for virus strains originating from different species, localized in their respiratory tract. Pigs are prone to mixed infections and may constitute a reservoir of potentially dangerous IAV strains resulting from genetic reassortment. It has been reported that a quadruple reassortant, A(H1N1pdm09, can be easily transmitted from humans to pigs and serve as a donor of genetic segments for new strains capable of infecting humans. Therefore, it is highly desirable to develop a simple, cost-effective, and rapid method for evaluation of IAV genetic variability. We describe a method based on multitemperature single-strand conformational polymorphism (MSSCP, using a fragment of the hemagglutinin (HA gene, for detection of coinfections and differentiation of genetic variants of the virus, difficult to identify by conventional diagnostic.
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Xu, Xiaofan; Drobná, Zuzana; Voruganti, V. Saroja; Barron, Keri; González-Horta, Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Cerón, Roberto Hernández; Morales, Damián Viniegra; Terrazas, Francisco A. Baeza; Ishida, María C.; Gutiérrez-Torres, Daniela S.; Saunders, R. Jesse; Crandell, Jamie; Fry, Rebecca C.; Loomis, Dana; García-Vargas, Gonzalo G.; Del Razo, Luz M.; Stýblo, Miroslav; Mendez, Michelle A.
2016-01-01
Abstract Variants in AS3MT, the gene encoding arsenic (+3 oxidation state) methyltranserase, have been shown to influence patterns of inorganic arsenic (iAs) metabolism. Several studies have suggested that capacity to metabolize iAs may vary depending on levels of iAs exposure. However, it is not known whether the influence of variants in AS3MT on iAs metabolism also vary by level of exposure. We investigated, in a population of Mexican adults exposed to drinking water As, whether associations between 7 candidate variants in AS3MT and urinary iAs metabolites were consistent with prior studies, and whether these associations varied depending on the level of exposure. Overall, associations between urinary iAs metabolites and AS3MT variants were consistent with the literature. Referent genotypes, defined as the genotype previously associated with a higher percentage of urinary dimethylated As (DMAs%), were associated with significant increases in the DMAs% and ratio of DMAs to monomethylated As (MAs), and significant reductions in MAs% and iAs%. For 3 variants, associations between genotypes and iAs metabolism were significantly stronger among subjects exposed to water As >50 versus ≤50 ppb (water As X genotype interaction P iAs exposure may influence the extent to which several AS3MT variants affect iAs metabolism. The variants most strongly associated with iAs metabolism—and perhaps with susceptibility to iAs-associated disease—may vary in settings with exposure level. PMID:27370415
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Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes
DEFF Research Database (Denmark)
Grarup, Niels; Moltke, Ida; Andersen, Mette K
2018-01-01
We have identified a variant in ADCY3 (encoding adenylate cyclase 3) associated with markedly increased risk of obesity and type 2 diabetes in the Greenlandic population. The variant disrupts a splice acceptor site, and carriers have decreased ADCY3 RNA expression. Additionally, we observe...
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Directory of Open Access Journals (Sweden)
Tatsuo Yamamoto
Full Text Available Two distinct classes of methicillin-resistant Staphylococcus aureus (MRSA are spreading in hospitals (as hospital-acquired MRSA, HA-MRSA and in the community (as community-acquired MRSA, CA-MRSA. Multilocus sequence type (ST 239 MRSA, one of the most worldwide-disseminated lineages, has been noted as a representative HA-MRSA. Here, we isolated ST239 MRSA (spa type 3 [t037] and staphylococcal cassette chromosome mec [SCCmec] type III.1.1.1 and its novel variant with ST239/spa351 (t030/SCCmecIII.1.1.4 (SCCmecIII(R not only from hospitals but also from patients with urethritis in the community in Russia. The Russian variant (strain 16K possessed a hybrid genome consisting of CC8 and CC30, similar to the ST239/spa3/SCCmecIII.1.1.1 HA-MRSA (TW20 genome, but with marked diversity. The 16K' CC30 section had SCCmecIII(R carrying the dcs-carrying unit (which corresponded to the SCCmecIVc J3 joining region of ST30 CA-MRSA, lacked SCCmercury, and possessed a novel mobile element structure (MES16K carrying the ccrC-carrying unit (with the recombinase gene ccrC1 allele 3 and drug resistance tranposons. The Russian variant included strains with a high ability to transfer its multiple drug resistance by conjugation; e.g., for strain 16K, the transfer frequency of a chloramphenicol resistance plasmid (p16K-1 with 2.9 kb in size reached 1.4×10(-2, followed by Tn554 conjugative transfer at 3.6×l0(-4. The Russian variant, which has been increasing recently, included divergent strains with different plasmid patterns and pulsed field gel electrophoresis profiles. The data demonstrate the alternative nature of ST239 MRSA as CA-MRSA and also as a drug resistance disseminator, and its micro but dynamic evolution in Russia.
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Reactive oxygen species (ROS) are very harmful to living organisms due to the potential oxidation of membrane lipids, DNA, proteins, and carbohydrates. Transformed E.coli strain QC 871, superoxide dismutase (SOD) double-mutant, with three sequence variant MnSOD1, MnSOD2, and MnSOD3 manganese supero...
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Nguyen, Hoang Anh; Denis, Olivier; Vergison, Anne; Theunis, Anne; Tulkens, Paul M; Struelens, Marc J; Van Bambeke, Françoise
2009-04-01
Small-colony variant (SCV) strains of Staphylococcus aureus show reduced antibiotic susceptibility and intracellular persistence, potentially explaining therapeutic failures. The activities of oxacillin, fusidic acid, clindamycin, gentamicin, rifampin, vancomycin, linezolid, quinupristin-dalfopristin, daptomycin, tigecycline, moxifloxacin, telavancin, and oritavancin have been examined in THP-1 macrophages infected by a stable thymidine-dependent SCV strain in comparison with normal-phenotype and revertant isogenic strains isolated from the same cystic fibrosis patient. The SCV strain grew slowly extracellularly and intracellularly (1- and 0.2-log CFU increase in 24 h, respectively). In confocal and electron microscopy, SCV and the normal-phenotype bacteria remain confined in acid vacuoles. All antibiotics tested, except tigecycline, caused a net reduction in bacterial counts that was both time and concentration dependent. At an extracellular concentration corresponding to the maximum concentration in human serum (total drug), oritavancin caused a 2-log CFU reduction at 24 h; rifampin, moxifloxacin, and quinupristin-dalfopristin caused a similar reduction at 72 h; and all other antibiotics had only a static effect at 24 h and a 1-log CFU reduction at 72 h. In concentration dependence experiments, response to oritavancin was bimodal (two successive plateaus of -0.4 and -3.1 log CFU); tigecycline, moxifloxacin, and rifampin showed maximal effects of -1.1 to -1.7 log CFU; and the other antibiotics produced results of -0.6 log CFU or less. Addition of thymidine restored intracellular growth of the SCV strain but did not modify the activity of antibiotics (except quinupristin-dalfopristin). All drugs (except tigecycline and oritavancin) showed higher intracellular activity against normal or revertant phenotypes than against SCV strains. The data may help rationalizing the design of further studies with intracellular SCV strains.
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Sata, F; Sapone, A; Elizondo, G; Stocker, P; Miller, V P; Zheng, W; Raunio, H; Crespi, C L; Gonzalez, F J
2000-01-01
To determine the existence of mutant and variant CgammaP3A4 alleles in three racial groups and to assess functions of the variant alleles by complementary deoxyribonucleic acid (cDNA) expression. A bacterial artificial chromosome that contains the complete CgammaP3A4 gene was isolated and the exons and surrounding introns were directly sequenced to develop primers to polymerase chain reaction (PCR) amplify and sequence the gene from lymphocyte DNA. DNA samples from Chinese, black, and white subjects were screened. Mutating the affected amino acid in the wild-type cDNA and expressing the variant enzyme with use of the baculovirus system was used to functionally evaluate the variant allele having a missense mutation. To investigate the existence of mutant and variant CgammaP3A4 alleles in humans, all 13 exons and the 5'-flanking region of the human CgammaP3A4 gene in three racial groups were sequenced and four alleles were identified. An A-->G point mutation in the 5'-flanking region of the human CgammaP3A4 gene, designated CgammaP3A4*1B, was found in the three different racial groups. The frequency of this allele in a white population was 4.2%, whereas it was 66.7% in black subjects. The CgammaP3A4*1B allele was not found in Chinese subjects. A second variant allele, designated CgammaP3A4*2, having a Ser222Pro change, was found at a frequency of 2.7% in the white population and was absent in the black subjects and Chinese subjects analyzed. Baculovirus-directed cDNA expression revealed that the CYP3A4*2 P450 had a lower intrinsic clearance for the CYP3A4 substrate nifedipine compared with the wild-type enzyme but was not significantly different from the wild-type enzyme for testosterone 6beta-hydroxylation. Another rare allele, designated CgammaP3A4*3, was found in a single Chinese subject who had a Met445Thr change in the conserved heme-binding region of the P450. These are the first examples of potential function polymorphisms resulting from missense mutations in
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DEFF Research Database (Denmark)
Jønsson, Rie; Struve, Carsten; Boll, Erik J.
2017-01-01
phylogenetically distinct, strains harboring the major pilin subunits from both AAF/III and AAF/V. Whole-genome and plasmid sequencing revealed that in these six strains the agg3A and agg5A genes were located on a novel pAA plasmid variant. Moreover, the plasmid also encoded several other virulence genes including...... some not previously found on pAA plasmids. Thus, this plasmid endows the host strains with a remarkably high number of EAEC associated virulence genes hereby likely promoting strain pathogenicity....
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Wen, Duancheng; Noh, Kyung-Min; Goldberg, Aaron D.; Allis, C. David; Rosenwaks, Zev; Rafii, Shahin; Banaszynski, Laura A.
2018-01-01
Summary Chromatin remodeling via incorporation of histone variants plays a key role in the regulation of embryonic development. The histone variant H3.3 has been associated with a number of early events including formation of the paternal pronucleus upon fertilization. The small number of amino acid differences between H3.3 and its canonical counterparts (H3.1 and H3.2) has limited studies of the developmental significance of H3.3 deposition into chromatin due to difficulties in distinguishing the H3 isoforms. To this end, we used zinc-finger nuclease (ZFN) mediated gene editing to introduce a small C-terminal hemagglutinin (HA) tag to the endogenous H3.3B locus in mouse embryonic stem cells (ESCs), along with an internal ribosome entry site (IRES) and a separately translated fluorescent reporter of expression. This system will allow detection of expression driven by the reporter in cells, animals, and embryos, and will facilitate investigation of differential roles of paternal and maternal H3.3 protein during embryogenesis that would not be possible using variant-specific antibodies. Further, the ability to monitor endogenous H3.3 protein in various cell lineages will enhance our understanding of the dynamics of this histone variant over the course of development. genesis PMID:25262655
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First Japanese case of infectious endocarditis due to Enterococcus faecalis small-colony variants.
Ogihara, Shinji; Saito, Ryoichi; Sawabe, Etsuko; Hagihara, Michio; Tohda, Shuji
2016-10-01
A male patient was admitted to our hospital due to infectious endocarditis. He had been treated with levofloxacin for 6 weeks, sulbactam/cefoperazone for 4 weeks, and benzylpenicillin for 2 days prior to valve replacement surgery. Gram-positive cocci, with morphology consistent with γ-Streptococcus, were detected in blood cultures obtained at admission, as well as in vegetation obtained from the aortic valve. However, the strain could not be identified using biochemical methods. Sequencing of the 16S rRNA gene indicated that the culture was a small-colony variant of Enterococcus faecalis. This is the first case in Japan of infectious endocarditis due to E. faecalis small-colony variants. Small-colony variants are subpopulations of bacteria with slow growth, reduced sugar fermentation, and unstable phenotype. As a result, these strains tend to be misidentified. Further, small-colony variants are associated with recurrent and persistent infections such as prosthetic joint infection and infectious endocarditis. These strains are found in various bacterial species, including Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa, but rarely in Enterococcus species. The case highlights the need to be vigilant of E. faecalis small-colony variants, especially in patients who received long-term courses of antibiotics. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
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Directory of Open Access Journals (Sweden)
T.C. Zangirolami
2002-03-01
Full Text Available Growth and product formation by a selected variant of Aspergillus oryzae showing high alpha-amylase production was studied in continuous cultivations carried out at six different specific growth rates, using glucose as the growth-limiting nutrient. The analysis of the steady-state data revealed that the variant and wild-type strains were similar with respect to glucose uptake system and stoichiometric coefficients. However, the variant was capable of maintaining an enzyme production as high as 40 FAUgDW-1h-1 at a dilution rate of 0.2 h-1, while the wild-type strain reached a maximum specific alpha-amylase production rate of 17 FAUgDW-1h-1 at a dilution rate of 0.1 h-1. Using a morphologically structured model originally proposed for the wild-type strain, it was possible to describe enzyme production, biomass formation and glucose consumption after modification of a few parameters to adjust the model to the characteristics of the selected variant.
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Biodegradation of furfural by Bacillus subtilis strain DS3.
Zheng, Dan; Bao, Jianguo; Lu, Jueming; Lv, Quanxi
2015-07-01
An aerobic bacterial strain DS3, capable of growing on furfural as sole carbon source, was isolated from actived sludge of wastewater treatment plant in a diosgenin factory after enrichment. Based on morphological physiological tests as well as 16SrDNA sequence and Biolog analyses it was identified as Bacillus subtilis. The study revealed that strain DS3 utilized furfural, as analyzed by high-performance liquid chromatography (HPLC). Under following conditions: pH 8.0, temperature 35 degrees C, 150 rpm and 10% inoculum, strain DS3 showed 31.2% furfural degradation. Furthermore, DS3 strain was found to tolerate furfural concentration as high as 6000 mg(-1). The ability of Bacillus subtilis strain DS3 to degrade furfural has been demonstrated for the first time in the present study.
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Genetic variants in IL-6/JAK/STAT3 pathway and the risk of CRC.
Wang, Shuwei; Zhang, Weidong
2016-05-01
Interleukin (IL)-6 and the downstream Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway have previously been reported to be important in the development of colorectal cancer (CRC), and several studies have shown the relationship between the polymorphisms of related genes in this pathway with the risk of CRC. However, the findings of these related studies are inconsistent. Moreover, there has no systematic review and meta-analysis to evaluate the relationship between genetic variants in IL-6/JAK/STAT3 pathway and CRC susceptibility. Hence, we conducted a meta-analysis to explore the relationship between polymorphisms in IL-6/JAK/STAT3 pathway genes and CRC risk. Eighteen eligible studies with a total of 13,795 CRC cases and 18,043 controls were identified by searching PubMed, Web of Science, Embase, and the Cochrane Library databases for the period up to September 15, 2015. Odds ratios (ORs) and their 95 % confidence intervals (CIs) were used to calculate the strength of the association. Our results indicated that IL-6 genetic variants in allele additive model (OR = 1.05, 95 % CI = 1.00, 1.09) and JAK2 genetic variants (OR = 1.40, 95 % CI = 1.15, 1.65) in genotype recessive model were significantly associated with CRC risk. Moreover, the pooled data revealed that IL-6 rs1800795 polymorphism significantly increased the risk of CRC in allele additive model in Europe (OR = 1.07, 95 % CI = 1.01, 1.14). In conclusion, the present findings indicate that IL-6 and JAK2 genetic variants are associated with the increased risk of CRC while STAT3 genetic variants not. We need more well-designed clinical studies covering more countries and population to definitively establish the association between genetic variants in IL-6/JAK/STAT3 pathway and CRC susceptibility.
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DEFF Research Database (Denmark)
Rembeck, Karolina; Maglio, Cristina; Lagging, Martin
2012-01-01
ABSTRACT: BACKGROUND: Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M...... sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients. METHODS: Three hundred...
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Strain induced optical properties of BaReO3
Kumavat, Sandip R.; Kansara, Shivam; Gupta, Sanjeev K.; Sonvane, Yogesh
2018-05-01
Here, we have performed strain induce optical properties of BaReO3 by using density functional theory (DFT). We noticed that after applying intrinsic and extrinsic strain to the BaReO3, it shows the metallic behavior. We also studied optical properties, which show good activity in the ultraviolet region. The results show that after applying intrinsic and extrinsic strain to BaReO3 the absorption peaks are shifted towards the high UV region of the spectrum. Thus, we concluded that, BaReO3 material with extrinsic strain can be useful for high frequency UV device and optoelectronic devices.
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Rare GABRA3 variants are associated with epileptic seizures, encephalopathy and dysmorphic features.
Niturad, Cristina Elena; Lev, Dorit; Kalscheuer, Vera M; Charzewska, Agnieszka; Schubert, Julian; Lerman-Sagie, Tally; Kroes, Hester Y; Oegema, Renske; Traverso, Monica; Specchio, Nicola; Lassota, Maria; Chelly, Jamel; Bennett-Back, Odeya; Carmi, Nirit; Koffler-Brill, Tal; Iacomino, Michele; Trivisano, Marina; Capovilla, Giuseppe; Striano, Pasquale; Nawara, Magdalena; Rzonca, Sylwia; Fischer, Ute; Bienek, Melanie; Jensen, Corinna; Hu, Hao; Thiele, Holger; Altmüller, Janine; Krause, Roland; May, Patrick; Becker, Felicitas; Balling, Rudi; Biskup, Saskia; Haas, Stefan A; Nürnberg, Peter; van Gassen, Koen L I; Lerche, Holger; Zara, Federico; Maljevic, Snezana; Leshinsky-Silver, Esther
2017-11-01
Genetic epilepsies are caused by mutations in a range of different genes, many of them encoding ion channels, receptors or transporters. While the number of detected variants and genes increased dramatically in the recent years, pleiotropic effects have also been recognized, revealing that clinical syndromes with various degrees of severity arise from a single gene, a single mutation, or from different mutations showing similar functional defects. Accordingly, several genes coding for GABAA receptor subunits have been linked to a spectrum of benign to severe epileptic disorders and it was shown that a loss of function presents the major correlated pathomechanism. Here, we identified six variants in GABRA3 encoding the α3-subunit of the GABAA receptor. This gene is located on chromosome Xq28 and has not been previously associated with human disease. Five missense variants and one microduplication were detected in four families and two sporadic cases presenting with a range of epileptic seizure types, a varying degree of intellectual disability and developmental delay, sometimes with dysmorphic features or nystagmus. The variants co-segregated mostly but not completely with the phenotype in the families, indicating in some cases incomplete penetrance, involvement of other genes, or presence of phenocopies. Overall, males were more severely affected and there were three asymptomatic female mutation carriers compared to only one male without a clinical phenotype. X-chromosome inactivation studies could not explain the phenotypic variability in females. Three detected missense variants are localized in the extracellular GABA-binding NH2-terminus, one in the M2-M3 linker and one in the M4 transmembrane segment of the α3-subunit. Functional studies in Xenopus laevis oocytes revealed a variable but significant reduction of GABA-evoked anion currents for all mutants compared to wild-type receptors. The degree of current reduction correlated partially with the phenotype
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Spus, Maciej; Liu, Hua; Wels, Michiel; Abee, Tjakko; Smid, Eddy J
2017-01-16
Lactobacillus helveticus is widely used in dairy fermentations and produces a range of enzymes, which upon cell lysis can be released into the cheese matrix and impact degradation of proteins, peptides and lipids. In our study we set out to explore the potential of Lb. helveticus DSM 20075 for increased autolytic capacity triggered by conditions such as low pH and high salt concentrations encountered in cheese environments. Lb. helveticus DSM 20075 was subjected to varied incubation temperatures (ranging from 37 to 50°C). High-temperature incubation (in the range of 45 to 50°C) allowed us to obtain a collection of six variant strains (V45-V50), which in comparison to the wild-type strain, showed higher growth rates at elevated temperatures (42°C-45°C). Moreover, variant strain V50 showed a 4-fold higher, in comparison to wild type, autolytic capacity in cheese-like conditions. Next, strain V50 was used as an adjunct in lab-scale cheese making trials to measure its impact on aroma formation during ripening. Specifically, in cheeses made with strain V50, the relative abundance of benzaldehyde increased 3-fold compared to cheeses made with the wild-type strain. Analysis of the genome sequence of strain V50 revealed multiple mutations in comparison to the wild-type strain DSM 20075 including a mutation found in a gene coding for a metal ion transporter, which can potentially be linked to intracellular accumulation of Mn 2+ and benzaldehyde formation. The approach of high-temperature incubation can be applied in dairy industry for the selection of (adjunct) cultures targeted at accelerated cheese ripening and aroma formation. Copyright © 2016 Elsevier B.V. All rights reserved.
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Jaumain, Emilie; Quadrio, Isabelle; Herzog, Laetitia; Reine, Fabienne; Rezaei, Human; Andréoletti, Olivier; Laude, Hubert; Perret-Liaudet, Armand; Haïk, Stéphane; Béringue, Vincent
2016-12-01
Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt-Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between the host cellular prion protein (PrP C ) and the infecting pathological PrP assemblies (PrP Sc ) constituting the prion. A BSE strain variant, designated L-BSE and responsible for atypical, supposedly spontaneous forms of prion diseases in aged cattle, demonstrates zoonotic potential, as evidenced by its capacity to propagate more easily than classical BSE in transgenic mice expressing human PrP C and in nonhuman primates. In humanized mice, L-BSE propagates without any apparent species barrier and shares similar biochemical PrP Sc signatures with the CJD subtype designated MM2-cortical, thus opening the possibility that certain CJD cases classified as sporadic may actually originate from L-type BSE cross-transmission. To address this issue, we compared the biological properties of L-BSE and those of a panel of CJD subtypes representative of the human prion strain diversity using standard strain-typing criteria in human PrP transgenic mice. We found no evidence that L-BSE causes a known form of sporadic CJD. Since the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD, and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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G2S: A web-service for annotating genomic variants on 3D protein structures.
Wang, Juexin; Sheridan, Robert; Sumer, S Onur; Schultz, Nikolaus; Xu, Dong; Gao, Jianjiong
2018-01-27
Accurately mapping and annotating genomic locations on 3D protein structures is a key step in structure-based analysis of genomic variants detected by recent large-scale sequencing efforts. There are several mapping resources currently available, but none of them provides a web API (Application Programming Interface) that support programmatic access. We present G2S, a real-time web API that provides automated mapping of genomic variants on 3D protein structures. G2S can align genomic locations of variants, protein locations, or protein sequences to protein structures and retrieve the mapped residues from structures. G2S API uses REST-inspired design conception and it can be used by various clients such as web browsers, command terminals, programming languages and other bioinformatics tools for bringing 3D structures into genomic variant analysis. The webserver and source codes are freely available at https://g2s.genomenexus.org. g2s@genomenexus.org. Supplementary data are available at Bioinformatics online. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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Stormer, R S; Falkinham, J O
1989-01-01
Unpigmented colonial variants were isolated from pigmented Mycobacterium avium isolates recovered from patients with acquired immunodeficiency syndrome and the environment. The variants were interconvertible: the rate of transition from unpigmented to pigmented type was 4.0 x 10(-5) variants per cell per generation. The unpigmented variants were more tolerant to antibiotics, especially beta-lactams, and Cd2+ and Cu2+ salts than were their pigmented parents. Both pigmented and unpigmented variants of the strains produced beta-lactamase, although beta-lactamase did not appear to be a determinant of beta-lactam susceptibility. Pigmented variants grew more rapidly in a number of commonly used mycobacterial media, were more hydrophobic, and had higher carotenoid contents than their unpigmented segregants. PMID:2808669
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Van Vaerenbergh, Johan; Baeyen, Steve; De Vos, Paul; Maes, Martine
2012-01-01
Worldwide, Dickeya (formerly Erwinia chrysanthemi) is causing soft rot diseases on a large diversity of crops and ornamental plants. Strains affecting potato are mainly found in D. dadantii, D. dianthicola and D. zeae, which appear to have a marked geographical distribution. Furthermore, a few Dickeya isolates from potato are attributed to D. chrysanthemi and D. dieffenbachiae. In Europe, isolates of Erwinia chrysanthemi biovar 1 and biovar 7 from potato are now classified in D. dianthicola. However, in the past few years, a new Dickeya biovar 3 variant, tentatively named 'Dickeya solani', has emerged as a common major threat, in particular in seed potatoes. Sequences of a fliC gene fragment were used to generate a phylogeny of Dickeya reference strains from culture collections and with this reference backbone, to classify pectinolytic isolates, i.e. Dickeya spp. from potato and ornamental plants. The reference strains of the currently recognized Dickeya species and 'D. solani' were unambiguously delineated in the fliC phylogram. D. dadantii, D. dianthicola and 'D. solani' displayed unbranched clades, while D. chrysanthemi, D. zeae and D. dieffenbachiae branched into subclades and lineages. Moreover, Dickeya isolates from diagnostic samples, in particular biovar 3 isolates from greenhouse ornamentals, formed several new lineages. Most of these isolates were positioned between the clade of 'D. solani' and D. dadantii as transition variants. New lineages also appeared in D. dieffenbachiae and in D. zeae. The strains and isolates of D. dianthicola and 'D. solani' were differentiated by a fliC sequence useful for barcode identification. A fliC TaqMan®real-time PCR was developed for 'D. solani' and the assay was provisionally evaluated in direct analysis of diagnostic potato samples. This molecular tool can support the efforts to control this particular phytopathogen in seed potato certification.
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Directory of Open Access Journals (Sweden)
Johan Van Vaerenbergh
Full Text Available Worldwide, Dickeya (formerly Erwinia chrysanthemi is causing soft rot diseases on a large diversity of crops and ornamental plants. Strains affecting potato are mainly found in D. dadantii, D. dianthicola and D. zeae, which appear to have a marked geographical distribution. Furthermore, a few Dickeya isolates from potato are attributed to D. chrysanthemi and D. dieffenbachiae. In Europe, isolates of Erwinia chrysanthemi biovar 1 and biovar 7 from potato are now classified in D. dianthicola. However, in the past few years, a new Dickeya biovar 3 variant, tentatively named 'Dickeya solani', has emerged as a common major threat, in particular in seed potatoes. Sequences of a fliC gene fragment were used to generate a phylogeny of Dickeya reference strains from culture collections and with this reference backbone, to classify pectinolytic isolates, i.e. Dickeya spp. from potato and ornamental plants. The reference strains of the currently recognized Dickeya species and 'D. solani' were unambiguously delineated in the fliC phylogram. D. dadantii, D. dianthicola and 'D. solani' displayed unbranched clades, while D. chrysanthemi, D. zeae and D. dieffenbachiae branched into subclades and lineages. Moreover, Dickeya isolates from diagnostic samples, in particular biovar 3 isolates from greenhouse ornamentals, formed several new lineages. Most of these isolates were positioned between the clade of 'D. solani' and D. dadantii as transition variants. New lineages also appeared in D. dieffenbachiae and in D. zeae. The strains and isolates of D. dianthicola and 'D. solani' were differentiated by a fliC sequence useful for barcode identification. A fliC TaqMan®real-time PCR was developed for 'D. solani' and the assay was provisionally evaluated in direct analysis of diagnostic potato samples. This molecular tool can support the efforts to control this particular phytopathogen in seed potato certification.
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A novel multi-variant epitope ensemble vaccine against avian leukosis virus subgroup J.
Wang, Xiaoyu; Zhou, Defang; Wang, Guihua; Huang, Libo; Zheng, Qiankun; Li, Chengui; Cheng, Ziqiang
2017-12-04
The hypervariable antigenicity and immunosuppressive features of avian leukosis virus subgroup J (ALV-J) has led to great challenges to develop effective vaccines. Epitope vaccine will be a perspective trend. Previously, we identified a variant antigenic neutralizing epitope in hypervariable region 1 (hr1) of ALV-J, N-LRDFIA/E/TKWKS/GDDL/HLIRPYVNQS-C. BLAST analysis showed that the mutation of A, E, T and H in this epitope cover 79% of all ALV-J strains. Base on this data, we designed a multi-variant epitope ensemble vaccine comprising the four mutation variants linked with glycine and serine. The recombinant multi-variant epitope gene was expressed in Escherichia coli BL21. The expressed protein of the variant multi-variant epitope gene can react with positive sera and monoclonal antibodies of ALV-J, while cannot react with ALV-J negative sera. The multi-variant epitope vaccine that conjugated Freund's adjuvant complete/incomplete showed high immunogenicity that reached the titer of 1:64,000 at 42 days post immunization and maintained the immune period for at least 126 days in SPF chickens. Further, we demonstrated that the antibody induced by the variant multi-variant ensemble epitope vaccine recognized and neutralized different ALV-J strains (NX0101, TA1, WS1, BZ1224 and BZ4). Protection experiment that was evaluated by clinical symptom, viral shedding, weight gain, gross and histopathology showed 100% chickens that inoculated the multi-epitope vaccine were well protected against ALV-J challenge. The result shows a promising multi-variant epitope ensemble vaccine against hypervariable viruses in animals. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Jia, Junting; Ma, Yuyuan; Zhao, Xiong; Huangfu, Chaoji; Zhong, Yadi; Fang, Chi; Fan, Rui; Lv, Maomin; Zhang, Jingang
2016-09-17
Human parvovirus B19 (B19V) is a frequent contaminant of blood and plasma-derived medicinal products. Three distinct genotypes of B19V have been identified. The distribution of the three B19V genotypes has been investigated in various regions or countries. However, in China, data on the existence of different B19V genotypes are limited. One hundred and eighteen B19V-DNA positive source plasma pool samples collected from three Chinese blood products manufacturers were analyzed. The subgenomic NS1/VP1u region junction of B19V was amplified by nested PCR. These amplified products were then cloned and subsequently sequenced. For genotyping, their phylogenetic inferences were constructed based on the NS1/VP1-unique region. Then putative recombination events were analyzed and identified. Phylogenetic analysis of 118 B19V sequences attributed 61.86 % to genotype 1a, 10.17 % to genotype 1b, and 17.80 % to genotype 3b. All the genotype 3b sequences obtained in this study grouped as a specific, closely related cluster with B19V strain D91.1. Four 1a/3b recombinants and 5 new atypical B19V variants with no recombination events were identified. There were at least 3 subtypes (1a, 1b and 3b) of B19V circulating in China. Furthermore, putative B19V 1a/3b recombinants and unclassified strains were identified as well. Such recombinant and unclassified strains may contribute to the genetic diversity of B19V and consequently complicate the B19V infection diagnosis and NAT screening. Further studies will be required to elucidate the biological significance of the recombinant and unclassified strains.
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In vitro selection of rape variants resistant to oxalic acid using haploid stem apexes
International Nuclear Information System (INIS)
Wang Yifei; Huang Jianhua; Lu Ruiju; Sun Yuefang; Zhou Runmei; Zhou Zhijiang; Xie Zhujie; Liu Chenghong
2002-01-01
Mutagenic treatment was made of the haploid stem apexes rape strain '9841' and '9885' with Pingyangmycin. As a result of positive selection with oxalic acid providing selection pressure, variants with significantly higher tolerance to oxalic acid than the original ones were obtained. 3 germplasm with significantly higher resistance to Sclerotinia sclerotiorum than cultivar Hu You 12 were selected from field test
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Directory of Open Access Journals (Sweden)
T.X. Castro
2010-12-01
Full Text Available Canine parvovirus (CPV is the most important enteric virus for dogs and it seems to be undergoing continuous evolution, generating new genetic and antigenic variants throughout the world. The aim of this study was to analyze the distribution of CPV variants from 1995 to 2009 and to investigate the circulation of the new variant CPV-2c in Rio de Janeiro, Brazil. In addition, the clinical features of CPV infection were also reported. After CPV laboratorial confirmation by HA/HI and PCR, thirty-two fecal samples were analyzed by sequencing a 583-bp fragment of the VP2 gene. One sample, collected in 2008 was typed as the new type CPV-2c. All samples from 1995 to 2003 were identified as "new CPV-2a". From 2004 to 2006, both "new CPV-2a" and CPV-2b were observed. From 2006 to 2009, most of the samples were characterized as CPV-2b. The classical signs of CPV enteritis were observed in 16/18 CPV-2a and 5/13 CPV-2b infected puppies. These results show that continuous epidemiological surveillance of CPV strain distribution is essential for studying the patterns of CPV-2a and 2b spread and for determining whether the new variant CPV-2c has become permanently established in Brazilian canine population.
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Directory of Open Access Journals (Sweden)
E Babaei
2009-07-01
Full Text Available Introduction: Survivin is a new member of the Inhibitor Apotosis Protein family (IAP which plays an important role in the regulation of both cell cycle and apoptosis. Its distinct expression in tumor cells as compared to normal adult cells introduces Survivin as the fourth transcriptom demonstrated in tumors. Breast cancer is the most common malignancy among women and scientist`s efforts to classify it has lead to various molecular subtypes and controversial results. Because of the high prevalence of these tumors and lack of suitable molecular markers for diagnosis and prognosis, there are ongoing efforts to find molecular markers which can distinguish nontumoral from tumor tissues. In this study we evaluate the potential usefulness of Survivin and its splice variants ΔEx3, 2b and 3b as molecular markers in breast cancer. Methods: We studied 18 tumor and 17 non tumor adjacent tissues. Transcription levels were measured by Semiquantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR and normalized by ß2m as an internal control. Results: 1Survivin and its splice variants; Δex3, 2b and 3b showed differentially higher expression levels in tumors than adjacent normal tissues. 2 The expression levels of Survivin, Survivin-ΔEx3 and Survivin-3b were significantly correlated with the type of tumors. 3 Survivin-2b was expressed in a few samples. 4 Survivin-3b was detected only in tumor samples. Also, our results showed that ΔEx3 variant can be introduced as a dominant expressed variant in breast cancer. Conclusion: Our data indicated that the expression of Survivin, Survivin ∆Ex3 and especially, Survivin-3b were correlated with cancerous nature of tumors and Survivin-∆Ex3 was the most common expressed variant in breast carcinomas. These results besides confirming the potential usefulness of Survivin and its splice variants as molecular markers in breast cancer, demonstrated the role of the gene and its splice variants, especially 3b
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Qian, Yuanchao; Zhong, Lixia; Hou, Yunhua; Qu, Yinbo; Zhong, Yaohua
2016-01-01
The filamentous fungus Trichoderma reesei is a widely used strain for cellulolytic enzyme production. A hypercellulolytic T. reesei variant SN1 was identified in this study and found to be different from the well-known cellulase producers QM9414 and RUT-C30. The cellulose-degrading enzymes of T. reesei SN1 show higher endoglucanase (EG) activity but lower β-glucosidase (BGL) activity than those of the others. A uracil auxotroph strain, SP4, was constructed by pyr4 deletion in SN1 to improve transformation efficiency. The BGL1-encoding gene bgl1 under the control of a modified cbh1 promoter was overexpressed in SP4. A transformant, SPB2, with four additional copies of bgl1 exhibited a 17.1-fold increase in BGL activity and a 30.0% increase in filter paper activity. Saccharification of corncob residues with crude enzyme showed that the glucose yield of SPB2 is 65.0% higher than that of SP4. These results reveal the feasibility of strain improvement through the development of an efficient genetic transformation platform to construct a balanced cellulase system for biomass conversion.
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Directory of Open Access Journals (Sweden)
Qian Yuanchao
2016-08-01
Full Text Available The filamentous fungus Trichoderma reesei is a widely used strain for cellulolytic enzyme production. A hypercellulolytic T. reesei variant SN1 was identified in this study and found to be different from the well-known cellulase producers QM9414 and RUT-C30. The cellulose-degrading enzymes of T. reesei SN1 show higher endoglucanase (EG activity but lower β-glucosidase (BGL activity than those of QM9414 and RUT-C30. A uracil auxotroph strain, SP4, was constructed by pyr4 deletion in SN1 to improve transformation efficiency. The BGL1-encoding gene bgl1 under the control of a modified cbh1 promoter was overexpressed in SP4. A transformant, SPB2, with four additional copies of bgl1 exhibited a 17.1-fold increase in BGL activity and a 30% increase in filter paper activity. Saccharification of corncob residues with crude enzyme showed that the glucose yield of SPB2 is 65% higher than that of SP4. These results reveal the feasibility of strain improvement through the development of an efficient genetic transformation platform to construct a balanced cellulase system for biomass conversion.
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Directory of Open Access Journals (Sweden)
Lam Hon-Ming
2009-07-01
Full Text Available Abstract Background Histone modifications and histone variants are of importance in many biological processes. To understand the biological functions of the global dynamics of histone modifications and histone variants in higher plants, we elucidated the variants and post-translational modifications of histones in soybean, a legume plant with a much bigger genome than that of Arabidopsis thaliana. Results In soybean leaves, mono-, di- and tri-methylation at Lysine 4, Lysine 27 and Lysine 36, and acetylation at Lysine 14, 18 and 23 were detected in HISTONE H3. Lysine 27 was prone to being mono-methylated, while tri-methylation was predominant at Lysine 36. We also observed that Lysine 27 methylation and Lysine 36 methylation usually excluded each other in HISTONE H3. Although methylation at HISTONE H3 Lysine 79 was not reported in A. thaliana, mono- and di-methylated HISTONE H3 Lysine 79 were detected in soybean. Besides, acetylation at Lysine 8 and 12 of HISTONE H4 in soybean were identified. Using a combination of mass spectrometry and nano-liquid chromatography, two variants of HISTONE H3 were detected and their modifications were determined. They were different at positions of A31F41S87S90 (HISTONE variant H3.1 and T31Y41H87L90 (HISTONE variant H3.2, respectively. The methylation patterns in these two HISTONE H3 variants also exhibited differences. Lysine 4 and Lysine 36 methylation were only detected in HISTONE H3.2, suggesting that HISTONE variant H3.2 might be associated with actively transcribing genes. In addition, two variants of histone H4 (H4.1 and H4.2 were also detected, which were missing in other organisms. In the histone variant H4.1 and H4.2, the amino acid 60 was isoleucine and valine, respectively. Conclusion This work revealed several distinct variants of soybean histone and their modifications that were different from A. thaliana, thus providing important biological information toward further understanding of the histone
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Typing of Lymphogranuloma Venereum Chlamydia trachomatis Strains
Christerson, Linus; de Vries, Henry J.C.; de Barbeyrac, Bertille; Gaydos, Charlotte A.; Henrich, Birgit; Hoffmann, Steen; Schachter, Julius; Thorvaldsen, Johannes; Vall-Mayans, Martí; Klint, Markus; Morré, Servaas A.
2010-01-01
We analyzed by multilocus sequence typing 77 lymphogranuloma venereum Chlamydia trachomatis strains from men who have sex with men in Europe and the United States. Specimens from an outbreak in 2003 in Europe were monoclonal. In contrast, several strains were in the United States in the 1980s, including a variant from Europe. PMID:21029543
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A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3
Murthy, Aditya; Li, Yun; Peng, Ivan; Reichelt, Mike; Katakam, Anand Kumar; Noubade, Rajkumar; Roose-Girma, Merone; Devoss, Jason; Diehl, Lauri; Graham, Robert R.; van Lookeren Campagne, Menno
2014-02-01
Crohn's disease is a debilitating inflammatory bowel disease (IBD) that can involve the entire digestive tract. A single-nucleotide polymorphism (SNP) encoding a missense variant in the autophagy gene ATG16L1 (rs2241880, Thr300Ala) is strongly associated with the incidence of Crohn's disease. Numerous studies have demonstrated the effect of ATG16L1 deletion or deficiency; however, the molecular consequences of the Thr300Ala (T300A) variant remains unknown. Here we show that amino acids 296-299 constitute a caspase cleavage motif in ATG16L1 and that the T300A variant (T316A in mice) significantly increases ATG16L1 sensitization to caspase-3-mediated processing. We observed that death-receptor activation or starvation-induced metabolic stress in human and murine macrophages increased degradation of the T300A or T316A variants of ATG16L1, respectively, resulting in diminished autophagy. Knock-in mice harbouring the T316A variant showed defective clearance of the ileal pathogen Yersinia enterocolitica and an elevated inflammatory cytokine response. In turn, deletion of the caspase-3-encoding gene, Casp3, or elimination of the caspase cleavage site by site-directed mutagenesis rescued starvation-induced autophagy and pathogen clearance, respectively. These findings demonstrate that caspase 3 activation in the presence of a common risk allele leads to accelerated degradation of ATG16L1, placing cellular stress, apoptotic stimuli and impaired autophagy in a unified pathway that predisposes to Crohn's disease.
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González-Peñas, Javier; Arrojo, Manuel; Paz, Eduardo; Brenlla, Julio; Páramo, Mario; Costas, Javier
2015-10-01
Schizophrenia may be considered a human-specific disorder arisen as a maladaptive by-product of human-specific brain evolution. Therefore, genetic variants involved in susceptibility to schizophrenia may be identified among those genes related to acquisition of human-specific traits. NPAS3, a transcription factor involved in central nervous system development and neurogenesis, seems to be implicated in the evolution of human brain, as it is the human gene with most human-specific accelerated elements (HAEs), i.e., .mammalian conserved regulatory sequences with accelerated evolution in the lineage leading to humans after human-chimpanzee split. We hypothesize that any nucleotide variant at the NPAS3 HAEs may lead to altered susceptibility to schizophrenia. Twenty-one variants at these HAEs detected by the 1000 genomes Project, as well as five additional variants taken from psychiatric genome-wide association studies, were genotyped in 538 schizophrenic patients and 539 controls from Galicia. Analyses at the haplotype level or based on the cumulative role of the variants assuming different susceptibility models did not find any significant association in spite of enough power under several plausible scenarios regarding direction of effect and the specific role of rare and common variants. These results suggest that, contrary to our hypothesis, the special evolution of the NPAS3 HAEs in Homo relaxed the strong constraint on sequence that characterized these regions during mammalian evolution, allowing some sequence changes without any effect on schizophrenia risk. © 2015 Wiley Periodicals, Inc.
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Wang, Xinhui; Ren, Hongyang; Liu, Dayu; Wang, Bing; Zhu, Wenyou; Wang, Wei
2013-02-01
Continued acid production by Lactobacillus delbrueckii subsp. bulgaricus during the chilled storage of yogurt is the major cause of postacidification, resulting in a short shelf life. Two H(+) -ATPase defective variants of L. delbrueckii subsp. bulgaricus were successfully isolated and their H(+) -ATPase activities were reduced by 51.3% and 34.3%, respectively. It was shown that growth and acid production of variants were remarkably inhibited. The variants were more sensitive to acidic condition and had a significant rate for inactivation of H(+) -ATPase by N, N-dicyclohexylcarbodiimide (DCCD), along with a low H(+) -extrusion, suggesting that H(+) -ATPase is direct response for H(+) -extrusion. In addition, the variants were also more sensitive to NaCl, while H(+) -ATPase activities of variants and parent strain were significantly enhanced by NaCl stress. Obviously, H(+) -ATPase might be involved in Na(+) transportation. Furthermore, variants were inoculated in fermented milk to ferment yogurt. There was no significant difference in flavor, whereas the postacidification of yogurt during chilled storage was remarkably inhibited. It is suggested that application of L. delbrueckii subsp. bulgaricus with reduced H(+) -ATPase activity in yogurt fermentation is one of effect, economic and simple avenues of inhibiting postacidification of yogurt during refrigerated storage, giving a longer shelf life. During yogurt fermentation, continued acid production by Lactobacillus delbrueckii subsp. bulgaricus during the chilled storage of yogurt leads to milk fermentation with high postacidification, resulting in a short shelf life. In this work, 2 acid-sensitive variant strains of L. delbrueckii subsp. bulgaricus were isolated. The characteristics related to H(+) -ATPase were compared and it was observed that milk fermented by the variants had lower postacidification, giving a longer shelf life. Application of L. delbrueckii subsp. bulgaricus with reduced H(+) -ATPase activity
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Siarkou, Victoria I; Vitti, Danai; Protonotariou, Efthimia; Ikonomidis, Alexandros; Sofianou, Danai
2009-04-01
A study was designed to investigate the molecular epidemiological characteristics of multidrug-resistant outbreak-related Pseudomonas aeruginosa isolates collected in a university hospital in northern Greece. Of 29 nonreplicate P. aeruginosa isolates resistant to carbapenems and ceftazidime, 14 were positive for metallo-beta-lactamase production. PCR analyses with primers specific for bla(VIM) and bla(IMP) revealed that 13 isolates carried a novel bla(VIM-2) gene variant, designated bla(VIM-17), and only 1 isolate carried bla(VIM-2), a gene predominant among P. aeruginosa strains in Greek hospitals. Pulsed-field gel electrophoresis of XbaI-digested genomic DNAs showed a close genetic relationship for 12 of 13 bla(VIM-17)-carrying outbreak-related isolates, which were of the O11 serotype; the clonally unrelated isolate carrying bla(VIM-17) was of the O12 serotype. PCR mapping strategies for the detection of class 1 integrons and sequencing approaches revealed the presence of integrons containing one bla(VIM) cassette flanked by two aacA29 cassettes. These integrons were similar but not identical to In59 (GenBank accession number AF263519) initially described in France. All isolates carrying bla(VIM-17), regardless of their genetic profile, had an identical integron, named In59.3, indicating that although the hospital outbreak was mainly due to clonal dissemination, the horizontal transmission of the bla(VIM-17)-containing integron among P. aeruginosa isolates should also have occurred. An outbreak-related isolate and a control strain, both of which carried the bla(VIM-2) gene but which were clonally distinct, had an identical integron, named In59.2, which differed only at the level of the bla(VIM) gene from In59.3 integrons, suggesting a common ancestry. The spread of the bla(VIM-17)-containing integron in clonally unrelated P. aeruginosa isolates without any evidence of plasmid carriage is probably associated with a transposon.
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Identification of Rare Variants in TNNI3 with Atrial Fibrillation in a Chinese GeneID Population
Wang, Chuchu; Wu, Manman; Qian, Jin; Li, Bin; Tu, Xin; Xu, Chengqi; Li, Sisi; Chen, Shanshan; Zhao, Yuanyuan; Huang, Yufeng; Shi, Lisong; Cheng, Xiang; Liao, Yuhua; Chen, Qiuyun; Xia, Yunlong; Yao, Wei; Wu, Gang; Cheng, Mian; Wang, Qing K.
2015-01-01
Despite advances by genome-wide association studies (GWAS), much of heritability of common human diseases remains missing, a phenomenon referred to as ‘missing heritability’. One potential cause for ‘missing heritability’ is the rare susceptibility variants overlooked by GWAS. Atrial fibrillation (AF) is the most common arrhythmia seen at hospitals and increases risk of stroke by 5-fold and doubles risk of heart failure and sudden death. Here we studied one large Chinese family with AF and hypertrophic cardiomyopathy (HCM). Whole-exome sequencing analysis identified a mutation in TNNI3, R186Q, that co-segregated with the disease in the family, but did not exist in >1,583 controls, suggesting that R186Q causes AF and HCM. High-resolution melting curve analysis and direct DNA sequence analysis were then used to screen mutations in all exons and exon-intron boundaries of TNNI3 in a panel of 1,127 unrelated AF patients and 1,583 non-AF subjects. Four novel missense variants were identified in TNNI3, including E64G, M154L, E187G and D196G in four independent AF patients, but no variant was found in 1,583 non-AF subjects. All variants were not found in public databases, including the ExAC Browser database with 60,706 exomes. These data suggests that rare TNNI3 variants are associated with AF (P=0.03). TNNI3 encodes troponin I, a key regulator of the contraction-relaxation function of cardiac muscle and was not previously implicated in AF. Thus, this study may identify a new biological pathway for the pathogenesis of AF and provides evidence to support the rare variant hypothesis for missing heritability. PMID:26169204
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Wang, Jichun; Guo, Rongli; Qiao, Yongfeng; Xu, Mengwei; Wang, Zhisheng; Liu, Yamei; Gu, Yiqi; Liu, Chang; Hou, Jibo
2016-12-07
Since the end of 2011 an outbreak of pseudorabies affected Chinese pig herds that had been vaccinated with the commercial vaccine made of Bartha K61 strain. It is now clear that the outbreak was caused by an emergent PRV variant. Even though vaccines made of PRV Bartha K61 strain can confer certain cross protection against PRV variants based on experimental data, less than optimal clinical protection and virus shedding reduction were observed, making the control or eradication of this disease difficult. An infectious clone of PRV AH02LA strain was constructed to generate a gE deletion mutant PRV(LA-A B ) strain. PRV(LA-A B ) strain can reach a titer of 10 8.43 TCID 50 /mL (50% tissue culture infectious dose) on BHK-21 cells. To evaluate the efficiency of the inactivated vaccine made of PRV(LA-A B ) strain, thirty 3-week-old PRV-negative piglets were divided randomly into six groups for vaccination and challenge test. All five piglets in the challenge control showed typical clinical symptoms of pseudorabies post challenge. Sneezing and nasal discharge were observed in four and three piglets in groups C(vaccinated with inactivated PRV Bartha K61 strain vaccine) and D(vaccinated with live PRV Bartha K61 strain vaccine) respectively. In contrast, piglets in both groups A(vaccinated with inactivated PRV LA-AB strain vaccine) and B(vaccinated with inactivated PRV LA-A B strain vaccine with adjuvant) presented mild or no clinical symptoms. Moreover, viral titers detected via nasal swabs were approximately 100 times lower in group B than in the challenge control, and the duration of virus shedding (3-4 days) was shorter than in either the challenge control (5-10 days) or groups C and D (5-6 days). The infectious clone constructed in this study harbors the whole genome of the PRV variant AH02LA strain. The gE deletion mutant PRV(LA-A B )strain generated from PRV AH02LA strain can reach a high titer on BHK-21 cells. An inactivated vaccine of PRV LA-A B provides clinical
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A population-specific uncommon variant in GRIN3A associated with schizophrenia.
Takata, Atsushi; Iwayama, Yoshimi; Fukuo, Yasuhisa; Ikeda, Masashi; Okochi, Tomo; Maekawa, Motoko; Toyota, Tomoko; Yamada, Kazuo; Hattori, Eiji; Ohnishi, Tetsuo; Toyoshima, Manabu; Ujike, Hiroshi; Inada, Toshiya; Kunugi, Hiroshi; Ozaki, Norio; Nanko, Shinichiro; Nakamura, Kazuhiko; Mori, Norio; Kanba, Shigenobu; Iwata, Nakao; Kato, Tadafumi; Yoshikawa, Takeo
2013-03-15
Genome-wide association studies have successfully identified several common variants showing robust association with schizophrenia. However, individually, these variants only produce a weak effect. To identify genetic variants with larger effect sizes, increasing attention is now being paid to uncommon and rare variants. From the 1000 Genomes Project data, we selected 47 candidate single nucleotide variants (SNVs), which were: 1) uncommon (minor allele frequency way to discover risk variants with larger effects. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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Satriano, Alessandro; Heydari, Bobak; Narous, Mariam; Exner, Derek V; Mikami, Yoko; Attwood, Monica M; Tyberg, John V; Lydell, Carmen P; Howarth, Andrew G; Fine, Nowell M; White, James A
2017-12-01
Two-dimensional (2D) strain analysis is constrained by geometry-dependent reference directions of deformation (i.e. radial, circumferential, and longitudinal) following the assumption of cylindrical chamber architecture. Three-dimensional (3D) principal strain analysis may overcome such limitations by referencing intrinsic (i.e. principal) directions of deformation. This study aimed to demonstrate clinical feasibility of 3D principal strain analysis from routine 2D cine MRI with validation to strain from 2D tagged cine analysis and 3D speckle tracking echocardiography. Thirty-one patients undergoing cardiac MRI were studied. 3D strain was measured from routine, multi-planar 2D cine SSFP images using custom software designed to apply 4D deformation fields to 3D cardiac models to derive principal strain. Comparisons of strain estimates versus those by 2D tagged cine, 2D non-tagged cine (feature tracking), and 3D speckle tracking echocardiography (STE) were performed. Mean age was 51 ± 14 (36% female). Mean LV ejection fraction was 66 ± 10% (range 37-80%). 3D principal strain analysis was feasible in all subjects and showed high inter- and intra-observer reproducibility (ICC range 0.83-0.97 and 0.83-0.98, respectively-p analysis is feasible using routine, multi-planar 2D cine MRI and shows high reproducibility with strong correlations to 2D conventional strain analysis and 3D STE-based analysis. Given its independence from geometry-related directions of deformation this technique may offer unique benefit for the detection and prognostication of myocardial disease, and warrants expanded investigation.
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3D Strain Modelling of Tear Fault Analogues
Hindle, D.; Vietor, T.
2005-12-01
Tear faults can be described as vertical discontinuities, with near fault parallel displacements terminating on some sort of shallow detachment. As such, they are difficult to study in "cross section" i.e. 2 dimensions as is often the case for fold-thrust systems. Hence, little attempt has been made to model the evolution of strain around tear faults and the processes of strain localisation in such structures due to the necessity of describing these systems in 3 dimensions and the problems this poses for both numerical and analogue modelling. Field studies suggest that strain in such regions can be distributed across broad zones on minor tear systems, which are often not easily mappable. Such strain is probably assumed to be due to distributed strain and to displacement gradients which are themselves necessary for the initiation of the tear itself. We present a numerical study of the effects of a sharp, basal discontinutiy parallel to the transport direction in a shortening wedge of material. The discontinuity is represented by two adjacent basal surfaces with strongly contrasting (0.5 and 0.05) friction coefficient. The material is modelled using PFC3D distinct element software for simulating granular material, whose properties are chosen to simulate upper crustal, sedimentary rock. The model geometry is a rectangular bounding box, 2km x 1km, and 0.35-0.5km deep, with a single, driving wall of constant velocity. We show the evolution of strain in the model in horizontal and vertical sections, and interpret strain localization as showing the spontaneous development of tear fault like features. The strain field in the model is asymmetrical, rotated towards the strong side of the model. Strain increments seem to oscillate in time, suggesting achievement of a steady state. We also note that our model cannot be treated as a critical wedge, since the 3rd dimension and the lateral variations of strength rule out this type of 2D approximation.
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The genomic landscape shaped by selection on transposable elements across 18 mouse strains.
Nellåker, Christoffer; Keane, Thomas M; Yalcin, Binnaz; Wong, Kim; Agam, Avigail; Belgard, T Grant; Flint, Jonathan; Adams, David J; Frankel, Wayne N; Ponting, Chris P
2012-06-15
Transposable element (TE)-derived sequence dominates the landscape of mammalian genomes and can modulate gene function by dysregulating transcription and translation. Our current knowledge of TEs in laboratory mouse strains is limited primarily to those present in the C57BL/6J reference genome, with most mouse TEs being drawn from three distinct classes, namely short interspersed nuclear elements (SINEs), long interspersed nuclear elements (LINEs) and the endogenous retrovirus (ERV) superfamily. Despite their high prevalence, the different genomic and gene properties controlling whether TEs are preferentially purged from, or are retained by, genetic drift or positive selection in mammalian genomes remain poorly defined. Using whole genome sequencing data from 13 classical laboratory and 4 wild-derived mouse inbred strains, we developed a comprehensive catalogue of 103,798 polymorphic TE variants. We employ this extensive data set to characterize TE variants across the Mus lineage, and to infer neutral and selective processes that have acted over 2 million years. Our results indicate that the majority of TE variants are introduced though the male germline and that only a minority of TE variants exert detectable changes in gene expression. However, among genes with differential expression across the strains there are twice as many TE variants identified as being putative causal variants as expected. Most TE variants that cause gene expression changes appear to be purged rapidly by purifying selection. Our findings demonstrate that past TE insertions have often been highly deleterious, and help to prioritize TE variants according to their likely contribution to gene expression or phenotype variation.
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Impact of Pathogen Population Heterogeneity and Stress-Resistant Variants on Food Safety.
Abee, T; Koomen, J; Metselaar, K I; Zwietering, M H; den Besten, H M W
2016-01-01
This review elucidates the state-of-the-art knowledge about pathogen population heterogeneity and describes the genotypic and phenotypic analyses of persister subpopulations and stress-resistant variants. The molecular mechanisms underlying the generation of persister phenotypes and genetic variants are identified. Zooming in on Listeria monocytogenes, a comparative whole-genome sequence analysis of wild types and variants that enabled the identification of mutations in variants obtained after a single exposure to lethal food-relevant stresses is described. Genotypic and phenotypic features are compared to those for persistent strains isolated from food processing environments. Inactivation kinetics, models used for fitting, and the concept of kinetic modeling-based schemes for detection of variants are presented. Furthermore, robustness and fitness parameters of L. monocytogenes wild type and variants are used to model their performance in food chains. Finally, the impact of stress-resistant variants and persistence in food processing environments on food safety is discussed.
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Antigenic variants of yellow fever virus with an altered neurovirulence phenotype in mice.
Ryman, K D; Xie, H; Ledger, T N; Campbell, G A; Barrett, A D
1997-04-14
The live-attenuated yellow fever (YF) vaccine virus, strain 17D-204, has long been known to consist of a heterologous population of virions. Gould et al. (J. Gen. Virol. 70, 1889-1894 (1989)) previously demonstrated that variant viruses exhibiting a YF wild-type-specific envelope (E) protein epitope are present at low frequency in the vaccine pool and were able to isolate representative virus variants with and without this epitope, designated 17D(+wt) and 17D(-wt), respectively. These variants were employed here in an investigation of YF virus pathogenesis in the mouse model. Both the 17D-204 parent and the 17D(+wt) variant viruses were lethal for adult outbred mice by the intracerebral route of inoculation. However, the 17D(-wt) variant was significantly attenuated (18% mortality rate) and replicated to much lower titer in the brains of infected mice. A single amino acid substitution in the envelope (E) protein at E-240 (Ala-->Val) was identified as responsible for the restricted replication of the 17D(-wt) variant in vivo. The 17D(+wt) variant has an additional second-site mutation, believed to encode a reversion to the neurovirulence phenotype of the 17D-204 parent virus. The amino acid substitution in the E protein at E-173 (Thr-->Ile) of the 17D(+wt) variant which results in the appearance of the wild-type-specific epitope or nucleotide changes in the 5' and 3' noncoding regions of the virus are proposed as a candidates.
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DEFF Research Database (Denmark)
Tvardovskiy, Andrey; Schwämmle, Veit; Kempf, Stefan J
2017-01-01
a causal relationship between H3 variant replacement and age-dependent changes in H3 methylation. Furthermore, the H3.3 level is drastically reduced in human hepatocarcinoma cells as compared to nontumoral hepatocytes, suggesting the potential utility of the H3.3 relative abundance as a biomarker...
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Proteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolates
Heunis, Tiaan
2017-08-18
Mycobacterium tuberculosis consists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosis isolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study we integrated whole-genome sequencing and mass spectrometry (GeLC-MS/MS) to reveal strain-specific characteristics in the proteomes of two clinical M. tuberculosis Latin American-Mediterranean isolates. Using this approach we identified 59 peptides containing single amino acid variants, which covered ~9% of all total coding nonsynonymous single nucleotide variants detected by whole-genome sequencing. Furthermore, we identified 29 distinct peptides that mapped to a hypothetical protein not present in the M. tuberculosis H37Rv reference proteome. Here we provide evidence for the expression of this protein in the clinical M. tuberculosis SAWC3651 isolate. The strain-specific databases enabled confirmation of genomic differences (i.e. large genomic regions of difference and nonsynonymous single nucleotide variants) in these two clinical M. tuberculosis isolates and allowed strain differentiation at the proteome level. Our results contribute to the growing field of clinical microbial proteogenomics and can improve our understanding of phenotypic variation in clinical M. tuberculosis isolates.
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Proteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolates
Heunis, Tiaan; Dippenaar, Anzaan; Warren, Robin M.; van Helden, Paul D.; van der Merwe, Ruben G.; Gey van Pittius, Nicolaas C.; Pain, Arnab; Sampson, Samantha L.; Tabb, David L.
2017-01-01
Mycobacterium tuberculosis consists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosis isolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study we integrated whole-genome sequencing and mass spectrometry (GeLC-MS/MS) to reveal strain-specific characteristics in the proteomes of two clinical M. tuberculosis Latin American-Mediterranean isolates. Using this approach we identified 59 peptides containing single amino acid variants, which covered ~9% of all total coding nonsynonymous single nucleotide variants detected by whole-genome sequencing. Furthermore, we identified 29 distinct peptides that mapped to a hypothetical protein not present in the M. tuberculosis H37Rv reference proteome. Here we provide evidence for the expression of this protein in the clinical M. tuberculosis SAWC3651 isolate. The strain-specific databases enabled confirmation of genomic differences (i.e. large genomic regions of difference and nonsynonymous single nucleotide variants) in these two clinical M. tuberculosis isolates and allowed strain differentiation at the proteome level. Our results contribute to the growing field of clinical microbial proteogenomics and can improve our understanding of phenotypic variation in clinical M. tuberculosis isolates.
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Proteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolates.
Heunis, Tiaan; Dippenaar, Anzaan; Warren, Robin M; van Helden, Paul D; van der Merwe, Ruben G; Gey van Pittius, Nicolaas C; Pain, Arnab; Sampson, Samantha L; Tabb, David L
2017-10-06
Mycobacterium tuberculosis consists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosis isolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of the utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study, we integrated whole-genome sequencing and mass spectrometry (GeLC-MS/MS) to reveal strain-specific characteristics in the proteomes of two clinical M. tuberculosis Latin American-Mediterranean isolates. Using this approach, we identified 59 peptides containing single amino acid variants, which covered ∼9% of all coding nonsynonymous single nucleotide variants detected by whole-genome sequencing. Furthermore, we identified 29 distinct peptides that mapped to a hypothetical protein not present in the M. tuberculosis H37Rv reference proteome. Here, we provide evidence for the expression of this protein in the clinical M. tuberculosis SAWC3651 isolate. The strain-specific databases enabled confirmation of genomic differences (i.e., large genomic regions of difference and nonsynonymous single nucleotide variants) in these two clinical M. tuberculosis isolates and allowed strain differentiation at the proteome level. Our results contribute to the growing field of clinical microbial proteogenomics and can improve our understanding of phenotypic variation in clinical M. tuberculosis isolates.
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SNCA 3'UTR genetic variants in patients with Parkinson's disease and REM sleep behavior disorder.
Toffoli, M; Dreussi, E; Cecchin, E; Valente, M; Sanvilli, N; Montico, M; Gagno, S; Garziera, M; Polano, M; Savarese, M; Calandra-Buonaura, G; Placidi, F; Terzaghi, M; Toffoli, G; Gigli, G L
2017-07-01
REM sleep behavior disorder (RBD) is an early marker of Parkinson's disease (PD); however, it is still unclear which patients with RBD will eventually develop PD. Single nucleotide polymorphisms (SNPs) in the 3'untranslated region (3'UTR) of alpha-synuclein (SNCA) have been associated with PD, but at present, no data is available about RBD. The 3'UTR hosts regulatory regions involved in gene expression control, such as microRNA binding sites. The aim of this study was to determine RBD specific genetic features associated to an increased risk of progression to PD, by sequencing of the SNCA-3'UTR in patients with "idiopathic" RBD (iRBD) and in patients with PD. We recruited 113 consecutive patients with a diagnosis of iRBD (56 patients) or PD (with or without RBD, 57 patients). Sequencing of SNCA-3'UTR was performed on genomic DNA extracted from peripheral blood samples. Bioinformatic analyses were carried out to predict the potential effect of the identified genetic variants on microRNA binding. We found three SNCA-3'UTR SNPs (rs356165, rs3857053, rs1045722) to be more frequent in PD patients than in iRBD patients (p = 0.014, 0.008, and 0.008, respectively). Four new or previously reported but not annotated specific genetic variants (KP876057, KP876056, NM_000345.3:c*860T>A, NM_000345.3:c*2320A>T) have been observed in the RBD population. The in silico approach highlighted that these variants could affect microRNA-mediated gene expression control. Our data show specific SNPs in the SNCA-3'UTR that may bear a risk for RBD to be associated with PD. Moreover, new genetic variants were identified in patients with iRBD.
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Reliability of poly 3,4-ethylenedioxythiophene strain gauge
DEFF Research Database (Denmark)
Mateiu, Ramona Valentina; Lillemose, Michael; Hansen, Thomas Steen
2007-01-01
We report on the experimentally observed reliability of the piezoresistive effect in strained poly 3,4-ethylenedioxythiophene (PEDT). PEDT is an intrinsic conductive polymer which can be patterned by conventional Cleanroom processing, and thus presents a promising material for all-polymer Microsy......We report on the experimentally observed reliability of the piezoresistive effect in strained poly 3,4-ethylenedioxythiophene (PEDT). PEDT is an intrinsic conductive polymer which can be patterned by conventional Cleanroom processing, and thus presents a promising material for all......-polymer Microsystems. The measurements are made on microfabricated test chips with PEDT resistors patterned by conventional UV-lithography and reactive ion etching (RIE). We determine a gauge factor of 3.41 ± 0.42 for the strained PEDT and we see an increase in resistivity from 1.98 · 104 X m to 2.22 · 104 X m when...
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Molecular insights into the evolutionary pathway of Vibrio cholerae O1 atypical El Tor variants.
Kim, Eun Jin; Lee, Dokyung; Moon, Se Hoon; Lee, Chan Hee; Kim, Sang Jun; Lee, Jae Hyun; Kim, Jae Ouk; Song, Manki; Das, Bhabatosh; Clemens, John D; Pape, Jean William; Nair, G Balakrish; Kim, Dong Wook
2014-09-01
Pandemic V. cholerae strains in the O1 serogroup have 2 biotypes: classical and El Tor. The classical biotype strains of the sixth pandemic, which encode the classical type cholera toxin (CT), have been replaced by El Tor biotype strains of the seventh pandemic. The prototype El Tor strains that produce biotype-specific cholera toxin are being replaced by atypical El Tor variants that harbor classical cholera toxin. Atypical El Tor strains are categorized into 2 groups, Wave 2 and Wave 3 strains, based on genomic variations and the CTX phage that they harbor. Whole-genome analysis of V. cholerae strains in the seventh cholera pandemic has demonstrated gradual changes in the genome of prototype and atypical El Tor strains, indicating that atypical strains arose from the prototype strains by replacing the CTX phages. We examined the molecular mechanisms that effected the emergence of El Tor strains with classical cholera toxin-carrying phage. We isolated an intermediary V. cholerae strain that carried two different CTX phages that encode El Tor and classical cholera toxin, respectively. We show here that the intermediary strain can be converted into various Wave 2 strains and can act as the source of the novel mosaic CTX phages. These results imply that the Wave 2 and Wave 3 strains may have been generated from such intermediary strains in nature. Prototype El Tor strains can become Wave 3 strains by excision of CTX-1 and re-equipping with the new CTX phages. Our data suggest that inter-chromosomal recombination between 2 types of CTX phages is possible when a host bacterial cell is infected by multiple CTX phages. Our study also provides molecular insights into population changes in V. cholerae in the absence of significant changes to the genome but by replacement of the CTX prophage that they harbor.
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Directory of Open Access Journals (Sweden)
Antonic V
2013-11-01
Full Text Available Vlado Antonic,1–3 Alexander Stojadinovic,3–5 Binxue Zhang,1–3 Mina J Izadjoo,1–3,5 Mohammad Alavi1–3 1Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; 2Diagnostic and Translational Research Center, Gaithersburg, MD, USA; 3Combat Wound Initiative Program, Bethesda, MD, USA; 4Walter Reed National Military Medical Center, Bethesda, MD, USA; 5Uniformed Services University of the Health Sciences, Bethesda, MD, USA Abstract: Staphyloxanthin is a virulence factor which protects Staphylococcus aureus in stress conditions. We isolated two pigment variants of S. aureus and one strain of Pseudomonas aeruginosa from a single wound infection. S. aureus variants displayed white and yellow colony phenotypes. The sequence of the operons for staphyloxanthin synthesis indicated that coding and promoter regions were identical between the two pigment variants. Quorum sensing controls pigment synthesis in some bacteria. It is also shown that P. aeruginosa quorum-sensing molecules affect S. aureus transcription. We explored whether the co-infecting P. aeruginosa can affect pigment production in the white S. aureus variant. In co-culture experiments between the white variants and a selected number of Gram-positive and Gram-negative bacteria, only P. aeruginosa induced pigment production in the white variant. Gene expression analysis of the white variant did not indicate upregulation of the crtM and other genes known to be involved in pigment production (sigB, sarA, farnesyl pyrophosphate synthase gene [FPP-synthase], hfq. In contrast, transcription of the catalase gene was significantly upregulated after co-culture. P. aeruginosa-induced pigment synthesis and catalase upregulation correlated with increased resistance to polymyxin B, hydrogen peroxide, and the intracellular environment of macrophages. Our data indicate the presence of silent but functional staphyloxanthin synthesis machinery in a white phenotypic variant
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Germline variant FGFR4 p.G388R exposes a membrane-proximal STAT3 binding site.
Ulaganathan, Vijay K; Sperl, Bianca; Rapp, Ulf R; Ullrich, Axel
2015-12-24
Variant rs351855-G/A is a commonly occurring single-nucleotide polymorphism of coding regions in exon 9 of the fibroblast growth factor receptor FGFR4 (CD334) gene (c.1162G>A). It results in an amino-acid change at codon 388 from glycine to arginine (p.Gly388Arg) in the transmembrane domain of the receptor. Despite compelling genetic evidence for the association of this common variant with cancers of the bone, breast, colon, prostate, skin, lung, head and neck, as well as soft-tissue sarcomas and non-Hodgkin lymphoma, the underlying biological mechanism has remained elusive. Here we show that substitution of the conserved glycine 388 residue to a charged arginine residue alters the transmembrane spanning segment and exposes a membrane-proximal cytoplasmic signal transducer and activator of transcription 3 (STAT3) binding site Y(390)-(P)XXQ(393). We demonstrate that such membrane-proximal STAT3 binding motifs in the germline of type I membrane receptors enhance STAT3 tyrosine phosphorylation by recruiting STAT3 proteins to the inner cell membrane. Remarkably, such germline variants frequently co-localize with somatic mutations in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Using Fgfr4 single nucleotide polymorphism knock-in mice and transgenic mouse models for breast and lung cancers, we validate the enhanced STAT3 signalling induced by the FGFR4 Arg388-variant in vivo. Thus, our findings elucidate the molecular mechanism behind the genetic association of rs351855 with accelerated cancer progression and suggest that germline variants of cell-surface molecules that recruit STAT3 to the inner cell membrane are a significant risk for cancer prognosis and disease progression.
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Association analysis of KIT, MITF, and PAX3 variants with white markings in Spanish horses.
Negro, S; Imsland, F; Valera, M; Molina, A; Solé, M; Andersson, L
2017-06-01
Several variants in the KIT, PAX3 and MITF genes have previously been associated with white markings in horses. In this study, we examined eight variants of these genes in 70 Menorca Purebred horses (PRMe, only black solid-coloured horses) and 70 Spanish Purebred horses (PRE, different coat colour patterns) that were scored for the extent of white markings. A maximum-likelihood chi-square test, logistic regression model and ridge regression analyses showed that a missense mutation (p.Arg682His) in KIT was associated with white facial markings (P horses. The relative contribution of this variant to white markings in PRMe horses was estimated at 47.6% (head) and 43.4% (total score). In PRE horses, this variant was also associated with hindlimb scores (P T intronic variant located 29.9 kb downstream from the transcription start site of the MITF gene was associated with less white markings on forelimbs (P horses, with a relative contribution of 63.9%, whereas in PRE horses this variant was associated with white facial markings (P horses, providing breeders with an opportunity to use genetic testing to aid in breeding for their desired level of white markings. © 2017 Stichting International Foundation for Animal Genetics.
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Kalscheuer, Vera M.; Hennig, Friederike; Leonard, Helen; Downs, Jenny; Clarke, Angus; Benke, Tim A.; Armstrong, Judith; Pineda, Mercedes; Bailey, Mark E.S.; Cobb, Stuart R.
2017-01-01
Objective: To provide new insights into the interpretation of genetic variants in a rare neurologic disorder, CDKL5 deficiency, in the contexts of population sequencing data and an updated characterization of the CDKL5 gene. Methods: We analyzed all known potentially pathogenic CDKL5 variants by combining data from large-scale population sequencing studies with CDKL5 variants from new and all available clinical cohorts and combined this with computational methods to predict pathogenicity. Results: The study has identified several variants that can be reclassified as benign or likely benign. With the addition of novel CDKL5 variants, we confirm that pathogenic missense variants cluster in the catalytic domain of CDKL5 and reclassify a purported missense variant as having a splicing consequence. We provide further evidence that missense variants in the final 3 exons are likely to be benign and not important to disease pathology. We also describe benign splicing and nonsense variants within these exons, suggesting that isoform hCDKL5_5 is likely to have little or no neurologic significance. We also use the available data to make a preliminary estimate of minimum incidence of CDKL5 deficiency. Conclusions: These findings have implications for genetic diagnosis, providing evidence for the reclassification of specific variants previously thought to result in CDKL5 deficiency. Together, these analyses support the view that the predominant brain isoform in humans (hCDKL5_1) is crucial for normal neurodevelopment and that the catalytic domain is the primary functional domain. PMID:29264392
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A Panel of Cytochrome P450 BM3 Variants To Produce Drug Metabolites and Diversify Lead Compounds
Sawayama, Andrew M.; Chen, Michael M. Y.; Kulanthaivel, Palaniappan; Kuo, Ming-Shang; Hemmerle, Horst; Arnold, Frances H.
2011-01-01
Here we demonstrate that a small panel of variants of cytochrome P450 BM3 from Bacillus megaterium covers the breadth of reactivity of human P450s by producing 12 of 13 mammalian metabolites for two marketed drugs, verapamil and astemizole, and one research compound. The most active enzymes support preparation of individual metabolites for preclinical bioactivity and toxicology evaluations. Underscoring their potential utility in drug lead diversification, engineered P450 BM3 variants also produce novel metabolites by catalyzing reactions at carbon centers beyond those targeted by animal and human P450s. Production of a specific metabolite can be improved by directed evolution of the enzyme catalyst. Some variants are more active on the more hydrophobic parent drug than on its metabolites, which limits production of multiply-hydroxylated species, a preference that appears to depend on the evolutionary history of the P450 variant. PMID:19774562
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Yu, Zhi-Qing; Tong, Wu; Zheng, Hao; Li, Li-Wei; Li, Guo-Xin; Gao, Fei; Wang, Tao; Liang, Chao; Ye, Chao; Wu, Ji-Qiang; Huang, Qinfeng; Tong, Guang-Zhi
2017-09-01
A newly emerged pseudorabies virus (PRV) variant has been identified in many Bartha-K61-vaccinated pig farms. This variant has caused great economic losses to the swine industry in China since 2011. Sequence analysis demonstrated that the gB gene of the emerging PRV variant JS-2012 had multiple variations compared with the vaccine strain Bartha-K61. In the study, a specific CRISPR/Cas9 system combined with homologous recombination was used to construct two recombinant viruses, BJB (Bartha-K61+JS-2012gB) and JBJ (JS-2012-ΔgE/gI+Bartha-K61gB), by interchanging the full-length gB genes between Bartha-K61 and JS-2012-ΔgE/gI. The two recombinant viruses showed similar characteristics in growth kinetics in vitro and similar pathogenicity in mice, as compared to their parental strains. Immunization of mice with inactivated BJB or JBJ followed by challenge of JS-2012 showed that BJB could increase protective efficacy to 80%, compared to only 40% protection by the parental Bartha-K61 strain. JBJ had a decreased protective efficacy of 65%, as compared to 90% protection by its parental JS-2012-ΔgE/gI strain. Exchange of the gB gene markedly altered the immunogenicity of the recombinant PRV. These data suggest that variations in gB might play an important role in the virulence of the reemergent PRV variant in China. Our results demonstrate the importance of gB in protective immunity and suggest that the recombinant virus BJB could be a promising vaccine candidate for eradication of the PRV variant. Copyright © 2017 Elsevier B.V. All rights reserved.
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Skauli, Nadia; Wallace, Sean; Chiang, Samuel C. C.; Bar?y, Tuva; Holmgren, Asbj?rn; Stray-Pedersen, Asbj?rg; Bryceson, Yenan T.; Str?mme, Petter; Frengen, Eirik; Misceo, Doriana
2016-01-01
Biallelic PIGT variants were previously reported in seven patients from three families with Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 (MCAHS3), characterized by epileptic encephalopathy, hypotonia, global developmental delay/intellectual disability, cerebral and cerebellar atrophy, craniofacial dysmorphisms, and skeletal, ophthalmological, cardiac, and genitourinary abnormalities. We report a novel homozygous PIGT missense variant c.1079G>T (p.Gly360Val) in two brothers w...
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Ultrastructural studies on variants of Streptomyces SP-765 obtained after gamma irradiation
International Nuclear Information System (INIS)
Spasova, D.I.; Krystev, Kh.I.; Todorov, I.O.; Dzhedzheva, G.M.; Popov, M.S.
1988-01-01
The study has been carried out with two variants of Streptomyces SP-765, gray and olygosporous, obtained after 1000 Gy gamma irradiation of spore suspension from the initial strain. The gray variant has chains of spores which are oval or oblong with rounded-off edges. Sporulation is highly inhibited in the olygosporous variant. Eleven electron-microscopic pictures of ultrathin sections from colonies of the two variants are presented. The gray variant reveals the presence of a large number of lyzed cells, spores, and scarce vegetative cells; typical of the lyzed cells are the spherical and highly osmiophilic formations on the outer and inner surface of their cytoplasmic membrane. The oligosporous variant shows lyzed cells of various sizes, cells void of content with thick walls, relativelly small number of vegetative cells and individual wall-less cells, shperoplast and protoplast formation, lamellar membrane structure of nearly all cells. Both lyzed and vegetable cells have individual anomalous form containing daughter cells. The conclusion is made that gray and oligosporous variants of Streptomyces SP-765, obtained after irradiation of its spores, possess different ultrastructural organization
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The association of XRCC3 Thr241Met genetic variant with risk of ...
African Journals Online (AJOL)
Background: Previous studies suggest that the X-ray repair cross-complementing group 3 gene (XRCC3) Thr241Met genetic variant could be potentially associated with the risk of prostate cancer. However, results from these published studies were conflicting rather than conclusive. Objectives:This meta-analysis aimed to ...
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Chen, Nanhua; Li, Shuangjie; Zhou, Rongyun; Zhu, Meiqin; He, Shan; Ye, Mengxue; Huang, Yucheng; Li, Shuai; Zhu, Cong; Xia, Pengpeng; Zhu, Jianzhong
2017-10-15
Porcine epidemic diarrhea virus (PEDV) causes devastating impact on global pig-breeding industry and current vaccines have become not effective against the circulating PEDV variants since 2011. During the up-to-date investigation of PEDV prevalence in Fujian China 2016, PEDV was identified in vaccinated pig farms suffering severe diarrhea while other common diarrhea-associated pathogens were not detected. Complete genomes of two PEDV representatives (XM1-2 and XM2-4) were determined. Genomic comparison showed that these two viruses share the highest nucleotide identities (99.10% and 98.79%) with the 2011 ZMDZY strain, but only 96.65% and 96.50% nucleotide identities with the attenuated CV777 strain. Amino acid alignment of spike (S) proteins indicated that they have the similar mutation, insertion and deletion pattern as other Chinese PEDV variants but also contain several unique substitutions. Phylogenetic analysis showed that 2016 PEDV variants belong to the cluster of recombination strains but form a new branch. Recombination detection suggested that both XM1-2 and XM2-4 are inter-subgroup recombinants with breakpoints within ORF1b. Remarkably, the natural recombinant HNQX-3 isolate serves as a parental virus for both natural recombinants identified in this study. This up-to-date investigation provides the direct evidence that natural recombinants may serve as parental viruses to generate recombined PEDV progenies that are probably associated with the vaccination failure. Copyright © 2017. Published by Elsevier B.V.
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Son, Mike S.; Megli, Christina J.; Kovacikova, Gabriela; Qadri, Firdausi; Taylor, Ronald K.
2011-01-01
Vibrio cholerae serogroup O1, the causative agent of the diarrheal disease cholera, is divided into two biotypes: classical and El Tor. Both biotypes produce the major virulence factors toxin-coregulated pilus (TCP) and cholera toxin (CT). Although possessing genotypic and phenotypic differences, El Tor biotype strains displaying classical biotype traits have been reported and subsequently were dubbed El Tor variants. Of particular interest are reports of El Tor variants that produce various levels of CT, including levels typical of classical biotype strains. Here, we report the characterization of 10 clinical isolates from the International Centre for Diarrhoeal Disease Research, Bangladesh, and a representative strain from the 2010 Haiti cholera outbreak. We observed that all 11 strains produced increased CT (2- to 10-fold) compared to that of wild-type El Tor strains under in vitro inducing conditions, but they possessed various TcpA and ToxT expression profiles. Particularly, El Tor variant MQ1795, which produced the highest level of CT and very high levels of TcpA and ToxT, demonstrated hypervirulence compared to the virulence of El Tor wild-type strains in the infant mouse cholera model. Additional genotypic and phenotypic tests were conducted to characterize the variants, including an assessment of biotype-distinguishing characteristics. Notably, the sequencing of ctxB in some El Tor variants revealed two copies of classical ctxB, one per chromosome, contrary to previous reports that located ctxAB only on the large chromosome of El Tor biotype strains. PMID:21880975
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Zangirolami,T.C.; Carlsen,M.; Nielsen,J.; Jørgensen,S.B.
2002-01-01
Growth and product formation by a selected variant of Aspergillus oryzae showing high alpha-amylase production was studied in continuous cultivations carried out at six different specific growth rates, using glucose as the growth-limiting nutrient. The analysis of the steady-state data revealed that the variant and wild-type strains were similar with respect to glucose uptake system and stoichiometric coefficients. However, the variant was capable of maintaining an enzyme production as high a...
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Overkamp, Wout; Beilharz, Katrin; Weme, Ruud Detert Oude; Solopova, Ana; Karsens, Harma; Kovacs, Akos T.; Kok, Jan; Kuipers, Oscar P.; Veening, Jan-Willem
2013-01-01
Green fluorescent protein (GFP) offers efficient ways of visualizing promoter activity and protein localization in vivo, and many different variants are currently available to study bacterial cell biology. Which of these variants is best suited for a certain bacterial strain, goal, or experimental
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Depth-variant blind restoration with pupil-phase constraints for 3D confocal microscopy
International Nuclear Information System (INIS)
Hadj, Saima Ben; Blanc-Féraud, Laure; Engler, Gilbert
2013-01-01
Three-dimensional images of confocal laser scanning microscopy suffer from a depth-variant blur, due to refractive index mismatch between the different mediums composing the system as well as the specimen, leading to optical aberrations. Our goal is to develop an image restoration method for 3D confocal microscopy taking into account the blur variation with depth. The difficulty is that optical aberrations depend on the refractive index of the biological specimen. The depth-variant blur function or the Point Spread Function (PSF) is thus different for each observation. A blind or semi-blind restoration method needs to be developed for this system. For that purpose, we use a previously developed algorithm for the joint estimation of the specimen function (original image) and the 3D PSF, the continuously depth-variant PSF is approximated by a convex combination of a set of space-invariant PSFs taken at different depths. We propose to add to that algorithm a pupil-phase constraint for the PSF estimation, given by the the optical instrument geometry. We thus define a blind estimation algorithm by minimizing a regularized criterion in which we integrate the Gerchberg-Saxton algorithm allowing to include these physical constraints. We show the efficiency of this method relying on some numerical tests
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Diversity of Lactobacillus reuteri Strains in Converting Glycerol into 3-Hydroxypropionic Acid.
Burgé, G; Saulou-Bérion, C; Moussa, M; Pollet, B; Flourat, A; Allais, F; Athès, V; Spinnler, H E
2015-10-01
The present study aims at comparing the performances of three Lactobacillus reuteri strains (DSM 20016, DSM 17938, and ATCC 53608) in producing 3-hydroxypropionic acid (3-HP) from glycerol and at exploring inhibition phenomena during this bioconversion. Differences were highlighted between the three strains in terms of 3-HP production yield, kinetics of substrate consumption, and metabolite production. With a maximal productivity in non-optimal conditions (free pH) around 2 g.L(-1).h(-1) of 3-HP and 4 g.L(-1).h(-1) of 3-hydroxypropionaldehyde (3-HPA) depending on the strain, this study confirmed the potential of L. reuteri for the biotechnological production of 3-HP. Moreover, the molar ratios of 3-HP to 1,3-propanediol (1,3-PDO) obtained for the three strains (comprised between 1.25 and 1.65) showed systematically a higher 3-HP production. From these results, the DSM 17938 strain appeared to be the most promising strain. The impact of glycerol bioconversion on the bacteria's physiological state (a decrease of around 40 % in DSM 17938 cells showing an enzymatic activity after 3 h) and survival (total loss of cultivability after 2 or 3 h depending on the strains) was revealed and discussed. The effect of each metabolite on L. reuteri DSM 17938 was further investigated, displaying a drastic inhibition caused by 3-HPA, while 3-HP induced lower impact and only at acidic pH.
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Multiphase nanodomains in a strained BaTiO3 film on a GdScO3 substrate
Kobayashi, Shunsuke; Inoue, Kazutoshi; Kato, Takeharu; Ikuhara, Yuichi; Yamamoto, Takahisa
2018-02-01
Controlling the crystal structure of ferroelectric materials via epitaxial strain, which is a well-known technique in strain engineering, can lead to the formation of unique domain structures generating non-intrinsic phenomena such as electronic conductivity, photovoltages, and enhanced piezoelectric characteristics. Strained BaTiO3 films are promising ferroelectric materials as theoretical modeling predicts that different domain morphologies can introduce additional properties not observed in conventional BaTiO3 ceramics. To rationally design materials for practical application, a thorough understanding of the formation mechanisms and stabilities of different domain structures in strained BaTiO3 films is required. However, there have been very few experimental reports on this topic, and details about the domain structures in strained BaTiO3 films are currently lacking. In this paper, we report multiphase nanodomains in a strained BaTiO3 film deposited on an orthorhombic GdScO3 substrate. The phase-transition behavior of the strained BaTiO3 film reveals that it contains multiple phases at room temperature; the film first undergoes a phase-transition upon heating at around 550 K, and then a paraelectric phase forms at temperatures above 690 K. A picometer-scale analysis of the Ti ion displacements, using an advanced scanning transmission electron microscopy technique, is used to characterize the complex multiphase nanodomains, providing useful insights into the control of domain structures in BaTiO3 films by applying epitaxial strain.
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The application of a 3 dimensional image scanner to the strain measurement
International Nuclear Information System (INIS)
Mazda, Taiji; Ogawa, Hiroshi; Suzuki, Michiaki; Nakano, Yasuo.
1993-01-01
A large strain measuring method for a laminated seismic isolation rubber, which will be introduced to reactor buildings of the Demonstration Fast Breeder Reactor (DFBR), was developed. With using strain gages, it is difficult to measure the large strain under the large displacement condition. With using the optical instruments, it is also impossible to measure the strain of a 3 dimensional object. We developed a new measuring method in which strain is calculated from a 3 dimensional deformation with using a 3 dimensional image scanner. This method is noncontact measuring method, and it can measure the strain of a 3 dimensional object under the large deformation. This work is one part of 'The Development of FBR Seismic Isolation system' operated by Central Research Institute of Electric Power Industry. (author)
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Characterization of 3 Strains of Yersinia Pestis
National Research Council Canada - National Science Library
Kournikakis, B
2000-01-01
.... Antibiotic sensitivities showed that the 3 strains were sensitive to aminoglycosides, the cephalosporins/ cephams, most of the beta lactams/penicillins (e.g. ampicillin) and quinolones (e.g. ciprofloxacin...
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Directory of Open Access Journals (Sweden)
Nadia Skauli
2016-11-01
Full Text Available Biallelic PIGT variants were previously reported in seven patients from three families with Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 (MCAHS3, characterized by epileptic encephalopathy, hypotonia, global developmental delay/intellectual disability, cerebral and cerebellar atrophy, craniofacial dysmorphisms, and skeletal, ophthalmological, cardiac, and genitourinary abnormalities. We report a novel homozygous PIGT missense variant c.1079G>T (p.Gly360Val in two brothers with several of the typical features of MCAHS3, but in addition, pyramidal tract neurological signs. Notably, they are the first patients with MCAHS3 without skeletal, cardiac, or genitourinary anomalies. PIGT encodes a crucial subunit of the glycosylphosphatidylinositol (GPI transamidase complex, which catalyzes the attachment of proteins to GPI-anchors, attaching the proteins to the cell membrane. In vitro studies in cells from the two brothers showed reduced levels of GPI-anchors and GPI-anchored proteins on the cell surface, supporting the pathogenicity of the novel PIGT variant.
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Micromechanics of transformation-induced plasticity and variant coalescence
International Nuclear Information System (INIS)
Marketz, F.; Fischer, F.D.; University for Mining and Metallurgy, Leoben; Tanaka, K.
1996-01-01
Quantitative micromechanics descriptions of both transformation-induced plasticity (TRIP) associated with the martensitic transformation in an Fe-Ni alloy and of variant coalescence in a Cu-Al-Ni shape memory alloy are presented. The macroscopic deformation behavior of a polycrystalline aggregate as a result of the rearrangements within the crystallites is modelled with the help of a finite element based periodic microfield approach. In the case of TRIP the parent→martensite transformation is described by microscale thermodynamic and kinetic equations taking into account internal stress states. The simulation of a classical experiment on TRIP allows to quantify the Magee-effect and the Greenwood-Johnson effect. Furthermore, the development of the martensitic microstructure is studied with respect to the stress-assisted transformation of preferred variants. In the case of variant coalescence the strain energy due to internal stress states has an important influence on the mechanical behavior. Formulating the reorientation process on the size scale of self-accommodating plate groups in terms of the mobility of the boundaries between martensitic variants the macroscopic behavior in uniaxial tension is predicted by an incremental modelling procedure. Furthermore, influence of energy dissipation on the overall behavior is quantified. (orig.)
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Strain tunable ferroelectric and dielectric properties of BaZrO3
International Nuclear Information System (INIS)
Zhang, Yajun; Liu, Man; Shimada, Takahiro; Kitamura, Takayuki; Wang, Jie
2014-01-01
The crucial role of epitaxial (in-plane) strain on the structural, electronic, energetic, ferroelectric, and dielectric properties of BaZrO 3 (BZO) is investigated using density-functional theory calculations. We demonstrate that the BZO crystal subjected to a critical compressive (or tensile) strain exhibits non-trivial spontaneous polarization that is higher than that of well-known ferroelectrics BaTiO 3 , while the BZO crystal is essentially paraelectric in the absence of strain. The electronic structure and Born-effective-charge analyses elucidate that the strain-induced paraelectric-to-ferroelectric transition is driven by the orbital hybridization of d-p electrons between zirconium and oxygen. Through the strain-induced paraelectric-to-ferroelectric phase transition, the dielectric response of BZO is significantly enhanced by the in-plane strain. The tensile strain increases the in-plane dielectric constant by a factor of seven with respect to that without the strain, while the compression tends to enhance the out-of-plane dielectric response. Therefore, strain engineering makes BZO an important electromechanical material due to the diversity in ferroelectric and dielectric properties.
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Oksanen, Ilona; Jokela, Jouni; Fewer, David P.; Wahlsten, Matti; Rikkinen, Jouko; Sivonen, Kaarina
2004-01-01
The production of hepatotoxic cyclic heptapeptides, microcystins, is almost exclusively reported from planktonic cyanobacteria. Here we show that a terrestrial cyanobacterium Nostoc sp. strain IO-102-I isolated from a lichen association produces six different microcystins. Microcystins were identified with liquid chromatography-UV mass spectrometry by their retention times, UV spectra, mass fragmentation, and comparison to microcystins from the aquatic Nostoc sp. strain 152. The dominant microcystin produced by Nostoc sp. strain IO-102-I was the highly toxic [ADMAdda5]microcystin-LR, which accounted for ca. 80% of the total microcystins. We assigned a structure of [DMAdda5]microcystin-LR and [d-Asp3,ADMAdda5]microcystin-LR and a partial structure of three new [ADMAdda5]-XR type of microcystin variants. Interestingly, Nostoc spp. strains IO-102-I and 152 synthesized only the rare ADMAdda and DMAdda subfamilies of microcystin variants. Phylogenetic analyses demonstrated congruence between genes involved directly in microcystin biosynthesis and the 16S rRNA and rpoC1 genes of Nostoc sp. strain IO-102-I. Nostoc sp. strain 152 and the Nostoc sp. strain IO-102-I are distantly related, revealing a sporadic distribution of toxin production in the genus Nostoc. Nostoc sp. strain IO-102-I is closely related to Nostoc punctiforme PCC 73102 and other symbiotic Nostoc strains and most likely belongs to this species. Together, this suggests that other terrestrial and aquatic strains of the genus Nostoc may have retained the genes necessary for microcystin biosynthesis. PMID:15466511
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Fitness of isogenic colony morphology variants of Pseudomonas aeruginosa in murine airway infection.
Directory of Open Access Journals (Sweden)
Elza Rakhimova
Full Text Available Chronic lung infections with Pseudomonas aeruginosa are associated with the diversification of the persisting clone into niche specialists and morphotypes, a phenomenon called 'dissociative behaviour'. To explore the potential of P. aeruginosa to change its morphotype by single step loss-of-function mutagenesis, a signature-tagged mini-Tn5 plasposon library of the cystic fibrosis airway isolate TBCF10839 was screened for colony morphology variants under nine different conditions in vitro. Transposon insertion into 1% of the genome changed colony morphology into eight discernable morphotypes. Half of the 55 targets encode features of primary or secondary metabolism whereby quinolone production was frequently affected. In the other half the transposon had inserted into genes of the functional categories transport, regulation or motility/chemotaxis. To mimic dissociative behaviour of isogenic strains in lungs, pools of 25 colony morphology variants were tested for competitive fitness in an acute murine airway infection model. Six of the 55 mutants either grew better or worse in vivo than in vitro, respectively. Metabolic proficiency of the colony morphology variant was a key determinant for survival in murine airways. The most common morphotype of self-destructive autolysis did unexpectedly not impair fitness. Transposon insertions into homologous genes of strain PAO1 did not reproduce the TBCF10839 mutant morphotypes for 16 of 19 examined loci pointing to an important role of the genetic background on colony morphology. Depending on the chosen P. aeruginosa strain, functional genome scans will explore other areas of the evolutionary landscape. Based on our discordant findings of mutant phenotypes in P. aeruginosa strains PAO1, PA14 and TBCF10839, we conclude that the current focus on few reference strains may miss modes of niche adaptation and dissociative behaviour that are relevant for the microevolution of complex traits in the wild.
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Directory of Open Access Journals (Sweden)
Katie Nicoll Baines
2017-05-01
Full Text Available Delaying the decline in skeletal muscle function will be critical to better maintenance of an active lifestyle in old age. The skeletal muscle ryanodine receptor, the major intracellular membrane channel through which calcium ions pass to elicit muscle contraction, is central to calcium ion balance and is hypothesized to be a significant factor for age-related decline in muscle function. The nematode Caenorhabditis elegans is a key model system for the study of human aging, and strains were generated with modified C. elegans ryanodine receptors corresponding to human myopathic variants linked with malignant hyperthermia and related conditions. The altered response of these strains to pharmacological agents reflected results of human diagnostic tests for individuals with these pathogenic variants. Involvement of nerve cells in the C. elegans responses may relate to rare medical symptoms concerning the central nervous system that have been associated with ryanodine receptor variants. These single amino acid modifications in C. elegans also conferred a reduction in lifespan and an accelerated decline in muscle integrity with age, supporting the significance of ryanodine receptor function for human aging.
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Complete Genomic Sequences of H3N8 Equine Influenza Virus Strains Used as Vaccine Strains in Japan.
Nemoto, Manabu; Yamanaka, Takashi; Bannai, Hiroshi; Tsujimura, Koji; Kokado, Hiroshi
2018-03-22
We sequenced the eight segments of influenza A virus strains A/equine/Ibaraki/1/2007 and A/equine/Yokohama/aq13/2010, which are strains of the Florida sublineage clades 1 and 2 of the H3N8 subtype equine influenza virus. These strains have been used as vaccine strains in Japan since 2016 in accordance with World Organization for Animal Health (OIE) recommendations. Copyright © 2018 Nemoto et al.
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Directory of Open Access Journals (Sweden)
Om Prakash Dwivedi
Full Text Available FTO variants are robustly associated with obesity and related traits in many population and shown to have variable impact during life course. Although studies have shown association of FTO variants with adiposity in adult Indian, its association in Indian children is yet to be confirmed.Here we examined association of FTO variants (rs9939609 and rs8050136 with obesity and related anthropometric and biochemical traits in 3,126 Indian children (aged 11-17 years including 2,230 normal-weight and 896 over-weight/obese children. We also compared effects observed in the present study with that observed in previous studies on South Asian adults and children of other ethnic groups.The variant rs9939609 showed significant association with risk of obesity [OR = 1.21, P = 2.5 × 10(-3] and its measures BMI, weight, waist circumference and hip circumference [β range = 0.11 to 0.14 Z-score units; P range = 1.3 × 10(-4 to 1.6 × 10(-7] in children. The observed effect sizes in Indian children were similar to those reported for European children. Variant rs9939609 explained 0.88% of BMI variance in Indian children. The effect sizes of rs9939609 on BMI and WC were ~2 fold higher in children than adults. Interestingly rs9939609 was also associated with serum levels of thyroid stimulating hormone (TSH [β = 0.10 Z-score, P = 5.8 × 10(-3]. The other variant rs8050136 was in strong linkage disequilibrium with rs9939609 (r(2 = 0.97 and provided similar association results.The study provides first report of association of FTO variants with obesity and related anthropometric traits in Indian children with higher impact in children compared to adults. We also demonstrated association of FTO variant with serum levels of TSH, indicating putative influence of FTO in hypothalamic-pituitary-thyroid axis.
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Directory of Open Access Journals (Sweden)
Stella Bortoli
Full Text Available Cyanobacteria are prokaryotic and photosynthetic organisms, which can produce a wide range of bioactive compounds with different properties; including a variety of toxic compounds, also known as cyanotoxins. In this work, we describe the isolation of seven cyanobacterial strains from two reservoirs in São Paulo State, Brazil. Seven different chemical variants of microcystins (MC-RR, MC-LR, MC-YR, MC-LF, MC-LW, and two demethylated variants, dm-MC-RR and dm-MC-LR were detected in three of the ten isolated strains. One particular Microcystis aeruginosa strain (LTPNA 02 was chosen to evaluate its growth by cell count, and its toxin production under seven different nutritional regimes. We observed different growth behaviors in the logarithmic growth period for only three experiments (p < 0.05. The total growth analysis identified four experiments as different from the control (p < 0.01. Three microcystin variants (MC-RR, MC-LR and MC-YR were quantified by liquid chromatography-tandem mass spectrometry. At the experimental end, the toxin content was unchanged when comparing cell growth in ASM-1 (N:P = 1, MLA and BG-11 (N:P = 10 medium. In all other experiments, the lowest microcystin production was observed from cells grown in Bold 3N medium during the exponential growth phase. The highest microcystin content was observed in cultures using BG-11(N:P = 100 medium.
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McClung, Joseph M; McCord, Timothy J; Ryan, Terence E; Schmidt, Cameron A; Green, Tom D; Southerland, Kevin W; Reinardy, Jessica L; Mueller, Sarah B; Venkatraman, Talaignair N; Lascola, Christopher D; Keum, Sehoon; Marchuk, Douglas A; Spangenburg, Espen E; Dokun, Ayotunde; Annex, Brian H; Kontos, Christopher D
2017-07-18
Critical limb ischemia is a manifestation of peripheral artery disease that carries significant mortality and morbidity risk in humans, although its genetic determinants remain largely unknown. We previously discovered 2 overlapping quantitative trait loci in mice, Lsq-1 and Civq-1 , that affected limb muscle survival and stroke volume after femoral artery or middle cerebral artery ligation, respectively. Here, we report that a Bag3 variant (Ile81Met) segregates with tissue protection from hind-limb ischemia. We treated mice with either adeno-associated viruses encoding a control (green fluorescent protein) or 2 BAG3 (Bcl-2-associated athanogene-3) variants, namely Met81 or Ile81, and subjected the mice to hind-limb ischemia. We found that the BAG3 Ile81Met variant in the C57BL/6 (BL6) mouse background segregates with protection from tissue necrosis in a shorter congenic fragment of Lsq-1 (C.B6- Lsq1-3 ). BALB/c mice treated with adeno-associated virus encoding the BL6 BAG3 variant (Ile81; n=25) displayed reduced limb-tissue necrosis and increased limb tissue perfusion compared with Met81- (n=25) or green fluorescent protein- (n=29) expressing animals. BAG3 Ile81 , but not BAG3 Met81 , improved ischemic muscle myopathy and muscle precursor cell differentiation and improved muscle regeneration in a separate, toxin-induced model of injury. Systemic injection of adeno-associated virus-BAG3 Ile81 (n=9), but not BAG3 Met81 (n=10) or green fluorescent protein (n=5), improved ischemic limb blood flow and limb muscle histology and restored muscle function (force production). Compared with BAG3 Met81 , BAG3 Ile81 displayed improved binding to the small heat shock protein (HspB8) in ischemic skeletal muscle cells and enhanced ischemic muscle autophagic flux. Taken together, our data demonstrate that genetic variation in BAG3 plays an important role in the prevention of ischemic tissue necrosis. These results highlight a pathway that preserves tissue survival and muscle
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Identification of rare paired box 3 variant in strabismus by whole exome sequencing
Directory of Open Access Journals (Sweden)
Hui-Min Gong
2017-08-01
Full Text Available AIM: To identify the potentially pathogenic gene variants that contributes to the etiology of strabismus. METHODS: A Chinese pedigree with strabismus was collected and the exomes of two affected individuals were sequenced using the next-generation sequencing technology. The resulting variants from exome sequencing were filtered by subsequent bioinformatics methods and the candidate mutation was verified as heterozygous in the affected proposita and her mother by sanger sequencing. RESULTS: Whole exome sequencing and filtering identified a nonsynonymous mutation c.434G-T transition in paired box 3 (PAX3 in the two affected individuals, which were predicted to be deleterious by more than 4 bioinformatics programs. This altered amino acid residue was located in the conserved PAX domain of PAX3. This gene encodes a member of the PAX family of transcription factors, which play critical roles during fetal development. Mutations in PAX3 were associated with Waardenburg syndrome with strabismus. CONCLUSION: Our results report that the c.434G-T mutation (p.R145L in PAX3 may contribute to strabismus, expanding our understanding of the causally relevant genes for this disorder.
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Identifying pathogenicity of human variants via paralog-based yeast complementation.
Directory of Open Access Journals (Sweden)
Fan Yang
2017-05-01
Full Text Available To better understand the health implications of personal genomes, we now face a largely unmet challenge to identify functional variants within disease-associated genes. Functional variants can be identified by trans-species complementation, e.g., by failure to rescue a yeast strain bearing a mutation in an orthologous human gene. Although orthologous complementation assays are powerful predictors of pathogenic variation, they are available for only a few percent of human disease genes. Here we systematically examine the question of whether complementation assays based on paralogy relationships can expand the number of human disease genes with functional variant detection assays. We tested over 1,000 paralogous human-yeast gene pairs for complementation, yielding 34 complementation relationships, of which 33 (97% were novel. We found that paralog-based assays identified disease variants with success on par with that of orthology-based assays. Combining all homology-based assay results, we found that complementation can often identify pathogenic variants outside the homologous sequence region, presumably because of global effects on protein folding or stability. Within our search space, paralogy-based complementation more than doubled the number of human disease genes with a yeast-based complementation assay for disease variation.
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[Vitamin B12-independent strains of Methylophaga marina isolated from Red Sea algae].
Li, Ts D; Doronina, N V; Ivanova, E G; Trotsenko, Iu A
2007-01-01
Two strains (KM3 and KM5) of halophilic methylobacteria isolated from Red Sea algae do not require vitamin B12 for growth and can use methanol, methylamine, dimethylamine, trimethylamine, dimethyl sulfide, and fructose as sources of carbon and energy. The cells of these strains are gram-negative motile monotrichous (strain KM3) or peritrichous (strain KM5) rods. The strains are strictly aerobic and require Na+ ions but not growth factors for growth. They are oxidase- and catalase-positive and reduce nitrates to nitrites. Both strains can grow in a temperature range of 4 to 37 degrees C (with optimal growth at 29-34 degrees C), at pH between 5.5 and 8.5 (with optimal growth at pH 7.5-8.0), and in a range of salt concentrations between 0.5 and 15% NaCl (with optimal growth at 5-9% NaCl). The phospholipids of these strains are dominated by phosphatidylethanolamine and phosphatidylglycerol and also include phosphatidylcholine, phosphatidylserine, and cardiolipin. The dominant fatty acids are C(16:1omega7c) and C(16:0). The major ubiquinone is Q8. The cells accumulate ectoin, glutamate, and sucrose as intracellular osmoprotectants. The strains implement the 2-keto-3-deoxy-6-phosphogluconate-dependent variant of the ribulose monophosphate pathway. The G+C content of the DNA is 44.4-44.7 mol %. Analysis of the 16S rRNA genes showed that both strains belong to Gammaproteobacteria and have a high degree of homology (99.4%) to Methylophaga marina ATCC 35842T . Based on the data of polyphasic taxonomy, strains KM3 and KM5 are identified as new strains M. marina KM3 (VKM B-2386) and M. marina KM5 (VKM B-2387). The ability of these strains to produce auxins (indole-3-acetic acid) suggests their metabolic association with marine algae.
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Directory of Open Access Journals (Sweden)
Didion John P
2012-01-01
Full Text Available Abstract Background High-density genotyping arrays that measure hybridization of genomic DNA fragments to allele-specific oligonucleotide probes are widely used to genotype single nucleotide polymorphisms (SNPs in genetic studies, including human genome-wide association studies. Hybridization intensities are converted to genotype calls by clustering algorithms that assign each sample to a genotype class at each SNP. Data for SNP probes that do not conform to the expected pattern of clustering are often discarded, contributing to ascertainment bias and resulting in lost information - as much as 50% in a recent genome-wide association study in dogs. Results We identified atypical patterns of hybridization intensities that were highly reproducible and demonstrated that these patterns represent genetic variants that were not accounted for in the design of the array platform. We characterized variable intensity oligonucleotide (VINO probes that display such patterns and are found in all hybridization-based genotyping platforms, including those developed for human, dog, cattle, and mouse. When recognized and properly interpreted, VINOs recovered a substantial fraction of discarded probes and counteracted SNP ascertainment bias. We developed software (MouseDivGeno that identifies VINOs and improves the accuracy of genotype calling. MouseDivGeno produced highly concordant genotype calls when compared with other methods but it uniquely identified more than 786000 VINOs in 351 mouse samples. We used whole-genome sequence from 14 mouse strains to confirm the presence of novel variants explaining 28000 VINOs in those strains. We also identified VINOs in human HapMap 3 samples, many of which were specific to an African population. Incorporating VINOs in phylogenetic analyses substantially improved the accuracy of a Mus species tree and local haplotype assignment in laboratory mouse strains. Conclusion The problems of ascertainment bias and missing
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Rubio, Mari-Paz; López-Bueno, Alberto; Almendral, José M
2005-09-01
The mechanisms involved in the emergence of virulent mammalian viruses were investigated in the adult immunodeficient SCID mouse infected by the attenuated prototype strain of the parvovirus Minute Virus of Mice (MVMp). Cloned MVMp intravenously inoculated in mice consistently evolved during weeks of subclinical infection to variants showing altered plaque phenotypes. All the isolated large-plaque variants spread systemically from the oronasal cavity and replicated in major organs (brain, kidney, liver), in sharp contrast to the absolute inability of the MVMp and small-plaque variants to productively invade SCID organs by this natural route of infection. The virulent variants retained the MVMp capacity to infect mouse fibroblasts, consistent with the lack of genetic changes across the 220-to-335 amino acid sequence of VP2, a capsid domain containing main determinants of MVM tropism. However, the capsid of the virulent variants shared a lower affinity than the wild type for a primary receptor used in the cytotoxic infection. The capsid gene of a virulent variant engineered in the MVMp background endowed the recombinant virus with a large-plaque phenotype, lower affinity for the receptor, and productive invasiveness by the oronasal route in SCID mice, eventually leading to 100% mortality. In the analysis of virulence in mice, both MVMp and the recombinant virus similarly gained the bloodstream 1 to 2 days postoronasal inoculation and remained infectious when adsorbed to blood cells in vitro. However, the wild-type MVMp was cleared from circulation a few days afterwards, in contrast to the viremia of the recombinant virus, which was sustained for life. Significantly, attachment to an abundant receptor of primary mouse kidney epithelial cells by both viruses could be quantitatively competed by wild-type MVMp capsids, indicating that virulence is not due to an extended receptor usage in target tissues. We conclude that the selection of capsid-receptor interactions of
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Mahrooz, Abdolkarim; Alizadeh, Ahad; Hashemi-Soteh, Mohammad Bagher; Ghaffari-Cherati, Maryam; Hosseyni-Talei, Seyyedeh Raheleh
2017-02-01
In this study, we investigated whether two common variants (rs3088442G>A and rs2292334G>A) in the organic cation transporter 3 (OCT3) gene, a high-capacity transporter widely expressed in various tissues, affect susceptibility to type 2 diabetes (T2D) in patients newly diagnosed with T2D. We performed a study with 150 newly diagnosed patients with T2D and 152 controls. The genetic analyses were performed using the restricted fragment length polymorphism (RFLP) after PCR amplification. For the rs3088442G>A variant, A allele carriers had a significantly lower odds ratio (OR) vs. GG homozygotes in the BMI A variant was associated with a decreased risk of T2D (OR = 0.016, p A in the 3'-untranslated region of the OCT3 gene in susceptibility to T2D, and that the protective role is maintained in the presence of risky alleles of the variant rs2292334G>A. The association of the A allele of rs3088442G>A with T2D become weaker in obese people than that of non-obese. If confirmed in other populations, the rs3088442G>A variant as a genetic marker may potentially assist in the identification of individuals at an increased risk of T2D. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.
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The Saccharomyces Genome Database Variant Viewer.
Sheppard, Travis K; Hitz, Benjamin C; Engel, Stacia R; Song, Giltae; Balakrishnan, Rama; Binkley, Gail; Costanzo, Maria C; Dalusag, Kyla S; Demeter, Janos; Hellerstedt, Sage T; Karra, Kalpana; Nash, Robert S; Paskov, Kelley M; Skrzypek, Marek S; Weng, Shuai; Wong, Edith D; Cherry, J Michael
2016-01-04
The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org) is the authoritative community resource for the Saccharomyces cerevisiae reference genome sequence and its annotation. In recent years, we have moved toward increased representation of sequence variation and allelic differences within S. cerevisiae. The publication of numerous additional genomes has motivated the creation of new tools for their annotation and analysis. Here we present the Variant Viewer: a dynamic open-source web application for the visualization of genomic and proteomic differences. Multiple sequence alignments have been constructed across high quality genome sequences from 11 different S. cerevisiae strains and stored in the SGD. The alignments and summaries are encoded in JSON and used to create a two-tiered dynamic view of the budding yeast pan-genome, available at http://www.yeastgenome.org/variant-viewer. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
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Splice variants of perlucin from Haliotis laevigata modulate the crystallisation of CaCO3.
Directory of Open Access Journals (Sweden)
Tanja Dodenhof
Full Text Available Perlucin is one of the proteins of the organic matrix of nacre (mother of pearl playing an important role in biomineralisation. This nacreous layer can be predominately found in the mollusc lineages and is most intensively studied as a compound of the shell of the marine Australian abalone Haliotis laevigata. A more detailed analysis of Perlucin will elucidate some of the still unknown processes in the complex interplay of the organic/inorganic compounds involved in the formation of nacre as a very interesting composite material not only from a life science-based point of view. Within this study we discovered three unknown Perlucin splice variants of the Australian abalone H. laevigata. The amplified cDNAs vary from 562 to 815 base pairs and the resulting translation products differ predominantly in the absence or presence of a varying number of a 10 mer peptide C-terminal repeat. The splice variants could further be confirmed by matrix-assisted laser desorption ionisation time of flight mass spectrometry (MALDI-ToF MS analysis as endogenous Perlucin, purified from decalcified abalone shell. Interestingly, we observed that the different variants expressed as maltose-binding protein (MBP fusion proteins in E. coli showed strong differences in their influence on precipitating CaCO3 and that these differences might be due to a splice variant-specific formation of large protein aggregates influenced by the number of the 10 mer peptide repeats. Our results are evidence for a more complex situation with respect to Perlucin functional regulation by demonstrating that Perlucin splice variants modulate the crystallisation of calcium carbonate. The identification of differentially behaving Perlucin variants may open a completely new perspective for the field of nacre biomineralisation.
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School District Fiscal Strain: Implications for State and Federal Financial Assistance.
Hentschke, Guilbert; Yagielski, John
1982-01-01
Uses a model portraying school district decision makers as "consumers" to analyze fiscal strain's causes (enrollment decline, input price increases, and changes in input mix) as variants of the general consumer model. Measures the impact of each cause of fiscal strain and discusses implications for state and federal aid. (Author/RW)
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Sims, Rebecca; van der Lee, Sven J.; Naj, Adam C.; Bellenguez, Céline; Badarinarayan, Nandini; Jakobsdottir, Johanna; Kunkle, Brian W.; Boland, Anne; Raybould, Rachel; Bis, Joshua C.; Martin, Eden R.; Grenier-Boley, Benjamin; Heilmann-Heimbach, Stefanie; Chouraki, Vincent; Kuzma, Amanda B.; Sleegers, Kristel; Vronskaya, Maria; Ruiz, Agustin; Graham, Robert R.; Olaso, Robert; Hoffmann, Per; Grove, Megan L.; Vardarajan, Badri N.; Hiltunen, Mikko; Nöthen, Markus M.; White, Charles C.; Hamilton-Nelson, Kara L.; Epelbaum, Jacques; Maier, Wolfgang; Choi, Seung-Hoan; Beecham, Gary W.; Dulary, Cécile; Herms, Stefan; Smith, Albert V.; Funk, Cory C.; Derbois, Céline; Forstner, Andreas J.; Ahmad, Shahzad; Li, Hongdong; Bacq, Delphine; Harold, Denise; Satizabal, Claudia L.; Valladares, Otto; Squassina, Alessio; Thomas, Rhodri; Brody, Jennifer A.; Qu, Liming; Sanchez-Juan, Pascual; Morgan, Taniesha; Wolters, Frank J.; Zhao, Yi; Garcia, Florentino Sanchez; Denning, Nicola; Fornage, Myriam; Malamon, John; Naranjo, Maria Candida Deniz; Majounie, Elisa; Mosley, Thomas H.; Dombroski, Beth; Wallon, David; Lupton, Michelle K; Dupuis, Josée; Whitehead, Patrice; Fratiglioni, Laura; Medway, Christopher; Jian, Xueqiu; Mukherjee, Shubhabrata; Keller, Lina; Brown, Kristelle; Lin, Honghuang; Cantwell, Laura B.; Panza, Francesco; McGuinness, Bernadette; Moreno-Grau, Sonia; Burgess, Jeremy D.; Solfrizzi, Vincenzo; Proitsi, Petra; Adams, Hieab H.; Allen, Mariet; Seripa, Davide; Pastor, Pau; Cupples, L. Adrienne; Price, Nathan D; Hannequin, Didier; Frank-García, Ana; Levy, Daniel; Chakrabarty, Paramita; Caffarra, Paolo; Giegling, Ina; Beiser, Alexa S.; Giedraitis, Vimantas; Hampel, Harald; Garcia, Melissa E.; Wang, Xue; Lannfelt, Lars; Mecocci, Patrizia; Eiriksdottir, Gudny; Crane, Paul K.; Pasquier, Florence; Boccardi, Virginia; Henández, Isabel; Barber, Robert C.; Scherer, Martin; Tarraga, Lluis; Adams, Perrie M.; Leber, Markus; Chen, Yuning; Albert, Marilyn S.; Riedel-Heller, Steffi; Emilsson, Valur; Beekly, Duane; Braae, Anne; Schmidt, Reinhold; Blacker, Deborah; Masullo, Carlo; Schmidt, Helena; Doody, Rachelle S.; Spalletta, Gianfranco; Longstreth, WT; Fairchild, Thomas J.; Bossù, Paola; Lopez, Oscar L.; Frosch, Matthew P.; Sacchinelli, Eleonora; Ghetti, Bernardino; Sánchez-Juan, Pascual; Yang, Qiong; Huebinger, Ryan M.; Jessen, Frank; Li, Shuo; Kamboh, M. Ilyas; Morris, John; Sotolongo-Grau, Oscar; Katz, Mindy J.; Corcoran, Chris; Himali, Jayanadra J.; Keene, C. Dirk; Tschanz, JoAnn; Fitzpatrick, Annette L.; Kukull, Walter A.; Norton, Maria; Aspelund, Thor; Larson, Eric B.; Munger, Ron; Rotter, Jerome I.; Lipton, Richard B.; Bullido, María J; Hofman, Albert; Montine, Thomas J.; Coto, Eliecer; Boerwinkle, Eric; Petersen, Ronald C.; Alvarez, Victoria; Rivadeneira, Fernando; Reiman, Eric M.; Gallo, Maura; O’Donnell, Christopher J.; Reisch, Joan S.; Bruni, Amalia Cecilia; Royall, Donald R.; Dichgans, Martin; Sano, Mary; Galimberti, Daniela; St George-Hyslop, Peter; Scarpini, Elio; Tsuang, Debby W.; Mancuso, Michelangelo; Bonuccelli, Ubaldo; Winslow, Ashley R.; Daniele, Antonio; Wu, Chuang-Kuo; Peters, Oliver; Nacmias, Benedetta; Riemenschneider, Matthias; Heun, Reinhard; Brayne, Carol; Rubinsztein, David C; Bras, Jose; Guerreiro, Rita; Hardy, John; Al-Chalabi, Ammar; Shaw, Christopher E; Collinge, John; Mann, David; Tsolaki, Magda; Clarimón, Jordi; Sussams, Rebecca; Lovestone, Simon; O’Donovan, Michael C; Owen, Michael J; Behrens, Timothy W.; Mead, Simon; Goate, Alison M.; Uitterlinden, Andre G.; Holmes, Clive; Cruchaga, Carlos; Ingelsson, Martin; Bennett, David A.; Powell, John; Golde, Todd E.; Graff, Caroline; De Jager, Philip L.; Morgan, Kevin; Ertekin-Taner, Nilufer; Combarros, Onofre; Psaty, Bruce M.; Passmore, Peter; Younkin, Steven G; Berr, Claudine; Gudnason, Vilmundur; Rujescu, Dan; Dickson, Dennis W.; Dartigues, Jean-Francois; DeStefano, Anita L.; Ortega-Cubero, Sara; Hakonarson, Hakon; Campion, Dominique; Boada, Merce; Kauwe, John “Keoni”; Farrer, Lindsay A.; Van Broeckhoven, Christine; Ikram, M. Arfan; Jones, Lesley; Haines, Johnathan; Tzourio, Christophe; Launer, Lenore J.; Escott-Price, Valentina; Mayeux, Richard; Deleuze, Jean-François; Amin, Najaf; Holmans, Peter A; Pericak-Vance, Margaret A.; Amouyel, Philippe; van Duijn, Cornelia M.; Ramirez, Alfredo; Wang, Li-San; Lambert, Jean-Charles; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D.
2017-01-01
Introduction We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development. PMID:28714976
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International Nuclear Information System (INIS)
Edgil, Dianna; Diamond, Michael S.; Holden, Katherine L.; Paranjape, Suman M.; Harris, Eva
2003-01-01
We have investigated the molecular basis for differences in the ability of natural variants of dengue virus type 2 (DEN2) to replicate in primary human cells. The rates of virus binding, virus entry, input strand translation, and RNA stability of low-passage Thai and Nicaraguan and prototype DEN2 strains were compared. All strains exhibited equivalent binding, entry, and uncoating, and displayed comparable stability of positive strand viral RNA over time in primary cells. However, the low-passage Nicaraguan isolates were much less efficient in their ability to translate viral proteins. Sequence analysis of the full-length low-passage Nicaraguan and Thai viral genomes identified specific differences in the 3' untranslated region (3'UTR). Substitution of the different sequences into chimeric RNA reporter constructs demonstrated that the changes in the 3'UTR directly affected the efficiency of viral translation. Thus, differences in infectivity among closely related DEN2 strains correlate with efficiency of translation of input viral RNA
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Peuchant, Olivia; Touati, Arabella; Sperandio, Clément; Hénin, Nadège; Laurier-Nadalié, Cécile; Bébéar, Cécile; de Barbeyrac, Bertille
2016-11-01
We describe a change in the molecular epidemiology of Chlamydia trachomatis strains involved in an outbreak of rectal lymphogranuloma venereum in France during January 2010-April 2015. Until 2012, the C. trachomatis L2b strain predominated; however, starting in 2013, most cases involved the L2 strain. We also identified 4 genetic L2b ompA variants.
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Strain dependence of interfacial antiferromagnetic coupling in La0.7Sr0.3MnO3/SrRuO3 superlattices
Das, Sujit; Herklotz, Andreas; Pippel, Eckhard; Guo, Er-Jia; Rata, Diana; Dörr, Kathrin
2015-03-01
We have investigated the magnetic response of La0.7Sr0.3MnO3/SrRuO3 superlattices to biaxial in-plane strain applied in-situ. Superlattices grown on piezoelectric substrates of 0.72PbMg1/3Nb2/3O3-0.28PbTiO3(001) (PMN-PT) show strong antiferromagnetic coupling of the two ferromagnetic components. The coupling field of μ0HAF = 1.8 T is found to change by μ0 ΔHAF / Δɛ ~ -520 mT %-1 under reversible biaxial strain (Δɛ) at 80 K in a [La0.7Sr0.3MnO3(22 Å)/SrRuO3(55 Å)]15 superlattice. This reveals a significant strain effect on interfacial coupling. The applied in-plane compression enhances the ferromagnetic order in the manganite layers which are under as-grown tensile strain. It is thus difficult to disentangle the contributions from strain-dependent antiferromagnetic Mn-O-Ru interface coupling and Mn-O-Mn ferromagnetic double exchange near the interface, since the enhanced magnetic order of Mn spins leads to a larger net coupling of SrRuO3 layers at the interface. We discuss our experimental findings taken into account both the strain-dependent orbital occupation in a single-ion picture and the enhanced Mn order at the interface. This work was supported by the DFG within the Collaborative Research Center SFB 762 ``Functionality of Oxide Interfaces.''
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[GM1-dot-EIA for the detection of toxin-producing Vibrio cholerae strains].
Markina, O V; Alekseeva, L P; Telesmanich, N R; Chemisova, O S; Akulova, M V; Markin, N V
2011-05-01
A new variant of enzyme immunoassay (EIA) has been developed on the basis of GM1 gangliosides to detect the toxin-producing Vibrio cholerae strains--GM1-dot-EIA. Experiments were run using a nitrocellulose membrane to bind GM1 gangliosides and polyclonal antitoxic serum to detect cholerogen. GM1-dot-EIA testing identified cholera toxin in 11 of 13 supernatants of V. cholerae eltor ctx(+) strains isolated from man and in 3 of 7 supernatants of V. cholerae eltor ctx(+) strains isolated from water. These data agree with those obtained in CM1-EIA. There was no reaction with the supernatants of other microorganisms. The sensitivity of the technique was 10 ng/ml. Thus, the simple and specific GM1-dot-EIA may be recommended to detect toxin-producing V cholerae strains isolated from man and water.
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Energy Technology Data Exchange (ETDEWEB)
Liu, Xiao, E-mail: liuxiao0105@163.com [Key Laboratory of High Temperature Wear Resistant Materials Preparation Technology of Hunan Province, Hunan University of Science and Technology, Xiangtan, Hunan 411201 (China); State Key Laboratory of Advanced Design and Manufacturing for Vehicle Body, Hunan University, Changsha, Hunan 410082 (China); Zhu, Biwu [Key Laboratory of High Temperature Wear Resistant Materials Preparation Technology of Hunan Province, Hunan University of Science and Technology, Xiangtan, Hunan 411201 (China); Huang, Guangjie [College of Materials Science and Engineering, Chongqing University, Chongqing, Chongqing 400045 (China); Li, Luoxing, E-mail: luoxing_li@yahoo.com [State Key Laboratory of Advanced Design and Manufacturing for Vehicle Body, Hunan University, Changsha, Hunan 410082 (China); Xie, Chao [Faculty of Mechanical Engineering and Mechanics, Ningbo University, Ningbo 315211 (China); Tang, Changping [Key Laboratory of High Temperature Wear Resistant Materials Preparation Technology of Hunan Province, Hunan University of Science and Technology, Xiangtan, Hunan 411201 (China)
2016-12-15
Uniaxial compression tests were carried out at 350 °C and a strain rate of 0.3 s{sup −1} on as-extruded AZ31 magnesium alloy samples. At a true strain of − 0.1, extension twin pairs in a grain and twin chains across adjacent grains were detected. The orientation of selected twins and their host grains were determined by electron backscattered diffraction (EBSD) techniques. The Schmid factors (SFs), accommodation strains and geometric compatibility factors (m{sup ′}) were calculated. Analysis of the data indicated that the formation of twin pair and twin chain was related to the SF and m{sup ′}. Regarding to twin chain across adjacent grains, accommodation strain was also involved. The selection of twin variants in twin chain was generally determined by m{sup ′}. When the twins required the operation of pyramidal slip or twinning in adjacent grain, the corresponding connected twins with a relative high m{sup ′} were selected in this adjacent grain. - Highlights: •The formation of paired twins is studied during high temperature deformation. •The initiation of twinning in twin pair and twin chain obeys the Schmid law. •The twin variants' selection in twin chain is related to the geometric compatibility factor. •The accommodation strain plays an important role on the formation of twin chain.
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A naturally occurring variant of the human prion protein completely prevents prion disease.
Asante, Emmanuel A; Smidak, Michelle; Grimshaw, Andrew; Houghton, Richard; Tomlinson, Andrew; Jeelani, Asif; Jakubcova, Tatiana; Hamdan, Shyma; Richard-Londt, Angela; Linehan, Jacqueline M; Brandner, Sebastian; Alpers, Michael; Whitfield, Jerome; Mead, Simon; Wadsworth, Jonathan D F; Collinge, John
2015-06-25
Mammalian prions, transmissible agents causing lethal neurodegenerative diseases, are composed of assemblies of misfolded cellular prion protein (PrP). A novel PrP variant, G127V, was under positive evolutionary selection during the epidemic of kuru--an acquired prion disease epidemic of the Fore population in Papua New Guinea--and appeared to provide strong protection against disease in the heterozygous state. Here we have investigated the protective role of this variant and its interaction with the common, worldwide M129V PrP polymorphism. V127 was seen exclusively on a M129 PRNP allele. We demonstrate that transgenic mice expressing both variant and wild-type human PrP are completely resistant to both kuru and classical Creutzfeldt-Jakob disease (CJD) prions (which are closely similar) but can be infected with variant CJD prions, a human prion strain resulting from exposure to bovine spongiform encephalopathy prions to which the Fore were not exposed. Notably, mice expressing only PrP V127 were completely resistant to all prion strains, demonstrating a different molecular mechanism to M129V, which provides its relative protection against classical CJD and kuru in the heterozygous state. Indeed, this single amino acid substitution (G→V) at a residue invariant in vertebrate evolution is as protective as deletion of the protein. Further study in transgenic mice expressing different ratios of variant and wild-type PrP indicates that not only is PrP V127 completely refractory to prion conversion but acts as a potent dose-dependent inhibitor of wild-type prion propagation.
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Beta-glucosidase variants and polynucleotides encoding same
Wogulis, Mark; Harris, Paul; Osborn, David
2017-06-27
The present invention relates to beta-glucosidase variants, e.g. beta-glucosidase variants of a parent Family GH3A beta-glucosidase from Aspergillus fumigatus. The present invention also relates to polynucleotides encoding the beta-glucosidase variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the beta-glucosidase variants.
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A duplex PCR assay for the detection of Ralstonia solanacearum phylotype II strains in Musa spp.
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Gilles Cellier
Full Text Available Banana wilt outbreaks that are attributable to Moko disease-causing strains of the pathogen Ralstonia solanacearum (Rs remain a social and economic burden for both multinational corporations and subsistence farmers. All known Moko strains belong to the phylotype II lineage, which has been previously recognized for its broad genetic basis. Moko strains are paraphyletic and are distributed among seven related but distinct phylogenetic clusters (sequevars that are potentially major threats to Musaceae, Solanaceae, and ornamental crops in many countries. Although clustered within the Moko IIB-4 sequevar, strains of the epidemiologically variant IIB-4NPB do not cause wilt on Cavendish or plantain bananas; instead, they establish a latent infection in the vascular tissues of plantains and demonstrate an expanded host range and high aggressiveness toward Solanaceae and Cucurbitaceae. Although most molecular diagnostic methods focus on strains that wilt Solanaceae (particularly potato, no relevant protocol has been described that universally detects strains of the Musaceae-infecting Rs phylotype II. Thus, a duplex PCR assay targeting Moko and IIB-4NPB variant strains was developed, and its performance was assessed using an extensive collection of 111 strains representing the known diversity of Rs Moko-related strains and IIB-4NPB variant strains along with certain related strains and families. The proposed diagnostic protocol demonstrated both high accuracy (inclusivity and exclusivity and high repeatability, detected targets on either pure culture or spiked plant extracts. Although they did not belong to the Moko clusters described at the time of the study, recently discovered banana-infecting strains from Brazil were also detected. According to our comprehensive evaluation, this duplex PCR assay appears suitable for both research and diagnostic laboratories and provides reliable detection of phylotype II Rs strains that infect Musaceae.
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Directory of Open Access Journals (Sweden)
Saasha Le
2017-06-01
Full Text Available Human breast and rat mammary cancer susceptibility are complex phenotypes where complete sets of risk associated loci remain to be identified for both species. We tested multiple congenic rat strains to physically confirm and positionally map rat Mammary carcinoma susceptibility 3 (Mcs3—a mammary cancer resistance allele previously predicted at Rattus norvegicus chromosome 1 (RNO1. The mammary cancer susceptible Wistar Furth (WF strain was the recipient, and the mammary cancer resistant Copenhagen (Cop strain was the RNO1-segment donor for congenics. Inbred WF females averaged 6.3 carcinogen-induced mammary carcinomas per rat. Two WF.Cop congenic strains averaged 2.8 and 3.4 mammary carcinomas per rat, which confirmed Mcs3 as an independently acting allele. Two other WF.Cop congenic strains averaged 6.6 and 8.1 mammary carcinomas per rat, and, thus, did not contain Mcs3. Rat Mcs3 was delimited to 27.8 Mb of RNO1 from rs8149408 to rs105131702 (RNO1:143700228-171517317 of RGSC 6.0/rn6. Human genetic variants with p values for association to breast cancer risk below 10−7 had not been reported for Mcs3 orthologous loci; however, human variants located in Mcs3-orthologous regions with potential association to risk (10−7 < p < 10−3 were listed in some population-based studies. Further, rat Mcs3 contains sequence orthologous to human 11q13/14—a region frequently amplified in female breast cancer. We conclude that Mcs3 is an independently acting mammary carcinoma resistance allele. Human population-based, genome-targeted association studies interrogating Mcs3 orthologous loci may yield novel breast cancer risk associated variants and genes.
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Gu, Zhenqing; Dong, Jing; Wang, Jichun; Hou, Chengcai; Sun, Haifeng; Yang, Wenping; Bai, Juan; Jiang, Ping
2015-01-02
A highly virulent and antigenic variant of pseudorabies virus (PRV) broke out in China at the end of 2011 and caused great economic loss in the pig industry. In this study, an infectious bacterial artificial chromosome (BAC) clone containing the full-length genome of the emerged variant PRV ZJ01 strain was generated. The BAC-derived viruses, vZJ01-GFPΔgE/gI (gE/gI deleted strain, and exhibiting green autofluorescence), vZJ01ΔgE/gI (gE/gI deleted strain), and vZJ01gE/gI-R (gE/gI revertant strain), showed similar in vitro growth to their parent strain. In pigs, inactivated vZJ01ΔgE/gI vaccine generated significantly high levels of neutralizing antibodies against ZJ01 compared with Bartha-K61 live vaccine (pvaccine group survived without exhibiting any clinical sings, but two of five animals exhibited central nervous signs in the Bartha-K61 group. Meanwhile, all the non-vaccinated control animals died at 7 days post-challenge. This indicates that the inactivated vZJ01ΔgE/gI vaccine is a promising vaccine candidate for controlling the variant strains of PRV now circulating in China. Copyright © 2014 Elsevier B.V. All rights reserved.
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Mutagenesis at the ad-3A and ad-3B loci in haploid UV-sensitive strains of Neurospora crassa. Pt. 3
International Nuclear Information System (INIS)
Schuepbach, M.E.; Serres, F.J. de
1981-01-01
γ-ray-induced inactivation and induction of mutations at the ad-3A and ad-3B loci of Neurospora crassa have been compared among 6 different UV- sensitive strains and a standard wild-type strain. The 6 strains show varying degrees of sensitivy to γ-ray-induced inactivation, with the relative sensitivy at 37% survival being uvs-6 > upr-1 > uvs-2 UE uvs-3 > wild-type > uvs-5 > uvs-4. Studies on the induction of ad-3 mutants by γ-rays show that when the dose-response curves (expressed in terms of ad-3 mutants among the surving colonies) of the UV-sensitive strains are compared with wild-type, the excision-repair-deficient mutants uvs-2 and upr-1 exhibit enhanced ad-3 mutant frequencies, uvs-3 exibits reduced ad-3 mutant frequencies whereas both uvs-4 and uvs-5 show lower mutant frequencies than wild-type. (orig.)
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Directory of Open Access Journals (Sweden)
Tomohiro Kitano
Full Text Available A variant in a transcription factor gene, POU4F3, is responsible for autosomal dominant nonsyndromic hereditary hearing loss, DFNA15. To date, 14 variants, including a whole deletion of POU4F3, have been reported to cause HL in various ethnic groups. In the present study, genetic screening for POU4F3 variants was carried out for a large series of Japanese hearing loss (HL patients to clarify the prevalence and clinical characteristics of DFNA15 in the Japanese population. Massively parallel DNA sequencing of 68 target candidate genes was utilized in 2,549 unrelated Japanese HL patients (probands to identify genomic variations responsible for HL. The detailed clinical features in patients with POU4F3 variants were collected from medical charts and analyzed. Novel 12 POU4F3 likely pathogenic variants (six missense variants, three frameshift variants, and three nonsense variants were successfully identified in 15 probands (2.5% among 602 families exhibiting autosomal dominant HL, whereas no variants were detected in the other 1,947 probands with autosomal recessive or inheritance pattern unknown HL. To obtain the audiovestibular configuration of the patients harboring POU4F3 variants, we collected audiograms and vestibular symptoms of the probands and their affected family members. Audiovestibular phenotypes in a total of 24 individuals from the 15 families possessing variants were characterized by progressive HL, with a large variation in the onset age and severity with or without vestibular symptoms observed. Pure-tone audiograms indicated the most prevalent configuration as mid-frequency HL type followed by high-frequency HL type, with asymmetry observed in approximately 20% of affected individuals. Analysis of the relationship between age and pure-tone average suggested that individuals with truncating variants showed earlier onset and slower progression of HL than did those with non-truncating variants. The present study showed that variants
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Gohil, Devanshi J; Kothari, Sweta T; Shinde, Pramod S; Chintakrindi, Anand S; Meharunkar, Rhuta; Warke, Rajas V; Kanyalkar, Meena A; Chowdhary, Abhay S; Deshmukh, Ranjana A
2015-01-01
From its first instance in 1977, resistance to amantadine, a matrix (M2) inhibitor has been increasing among influenza A/H3N2, thus propelling the use of oseltamivir, a neuraminidase (NA) inhibitor as a next line drug. Information on drug susceptibility to amantadine and neuraminidase inhibitors for influenza A/H3N2 viruses in India is limited with no published data from Mumbai. This study aimed at examining the sensitivity to M2 and NA inhibitors of influenza A/H3N2 strains isolated from 2009 to 2011 in Mumbai. Nasopharyngeal swabs positive for influenza A/H3N2 virus were inoculated on Madin-Darby canine kidney (MDCK) cell line for virus isolation. Molecular analysis of NA and M2 genes was used to detect known mutations contributing to resistance. Resistance to neuraminidase was assayed using a commercially available chemiluminescence based NA-Star assay kit. Genotypically, all isolates were observed to harbor mutations known to confer resistance to amantadine. However, no know mutations conferring resistance to NA inhibitors were detected. The mean IC50 value for oseltamivir was 0.25 nM. One strain with reduced susceptibility to the neuraminidase inhibitor (IC₅₀=4.08 nM) was isolated from a patient who had received oseltamivir treatment. Phylogenetic analysis postulate the emergence of amantadine resistance in Mumbai may be due to genetic reassortment with the strains circulating in Asia and North America. Surveillance of drug susceptibility helped us to identify an isolate with reduced sensitivity to oseltamivir. Therefore, we infer that such surveillance would help in understanding possible trends underlying the emergence of resistant variants in humans. Copyright © 2014 Elsevier B.V. All rights reserved.
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Molecular characterization of different equine-like G3 rotavirus strains from Germany.
Pietsch, Corinna; Liebert, Uwe G
2018-01-01
The genetic heterogeneity of rotaviruses constitutes a substantial burden to human and animal health. Occasional interspecies transmissions can generate novel virus strains in the human population. We detected equine-like G3P[8] strains in feces sampled from three children in Germany in 2015 and 2016, respectively. Thereof two showed a DS-1-like backbone. In one strain the NSP2 gene segment was of distinct genotype (G3-P[8]-I2-R2-C2-M2-A2-N1-T2-E2-H2). Phylogenetic analyses of the German strains showed a relation to other equine-like G3 rotaviruses circulating in different countries. The reconstruction of reassortment events in the evolution of novel equine-like G3 rotaviruses suggests an independent introduction of the three strains into the local human rotavirus population. Copyright © 2017 Elsevier B.V. All rights reserved.
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Directory of Open Access Journals (Sweden)
Simona Capone
2015-09-01
Full Text Available Horseradish peroxidase (HRP, conjugated to antibodies and lectins, is widely used in medical diagnostics. Since recombinant production of the enzyme is difficult, HRP isolated from plant is used for these applications. Production in the yeast Pichia pastoris (P. pastoris, the most promising recombinant production platform to date, causes hyperglycosylation of HRP, which in turn complicates conjugation to antibodies and lectins. In this study we combined protein and strain engineering to obtain an active and stable HRP variant with reduced surface glycosylation. We combined four mutations, each being beneficial for either catalytic activity or thermal stability, and expressed this enzyme variant as well as the unmutated wildtype enzyme in both a P. pastoris benchmark strain and a strain where the native α-1,6-mannosyltransferase (OCH1 was knocked out. Considering productivity in the bioreactor as well as enzyme activity and thermal stability, the mutated HRP variant produced in the P. pastoris benchmark strain turned out to be interesting for medical diagnostics. This variant shows considerable catalytic activity and thermal stability and is less glycosylated, which might allow more controlled and efficient conjugation to antibodies and lectins.
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International Nuclear Information System (INIS)
Usami, Takashi; Yoshida, Yutaka; Ichino, Yusuke; Sugano, Michinaka; Machiya, Shutaro; Ibi, Akira; Izumi, Teruo
2016-01-01
The strain effect of REBa_2Cu_3O_y (REBCO: RE = Y, Gd, Sm)-coated conductors (CCs) on critical current (I_c) is one of the most fundamental factors for superconducting coil applications. In this study, we aim to clarify the effect of artificial pinning center shapes on the strain effect in BHO-doped GdBCO CCs. To achieve this, we fabricated a Pure-GdBCO CC, a BHO nanorod-doped GdBCO CC and a multilayered-GdBCO (ML-GdBCO) CC, and carried out bending tests. As the result, the strain dependence of I_c for each CC showed an upward convex and the peak strain of the BHO-doped GdBCO CC shifts towards the compressive strain independent of the BHO shapes. In addition, the strain sensitivity of I_c in the GdBCO CCs including BHO becomes smaller. To clarify the difference between the strain sensitivity of I_c and the peak strain among the CCs, we evaluated the residual strain and the slopes of the internal lattice strains against the applied tensile strain (β). From this measurement, the residual strains for the Pure-GdBCO CC and the ML-GdBCO CC were almost the same. In addition, there was no change in the β value between the Pure-GdBCO and ML-GdBCO CCs. These results suggest that the changes in peak strain and strain sensitivity were not related to the internal lattice strain. (author)
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2013-01-01
Background Mycoplasma hyopneumoniae is the causative agent of porcine enzootic pneumonia (EP), a mild, chronic pneumonia of swine. Despite presenting with low direct mortality, EP is responsible for major economic losses in the pig industry. To identify the virulence-associated determinants of M. hyopneumoniae, we determined the whole genome sequence of M. hyopneumoniae strain 168 and its attenuated high-passage strain 168-L and carried out comparative genomic analyses. Results We performed the first comprehensive analysis of M. hyopneumoniae strain 168 and its attenuated strain and made a preliminary survey of coding sequences (CDSs) that may be related to virulence. The 168-L genome has a highly similar gene content and order to that of 168, but is 4,483 bp smaller because there are 60 insertions and 43 deletions in 168-L. Besides these indels, 227 single nucleotide variations (SNVs) were identified. We further investigated the variants that affected CDSs, and compared them to reported virulence determinants. Notably, almost all of the reported virulence determinants are included in these variants affected CDSs. In addition to variations previously described in mycoplasma adhesins (P97, P102, P146, P159, P216, and LppT), cell envelope proteins (P95), cell surface antigens (P36), secreted proteins and chaperone protein (DnaK), mutations in genes related to metabolism and growth may also contribute to the attenuated virulence in 168-L. Furthermore, many mutations were located in the previously described repeat motif, which may be of primary importance for virulence. Conclusions We studied the virulence attenuation mechanism of M. hyopneumoniae by comparative genomic analysis of virulent strain 168 and its attenuated high-passage strain 168-L. Our findings provide a preliminary survey of CDSs that may be related to virulence. While these include reported virulence-related genes, other novel virulence determinants were also detected. This new information will form
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Yoshikawa, Rokusuke; Izumi, Taisuke; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Ren, Fengrong; Carpenter, Michael A; Ikeda, Terumasa; Münk, Carsten; Harris, Reuben S; Miyazawa, Takayuki; Koyanagi, Yoshio; Sato, Kei
2016-01-01
Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) DNA cytosine deaminases can be incorporated into progeny virions and inhibit lentiviral replication. On the other hand, viral infectivity factor (Vif) of lentiviruses antagonizes A3-mediated antiviral activities by degrading A3 proteins. It is known that domestic cat (Felis catus) APOBEC3Z3 (A3Z3), the ortholog of human APOBEC3H, potently suppresses the infectivity of vif-defective feline immunodeficiency virus (FIV). Although a recent report has shown that domestic cat encodes 7 haplotypes (hap I to hap VII) of A3Z3, the relevance of A3Z3 polymorphism in domestic cats with FIV Vif has not yet been addressed. In this study, we demonstrated that these feline A3Z3 variants suppress vif-defective FIV infectivity. We also revealed that codon 65 of feline A3Z3 is a positively selected site and that A3Z3 hap V is subject to positive selection during evolution. It is particularly noteworthy that feline A3Z3 hap V is resistant to FIV Vif-mediated degradation and still inhibits vif-proficient viral infection. Moreover, the side chain size, but not the hydrophobicity, of the amino acid at position 65 determines the resistance to FIV Vif-mediated degradation. Furthermore, phylogenetic analyses have led to the inference that feline A3Z3 hap V emerged approximately 60,000 years ago. Taken together, these findings suggest that feline A3Z3 hap V may have been selected for escape from an ancestral FIV. This is the first evidence for an evolutionary "arms race" between the domestic cat and its cognate lentivirus. Gene diversity and selective pressure are intriguing topics in the field of evolutionary biology. A direct interaction between a cellular protein and a viral protein can precipitate an evolutionary arms race between host and virus. One example is primate APOBEC3G, which potently restricts the replication of primate lentiviruses (e.g., human immunodeficiency virus type 1 [HIV-1] and simian
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Haemophilus ducreyi Cutaneous Ulcer Strains Are Nearly Identical to Class I Genital Ulcer Strains.
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Dharanesh Gangaiah
Full Text Available Although cutaneous ulcers (CU in the tropics is frequently attributed to Treponema pallidum subspecies pertenue, the causative agent of yaws, Haemophilus ducreyi has emerged as a major cause of CU in yaws-endemic regions of the South Pacific islands and Africa. H. ducreyi is generally susceptible to macrolides, but CU strains persist after mass drug administration of azithromycin for yaws or trachoma. H. ducreyi also causes genital ulcers (GU and was thought to be exclusively transmitted by microabrasions that occur during sex. In human volunteers, the GU strain 35000HP does not infect intact skin; wounds are required to initiate infection. These data led to several questions: Are CU strains a new variant of H. ducreyi or did they evolve from GU strains? Do CU strains contain additional genes that could allow them to infect intact skin? Are CU strains susceptible to azithromycin?To address these questions, we performed whole-genome sequencing and antibiotic susceptibility testing of 5 CU strains obtained from Samoa and Vanuatu and 9 archived class I and class II GU strains. Except for single nucleotide polymorphisms, the CU strains were genetically almost identical to the class I strain 35000HP and had no additional genetic content. Phylogenetic analysis showed that class I and class II strains formed two separate clusters and CU strains evolved from class I strains. Class I strains diverged from class II strains ~1.95 million years ago (mya and CU strains diverged from the class I strain 35000HP ~0.18 mya. CU and GU strains evolved under similar selection pressures. Like 35000HP, the CU strains were highly susceptible to antibiotics, including azithromycin.These data suggest that CU strains are derivatives of class I strains that were not recognized until recently. These findings require confirmation by analysis of CU strains from other regions.
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[Cloning and sequencing of the papA gene from uropathogenic Escherichia coli 4030 strain].
Wu, Qinggang; Zhang, Jingping; Zhao, Chuncheng; Zhu, Jianguo
2008-09-01
Cloning and sequencing of the papA gene from uropathogenic Escherichia coli 4030 strain to investigate the differences of the sequences of the papA of UPEC4030 strain and the ones of related genes, in order to make whether or not it was a new genotype. Cloning and sequencing methods were used to analyze the sequence of the papA of UPEC4030 strain in comparison with related sequences. The sequence analysis of papA revealed a 722 bp gene and encode 192 amino acid polypeptide. The overall homology of the papA genes between UPEC4030 and the standard strains of ten F types were 36.11%-77.95% and 22.20%-78.34% at nucleotide and deduced amino acid levels. The homology between the sequence of the reverse primers and the corresponding sequence of UPEC4030 papA was 10%-66.67%. The results confirmed that UPEC4030 strain contained a novel papA variant. UPEC4030 strain could contain an unknown papA variant or the novel genotype. The pathogenic mechanism and epidemiology related need to be further studied.
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Directory of Open Access Journals (Sweden)
Frank Dunemann
Full Text Available In eukaryotes, centromeres are the assembly sites for the kinetochore, a multi-protein complex to which spindle microtubules are attached at mitosis and meiosis, thereby ensuring segregation of chromosomes during cell division. They are specified by incorporation of CENH3, a centromere specific histone H3 variant which replaces canonical histone H3 in the nucleosomes of functional centromeres. To lay a first foundation of a putative alternative haploidization strategy based on centromere-mediated genome elimination in cultivated carrots, in the presented research we aimed at the identification and cloning of functional CENH3 genes in Daucus carota and three distantly related wild species of genus Daucus varying in basic chromosome numbers. Based on mining the carrot transcriptome followed by a subsequent PCR-based cloning, homologous coding sequences for CENH3s of the four Daucus species were identified. The ORFs of the CENH3 variants were very similar, and an amino acid sequence length of 146 aa was found in three out of the four species. Comparison of Daucus CENH3 amino acid sequences with those of other plant CENH3s as well as their phylogenetic arrangement among other dicot CENH3s suggest that the identified genes are authentic CENH3 homologs. To verify the location of the CENH3 protein in the kinetochore regions of the Daucus chromosomes, a polyclonal antibody based on a peptide corresponding to the N-terminus of DcCENH3 was developed and used for anti-CENH3 immunostaining of mitotic root cells. The chromosomal location of CENH3 proteins in the centromere regions of the chromosomes could be confirmed. For genetic localization of the CENH3 gene in the carrot genome, a previously constructed linkage map for carrot was used for mapping a CENH3-specific simple sequence repeat (SSR marker, and the CENH3 locus was mapped on the carrot chromosome 9.
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Myocardial strains from 3D displacement encoded magnetic resonance imaging
International Nuclear Information System (INIS)
Kindberg, Katarina; Haraldsson, Henrik; Sigfridsson, Andreas; Engvall, Jan; Ingels, Neil B Jr; Ebbers, Tino; Karlsson, Matts
2012-01-01
The ability to measure and quantify myocardial motion and deformation provides a useful tool to assist in the diagnosis, prognosis and management of heart disease. The recent development of magnetic resonance imaging methods, such as harmonic phase analysis of tagging and displacement encoding with stimulated echoes (DENSE), make detailed non-invasive 3D kinematic analyses of human myocardium possible in the clinic and for research purposes. A robust analysis method is required, however. We propose to estimate strain using a polynomial function which produces local models of the displacement field obtained with DENSE. Given a specific polynomial order, the model is obtained as the least squares fit of the acquired displacement field. These local models are subsequently used to produce estimates of the full strain tensor. The proposed method is evaluated on a numerical phantom as well as in vivo on a healthy human heart. The evaluation showed that the proposed method produced accurate results and showed low sensitivity to noise in the numerical phantom. The method was also demonstrated in vivo by assessment of the full strain tensor and to resolve transmural strain variations. Strain estimation within a 3D myocardial volume based on polynomial functions yields accurate and robust results when validated on an analytical model. The polynomial field is capable of resolving the measured material positions from the in vivo data, and the obtained in vivo strains values agree with previously reported myocardial strains in normal human hearts
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Miyake, B
1989-02-01
In a survey of the proteins from human hair, a genetic electrophoretic variant has been observed in the high-sulfur protein region. S-carboxymethylated proteins were examined by 15% polyacrylamide gel electrophoresis at pH 8.9. Out of 150 unrelated samples of Japanese head hairs analyzed, 107 showed 6 major high-sulfur protein bands (normal) and the remaining 43 samples showed an additional high-sulfur protein band (variant). Of 21 Caucasian samples analyzed only one variant sample was found. Characterization of the proteins by two-dimensional electrophoresis evidenced a variant protein spot which showed an apparent molecular weight of 30 k Da. Isoelectric points of the high-sulfur proteins ranged from 3.25-3.55 and that of variant protein band from 3.3-3.4. Family studies of 21 matings resulting in 49 children indicated that this variant was inherited in an autosomal fashion.
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Chooi, Kar Mun; Cohen, Daniel; Pearson, Michael N
2013-04-01
Grapevine leafroll-associated virus 3 (GLRaV-3) is an economically important virus, which is found in all grapevine growing regions worldwide. Its accurate detection in nursery and field samples is of high importance for certification schemes and disease management programmes. To reduce false negatives that can be caused by sequence variability, a new universal primer pair was designed against a divergent sequence data set, targeting the open reading frame 4 (heat shock protein 70 homologue gene), and optimised for conventional one-step RT-PCR and one-step SYBR Green real-time RT-PCR assays. In addition, primer pairs for the simultaneous detection of specific GLRaV-3 variants from groups 1, 2, 6 (specifically NZ-1) and the outlier NZ2 variant, and the generic detection of variants from groups 1 to 5 were designed and optimised as a conventional one-step multiplex RT-PCR assay using the plant nad5 gene as an internal control (i.e. one-step hexaplex RT-PCR). Results showed that the generic and variant specific assays detected in vitro RNA transcripts from a range of 1×10(1)-1×10(8) copies of amplicon per μl diluted in healthy total RNA from Vitis vinifera cv. Cabernet Sauvignon. Furthermore, the assays were employed effectively to screen 157 germplasm and 159 commercial field samples. Thus results demonstrate that the GLRaV-3 generic and variant-specific assays are prospective tools that will be beneficial for certification schemes and disease management programmes, as well as biological and epidemiological studies of the divergent GLRaV-3 populations. Copyright © 2013 Elsevier B.V. All rights reserved.
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Vibrio cholerae O1 epidemic variants in Angola: a retrospective study between 1992 and 2006.
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Romy eValia
2013-11-01
Full Text Available Cholera is still a major public health concern in many African countries. In Angola, after a decade of absence, cholera reemerged in 1987, spreading throughout the country until 1996, with outbreaks recurring in a seasonal pattern. In 2006 Angola was hit by one of the most severe outbreaks of the last decade, with ca. 240,000 cases reported.We analyzed 21 clinical strains isolated between 1992 and 2006 from several provinces throughout the country: Benguela, Bengo, Luanda, Cuando Cubango and Cabinda. We used two multiplex PCR assays to investigate discriminatory mobile genetic elements (ICEs, VSP-II, GI12, GI14, GI15, K and TLC phages and we compared the profiles obtained with those of different reference V. cholerae O1 variants (prototypical, altered and hybrid, responsible for the ongoing 7th pandemic. We also tested the strains for the presence of specific VSP-II variants and for the presence of a genomic island (WASA-1, correlated with the transmission of seventh pandemic cholera from Africa to South America. Based on the presence/absence of the analyzed genetic elements, five novel profiles were detected in the epidemic strains circulating in the 1990s. The most frequent profiles, F and G, were characterized by the absence of ICEs and the three GIs tested, and the presence of genomic island WASA-1 and the WASA variant of the VSP-II island. Our results identified unexpected variability within the 1990s epidemic, showing different rearrangements in a dynamic part of the genome not present in the prototypical V. cholerae O1 N16961. Moreover the 2006 strains differed from the current pandemic V. cholerae O1 strain. Taken together, our results highlight the role of horizontal gene transfer in diversifying the genetic background of V. cholerae within a single epidemic.
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Vibrio cholerae O1 epidemic variants in Angola: a retrospective study between 1992 and 2006.
Valia, Romy; Taviani, Elisa; Spagnoletti, Matteo; Ceccarelli, Daniela; Cappuccinelli, Piero; Colombo, Mauro M
2013-01-01
Cholera is still a major public health concern in many African countries. In Angola, after a decade of absence, cholera reemerged in 1987, spreading throughout the country until 1996, with outbreaks recurring in a seasonal pattern. In 2006 Angola was hit by one of the most severe outbreaks of the last decade, with ca. 240,000 cases reported. We analyzed 21 clinical strains isolated between 1992 and 2006 from several provinces throughout the country: Benguela, Bengo, Luanda, Cuando Cubango, and Cabinda. We used two multiplex PCR assays to investigate discriminatory mobile genetic elements (MGE) [Integrative Conjugative Elements (ICEs), VSP-II, GI12, GI14, GI15, K, and TLC phages] and we compared the profiles obtained with those of different reference V. cholerae O1 variants (prototypical, altered, and hybrid), responsible for the ongoing 7th pandemic. We also tested the strains for the presence of specific VSP-II variants and for the presence of a genomic island (GI) (WASA-1), correlated with the transmission of seventh pandemic cholera from Africa to South America. Based on the presence/absence of the analyzed genetic elements, five novel profiles were detected in the epidemic strains circulating in the 1990s. The most frequent profiles, F and G, were characterized by the absence of ICEs and the three GIs tested, and the presence of GI WASA-1 and the WASA variant of the VSP-II island. Our results identified unexpected variability within the 1990s epidemic, showing different rearrangements in a dynamic part of the genome not present in the prototypical V. cholerae O1 N16961. Moreover the 2006 strains differed from the current pandemic V. cholerae O1 strain. Taken together, our results highlight the role of horizontal gene transfer (HGT) in diversifying the genetic background of V. cholerae within a single epidemic.
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Identification of coagulation gene 3′UTR variants that are potentially regulated by microRNAs
Vossen, Carla Y.; van Hylckama Vlieg, Astrid; Teruel-Montoya, Raúl; Salloum-Asfar, Salam; de Haan, Hugoline G.; Corral, Javier; Reitsma, Pieter H.; Koeleman, Bobby P.C.; Martínez, Constantino
2017-01-01
MicroRNAs have been recognized as critical regulators of gene expression and might affect the risk of venous thrombosis. We aimed to identify 3′ untranslated region (UTR) variants in coagulation genes that influence coagulation factor levels and venous thrombosis risk. The 3′UTR of coagulation genes
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Directory of Open Access Journals (Sweden)
Stefanie Forler
2015-06-01
Full Text Available We investigated to which extent polymorphisms of an individual affect the proteomic network. Consomic mouse strains (CS were used to study the trans-effect of the cis-variant (polymorphic proteins of the strain PWD/Ph on the proteins of the host strain C57BL/6J. The cardiac proteome of ten CSs was analyzed by 2-DE and MS. Cis-variant PWD proteins altered a high number of C57BL/6J proteins, but the number of trans-variant proteins differed considerably between different CSs. Cardiac hypertrophy was induced in CSs. We found that high variability of the proteome, as induced by polymorphisms in CS14, acts protective against the complex disease.
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Rotroff, Daniel M; Pijut, Sonja S; Marvel, Skylar W; Jack, John R; Havener, Tammy M; Pujol, Aurora; Schluter, Agatha; Graf, Gregory A; Ginsberg, Henry N; Shah, Hetal S; Gao, He; Morieri, Mario-Luca; Doria, Alessandro; Mychaleckyi, Josyf C; McLeod, Howard L; Buse, John B; Wagner, Michael J; Motsinger-Reif, Alison A
2018-04-01
Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin-treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed-up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10 -6 ). Rare variant and gene expression changes were assessed using a false discovery rate approach. AKR7A3 and HSD17B13 were associated with lipid changes in white subjects (q < 0.2). Mice fed fenofibrate displayed reductions in Hsd17b13 gene expression (q < 0.1). Associations of variants in SMAD3, IPO11, and HSD17B13, with gene expression changes in mice indicate that transforming growth factor-beta (TGF-β) and NRF2 signaling pathways may influence fenofibrate effects on dyslipidemia in patients with T2D. © 2017 American Society for Clinical Pharmacology and Therapeutics.
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Lesch-Nyhan variant syndrome: variable presentation in 3 affected family members.
Sarafoglou, Kyriakie; Grosse-Redlinger, Krista; Boys, Christopher J; Charnas, Laurence; Otten, Noelle; Broock, Robyn; Nyhan, William L
2010-06-01
Lesch-Nyhan disease is an inborn error of purine metabolism that results from deficiency of the activity of hypoxanthine phosphoribosyltransferase (HPRT). The heterogeneity of clinical phenotypes seen in HPRT deficiency corresponds to an inverse relationship between HPRT enzyme activity and clinical severity. With rare exception, each mutation produces a stereotypical pattern of clinical disease; onset of neurologic symptoms occurs during infancy and is thought to be nonprogressive. To document a family in which a single HPRT gene mutation has led to 3 different clinical and enzymatic phenotypes. Case report. Settings A university-based outpatient metabolic clinic and a biochemical genetics laboratory. Patients Three males (2 infants and their grandfather) from the same family with Lesch-Nyhan variant, including one of the oldest patients with Lesch-Nyhan variant at diagnosis (65 years). Clinical and biochemical observations. Sequencing of 5 family members revealed a novel mutation c.550G>T in exon 7 of the HPRT gene. The considerably variable clinical phenotype corresponded with the variable enzymatic activity in the 3 males, with the grandfather being the most severely affected. The different phenotypes encountered in the enzymatic analysis of cultured fibroblasts from a single mutation in the same family is unprecedented. The significant decrease in the grandfather's HPRT enzymatic activity compared with that of his grandchildren could be a function of the Hayflick Limit Theory of cell senescence.
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Hall, R N; Mahar, J E; Read, A J; Mourant, R; Piper, M; Huang, N; Strive, T
2018-04-01
Rabbit haemorrhagic disease virus (RHDV, or GI.1) is a calicivirus in the genus Lagovirus that has been widely utilized in Australia as a biological control agent for the management of overabundant wild European rabbit (Oryctolagus cuniculus) populations since 1996. Recently, two exotic incursions of pathogenic lagoviruses have been reported in Australia; GI.1a-Aus, previously called RHDVa-Aus, is a GI.1a virus detected in January 2014, and the novel lagovirus GI.2 (previously known as RHDV2). Furthermore, an additional GI.1a strain, GI.1a-K5 (also known as 08Q712), was released nationwide in March 2017 as a supplementary tool for wild rabbit management. To discriminate between these lagoviruses, a highly sensitive strain-specific multiplex RT-PCR assay was developed, which allows fast, cost-effective and sensitive detection of the four pathogenic lagoviruses currently known to be circulating in Australia. In addition, we developed a universal RT-qPCR assay to be used in conjunction with the multiplex assay that broadly detects all four viruses and facilitates quantification of viral RNA load in samples. These assays enable rapid detection, identification and quantification of pathogenic lagoviruses in the Australian context. Using these assays, a novel recombinant lagovirus was detected in rabbit tissue samples, which contained the non-structural genes of GI.1a-Aus and the structural genes of GI.2. This variant was also recovered from the liver of a European brown hare (Lepus europaeus). The impact of this novel recombinant on Australian wild lagomorph populations and its competitiveness in relation to circulating field strains, particularly GI.2, requires further studies. © 2017 Blackwell Verlag GmbH.
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Strain engineering on electronic structure and carrier mobility in monolayer GeP3
Zeng, Bowen; Long, Mengqiu; Zhang, Xiaojiao; Dong, Yulan; Li, Mingjun; Yi, Yougen; Duan, Haiming
2018-06-01
Using density functional theory coupled with the Boltzmann transport equation with relaxation time approximation, we have studied the strain effect on the electronic structure and carrier mobility of two-dimensional monolayer GeP3. We find that the energies of valence band maximum and conduction band minimum are nearly linearly shifted with a biaxial strain in the range of ‑4% to 6%, and the band structure experiences a remarkable transition from semiconductor to metal with the appropriate compression (‑5% strain). Under biaxial strain, the mobility of the electron and hole in monolayer GeP3 reduces and increases by more than one order of magnitude, respectively. It is suggested that it is possible to perform successive transitions from an n-type semiconductor (‑4% strain) to a good performance p-semiconductor (+6% strain) by applying strain in monolayer GeP3, which is potentially useful for flexible electronics and nanosized mechanical sensors.
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Dynamic scattering theory for dark-field electron holography of 3D strain fields.
Lubk, Axel; Javon, Elsa; Cherkashin, Nikolay; Reboh, Shay; Gatel, Christophe; Hÿtch, Martin
2014-01-01
Dark-field electron holography maps strain in crystal lattices into reconstructed phases over large fields of view. Here we investigate the details of the lattice strain-reconstructed phase relationship by applying dynamic scattering theory both analytically and numerically. We develop efficient analytic linear projection rules for 3D strain fields, facilitating a straight-forward calculation of reconstructed phases from 3D strained materials. They are used in the following to quantify the influence of various experimental parameters like strain magnitude, specimen thickness, excitation error and surface relaxation. © 2013 Elsevier B.V. All rights reserved.
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Measured Strain of Nb3Sn Coils During Excitation and Quench
International Nuclear Information System (INIS)
Caspi, S.; Bartlett, S.E.; Dietderich, D.R.; Ferracin, P.; Gourlay, S.A.; Hannaford, C.R.; Hafalia, A.R.; Lietzke, S.; Mattafirri, M.; Nyman, M.; Sabbi, G.
2005-01-01
The strain in a high field Nb 3 Sn coil was measured during magnet assembly, cool-down, excitation and spot heater quenches. Strain was measured with a full bridge strain gauge mounted directly over the turns and impregnated with the coil. Two such coils were placed in a ''common coil'' fashion capable of reaching 11T at 4.2K. The measured steady state strain in the coil is compared with results obtained using the FEM code ANSYS. During quenches, the transient strain (due to temperature rise) was also measured and compared with the calculated mechanical time response to a quench
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Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease.
Directory of Open Access Journals (Sweden)
Johanna Jakobsdottir
2016-10-01
Full Text Available We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L in TM2D3 was enriched in Icelanders (~0.5% versus <0.05% in other European populations. In 433 LOAD cases and 3903 controls from the Icelandic AGES sub-study, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI = 7.5 (3.5-15.9, p = 6.6x10-9]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the β-amyloid cascade.
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Sarute, Nicolás; Pérez, Ruben; Aldaz, Jaime; Alfieri, Amauri A; Alfieri, Alice F; Name, Daniela; Llanes, Jessika; Hernández, Martín; Francia, Lourdes; Panzera, Yanina
2014-06-01
Canine distemper virus (CDV, Paramyxoviridae, Morbillivirus) is the causative agent of a severe infectious disease affecting terrestrial and marine carnivores worldwide. Phylogenetic relationships and the genetic variability of the hemagglutinin (H) protein and the fusion protein signal-peptide (Fsp) allow for the classification of field strains into genetic lineages. Currently, there are nine CDV lineages worldwide, two of them co-circulating in South America. Using the Fsp-coding region, we analyzed the genetic variability of strains from Uruguay, Brazil, and Ecuador, and compared them with those described previously in South America and other geographical areas. The results revealed that the Brazilian and Uruguayan strains belong to the already described South America lineage (EU1/SA1), whereas the Ecuadorian strains cluster in a new clade, here named South America 3, which may represent the third CDV lineage described in South America.
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Germline Variants of Prostate Cancer in Japanese Families.
Directory of Open Access Journals (Sweden)
Takahide Hayano
Full Text Available Prostate cancer (PC is the second most common cancer in men. Family history is the major risk factor for PC. Only two susceptibility genes were identified in PC, BRCA2 and HOXB13. A comprehensive search of germline variants for patients with PC has not been reported in Japanese families. In this study, we conducted exome sequencing followed by Sanger sequencing to explore responsible germline variants in 140 Japanese patients with PC from 66 families. In addition to known susceptibility genes, BRCA2 and HOXB13, we identified TRRAP variants in a mutually exclusive manner in seven large PC families (three or four patients per family. We also found shared variants of BRCA2, HOXB13, and TRRAP from 59 additional small PC families (two patients per family. We identified two deleterious HOXB13 variants (F127C and G132E. Further exploration of the shared variants in rest of the families revealed deleterious variants of the so-called cancer genes (ATP1A1, BRIP1, FANCA, FGFR3, FLT3, HOXD11, MUTYH, PDGFRA, SMARCA4, and TCF3. The germline variant profile provides a new insight to clarify the genetic etiology and heterogeneity of PC among Japanese men.
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Touati, Arabella; Sperandio, Clément; Hénin, Nadège; Laurier-Nadalié, Cécile; Bébéar, Cécile; de Barbeyrac, Bertille
2016-01-01
We describe a change in the molecular epidemiology of Chlamydia trachomatis strains involved in an outbreak of rectal lymphogranuloma venereum in France during January 2010–April 2015. Until 2012, the C. trachomatis L2b strain predominated; however, starting in 2013, most cases involved the L2 strain. We also identified 4 genetic L2b ompA variants. PMID:27767927
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Myocardial strains from 3D displacement encoded magnetic resonance imaging
Directory of Open Access Journals (Sweden)
Kindberg Katarina
2012-04-01
Full Text Available Abstract Background The ability to measure and quantify myocardial motion and deformation provides a useful tool to assist in the diagnosis, prognosis and management of heart disease. The recent development of magnetic resonance imaging methods, such as harmonic phase analysis of tagging and displacement encoding with stimulated echoes (DENSE, make detailed non-invasive 3D kinematic analyses of human myocardium possible in the clinic and for research purposes. A robust analysis method is required, however. Methods We propose to estimate strain using a polynomial function which produces local models of the displacement field obtained with DENSE. Given a specific polynomial order, the model is obtained as the least squares fit of the acquired displacement field. These local models are subsequently used to produce estimates of the full strain tensor. Results The proposed method is evaluated on a numerical phantom as well as in vivo on a healthy human heart. The evaluation showed that the proposed method produced accurate results and showed low sensitivity to noise in the numerical phantom. The method was also demonstrated in vivo by assessment of the full strain tensor and to resolve transmural strain variations. Conclusions Strain estimation within a 3D myocardial volume based on polynomial functions yields accurate and robust results when validated on an analytical model. The polynomial field is capable of resolving the measured material positions from the in vivo data, and the obtained in vivo strains values agree with previously reported myocardial strains in normal human hearts.
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Studies on emerging radiation leukemia virus variants in C57BL/Ka mice
International Nuclear Information System (INIS)
Rassart, E.; Shang, M.; Boie, Y.; Jolicoeur, P.
1986-01-01
To analyze the emergence of radiation leukemia virus (RadLV) variants in primary X-ray-induced C57BL/Ka thymoma and to identify the virus responsible for the very high leukemogenic potential of passaged Kaplan strain BL/VL3 preparation, we cloned several primary and passaged ecotropic RadLV infectious genomes. By restriction analysis, we found that BL/VL3 cells harbor three related but different ecotropic RadLVs. Their restriction map differs significantly from those of primary RadLVs. Hybridization analysis also indicated that BL/VL3 and primary RadLVs differ in their p15E and long terminal repeat (LTR) regions. The LTR sequence of primary weakly leukemogenic RadLV has only one change, a C-rich sequence, generating a 6-base-pair direct repeat just in front of the promotor. The LTR of the primary nonleukemogenic RadLV only showed few base changes, mainly clustered in R and U5. The LTR from a moderately leukemogenic passaged BL/VL3 RadLV had conserved the C-rich sequence and acquired a 43-base-pair direct repeat in U3 and several other point mutations, small insertions, and deletions scattered in U3, R, and U5. All cloned primary RadLVs were fibrotropic, and some were weakly leukemogenic. All cloned BL/VL3 RadLVs were thymotropic and nonfibrotropic. The block of their replication was found to be after the synthesis of unintegrated linear and supercoiled viral DNA. Most of the BL/VL3 RadLVs were moderately leukemogenic, and one (V-13) was highly leukemogenic, being as virulent as the Moloney strain. We propose a model for the emergence of the RadLV variants and show that the virus responsible for the high leukemogenic potential of BL/VL3 preparation is a nondefective, ecotropic, lymphotropic, nonfibrotropic, unique retrovirus which most likely arose from a parental primary RadLV similar to those studied here
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Analysis of critical current-bend strain relationships in composite Nb3Sn superconducting wires
International Nuclear Information System (INIS)
Luhman, T.; Welch, D.O.
1979-01-01
In order to be used successfully in fusion magnets, Nb 3 Sn conductors must meet several mechanical strain criteria, including tolerance to bending strains encountered during magnet construction. Since Nb 3 Sn is extremely brittle much information has been generated regarding the sensitivity of these conductros to tensile strain. A recent comparison of critical current-bend and tensile test data indicates that the strain required to initiate compound cracking during bending is significantly less than the strain required to do so by tensile of critical current on bending strains in monofilamentary Nb 3 Sn wires is calculated and compared with experimental data. The calculation takes into account a shift in the composite's neutral axis which occurs during bending. The analysis correctly predicts the observed depdndence of the critical current on bending strains
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Sawada, Akihisa; Croom-Carter, Deborah; Kondo, Osamu; Yasui, Masahiro; Koyama-Sato, Maho; Inoue, Masami; Kawa, Keisei; Rickinson, Alan B; Tierney, Rosemary J
2011-05-01
Polymorphisms in Epstein-Barr virus (EBV) latent genes can identify virus strains from different human populations and individual strains within a population. An Asian EBV signature has been defined almost exclusively from Chinese viruses, with little information from other Asian countries. Here we sequenced polymorphic regions of the EBNA1, 2, 3A, 3B, 3C and LMP1 genes of 31 Japanese strains from control donors and EBV-associated T/NK-cell lymphoproliferative disease (T/NK-LPD) patients. Though identical to Chinese strains in their dominant EBNA1 and LMP1 alleles, Japanese viruses were subtly different at other loci. Thus, while Chinese viruses mainly fall into two families with strongly linked 'Wu' or 'Li' alleles at EBNA2 and EBNA3A/B/C, Japanese viruses all have the consensus Wu EBNA2 allele but fall into two families at EBNA3A/B/C. One family has variant Li-like sequences at EBNA3A and 3B and the consensus Li sequence at EBNA3C; the other family has variant Wu-like sequences at EBNA3A, variants of a low frequency Chinese allele 'Sp' at EBNA3B and a consensus Sp sequence at EBNA3C. Thus, EBNA3A/B/C allelotypes clearly distinguish Japanese from Chinese strains. Interestingly, most Japanese viruses also lack those immune-escape mutations in the HLA-A11 epitope-encoding region of EBNA3B that are so characteristic of viruses from the highly A11-positive Chinese population. Control donor-derived and T/NK-LPD-derived strains were similarly distributed across allelotypes and, by using allelic polymorphisms to track virus strains in patients pre- and post-haematopoietic stem-cell transplant, we show that a single strain can induce both T/NK-LPD and B-cell-lymphoproliferative disease in the same patient.
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Hou, Minbo; Zhou, Defang; Li, Gen; Guo, Huijun; Liu, Jianzhu; Wang, Guihua; Zheng, Qiankun; Cheng, Ziqiang
2016-03-08
Avian leukosis virus subgroup J (ALV-J) is a hypervariable oncogenic retrovirus that causes great economic loss in poultry. Antigenic variations in the variable regions make the development of an effective vaccine a challenging task. In the present study, we identified a variant antigenic neutralizing epitope using reverse vaccinology methods. First, we predicted the B-cell epitopes in gp85 gene of ALV-J strains by DNAman and bioinformatics. Fourteen candidate epitopes were selected and linked in tandem with glycines or serines as a multi-epitope gene. The expressed protein of multi-epitope gene can induce high-titer antibody that can recognize nature ALV-J and neutralize the infectivity of ALV-J strains. Next, we identified a high effective epitope using eight overlapping fragments of gp85 gene reacting with mAb 2D5 and anti-multi-epitope sera. The identified epitope contained one of the predicted epitopes and localized in hyervariable region 1 (hr1), indicating a variant epitope. To better understand if the variants of the epitope have a good antigenicity, we synthesized four variants to react with mAb 2D5 and anti-ALV-J sera. The result showed that all variants could react with the two kinds of antibodies though they showed different antigenicity, while could not react with ALV-J negative sera. Thus, the variant antigenic neutralizing epitope was determined as 137-LRDFIA/E/TKWKS/GDDL/HLIRPYVNQS-158. The result shows a potential use of this variant epitopes as a novel multi-epitope vaccine against ALV-J in poultry. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Strain-Induced Ferromagnetism in Antiferromagnetic LuMnO3 Thin Films
White, J. S.; Bator, M.; Hu, Y.; Luetkens, H.; Stahn, J.; Capelli, S.; Das, S.; Döbeli, M.; Lippert, Th.; Malik, V. K.; Martynczuk, J.; Wokaun, A.; Kenzelmann, M.; Niedermayer, Ch.; Schneider, C. W.
2013-07-01
Single phase and strained LuMnO3 thin films are discovered to display coexisting ferromagnetic and antiferromagnetic orders. A large moment ferromagnetism (≈1μB), which is absent in bulk samples, is shown to display a magnetic moment distribution that is peaked at the highly strained substrate-film interface. We further show that the strain-induced ferromagnetism and the antiferromagnetic order are coupled via an exchange field, therefore demonstrating strained rare-earth manganite thin films as promising candidate systems for new multifunctional devices.
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[3H] Thymidine incorporation to estimate growth rates of anaerobic bacterial strains
International Nuclear Information System (INIS)
Winding, A.
1992-01-01
The incorporation of [ 3 H] thymidine by axenic cultures of anaerobic bacteria was investigated as a means to measure growth. The three fermentative strains and one of the methanogenic strains tested incorporated [ 3 H] thymidine during growth. It is concluded that the [ 3 H] thymidine incorporation method underestimates bacterial growth in anaerobic environments
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Directory of Open Access Journals (Sweden)
Kariuki S. Muiruri
2017-06-01
Full Text Available Centromeres are specified by a centromere specific histone 3 (CENH3 protein, which exists in a complex environment, interacting with conserved proteins and rapidly evolving satellite DNA sequences. The interactions may become more challenging if multiple CENH3 versions are introduced into the zygote as this can affect post-zygotic mitosis and ultimately sexual reproduction. Here, we characterize CENH3 variant transcripts expressed in cultivated triploid and wild diploid progenitor bananas. We describe both splice- and allelic-[Single Nucleotide Polymorphisms (SNP] variants and their effects on the predicted secondary structures of protein. Expressed CENH3 transcripts from six banana genotypes were characterized and clustered into three groups (MusaCENH-1A, MusaCENH-1B, and MusaCENH-2 based on similarity. The CENH3 groups differed with SNPs as well as presence of indels resulting from retained and/or skipped exons. The CENH3 transcripts from different banana genotypes were spliced in either 7/6, 5/4 or 6/5 exons/introns. The 7/6 and the 5/4 exon/intron structures were found in both diploids and triploids, however, 7/6 was most predominant. The 6/5 exon/introns structure was a result of failure of the 7/6 to splice correctly. The various transcripts obtained were predicted to encode highly variable N-terminal tails and a relatively conserved C-terminal histone fold domain (HFD. The SNPs were predicted in some cases to affect the secondary structure of protein by lengthening or shorting the affected domains. Sequencing of banana CENH3 transcripts predicts SNP variations that affect amino acid sequences and alternatively spliced transcripts. Most of these changes affect the N-terminal tail of CENH3.
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Dumas, Pascaline; Legeai, Fabrice; Lemaitre, Claire; Scaon, Erwan; Orsucci, Marion; Labadie, Karine; Gimenez, Sylvie; Clamens, Anne-Laure; Henri, Hélène; Vavre, Fabrice; Aury, Jean-Marc; Fournier, Philippe; Kergoat, Gael J; d'Alençon, Emmanuelle
2015-06-01
The moth Spodoptera frugiperda is a well-known pest of crops throughout the Americas, which consists of two strains adapted to different host-plants: the first feeds preferentially on corn, cotton and sorghum whereas the second is more associated with rice and several pasture grasses. Though morphologically indistinguishable, they exhibit differences in their mating behavior, pheromone compositions, and show development variability according to the host-plant. Though the latter suggest that both strains are different species, this issue is still highly controversial because hybrids naturally occur in the wild, not to mention the discrepancies among published results concerning mating success between the two strains. In order to clarify the status of the two host-plant strains of S. frugiperda, we analyze features that possibly reflect the level of post-zygotic isolation: (1) first generation (F1) hybrid lethality and sterility; (2) patterns of meiotic segregation of hybrids in reciprocal second generation (F2), as compared to the meiosis of the two parental strains. We found a significant reduction of mating success in F1 in one direction of the cross and a high level of microsatellite markers showing transmission ratio distortion in the F2 progeny. Our results support the existence of post-zygotic reproductive isolation between the two laboratory strains and are in accordance with the marked level of genetic differentiation that was recovered between individuals of the two strains collected from the field. Altogether these results provide additional evidence in favor of a sibling species status for the two strains.
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DEFF Research Database (Denmark)
Tesli, Martin; Koefoed, Pernille; Athanasiu, Lavinia
2011-01-01
Genetic variants in ankyrin 3 (ANK3) have recently been shown to be associated with bipolar disorder (BD). We genotyped three ANK3 SNPs previously found to be associated with BD (rs10994336, rs1938526, and rs9804190) in a Scandinavian BD case–control sample (N¿=¿854/2,614). Due to evidence...
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Sims, Rebecca; van der Lee, Sven J; Naj, Adam C; Bellenguez, Céline; Badarinarayan, Nandini; Jakobsdottir, Johanna; Kunkle, Brian W; Boland, Anne; Raybould, Rachel; Bis, Joshua C; Martin, Eden R; Grenier-Boley, Benjamin; Heilmann-Heimbach, Stefanie; Chouraki, Vincent; Kuzma, Amanda B; Sleegers, Kristel; Vronskaya, Maria; Ruiz, Agustin; Graham, Robert R; Olaso, Robert; Hoffmann, Per; Grove, Megan L; Vardarajan, Badri N; Hiltunen, Mikko; Nöthen, Markus M; White, Charles C; Hamilton-Nelson, Kara L; Epelbaum, Jacques; Maier, Wolfgang; Choi, Seung-Hoan; Beecham, Gary W; Dulary, Cécile; Herms, Stefan; Smith, Albert V; Funk, Cory C; Derbois, Céline; Forstner, Andreas J; Ahmad, Shahzad; Li, Hongdong; Bacq, Delphine; Harold, Denise; Satizabal, Claudia L; Valladares, Otto; Squassina, Alessio; Thomas, Rhodri; Brody, Jennifer A; Qu, Liming; Sánchez-Juan, Pascual; Morgan, Taniesha; Wolters, Frank J; Zhao, Yi; Garcia, Florentino Sanchez; Denning, Nicola; Fornage, Myriam; Malamon, John; Naranjo, Maria Candida Deniz; Majounie, Elisa; Mosley, Thomas H; Dombroski, Beth; Wallon, David; Lupton, Michelle K; Dupuis, Josée; Whitehead, Patrice; Fratiglioni, Laura; Medway, Christopher; Jian, Xueqiu; Mukherjee, Shubhabrata; Keller, Lina; Brown, Kristelle; Lin, Honghuang; Cantwell, Laura B; Panza, Francesco; McGuinness, Bernadette; Moreno-Grau, Sonia; Burgess, Jeremy D; Solfrizzi, Vincenzo; Proitsi, Petra; Adams, Hieab H; Allen, Mariet; Seripa, Davide; Pastor, Pau; Cupples, L Adrienne; Price, Nathan D; Hannequin, Didier; Frank-García, Ana; Levy, Daniel; Chakrabarty, Paramita; Caffarra, Paolo; Giegling, Ina; Beiser, Alexa S; Giedraitis, Vilmantas; Hampel, Harald; Garcia, Melissa E; Wang, Xue; Lannfelt, Lars; Mecocci, Patrizia; Eiriksdottir, Gudny; Crane, Paul K; Pasquier, Florence; Boccardi, Virginia; Henández, Isabel; Barber, Robert C; Scherer, Martin; Tarraga, Lluis; Adams, Perrie M; Leber, Markus; Chen, Yuning; Albert, Marilyn S; Riedel-Heller, Steffi; Emilsson, Valur; Beekly, Duane; Braae, Anne; Schmidt, Reinhold; Blacker, Deborah; Masullo, Carlo; Schmidt, Helena; Doody, Rachelle S; Spalletta, Gianfranco; Longstreth, W T; Fairchild, Thomas J; Bossù, Paola; Lopez, Oscar L; Frosch, Matthew P; Sacchinelli, Eleonora; Ghetti, Bernardino; Yang, Qiong; Huebinger, Ryan M; Jessen, Frank; Li, Shuo; Kamboh, M Ilyas; Morris, John; Sotolongo-Grau, Oscar; Katz, Mindy J; Corcoran, Chris; Dunstan, Melanie; Braddel, Amy; Thomas, Charlene; Meggy, Alun; Marshall, Rachel; Gerrish, Amy; Chapman, Jade; Aguilar, Miquel; Taylor, Sarah; Hill, Matt; Fairén, Mònica Díez; Hodges, Angela; Vellas, Bruno; Soininen, Hilkka; Kloszewska, Iwona; Daniilidou, Makrina; Uphill, James; Patel, Yogen; Hughes, Joseph T; Lord, Jenny; Turton, James; Hartmann, Annette M; Cecchetti, Roberta; Fenoglio, Chiara; Serpente, Maria; Arcaro, Marina; Caltagirone, Carlo; Orfei, Maria Donata; Ciaramella, Antonio; Pichler, Sabrina; Mayhaus, Manuel; Gu, Wei; Lleó, Alberto; Fortea, Juan; Blesa, Rafael; Barber, Imelda S; Brookes, Keeley; Cupidi, Chiara; Maletta, Raffaele Giovanni; Carrell, David; Sorbi, Sandro; Moebus, Susanne; Urbano, Maria; Pilotto, Alberto; Kornhuber, Johannes; Bosco, Paolo; Todd, Stephen; Craig, David; Johnston, Janet; Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn; Fox, Nick C; Hardy, John; Albin, Roger L; Apostolova, Liana G; Arnold, Steven E; Asthana, Sanjay; Atwood, Craig S; Baldwin, Clinton T; Barnes, Lisa L; Barral, Sandra; Beach, Thomas G; Becker, James T; Bigio, Eileen H; Bird, Thomas D; Boeve, Bradley F; Bowen, James D; Boxer, Adam; Burke, James R; Burns, Jeffrey M; Buxbaum, Joseph D; Cairns, Nigel J; Cao, Chuanhai; Carlson, Chris S; Carlsson, Cynthia M; Carney, Regina M; Carrasquillo, Minerva M; Carroll, Steven L; Diaz, Carolina Ceballos; Chui, Helena C; Clark, David G; Cribbs, David H; Crocco, Elizabeth A; DeCarli, Charles; Dick, Malcolm; Duara, Ranjan; Evans, Denis A; Faber, Kelley M; Fallon, Kenneth B; Fardo, David W; Farlow, Martin R; Ferris, Steven; Foroud, Tatiana M; Galasko, Douglas R; Gearing, Marla; Geschwind, Daniel H; Gilbert, John R; Graff-Radford, Neill R; Green, Robert C; Growdon, John H; Hamilton, Ronald L; Harrell, Lindy E; Honig, Lawrence S; Huentelman, Matthew J; Hulette, Christine M; Hyman, Bradley T; Jarvik, Gail P; Abner, Erin; Jin, Lee-Way; Jun, Gyungah; Karydas, Anna; Kaye, Jeffrey A; Kim, Ronald; Kowall, Neil W; Kramer, Joel H; LaFerla, Frank M; Lah, James J; Leverenz, James B; Levey, Allan I; Li, Ge; Lieberman, Andrew P; Lunetta, Kathryn L; Lyketsos, Constantine G; Marson, Daniel C; Martiniuk, Frank; Mash, Deborah C; Masliah, Eliezer; McCormick, Wayne C; McCurry, Susan M; McDavid, Andrew N; McKee, Ann C; Mesulam, Marsel; Miller, Bruce L; Miller, Carol A; Miller, Joshua W; Morris, John C; Murrell, Jill R; Myers, Amanda J; O'Bryant, Sid; Olichney, John M; Pankratz, Vernon S; Parisi, Joseph E; Paulson, Henry L; Perry, William; Peskind, Elaine; Pierce, Aimee; Poon, Wayne W; Potter, Huntington; Quinn, Joseph F; Raj, Ashok; Raskind, Murray; Reisberg, Barry; Reitz, Christiane; Ringman, John M; Roberson, Erik D; Rogaeva, Ekaterina; Rosen, Howard J; Rosenberg, Roger N; Sager, Mark A; Saykin, Andrew J; Schneider, Julie A; Schneider, Lon S; Seeley, William W; Smith, Amanda G; Sonnen, Joshua A; Spina, Salvatore; Stern, Robert A; Swerdlow, Russell H; Tanzi, Rudolph E; Thornton-Wells, Tricia A; Trojanowski, John Q; Troncoso, Juan C; Van Deerlin, Vivianna M; Van Eldik, Linda J; Vinters, Harry V; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A; Wilhelmsen, Kirk C; Williamson, Jennifer; Wingo, Thomas S; Woltjer, Randall L; Wright, Clinton B; Yu, Chang-En; Yu, Lei; Garzia, Fabienne; Golamaully, Feroze; Septier, Gislain; Engelborghs, Sebastien; Vandenberghe, Rik; De Deyn, Peter P; Fernadez, Carmen Muñoz; Benito, Yoland Aladro; Thonberg, Hakan; Forsell, Charlotte; Lilius, Lena; Kinhult-Stählbom, Anne; Kilander, Lena; Brundin, RoseMarie; Concari, Letizia; Helisalmi, Seppo; Koivisto, Anne Maria; Haapasalo, Annakaisa; Dermecourt, Vincent; Fievet, Nathalie; Hanon, Olivier; Dufouil, Carole; Brice, Alexis; Ritchie, Karen; Dubois, Bruno; Himali, Jayanadra J; Keene, C Dirk; Tschanz, JoAnn; Fitzpatrick, Annette L; Kukull, Walter A; Norton, Maria; Aspelund, Thor; Larson, Eric B; Munger, Ron; Rotter, Jerome I; Lipton, Richard B; Bullido, María J; Hofman, Albert; Montine, Thomas J; Coto, Eliecer; Boerwinkle, Eric; Petersen, Ronald C; Alvarez, Victoria; Rivadeneira, Fernando; Reiman, Eric M; Gallo, Maura; O'Donnell, Christopher J; Reisch, Joan S; Bruni, Amalia Cecilia; Royall, Donald R; Dichgans, Martin; Sano, Mary; Galimberti, Daniela; St George-Hyslop, Peter; Scarpini, Elio; Tsuang, Debby W; Mancuso, Michelangelo; Bonuccelli, Ubaldo; Winslow, Ashley R; Daniele, Antonio; Wu, Chuang-Kuo; Peters, Oliver; Nacmias, Benedetta; Riemenschneider, Matthias; Heun, Reinhard; Brayne, Carol; Rubinsztein, David C; Bras, Jose; Guerreiro, Rita; Al-Chalabi, Ammar; Shaw, Christopher E; Collinge, John; Mann, David; Tsolaki, Magda; Clarimón, Jordi; Sussams, Rebecca; Lovestone, Simon; O'Donovan, Michael C; Owen, Michael J; Behrens, Timothy W; Mead, Simon; Goate, Alison M; Uitterlinden, Andre G; Holmes, Clive; Cruchaga, Carlos; Ingelsson, Martin; Bennett, David A; Powell, John; Golde, Todd E; Graff, Caroline; De Jager, Philip L; Morgan, Kevin; Ertekin-Taner, Nilufer; Combarros, Onofre; Psaty, Bruce M; Passmore, Peter; Younkin, Steven G; Berr, Claudine; Gudnason, Vilmundur; Rujescu, Dan; Dickson, Dennis W; Dartigues, Jean-François; DeStefano, Anita L; Ortega-Cubero, Sara; Hakonarson, Hakon; Campion, Dominique; Boada, Merce; Kauwe, John Keoni; Farrer, Lindsay A; Van Broeckhoven, Christine; Ikram, M Arfan; Jones, Lesley; Haines, Jonathan L; Tzourio, Christophe; Launer, Lenore J; Escott-Price, Valentina; Mayeux, Richard; Deleuze, Jean-François; Amin, Najaf; Holmans, Peter A; Pericak-Vance, Margaret A; Amouyel, Philippe; van Duijn, Cornelia M; Ramirez, Alfredo; Wang, Li-San; Lambert, Jean-Charles; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D
2017-09-01
We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10 -4 ) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10 -8 ) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10 -10 , odds ratio (OR) = 0.68, minor allele frequency (MAF) cases = 0.0059, MAF controls = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10 -10 , OR = 1.43, MAF cases = 0.011, MAF controls = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10 -14 , OR = 1.67, MAF cases = 0.0143, MAF controls = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
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Dynamic scattering theory for dark-field electron holography of 3D strain fields
International Nuclear Information System (INIS)
Lubk, Axel; Javon, Elsa; Cherkashin, Nikolay; Reboh, Shay; Gatel, Christophe; Hÿtch, Martin
2014-01-01
Dark-field electron holography maps strain in crystal lattices into reconstructed phases over large fields of view. Here we investigate the details of the lattice strain–reconstructed phase relationship by applying dynamic scattering theory both analytically and numerically. We develop efficient analytic linear projection rules for 3D strain fields, facilitating a straight-forward calculation of reconstructed phases from 3D strained materials. They are used in the following to quantify the influence of various experimental parameters like strain magnitude, specimen thickness, excitation error and surface relaxation. - Author-Highlights: • We derive a simple dynamic scattering formalism for dark field electron holography based on a perturbative two-beam theory. • The formalism facilitates the projection of 3D strain fields by a simple weighting integral. • The weighted projection depends analytically on the diffraction order, the excitation error and the specimen thickness. • The weighting integral formalism represents an important prerequisite towards the development of tomographic strain reconstruction techniques
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International Nuclear Information System (INIS)
Tsuyama, Naohiro; Danjoh, Inaho; Otsuyama, Ken-ichiro; Obata, Masanori; Tahara, Hidetoshi; Ohta, Tsutomu; Ishikawa, Hideaki
2005-01-01
IL-6 is a growth and survival factor for myeloma cells, although the mechanism by which it induces myeloma cell proliferation through gene expression is largely unknown. Microarray analysis showed that some B-cell lymphoma-associated oncogenes such as Bcl6, which is absent in normal plasma cells, were upregulated by IL-6 in IL-6-dependent myeloma cell lines. We found that Bcl6 variant 2 was upregulated by STAT3. ChIP assay and EMSA showed that STAT3 bound to the upstream region of variant 2 DNA. Expression of p53, a direct target gene of Bcl6, was downregulated in the IL-6-stimulated cells, and this process was impaired by an HDAC inhibitor. Bcl6 was knocked down by introducing small hairpin RNA, resulting in decreased proliferation and increased sensitivity to a DNA damaging agent. Thus, STAT3-inducible Bcl6 variant 2 appears to generate an important IL-6 signal that supports proliferation and survival of IL-6-dependent myeloma cells
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International Nuclear Information System (INIS)
Manab Sarma, P.; Bhattacharya, D.; Krishnan, S.; Lal, B.
2004-01-01
Intra-species diversity among Acinetobacter baumannii strains isolated from crude oil-contaminated soils from different geographic regions in India was assessed, including their capability to degrade different fractions of total petroleum hydrocarbons. A total of 96 strains were isolated from five different sites. Of the 96 isolates, 25 strains were identified as Acinetobacter baumannii; all of these strains were biochemically profiled and grouped into eight phenovars on the basis of multivariate analysis of their substrate utilization profiles. All strains were able to degrade the total petroleum hydrocarbon fractions of crude oil. Intraspecies relatedness among the 25 strains was determined using tRNA intergenic spacer length polymorphism. Specific variants among the strains with different degradation capacities for different fractions of crude oil were detected. Environmental influences that cause intra-species diversity, such as functional resilience, within the selected strains of A. baumannii were also noted. It is suggested that such diversities may make it possible to select contaminant-specific strains for efficient biotechnological strategies in environmental remediation. 19 refs., 4 tabs., 3 figs
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Energy Technology Data Exchange (ETDEWEB)
Manab Sarma, P.; Bhattacharya, D.; Krishnan, S. [TERI School of Advanced Studies, Center of Bioresources and Biotechnology, New Delhi (India); Lal, B. [TERI School of Advanced Studies, Microbial Biotechnology Division, New Delhi (India)
2004-06-01
Intra-species diversity among Acinetobacter baumannii strains isolated from crude oil-contaminated soils from different geographic regions in India was assessed, including their capability to degrade different fractions of total petroleum hydrocarbons. A total of 96 strains were isolated from five different sites. Of the 96 isolates, 25 strains were identified as Acinetobacter baumannii; all of these strains were biochemically profiled and grouped into eight phenovars on the basis of multivariate analysis of their substrate utilization profiles. All strains were able to degrade the total petroleum hydrocarbon fractions of crude oil. Intraspecies relatedness among the 25 strains was determined using tRNA intergenic spacer length polymorphism. Specific variants among the strains with different degradation capacities for different fractions of crude oil were detected. Environmental influences that cause intra-species diversity, such as functional resilience, within the selected strains of A. baumannii were also noted. It is suggested that such diversities may make it possible to select contaminant-specific strains for efficient biotechnological strategies in environmental remediation. 19 refs., 4 tabs., 3 figs.
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Directory of Open Access Journals (Sweden)
Silvia N. Kariuki
2010-01-01
Full Text Available The PIK3C3 locus was implicated in case-case genome-wide association study of systemic lupus erythematosus (SLE which we had performed to detect genes associated with autoantibodies and serum interferon-alpha (IFN-α. Herein, we examine a PIK3C3 promoter variant (rs3813065/-442 C/T in an independent multiancestral cohort of 478 SLE cases and 522 controls. rs3813065 C was strongly associated with the simultaneous presence of both anti-Ro and anti-Sm antibodies in African-American patients [OR=2.24 (1.34–3.73, P=2.0×10−3]. This autoantibody profile was associated with higher serum IFN-α (P=7.6×10−6. In the HapMap Yoruba population, rs3813065 was associated with differential expression of ERAP2 (P=2.0×10−5, which encodes an enzyme involved in MHC class I peptide processing. Thus, rs3813065 C is associated with a particular autoantibody profile and altered expression of an MHC peptide processing enzyme, suggesting that this variant modulates serologic autoimmunity in African-American SLE patients.
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Directory of Open Access Journals (Sweden)
Emma L Bradford
Full Text Available European honey bees (Apis mellifera are critically important to global food production by virtue of their pollination services but are severely threatened by deformed wing virus (DWV especially in the presence of the external parasite Varroa destructor. DWV exists as many viral strains with the two major variants (DWV-A and DWV-B varying in virulence. A single plasmid standard was constructed containing three sections for the specific determination of DWV-A (VP2 capsid region, DWV-B (IRES and a conserved region suitable for total DWV (helicase region. The assays were confirmed as specific and discriminatory with limits of detections of 25, 25 and 50 genome equivalents for DWV-A, DWV-B and total-DWV, respectively. The methods were successfully tested on Apis mellifera and V. destructor samples with varying DWV profiles. The new method determined a more accurate total DWV titre in samples with substantial DWV-B than the method currently described in the COLOSS Beebook. The proposed assays could be utilized for the screening of large quantities of bee material for both a total DWV load overview along with more detailed investigations into DWV-A and DWV-B profiles.
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Yan, Yu; He, Jianzhong
2017-08-01
Conversion of lignocellulosic hydrolysate to biofuels is impeded by the toxic effects of inhibitors that are generated during pretreatment and hydrolysis processes. Here we describe a wild-type Clostridium sp. strain BOH3 with high tolerance to the lignocellulose-derived inhibitors and its capability to transform these inhibitors. Strain BOH3 is capable of tolerating over 60 mM furfural, 60 mM hydroxymethylfurfural, and 6.6 mM vanillin, respectively, and is able to convert 53.74 ± 0.37 mM furfural into furfuryl alcohol within 90 h. The high furfural tolerance and its biotransformation by strain BOH3, which is correlated to the high transcription levels of two short-chain dehydrogenase/reductases, enable strain BOH3 to produce 5.15 ± 0.52 g/L butanol from dilute sulfuric acid pretreated horticultural waste hydrolysate (HWH) that bypassed the detoxification step. The capability of strain BOH3 to produce butanol from un-detoxified HWH lays the foundation of cost-effective biofuel production from lignocellulosic materials.
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Degradation mechanism of Nb3Sn composite wires under tensile strain at 4.2 K
International Nuclear Information System (INIS)
Luhman, T.; Suenaga, M.; Welch, D.O.; Kaiho, K.
1978-01-01
Bronze-processed Nb 3 Sn composite wire conductors exhibit changes in their superconducting parameters when strained in tension. This paper describes a detailed study of the effect of strain on critical current and an analysis by optical and SEM techniques of crack formation in the Nb 3 Sn layer under strain. The effect of strain history on both reversible and irreversible changes in critical current and the roles of differential thermal contraction induced residual strains and of Nb 3 Sn cracking are discussed
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Directory of Open Access Journals (Sweden)
Timothy Read
2016-01-01
Full Text Available Most genetic variants associated with disease occur within regulatory regions of the genome, underscoring the importance of defining the mechanisms underlying differences in regulation of gene expression between individuals. We discovered a pair of co-regulated, divergently oriented transcripts, AQY2 and ncFRE6, that are expressed in one strain of Saccharomyces cerevisiae, ∑1278b, but not in another, S288c. By combining classical genetics techniques with high-throughput sequencing, we identified a trans-acting single nucleotide polymorphism within the transcription factor RIM101 that causes the background-dependent expression of both transcripts. Subsequent RNA-seq experiments revealed that RIM101 regulates many more targets in S288c than in ∑1278b and that deletion of RIM101 in both backgrounds abrogates the majority of differential expression between the strains. Strikingly, only three transcripts undergo a significant change in expression after swapping RIM101 alleles between backgrounds, implying that the differences in the RIM101 allele lead to a remarkably focused transcriptional response. However, hundreds of RIM101-dependent targets undergo a subtle but consistent shift in expression in the S288c RIM101-swapped strain, but not its ∑1278b counterpart. We conclude that ∑1278b may harbor a variant(s that buffers against widespread transcriptional dysregulation upon introduction of a non-native RIM101 allele, emphasizing the importance of accounting for genetic background when assessing the impact of a regulatory variant.
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Directory of Open Access Journals (Sweden)
Tanya Bardakjian
2017-09-01
Conclusions and importance: Although transfection studies with the p.Arg266Cys mutation have shown that this amino acid substitution is likely to impair function, non-penetrance for the ocular defects was apparent in this family and has been observed in other families with sequence variants in GDF3. We conclude p.Arg266Cys and other GDF3 mutations can be non-penetrant, making pathogenicity more difficult to establish when sequence variants in this gene are present in patients with structural eye defects.
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Magnetic engineering in 3d transition metals on phosphorene by strain
International Nuclear Information System (INIS)
Cai, Xiaolin; Niu, Chunyao; Wang, Jianjun; Yu, Weiyang; Ren, XiaoYan; Zhu, Zhili
2017-01-01
Using first-principles density functional theory (DFT) calculations, we systematically investigate the strain effects on the adsorption energies, magnetic ordering and electronic properties of 3d transition metal (TM) atoms (from Sc to Co) adsorbed on phosphorene (P). We find that the adsorption energy of TM can be enhanced by compressive strain whereas weakened by tensile strain. Our results show that strain plays a decisive role in the magnetic moments as well as the magnetic coupling states of TM adatoms. Importantly, the transitions from antiferromagnetic (AFM) state to ferromagnetic (FM) state or to another different AFM ordering can be induced by strain effect. In addition, we observe the semiconductor to metal or half-metal transitions in some TM@P systems by applying strain. Our findings shed a new light on precisely engineering the magnetic properties and electronic properties of the TM@P systems, which will have great potential applications in spin electronics and other related fields. - Highlights: • The adsorption of TM atoms on phosphorene can be enhanced by compressive strain whereas weakened by tensile strain. • Strain plays a decisive role in the magnetic moments as well as the magnetic coupling states of TM adatoms. • Applying strain can induce the semiconductor to metal or half-metal transitions in some TM@P systems.
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Magnetic engineering in 3d transition metals on phosphorene by strain
Energy Technology Data Exchange (ETDEWEB)
Cai, Xiaolin [International Laboratory for Quantum Functional Materials of Henan and School of Physics and Engineering, Zhengzhou University, Zhengzhou, 450001 (China); School of Physics and Electronic Information Engineering, Henan Polytechnic University, Jiaozuo, 454000 (China); Niu, Chunyao, E-mail: niuchunyao@zzu.edu.cn [International Laboratory for Quantum Functional Materials of Henan and School of Physics and Engineering, Zhengzhou University, Zhengzhou, 450001 (China); Wang, Jianjun [College of Science, Zhongyuan University of Technology, Zhengzhou 450007 (China); Yu, Weiyang [International Laboratory for Quantum Functional Materials of Henan and School of Physics and Engineering, Zhengzhou University, Zhengzhou, 450001 (China); School of Physics and Electronic Information Engineering, Henan Polytechnic University, Jiaozuo, 454000 (China); Ren, XiaoYan; Zhu, Zhili [International Laboratory for Quantum Functional Materials of Henan and School of Physics and Engineering, Zhengzhou University, Zhengzhou, 450001 (China)
2017-04-11
Using first-principles density functional theory (DFT) calculations, we systematically investigate the strain effects on the adsorption energies, magnetic ordering and electronic properties of 3d transition metal (TM) atoms (from Sc to Co) adsorbed on phosphorene (P). We find that the adsorption energy of TM can be enhanced by compressive strain whereas weakened by tensile strain. Our results show that strain plays a decisive role in the magnetic moments as well as the magnetic coupling states of TM adatoms. Importantly, the transitions from antiferromagnetic (AFM) state to ferromagnetic (FM) state or to another different AFM ordering can be induced by strain effect. In addition, we observe the semiconductor to metal or half-metal transitions in some TM@P systems by applying strain. Our findings shed a new light on precisely engineering the magnetic properties and electronic properties of the TM@P systems, which will have great potential applications in spin electronics and other related fields. - Highlights: • The adsorption of TM atoms on phosphorene can be enhanced by compressive strain whereas weakened by tensile strain. • Strain plays a decisive role in the magnetic moments as well as the magnetic coupling states of TM adatoms. • Applying strain can induce the semiconductor to metal or half-metal transitions in some TM@P systems.
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Hamdani, Mehdi; Chassot, Olivier; Fournier, Roxane
2014-01-01
Automated bolus delivery has recently been shown to reduce local anesthetic consumption and improve analgesia, compared with continuous infusion, in continuous sciatic and epidural block. However, there are few data on the influence of local anesthetic delivery method on local anesthetic consumption following interscalene blockade. This randomized, double-blind trial was designed to determine whether hourly automated perineural boluses (4 mL) of local anesthesia delivered with patient-controlled pro re nata (PRN, on demand) boluses would result in a reduction in total local anesthesia consumption during continuous interscalene blockade after shoulder surgery compared with continuous perineural infusion (4 mL/h) plus patient-controlled PRN boluses. One hundred one patients undergoing major shoulder surgery under general anesthesia with ultrasound-guided continuous interscalene block were randomly assigned to receive 0.2% ropivacaine via interscalene end-hole catheter either by continuous infusion 4 mL/h (n = 50) or as automated bolus 4 mL/h (n = 51). Both delivery methods were combined with 5 mL PRN boluses of 0.2% ropivacaine with a lockout time of 30 minutes. Postoperative number of PRN boluses, 24- and 48-hour local anesthetic consumption, pain scores, rescue analgesia (morphine), and adverse events were recorded. There were no significant differences in either the number of PRN ropivacaine boluses or total 48 hour local anesthetic consumption between the groups (18.5 [11-25.2] PRN boluses in the continuous infusion group vs 17 [8.5-29] PRN boluses in the automated bolus group). Postoperative pain was similar in both groups; on day 2, the median average pain score was 4 (2-6) in the continuous infusion group versus 3 (2-5) in the automated bolus group (P = 0.54). Nor were any statistically significant intergroup differences observed with respect to morphine rescue, incidence of adverse events, or patient satisfaction. In continuous interscalene blockade under
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Directory of Open Access Journals (Sweden)
Anna Bachmann
Full Text Available Avoidance of antibody-mediated immune recognition allows parasites to establish chronic infections and enhances opportunities for transmission. The human malaria parasite Plasmodium falciparum possesses a number of multi-copy gene families, including var, rif, stevor and pfmc-2tm, which encode variant antigens believed to be expressed on the surfaces of infected erythrocytes. However, most studies of these antigens are based on in vitro analyses of culture-adapted isolates, most commonly the laboratory strain 3D7, and thus may not be representative of the unique challenges encountered by P. falciparum in the human host. To investigate the expression of the var, rif-A, rif-B, stevor and pfmc-2tm family genes under conditions that mimic more closely the natural course of infection, ex vivo clinical P. falciparum isolates were analyzed using a novel quantitative real-time PCR approach. Expression patterns in the clinical isolates at various time points during the first intraerythrocytic developmental cycle in vitro were compared to those of strain 3D7. In the clinical isolates, in contrast to strain 3D7, there was a peak of expression of the multi-copy gene families rif-A, stevor and pfmc-2tm at the young ring stage, in addition to the already known expression peak in trophozoites. Furthermore, most of the variant surface antigen families were overexpressed in the clinical isolates relative to 3D7, with the exception of the pfmc-2tm family, expression of which was higher in 3D7 parasites. Immunofluorescence analyses performed in parallel revealed two stage-dependent localization patterns of RIFIN, STEVOR and PfMC-2TM. Proteins were exported into the infected erythrocyte at the young trophozoite stage, whereas they remained inside the parasite membrane during schizont stage and were subsequently observed in different compartments in the merozoite. These results reveal a complex pattern of expression of P. falciparum multi-copy gene families during
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Directory of Open Access Journals (Sweden)
Long Zhou
2018-06-01
Full Text Available Recombination among porcine reproductive and respiratory syndrome viruses (PRRSVs is thought to contribute to the emergence of new PRRSV variants. In this study, two newly emerged PRRSV strains, designated SCcd16 and SCya17, are isolated from lung tissues of piglets in Southwestern China. Genome comparative analysis reveals that SCcd16/SCya17 exhibit 93.1%/93.2%, 86.9%/87.0%, 85.3%/85.7%, and 83.6%/82.0% nucleotide similarity to PRRSVs JXA1, VR-2332, QYYZ and NADC30, respectively. They only exhibit 44.8%/45.1% sequence identity with LV (PRRSV-1, indicating that both emergent strains belong to the PRRSV-2 genotype. Genomic sequence alignment shows that SCcd16 and SCya17 have the same discontinuous 30-amino acid (aa deletion in Nsp2 of the highly pathogenic Chinese PRRSV strain JXA1, when compared to strain VR-2332. Notably, SCya17 shows a unique 5-nt deletion in its 3’-UTR. Phylogenetic analysis shows that both of the isolates are classified in the QYYZ-like lineage based on ORF5 genotyping, whereas they appear to constitute an inter-lineage between JXA1-like and QYYZ-like lineages based on their genomic sequences. Furthermore, recombination analyses reveal that the two newly emerged PRRSV isolates share the same novel recombination pattern. They have both likely originated from multiple recombination events between lineage 8 (JXA1-like, lineage 1 (NADC30-like, and lineage 3 (QYYZ-like strains that have circulated in China recently. The genomic data from SCcd16 and SCya17 indicate that there is on going evolution of PRRSV field strains through genetic recombination, leading to outbreaks in the pig populations in Southwestern China.
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Helbig, K L; Mroske, C; Moorthy, D; Sajan, S A; Velinov, M
2017-10-01
DOCK3 encodes the dedicator of cytokinesis 3 protein, a member of the DOCK180 family of proteins that are characterized by guanine-nucleotide exchange factor activity. DOCK3 is expressed exclusively in the central nervous system and plays an important role in axonal outgrowth and cytoskeleton reorganization. Dock3 knockout mice exhibit motor deficiencies with abnormal ataxic gait and impaired learning. We report 2 siblings with biallelic loss-of-function variants in DOCK3. Diagnostic whole-exome sequencing (WES) and chromosomal microarray were performed on a proband with severe developmental disability, hypotonia, and ataxic gait. Testing was also performed on the proband's similarly affected brother. A paternally inherited 458 kb deletion in chromosomal region 3p21.2 disrupting the DOCK3 gene was identified in both affected siblings. WES identified a nonsense variant c.382C>G (p.Gln128*) in the DOCK3 gene (NM_004947) on the maternal allele in both siblings. Common features in both affected individuals include severe developmental disability, ataxic gait, and severe hypotonia, which recapitulates the Dock3 knockout mouse phenotype. We show that complete DOCK3 deficiency in humans leads to developmental disability with significant hypotonia and gait ataxia, probably due to abnormal axonal development. © 2017 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Krayter, Lena; Alam, Mohammad Zahangir; Rhajaoui, Mohamed; Schnur, Lionel F; Schönian, Gabriele
2014-12-01
In Morocco, cutaneous leishmaniasis (CL) caused by Leishmania (L.) tropica is a major public health threat. Strains of this species have been shown to display considerable serological, biochemical, molecular biological and genetic heterogeneity; and Multilocus Enzyme Electrophoresis (MLEE), has shown that in many countries including Morocco heterogenic variants of L. tropica can co-exist in single geographical foci. Here, the microsatellite profiles discerned by MLMT of nine Moroccan strains of L. tropica isolated in 2000 from human cases of CL from Chichaoua Province were compared to those of nine Moroccan strains of L. tropica isolated between 1988 and 1990 from human cases of CL from Marrakech Province, and also to those of 147 strains of L. tropica isolated at different times from different worldwide geographical locations within the range of distribution of the species. Several programs, each employing a different algorithm, were used for population genetic analysis. The strains from each of the two Moroccan foci separated into two phylogenetic clusters independent of their geographical origin. Genetic diversity and heterogeneity existed in both foci, which are geographically close to each other. This intra-focal distribution of genetic variants of L. tropica is not considered owing to in situ mutation. Rather, it is proposed to be explained by the importation of pre-existing variants of L. tropica into Morocco. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
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Directory of Open Access Journals (Sweden)
Soleimanifard Sahar
2012-12-01
Full Text Available Abstract Background Previous studies of mechanical strain anomalies in myocardial infarction (MI have been largely limited to analysis of one-dimensional (1D and two-dimensional (2D strain parameters. Advances in cardiovascular magnetic resonance (CMR methods now permit a complete three-dimensional (3D interrogation of myocardial regional strain. The aim of this study was to investigate the incremental value of CMR-based 3D strain and to test the hypothesis that 3D strain is superior to 1D or 2D strain analysis in the assessment of viability using a porcine model of infarction. Methods Infarction was induced surgically in 20 farm pigs. Cine, late gadolinium enhancement, and CMR tagging images were acquired at 11 days before (baseline, and 11 days (early and 1 month (late after induction of infarct. Harmonic phase analysis was performed to measure circumferential, longitudinal, and radial strains in myocardial segments, which were defined based on the transmurality of delayed enhancement. Univariate, bivariate, and multivariate logistic regression models of strain parameters were created and analyzed to compare the overall diagnostic accuracy of 3D strain analysis with 1D and 2D analyses in identifying the infarct and its adjacent regions from healthy myocardium. Results 3D strain differed significantly in infarct, adjacent, and remote segments (p Conclusions Cumulative 3D strain information accurately identifies infarcts and their neighboring regions from healthy myocardium. The 3D interrogation of myocardial contractility provides incremental diagnostic accuracy in delineating the dysfunctional and nonviable myocardium in comparison with 1D or 2D quantification of strain. The infarct neighboring regions are the major beneficiaries of the 3D assessment of regional strain.
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Accurate genotyping across variant classes and lengths using variant graphs
DEFF Research Database (Denmark)
Sibbesen, Jonas Andreas; Maretty, Lasse; Jensen, Jacob Malte
2018-01-01
of read k-mers to a graph representation of the reference and variants to efficiently perform unbiased, probabilistic genotyping across the variation spectrum. We demonstrate that BayesTyper generally provides superior variant sensitivity and genotyping accuracy relative to existing methods when used...... collecting a set of candidate variants across discovery methods, individuals and databases, and then realigning the reads to the variants and reference simultaneously. However, this realignment problem has proved computationally difficult. Here, we present a new method (BayesTyper) that uses exact alignment...... to integrate variants across discovery approaches and individuals. Finally, we demonstrate that including a ‘variation-prior’ database containing already known variants significantly improves sensitivity....
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Strain-induced large spin splitting and persistent spin helix at LaAlO$_3$/SrTiO$_3$ interface
Yamaguchi, Naoya; Ishii, Fumiyuki
2017-01-01
We investigated the effect of the tensile strain on the spin splitting at the n-type interface in LaAlO$_3$/SrTiO$_3$ in terms of the spin-orbit coupling coefficient $\\alpha$ and spin texture in the momentum space using first-principles calculations. We found that the $\\alpha$ could be controlled by the tensile strain and be enhanced up to 5 times for the tensile strain of 7%, and the effect of the tensile strain leads to a persistent spin helix, which has a long spin lifetime. These results ...
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Haque, Ezazul; Banik, Urmila; Monwar, Tahmina; Anthony, Leela; Adhikary, Arun Kumar
2018-01-01
Human adenovirus type 3 (HAdV-3) respiratory infections occurs worldwide in both children and adults, leading to severe morbidity and mortality, particularly in the paediatric age group and especially in neonates. During HAdV infection, neutralizing antibodies are formed against the epitopes located in the hyper variable regions (HVRs) of the hexon protein. These neutralizing antibodies provide protection against reinfection by viruses of the same type. Therefore it is reasonable to speculate that variations of HAdV-3 in the HVRs could impair the immunity acquired by previous infection with a different strain with variation in its HVRs. HAdV-3 has recently become the major agent of acute respiratory infection worldwide, being responsible for 15% to 87% of all adenoviral respiratory infections. However, despite the increased prevalence of HAdV-3 as respiratory pathogen, the diversity of hexon proteins in circulating strains remains unexplored. This study was designed to explore the variation in HVRs of hexon among globally distributed strains of HAdV-3 as well as to discover possible relationship among them, thus possibly shedding light on the cause for the increased prevalence of HAdV-3. In this study, for the first time we analysed the hexon proteins of all 248 available strains of HAdV-3 from the NCBI database and compared them with those of the HAdV-3 prototype (GB stain). We found that the HVRs of HAdV-3 strains circulating worldwide were highly heterogeneous and have been mutating continuously since -their original isolation. Based on their immense heterogeneity, the strains can be categorized into 25 hexon variants (3Hv-1 to 3Hv-25), 4 of which (3Hv-1 to 3Hv-4) comprises 80% of the strains. This heterogeneity may explain why HAdV-3 has become the most prevalent HAdVs type worldwide. The heterogeneity of hexon proteins also shows that the development of a vaccine against HAdV-3 might be challenging. The data on hexon variants provided here may be useful for
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Accessible switching of electronic defect type in SrTi O3 via biaxial strain
Chi, Yen-Ting; Youssef, Mostafa; Sun, Lixin; Van Vliet, Krystyn J.; Yildiz, Bilge
2018-05-01
Elastic strain is used widely to alter the mobility of free electronic carriers in semiconductors, but a predictive relationship between elastic lattice strain and the extent of charge localization of electronic defects is still underdeveloped. Here we considered SrTi O3 , a prototypical perovskite as a model functional oxide for thin film electronic devices and nonvolatile memories. We assessed the effects of biaxial strain on the stability of electronic defects at finite temperature by combining density functional theory (DFT) and quasiharmonic approximation (QHA) calculations. We constructed a predominance diagram for free electrons and small electron polarons in this material, as a function of biaxial strain and temperature. We found that biaxial tensile strain in SrTi O3 can stabilize the small polaron, leading to a thermally activated and slower electronic transport, consistent with prior experimental observations on SrTi O3 and distinct from our prior theoretical assessment of the response of SrTi O3 to hydrostatic stress. These findings also resolved apparent conflicts between prior atomistic simulations and conductivity experiments for biaxially strained SrTi O3 thin films. Our computational approach can be extended to other functional oxides, and for the case of SrTi O3 our findings provide concrete guidance for conditions under which strain engineering can shift the electronic defect type and concentration to modulate electronic transport in thin films.
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Göhler, Stella; Da Silva Filho, Miguel Inacio; Johansson, Robert; Enquist-Olsson, Kerstin; Henriksson, Roger; Hemminki, Kari; Lenner, Per; Försti, Asta
2016-01-01
The C → T mutation signature caused by APOBEC family members contributes to the development of breast cancer (BC). Also overexpression of APOBEC3B and a ~29.5-kb deletion polymorphism between APOBEC3A and APOBEC3B have been associated with increased BC risk. We investigated in a population-based study, with 782 Swedish BC cases and 1559 controls, associations between potentially functional germline variants in APOBEC3A or APOBEC3B gene and BC risk and survival. Additionally, we identified deletion polymorphism carriers and explored possible associations with BC. No evidence of association between any germline variant, including the deletion polymorphism, and BC risk or survival was observed. Only APOBEC3A promoter polymorphism rs5757402 was associated with low stage (OR = 0.69, 95 % CI 0.50-0.96, dominant model). The reported association between the deletion polymorphism and BC risk was not confirmed in the Swedish population, nor did any genotyped germline variant show any association with BC risk or survival.
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Pathogenicity and genetic variation of 3 strains of Corynebacterium bovis in immunodeficient mice.
Dole, Vandana S; Henderson, Kenneth S; Fister, Richard D; Pietrowski, Michael T; Maldonado, Geomaris; Clifford, Charles B
2013-07-01
Corynebacterium bovis has been associated with hyperkeratotic dermatitis and acanthosis in mice. We studied 3 different strains of C. bovis: one previously described to cause hyperkeratotic dermatitis (HAC), one that infected athymic nude mice without leading to the classic clinical signs, and one of bovine origin (ATCC 7715). The 3 strains showed a few biochemical and genetic differences. Immunodeficient nude mice were housed in 3 independent isolators and inoculated with pure cultures of the 3 strains. We studied the transmission of these C. bovis studies to isolator-bedding and contact sentinels housed for 5 to 12 wk in filter-top or wire-top cages in the respective isolators. Using a 16S rRNA-based qPCR assay, we did not find consistent differences in growth and transmission among the 3 C. bovis strains, and neither the incidence nor severity of hyperkeratosis or acanthosis differed between strains. Housing in filter-top compared with wire-top cages did not alter the morbidity associated with any of the strains. Our findings confirmed the variability in the gross and histologic changes associated with C. bovis infection of mice. Although bacteriology was a sensitive method for the detection of Corynebacterium spp., standard algorithms occasionally misidentified C. bovis and several related species. Our study demonstrates that PCR of skin swabs or feces is a sensitive and specific method for the detection of C. bovis infection in mice. An rpoB-based screen of samples from North American vivaria revealed that HAC is the predominant C. bovis strain in laboratory mice.
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Garcés-Ayala, Fabiola; Aréchiga-Ceballos, Nidia; Ortiz-Alcántara, Joanna M; González-Durán, Elizabeth; Pérez-Agüeros, Sandra I; Méndez-Tenorio, Alfonso; Torres-Longoria, Belem; López-Martínez, Irma; Hernández-Rivas, Lucía; Díaz-Quiñonez, José Alberto; Ramírez-González, José Ernesto
2017-12-01
Rabies is an infectious viral disease that is practically always fatal following the onset of clinical signs. In Mexico, the last case of human rabies transmitted by dogs was reported in 2006 and canine rabies has declined significantly due to vaccination campaigns implemented in the country. Here we report on the molecular characterization of six rabies virus strains found in Yucatan and Chiapas, remarkably, four of them showed an atypical reaction pattern when antigenic characterization with a reduced panel of eight monoclonal antibodies was performed. Phylogenetic analyses on the RNA sequences unveiled that the three atypical strains from Yucatan are associated with skunks. Analysis using the virus entire genome showed that they belong to a different lineage distinct from the variants described for this animal species in Mexico. The Chiapas atypical strain was grouped in a lineage that was considered extinct, while the others are clustered within classic dog variants.
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3D Tendon Strain Estimation Using High-frequency Volumetric Ultrasound Images: A Feasibility Study.
Carvalho, Catarina; Slagmolen, Pieter; Bogaerts, Stijn; Scheys, Lennart; D'hooge, Jan; Peers, Koen; Maes, Frederik; Suetens, Paul
2018-03-01
Estimation of strain in tendons for tendinopathy assessment is a hot topic within the sports medicine community. It is believed that, if accurately estimated, existing treatment and rehabilitation protocols can be improved and presymptomatic abnormalities can be detected earlier. State-of-the-art studies present inaccurate and highly variable strain estimates, leaving this problem without solution. Out-of-plane motion, present when acquiring two-dimensional (2D) ultrasound (US) images, is a known problem and may be responsible for such errors. This work investigates the benefit of high-frequency, three-dimensional (3D) US imaging to reduce errors in tendon strain estimation. Volumetric US images were acquired in silico, in vitro, and ex vivo using an innovative acquisition approach that combines the acquisition of 2D high-frequency US images with a mechanical guided system. An affine image registration method was used to estimate global strain. 3D strain estimates were then compared with ground-truth values and with 2D strain estimates. The obtained results for in silico data showed a mean absolute error (MAE) of 0.07%, 0.05%, and 0.27% for 3D estimates along axial, lateral direction, and elevation direction and a respective MAE of 0.21% and 0.29% for 2D strain estimates. Although 3D could outperform 2D, this does not occur in in vitro and ex vivo settings, likely due to 3D acquisition artifacts. Comparison against the state-of-the-art methods showed competitive results. The proposed work shows that 3D strain estimates are more accurate than 2D estimates but acquisition of appropriate 3D US images remains a challenge.
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Strain Induced Magnetism in SrRuO3 Epitaxial Thin Films
Energy Technology Data Exchange (ETDEWEB)
Grutter, A.; Wong, F.; Arenholz, E.; Liberati, M.; Suzuki, Y.
2010-01-10
Epitaxial SrRuO{sub 3} thin films were grown on SrTiO{sub 3}, (LaAlO{sub 3}){sub 0.3}(SrAlO{sub 3}){sub 0.7} and LaAlO{sub 3} substrates inducing different biaxial compressive strains. Coherently strained SrRuO{sub 3} films exhibit enhanced magnetization compared to previously reported bulk and thin film values of 1.1-1.6 {micro}{sub B} per formula unit. A comparison of (001) and (110) SrRuO{sub 3} films on each substrate indicates that films on (110) oriented have consistently higher saturated moments than corresponding (001) films. These observations indicate the importance of lattice distortions in controlling the magnetic ground state in this transitional metal oxide.
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Primadharsini, Putu Prathiwi; Mulyanto; Wibawa, I Dewa Nyoman; Anggoro, Joko; Nishizawa, Tsutomu; Takahashi, Masaharu; Jirintai, Suljid; Okamoto, Hiroaki
2018-05-01
All three genetic groups of ratHEV have been found in Indonesia, suggesting the presence of additional variants of ratHEV in unexamined areas of Indonesia. A total of 242 wild rats were captured in Bali and Sumbawa, Indonesia, during 2014-2016. Among them, 4.1% were seropositive for anti-ratHEV IgG and two (0.8%) had detectable ratHEV RNA: ratESUMBAWA-140L and ratEBali2016D-047L, sharing 84.9-85.4% and 86.9-92.1% nucleotide identity with the reported G2 strains, respectively. The provisional criteria supported the notion that the ratEBali2016D-047L and ratESUMBAWA-140L strains were novel G2 variants. These results suggested the spatial distribution of further divergent ratHEV strains in Indonesia.
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A Prediction Model to Help with the Assessment of Adenopathy in Lung Cancer: HAL.
O'Connell, Oisin J; Almeida, Francisco A; Simoff, Michael J; Yarmus, Lonny; Lazarus, Ray; Young, Benjamin; Chen, Yu; Semaan, Roy; Saettele, Timothy M; Cicenia, Joseph; Bedi, Harmeet; Kliment, Corrine; Li, Liang; Sethi, Sonali; Diaz-Mendoza, Javier; Feller-Kopman, David; Song, Juhee; Gildea, Thomas; Lee, Hans; Grosu, Horiana B; Machuzak, Michael; Rodriguez-Vial, Macarena; Eapen, George A; Jimenez, Carlos A; Casal, Roberto F; Ost, David E
2017-06-15
Estimating the probability of finding N2 or N3 (prN2/3) malignant nodal disease on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with non-small cell lung cancer (NSCLC) can facilitate the selection of subsequent management strategies. To develop a clinical prediction model for estimating the prN2/3. We used the AQuIRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) registry to identify patients with NSCLC with clinical radiographic stage T1-3, N0-3, M0 disease that had EBUS-TBNA for staging. The dependent variable was the presence of N2 or N3 disease (vs. N0 or N1) as assessed by EBUS-TBNA. Univariate followed by multivariable logistic regression analysis was used to develop a parsimonious clinical prediction model to estimate prN2/3. External validation was performed using data from three other hospitals. The model derivation cohort (n = 633) had a 25% prevalence of malignant N2 or N3 disease. Younger age, central location, adenocarcinoma histology, and higher positron emission tomography-computed tomography N stage were associated with a higher prN2/3. Area under the receiver operating characteristic curve was 0.85 (95% confidence interval, 0.82-0.89), model fit was acceptable (Hosmer-Lemeshow, P = 0.62; Brier score, 0.125). We externally validated the model in 722 patients. Area under the receiver operating characteristic curve was 0.88 (95% confidence interval, 0.85-0.90). Calibration using the general calibration model method resulted in acceptable goodness of fit (Hosmer-Lemeshow test, P = 0.54; Brier score, 0.132). Our prediction rule can be used to estimate prN2/3 in patients with NSCLC. The model has the potential to facilitate clinical decision making in the staging of NSCLC.
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Isolation and characterization of the E. coli membrane protein production strain Mutant56(DE3)
DEFF Research Database (Denmark)
Baumgarten, Thomas; Schlegel, Susan; Wagner, Samuel
2017-01-01
Membrane protein production is usually toxic to E. coli. However, using genetic screens strains can be isolated in which the toxicity of membrane protein production is reduced, thereby improving production yields. Best known examples are the C41(DE3) and C43(DE3) strains, which are both derived...... from the T7 RNA polymerase (P)-based BL21(DE3) protein production strain. In C41(DE3) and C43(DE3) mutations lowering t7rnap expression levels result in strongly reduced T7 RNAP accumulation levels. As a consequence membrane protein production stress is alleviated in the C41(DE3) and C43(DE3) strains......, thereby increasing membrane protein yields. Here, we isolated Mutant56(DE3) from BL21(DE3) using a genetic screen designed to isolate BL21(DE3)-derived strains with mutations alleviating membrane protein production stress other than the ones in C41(DE3) and C43(DE3). The defining mutation of Mutant56(DE3...
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Novel method for measuring a dense 3D strain map of robotic flapping wings
Li, Beiwen; Zhang, Song
2018-04-01
Measuring dense 3D strain maps of the inextensible membranous flapping wings of robots is of vital importance to the field of bio-inspired engineering. Conventional high-speed 3D videography methods typically reconstruct the wing geometries through measuring sparse points with fiducial markers, and thus cannot obtain the full-field mechanics of the wings in detail. In this research, we propose a novel system to measure a dense strain map of inextensible membranous flapping wings by developing a superfast 3D imaging system and a computational framework for strain analysis. Specifically, first we developed a 5000 Hz 3D imaging system based on the digital fringe projection technique using the defocused binary patterns to precisely measure the dynamic 3D geometries of rapidly flapping wings. Then, we developed a geometry-based algorithm to perform point tracking on the precisely measured 3D surface data. Finally, we developed a dense strain computational method using the Kirchhoff-Love shell theory. Experiments demonstrate that our method can effectively perform point tracking and measure a highly dense strain map of the wings without many fiducial markers.
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Xia, Yongzhen; Wübbeler, Jan Hendrik; Qi, Qingsheng
2012-01-01
Advenella mimigardefordensis strain DPN7T was genetically modified to produce poly(3-mercaptopropionic acid) (PMP) homopolymer by exploiting the recently unraveled process of 3,3′-dithiodipropionic acid (DTDP) catabolism. Production was achieved by systematically engineering the metabolism of this strain as follows: (i) deletion of its inherent 3MP dioxygenase-encoding gene (mdo), (ii) introduction of the buk-ptb operon (genes encoding the butyrate kinase, Buk, and the phosphotransbutyrylase, Ptb, from Clostridium acetobutylicum), and (iii) overexpression of its own polyhydroxyalkanoate synthase (phaCAm). These measures yielded the potent PMP production strain A. mimigardefordensis strain SHX22. The deletion of mdo was required for adequate synthesis of PMP due to the resulting accumulation of 3MP during utilization of DTDP. Overexpression of the plasmid-borne buk-ptb operon caused a severe growth repression. This effect was overcome by inserting this operon into the genome. Polyhydroxyalkanoate (PHA) synthases from different origins were compared. The native PHA synthase of A. mimigardefordensis (phaCAm) was obviously the best choice to establish homopolythioester production in this strain. In addition, the cultivation conditions, including an appropriate provision of the carbon source, were further optimized to enhance PMP production. The engineered strain accumulated PMP up to approximately 25% (wt/wt) of the cell dry weight when cultivated in mineral salts medium containing glycerol as the carbon source in addition to DTDP as the sulfur-providing precursor. According to our knowledge, this is the first report of PMP homopolymer production by a metabolically engineered bacterium using DTDP, which is nontoxic, as the precursor substrate. PMID:22344658
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Constant Transmission Properties of Variant Creutzfeldt-Jakob Disease in 5 Countries
Diack, Abigail B.; Ritchie, Diane; Bishop, Matthew; Pinion, Victoria; Brandel, Jean-Philippe; Haik, Stephane; Tagliavini, Fabrizio; Van Duijn, Cornelia; Belay, Ermias D.; Gambetti, Pierluigi; Schonberger, Lawrence B.; Piccardo, Pedro; Will, Robert G.
2012-01-01
Variant Creutzfeldt-Jakob disease (vCJD) has been reported in 12 countries. We hypothesized that a common strain of agent is responsible for all vCJD cases, regardless of geographic origin. To test this hypothesis, we inoculated strain-typing panels of wild-type mice with brain material from human vCJD case-patients from France, the Netherlands, Italy, and the United States. Mice were assessed for clinical disease, neuropathologic changes, and glycoform profile; results were compared with those for 2 reference vCJD cases from the United Kingdom. Transmission to mice occurred from each sample tested, and data were similar between non-UK and UK cases, with the exception of the ranking of mean clinical incubation times of mouse lines. These findings support the hypothesis that a single strain of infectious agent is responsible for all vCJD infections. However, differences in incubation times require further subpassage in mice to establish any true differences in strain properties between cases. PMID:23017202
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Blazej, Robert; Toriello, Nicholas; Emrich, Charles; Cohen, Richard N.; Koppel, Nitzan
2015-07-14
This invention provides novel variant cellulolytic enzymes having improved activity and/or stability. In certain embodiments the variant cellulotyic enzymes comprise a glycoside hydrolase with or comprising a substitution at one or more positions corresponding to one or more of residues F64, A226, and/or E246 in Thermobifida fusca Cel9A enzyme. In certain embodiments the glycoside hydrolase is a variant of a family 9 glycoside hydrolase. In certain embodiments the glycoside hydrolase is a variant of a theme B family 9 glycoside hydrolase.
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International Nuclear Information System (INIS)
Charrel, R.N.; Brault, A.C.; Gallian, P.; Lemasson, J.-J.; Murgue, B.; Murri, S.; Pastorino, B.; Zeller, H.; Chesse, R. de; Micco, P. de; Lamballerie, X. de
2003-01-01
Little is known about the genetic relationships between European and other Old-World strains of West Nile virus (WNV) and persistence of WNV North of Mediterranean. We characterized the complete genomes of three WNV strains from France (horse-2000), Tunisia (human-1997) and Kenya (mosquito-1998), and the envelope, NS3 and NS5 genes of the Koutango virus. Phylogenetic analyses including all available full-length sequences showed that: (1) Koutango virus is a distant variant of WNV; (2) the three characterized strains belong to lineage 1, clade 1a; (3) the Tunisian strain roots the lineage of viruses introduced in North America. We established that currently available partial envelope sequences do not generate reliable phylogenies. Accordingly, establishing a large WNV sequence database is pivotal for the understanding of spatial and temporal epidemiology of this virus. For rapid completion of that purpose, colinearized E-NS3-NS5 gene sequences were shown to constitute a valuable surrogate for complete sequences
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Roesler, Keith; Shen, Bo; Bermudez, Ericka; Li, Changjiang; Hunt, Joanne; Damude, Howard G; Ripp, Kevin G; Everard, John D; Booth, John R; Castaneda, Leandro; Feng, Lizhi; Meyer, Knut
2016-06-01
Kinetically improved diacylglycerol acyltransferase (DGAT) variants were created to favorably alter carbon partitioning in soybean (Glycine max) seeds. Initially, variants of a type 1 DGAT from a high-oil, high-oleic acid plant seed, Corylus americana, were screened for high oil content in Saccharomyces cerevisiae Nearly all DGAT variants examined from high-oil strains had increased affinity for oleoyl-CoA, with S0.5 values decreased as much as 4.7-fold compared with the wild-type value of 0.94 µm Improved soybean DGAT variants were then designed to include amino acid substitutions observed in promising C. americana DGAT variants. The expression of soybean and C. americana DGAT variants in soybean somatic embryos resulted in oil contents as high as 10% and 12%, respectively, compared with only 5% and 7.6% oil achieved by overexpressing the corresponding wild-type DGATs. The affinity for oleoyl-CoA correlated strongly with oil content. The soybean DGAT variant that gave the greatest oil increase contained 14 amino acid substitutions out of a total of 504 (97% sequence identity with native). Seed-preferred expression of this soybean DGAT1 variant increased oil content of soybean seeds by an average of 3% (16% relative increase) in highly replicated, single-location field trials. The DGAT transgenes significantly reduced the soluble carbohydrate content of mature seeds and increased the seed protein content of some events. This study demonstrated that engineering of the native DGAT enzyme is an effective strategy to improve the oil content and value of soybeans. © 2016 American Society of Plant Biologists. All Rights Reserved.
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International Nuclear Information System (INIS)
Wang Haiou; Liu Hao; Dai Ping; Tan Weishi; Wu Xiaoshan; Jia Quanjie; Li Xiaolong
2012-01-01
Pr 0.7 Sr 0.3 MnO 3 /La 0.5 Ca 0.5 MnO 3 /Pr 0.7 Sr 0.3 MnO 3 (PSMO/LCMO/PSMO) trilayers were deposited on (001)-oriented single crystal MgO by pulsed laser deposition. The thickness of both PSMO layers was 36 nm while the thickness of LCMO layer was 6, 12, 18, 24, 30 and 36 nm, respectively. Out-of-plane and in-plane lattice parameters of trilayers were obtained by using symmetric scanning and asymmetric scanning mode of high resolution X-ray diffraction. Strain states of trilayers have been studied. The results showed that strain relaxation states of trilayers were decided by bulk strain and Jahn-Teller (JT) strain together: The mechanism for strain relaxation in trilayers is different from that for tetragonal distortion. The competition between bulk strain and Jahn-Teller (JT) strain played an important role in the magnetotransport and magnetic properties of trilayers. (authors)
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Strain-Mediated Inverse Photoresistivity in SrRuO3/La0.7Sr0.3MnO3Superlattices
Liu, Heng-Jui
2015-12-09
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. In the pursuit of novel functionalities by utilizing the lattice degree of freedom in complex oxide heterostructure, the control mechanism through direct strain manipulation across the interfaces is still under development, especially with various stimuli, such as electric field, magnetic field, light, etc. In this study, the superlattices consisting of colossal-magnetoresistive manganites La0.7Sr0.3MnO3 (LSMO) and photostrictive SrRuO3 (SRO) have been designed to investigate the light-dependent controllability of lattice order in the corresponding functionalities and rich interface physics. Two substrates, SrTiO3 (STO) and LaAlO3 (LAO), have been employed to provide the different strain environments to the superlattice system, in which the LSMO sublayers exhibit different orbital occupations. Subsequently, by introducing light, we can modulate the strain state and orbital preference of LSMO sublayers through light-induced expansion of SRO sublayers, leading to surprisingly opposite changes in photoresistivity. The observed photoresistivity decreases in the superlattice grown on STO substrate while increases in the superlattice grown on LAO substrate under light illumination. This work has presented a model system that demonstrates the manipulation of orbital-lattice coupling and the resultant functionalities in artificial oxide superlattices via light stimulus. A fascinating model system of optic-driven functionalities has been achieved by artificial superlattices consisting of manganite La0.7Sr0.3MnO3 (LSMO) and photostrictive SrRuO3 (SRO). With design of different initial strain and orbital states in superlattices, we can even control the photoresistivity of the superlattices in an opposite trend that cannot be achieved in pure single film.
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Survey on the phage resistance mechanisms displayed by a dairy Lactobacillus helveticus strain.
Zago, Miriam; Orrù, Luigi; Rossetti, Lia; Lamontanara, Antonella; Fornasari, Maria Emanuela; Bonvini, Barbara; Meucci, Aurora; Carminati, Domenico; Cattivelli, Luigi; Giraffa, Giorgio
2017-09-01
In this study the presence and functionality of phage defence mechanisms in Lactobacillus helveticus ATCC 10386, a strain of dairy origin which is sensitive to ΦLh56, were investigated. After exposure of ATCC 10386 to ΦLh56, the whole-genome sequences of ATCC 10386 and of a phage-resistant derivative (LhM3) were compared. LhM3 showed deletions in the S-layer protein and a higher expression of the genes involved in the restriction/modification (R/M) system. Genetic data were substantiated by measurements of bacteriophage adsorption rates, efficiency of plaquing, cell wall protein size and by gene expression analysis. In LhM3 two phage resistance mechanisms, the inhibition of phage adsorption and the upregulation of Type I R/M genes, take place and explain its resistance to ΦLh56. Although present in both ATCC 10386 and LhM3 genomes, the CRISPR machinery did not seem to play a role in the phage resistance of LhM3. Overall, the natural selection of phage resistant strains resulted successful in detecting variants carrying multiple phage defence mechanisms in L. helveticus. The concurrent presence of multiple phage-resistance systems should provide starter strains with increased fitness and robustness in dairy ecosystems. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Strain-dependent magnetism and electrical conductivity of La1-xSrxCoO3
International Nuclear Information System (INIS)
Zeneli, Orkidia
2011-01-01
In this work, the effects of epitaxial strain and film thickness on the lattice structure, microstructure, magnetization and electrical conduction of La 1-x Sr x CoO 3 (LSCO) (x=0.18 and 0.30) thin films have been studied using thickness-dependent film series on several types of single-crystalline substrates. Alternatively, the direct effect of strain has been probed using a piezoelectric substrate. La 0.7 Sr 0.3 CoO 3 is a ferromagnetic metal, whereas La 0.82 Sr 0.18 CoO 3 is at the phase boundary between the ferromagnetic metal and an insulating spin glass phase. Epitaxial biaxial strain in La 1-x Sr x CoO 3 (x=0.18-0.3) films is known to reduce the ferromagnetic double exchange interactions. It has further been suggested for the control of the crystal field splitting of the Co ions which may be utilized to manipulate the spin state. The LSCO (x = 0.18 and 0.30) films have been grown by pulsed laser deposition (PLD) on substrates of LaAlO 3 , SrTiO 3 , (PbMg 1/3 Nb 2/3 O 3 ) 0.72 (PbTiO 3 ) 0.28 (PMN-PT) and (LaAlO 3 ) 0.3 (Sr 2 TaAlO 6 ) 0.7 (LSAT), which provide different strain states and, in the case of PMN-PT, a reversibly controllable strain. Thickness-dependent series of La 0.82 Sr 0.18 CoO 3 on SrTiO 3 and LaAlO 3 as well as of La 0.7 Sr 0.3 CoO 3 on LSAT have been studied. The lattice parameters of the epitaxially grown films were determined from X-ray diffraction measurements (Bragg-Brentano method and reciprocal space mapping). Large tensile strains of 2% can be achieved in thicker films of up to 100 nm. On the other hand, the films under larger tensile strain have cracks and reveal ordered superstructures in HRTEM images which are tentatively attributed to ordered oxygen vacancies. The Curie temperature and the magnetic moment of the x=0.18 films increases towards larger film thickness in qualitative agreement with the joined effects of strain relaxation and finite thickness on magnetic ordering. In order to separate the direct strain effect from the
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Strain effect on the magnetic and transport properties of LaCoO3 thin films
Li, Y.; Peng, S. J.; Wang, D. J.; Wu, K. M.; Wang, S. H.
2018-05-01
LaCoO3 (LCO) has attracted much attention due to the unique magnetic transition and spin transition of Co3+ ions. Epitaxial LCO film exhibits an unexpected ferromagnetism, in contrast to the non-magnetism of bulk LCO. An in-depth study on the property of strained LCO film is of great importance. We have fabricated 30 nm LCO films on various substrates and studied the magnetic and transport properties of films in different strain states (compressed strain for LCO/LaAlO3, tensile strain for LCO/(LaAlO3)0.3(Sr2TaAlO6)0.35, SrTiO3). The in-plane tensiled LCO films exhibit ferromagnetic ground state at 5K and magnetic transition with TC around 85K, while compressed LCO/LaAlO3 film has a negligibly small moment signal. Our results reveal that in-plane tensile strain and tetragonal distortion are much more favorable for stabilizing the FM order in LCO films.
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Beck, Andrew; Tesh, Robert B; Wood, Thomas G; Widen, Steven G; Ryman, Kate D; Barrett, Alan D T
2014-02-01
The first comparison of a live RNA viral vaccine strain to its wild-type parental strain by deep sequencing is presented using as a model the yellow fever virus (YFV) live vaccine strain 17D-204 and its wild-type parental strain, Asibi. The YFV 17D-204 vaccine genome was compared to that of the parental strain Asibi by massively parallel methods. Variability was compared on multiple scales of the viral genomes. A modeled exploration of small-frequency variants was performed to reconstruct plausible regions of mutational plasticity. Overt quasispecies diversity is a feature of the parental strain, whereas the live vaccine strain lacks diversity according to multiple independent measurements. A lack of attenuating mutations in the Asibi population relative to that of 17D-204 was observed, demonstrating that the vaccine strain was derived by discrete mutation of Asibi and not by selection of genomes in the wild-type population. Relative quasispecies structure is a plausible correlate of attenuation for live viral vaccines. Analyses such as these of attenuated viruses improve our understanding of the molecular basis of vaccine attenuation and provide critical information on the stability of live vaccines and the risk of reversion to virulence.
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3D-Structured Stretchable Strain Sensors for Out-of-Plane Force Detection.
Liu, Zhiyuan; Qi, Dianpeng; Leow, Wan Ru; Yu, Jiancan; Xiloyannnis, Michele; Cappello, Leonardo; Liu, Yaqing; Zhu, Bowen; Jiang, Ying; Chen, Geng; Masia, Lorenzo; Liedberg, Bo; Chen, Xiaodong
2018-05-17
Stretchable strain sensors, as the soft mechanical interface, provide the key mechanical information of the systems for healthcare monitoring, rehabilitation assistance, soft exoskeletal devices, and soft robotics. Stretchable strain sensors based on 2D flat film have been widely developed to monitor the in-plane force applied within the plane where the sensor is placed. However, to comprehensively obtain the mechanical feedback, the capability to detect the out-of-plane force, caused by the interaction outside of the plane where the senor is located, is needed. Herein, a 3D-structured stretchable strain sensor is reported to monitor the out-of-plane force by employing 3D printing in conjunction with out-of-plane capillary force-assisted self-pinning of carbon nanotubes. The 3D-structured sensor possesses large stretchability, multistrain detection, and strain-direction recognition by one single sensor. It is demonstrated that out-of-plane forces induced by the air/fluid flow are reliably monitored and intricate flow details are clearly recorded. The development opens up for the exploration of next-generation 3D stretchable sensors for electronic skin and soft robotics. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Directory of Open Access Journals (Sweden)
Kazuaki Miyamoto
Full Text Available Clostridium perfringens enterotoxin (CPE is a major virulence factor for human gastrointestinal diseases, such as food poisoning and antibiotic associated diarrhea. The CPE-encoding gene (cpe can be chromosomal or plasmid-borne. Recent development of conventional PCR cpe-genotyping assays makes it possible to identify cpe location (chromosomal or plasmid in type A isolates. Initial studies for developing cpe genotyping assays indicated that all cpe-positive strains isolated from sickened patients were typable by cpe-genotypes, but surveys of C. perfringens environmental strains or strains from feces of healthy people suggested that this assay might not be useful for some cpe-carrying type A isolates. In the current study, a pulsed-field gel electrophoresis Southern blot assay showed that four cpe-genotype untypable isolates carried their cpe gene on a plasmid of ∼65 kb. Complete sequence analysis of the ∼65 kb variant cpe-carrying plasmid revealed no intact IS elements and a disrupted cytosine methyltransferase (dcm gene. More importantly, this plasmid contains a conjugative transfer region, a variant cpe gene and variant iota toxin genes. The toxin genes encoded by this plasmid are expressed based upon the results of RT-PCR assays. The ∼65 kb plasmid is closely related to the pCPF4969 cpe plasmid of type A isolates. MLST analyses indicated these isolates belong to a unique cluster of C. perfringens. Overall, these isolates carrying a variant functional cpe gene and iota toxin genes represent unique type E strains.
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Fernlund, Eva; Österberg, A Wålinder; Kuchinskaya, E; Gustafsson, M; Jansson, K; Gunnarsson, C
2017-08-01
Familial dilated cardiomyopathy is a rare cause of dilated cardiomyopathy (DCM), especially in childhood. Our aim was to describe the clinical course and the genetic variants in a family where the proband was a four-month-old infant presenting with respiratory problems due to DCM. In the family, there was a strong family history of DCM and sudden cardiac death in four generations. DNA was analyzed initially from the deceased girl using next-generation sequencing including 50 genes involved in cardiomyopathy. A cascade family screening was performed in the family after identification of the TNNT2 and the BAG3 variants in the proband. The first-degree relatives underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, exercise stress test, and targeted genetic testing. The index patient presented with advanced DCM. After a severe clinical course, the baby had external left ventricular assist as a bridge to heart transplantation. 1.5 months after transplantation, the baby suffered sudden cardiac death (SCD) despite maximal treatment in the pediatric intensive care unit. The patient was shown to carry two heterozygous genetic variants in the TNNT2 gene [TNNT2 c.518G>A(p.Arg173Gln)] and BAG3 [BAG3 c.785C>T(p.Ala262Val)]. Two of the screened individuals (two females) appeared to carry both the familial variants. All the individuals carrying the TNNT2 variant presented with DCM, the two adult patients had mild or moderate symptoms of heart failure and reported palpitations but no syncope or presyncopal attacks prior to the genetic diagnosis. The female carriers of TNNT2 and BAG3 variants had more advanced DCM. In the family history, there were three additional cases of SCD due to DCM, diagnosed by autopsy, but no genetic analysis was possible in these cases. Our findings suggest that the variants in TNNT2 and BAG3 are associated with a high propensity to life-threatening cardiomyopathy presenting from childhood and young adulthood.
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Sun, Ming-Jun; Di, Dong-Dong; Li, Yan; Zhang, Zhi-Cheng; Yan, Hao; Tian, Li-Li; Jing, Zhi-Gang; Li, Jin-Ping; Jiang, Hai; Fan, Wei-Xing
2016-10-01
Brucellosis is a well-known zoonotic disease that can cause severe economic and healthcare losses. Xinjiang, one of the biggest livestock husbandry sectors in China, has gone through increasing incidence of brucellosis in cattle and small ruminants recently. In this paper, 50 B. melitensis strains and 9 B. abortus strains collected from across Xinjiang area (from 2010 to 2015) were genotyped using multiple locus variable-number tandem-repeat (VNTR) analysis (MLVA) and multi-locus sequence typing (MLST). Based on 8 loci (MLVA-8), 50 B. melitensis strains were classified into three genotypes. Genotypes 42 (n=38, 76%) and 63 (n=11, 22%) were part of the East Mediterranean group, and one genotype with pattern of 1-5-3-13-2-4-3-2 represents a single-locus variant from genotype 63. MLVA-16 resolved 50 B. melitensis strains into 28 genotypes, of which 15 are unique to Xinjiang and 10 are in common with those in adjacent country Kazakhstan and neighboring provinces of China. Minimum Spanning Tree (MST) analysis implies that B. melitensis strains collected from across Kazakhstan, Xinjiang and China areas may share a common origin. Nine B. abortus strains were sorted into three genotypes by MLVA-8, genotypes 36 (n=7, 77.8%), 86 (n=1, 11.1%) and a new genotype with pattern of 4-5-3-13-2-2-3-1. Each B. abortus strain showed distinct MLVA-16 genotypes, suggesting that B. abortus species may possess more genetic diversity than B. melitensis. Using MLST, most B. melitensis strains (n=49) were identified as sequence type ST8, and most B. abortus strains (n=8) were recognized as ST2. Two new sequence types, ST37 and ST38, represented by single strain from B. melitensis and B. abortus species respectively, were also detected in this study. These results could facilitate the pathogen surveillance in the forthcoming eradication programs and serve as a guide in source tracking in case of new outbreaks occur. Copyright © 2016 Elsevier B.V. All rights reserved.
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3D printed high performance strain sensors for high temperature applications
Rahman, Md Taibur; Moser, Russell; Zbib, Hussein M.; Ramana, C. V.; Panat, Rahul
2018-01-01
Realization of high temperature physical measurement sensors, which are needed in many of the current and emerging technologies, is challenging due to the degradation of their electrical stability by drift currents, material oxidation, thermal strain, and creep. In this paper, for the first time, we demonstrate that 3D printed sensors show a metamaterial-like behavior, resulting in superior performance such as high sensitivity, low thermal strain, and enhanced thermal stability. The sensors were fabricated using silver (Ag) nanoparticles (NPs), using an advanced Aerosol Jet based additive printing method followed by thermal sintering. The sensors were tested under cyclic strain up to a temperature of 500 °C and showed a gauge factor of 3.15 ± 0.086, which is about 57% higher than that of those available commercially. The sensor thermal strain was also an order of magnitude lower than that of commercial gages for operation up to a temperature of 500 °C. An analytical model was developed to account for the enhanced performance of such printed sensors based on enhanced lateral contraction of the NP films due to the porosity, a behavior akin to cellular metamaterials. The results demonstrate the potential of 3D printing technology as a pathway to realize highly stable and high-performance sensors for high temperature applications.
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Fortini, Daniela; Villa, Laura; Feudi, Claudia; Pires, João; Bonura, Celestino; Mammina, Caterina; Endimiani, Andrea; Carattoli, Alessandra
2016-01-01
A carbapenem-resistant sequence type 512 (ST512) Klebsiella pneumoniae carbapenemase 3 (KPC-3)-producing K. pneumoniae strain showing a novel variant plasmid content was isolated in Palermo, Italy, in 2014. ST512 is a worldwide successful clone associated with the spread of bla(KPC) genes located on the IncFIIk pKpQIL plasmid. In our ST512 strain, the bla(KPC-3) gene was unusually located on an IncX3 plasmid, whose complete sequence was determined. Two copies of bla(KPC-3)::Tn4401a caused by intramolecular transposition events were detected in the plasmid. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
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Prahalad, Sampath; Hansen, Sterling; Whiting, April; Guthery, Stephen L.; Clifford, Bronte; McNally, Bernadette; Zeft, Andrew S.; Bohnsack, John F.; Jorde, Lynn B.
2010-01-01
Objectives Subtypes of juvenile idiopathic arthritis (JIA) share phenotypic features with other autoimmune disorders. We investigated several genetic variants associated with rheumatoid arthritis (RA) and other autoimmune disorders for association with JIA, to test the hypothesis that clinically distinct phenotypes share common genetic susceptibility factors. Methods Cases were 445 children with JIA, and controls were 643 healthy adults. Eight single nucleotide polymorphisms (SNPs) in 7 loci [TNFAIP3 (rs10499194 and rs6920220), RSBN1 (rs6679677), C12ORF30 (rs17696736), TRAF1 (rs3761847), IL2RA (rs2104286), PTPN2 (rs2542151), and STAT4 (rs7574865)] were genotyped by the TaqMan assay. Alleles and genotypes were analyzed for association with JIA and JIA subtypes. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. Results The strongest associations were observed for TNFAIP3 variants rs10499194 (OR: 0.74 (0.61-0.91); p <0.004), and TNFAIP3 rs6920220 (OR: 1.3 (1.05-1.61); p <0.02). We also observed associations between JIA and STAT4 (OR: 1.24 (1.02-1.51); p <0.03) and C12ORF30 (OR: 1.2 (1.01-1.43); p <0.04) variants. The PTPN2 variant rs2542151 deviated from Hardy-Weinberg equilibrium and was excluded from analyses. Variants in IL2RA, TRAF1, and RSBN1 were not associated with JIA. After stratification by JIA subtype, TNFAIP3 and C12ORF30 variants were associated with oligoarticular JIA, while the STAT4 variant was associated primarily with polyarticular JIA. Conclusions We have demonstrated associations between JIA and variants in TNFAIP3, STAT4 and C12ORF30 regions that have previously shown associations with other autoimmune diseases, including RA and systemic lupus erythematosus. Our results suggest that clinically distinct autoimmune phenotypes share common genetic susceptibility factors. PMID:19565500
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Evolution and Strain Variation in BCG
Abdallah, Abdallah
2017-11-07
BCG vaccines were derived by in vitro passage, during the years 1908–1921, at the Pasteur Institute of Lille. Following the distribution of stocks of BCG to vaccine production laboratories around the world, it was only a few decades before different BCG producers recognized that there were variants of BCG, likely due to different passaging conditions in the different laboratories. This ultimately led to the lyophilization of stable BCG products in the 1950s and 1960s, but not before considerable evolution of the different BCG strains had taken place. The application of contemporary research methodologies has now revealed genomic, transcriptomic and proteomic differences between BCG strains. These molecular differences in part account for phenotypic differences in vitro between BCG strains, such as their variable secretion of antigenic proteins. Yet, the relevance of BCG variability for immunization policy remains elusive. In this chapter we present an overview of what is known about BCG evolution and its resulting strain variability, and provide some speculation as to the potential relevance for a vaccine given to over 100 million newborns each year.
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Mutagenesis at the ad-3A and ad-3B loci in haploid UV-sensitive strains of Neurospora crassa. Pt. 2
International Nuclear Information System (INIS)
Serres, F.J. de
1980-01-01
UV-induced inactivation and induction of mutations at the ad-3A and ad-3B loci of Neurospora crassa have been compared among 7 different UV-sensitive strains and a standard wild-type strain. The 7 strains show varying degrees of sensitivity to UV-induced inactivation, with the relative sensitivity being: uvs-2 > uvs-3 > uvs-4 > uvs-6 > upr-1 > uvs-5 > uvs-1. Studies on the induction of ad-3 mutants by UV show that the 2 excision-repair deficient mutants uvs-2 and upr-1 exhibit enhanced ad-3 mutant frequencies, while uvs-4 and uvs-5 exhibit reduced ad-3 mutant frequencies, and uvs-3 completely eliminates UV mutagenesis. The ad-3 mutation-induction curves obtained with uvs-1 or uvs-6 are not significantly different from that found with the wild-type strain. (orig.)
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Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis
Directory of Open Access Journals (Sweden)
Jun Ueda
2017-01-01
Full Text Available Cellular differentiation is associated with dynamic chromatin remodeling in establishing a cell-type-specific epigenomic landscape. Here, we find that mouse testis-specific and replication-dependent histone H3 variant H3t is essential for very early stages of spermatogenesis. H3t gene deficiency leads to azoospermia because of the loss of haploid germ cells. When differentiating spermatogonia emerge in normal spermatogenesis, H3t appears and replaces the canonical H3 proteins. Structural and biochemical analyses reveal that H3t-containing nucleosomes are more flexible than the canonical nucleosomes. Thus, by incorporating H3t into the genome during spermatogonial differentiation, male germ cells are able to enter meiosis and beyond.
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Paraszkiewicz, Katarzyna; Bernat, Przemysław; Kuśmierska, Anna; Chojniak, Joanna; Płaza, Grażyna
2018-03-01
The aim of the study was to identify and characterize lipopeptide (LP) biosurfactants produced by two Bacillus subtilis strains (KP7 and I'-1a) grown on various media prepared from renewable natural resources: two different brewery wastewaters (BW#4 and BW#6), 2% beet molasses (M), apple peels extract (APE) supplemented with 0.25% of yeast extract (YE) or 0.25% peptone (P), and similarly supplemented carrot peels extract (CPE). In all used media both strains retained their individual LP production signature characterized by surfactin and iturin overproduction exhibited by KP7 and I'-1a strain, respectively. The production level and the structural diversity of synthesized LPs were dependent on the medium composition. In the CPE+YE medium it was higher than the yield obtained in Luria-Bertani (140.6 and 100.3 mg L -1 , respectively). Surfactins were produced by both strains as a mixture of four homologues (C13-C16) with the domination of variant C14. All other broths prepared from renewable resources strongly stimulated the iturin production by I'-1a strain with the exception of BW media. The highest iturin concentration (428.7 mg L -1 ) obtained in the CPE+P culture of I'-1a strain was about seven-fold higher than in LB. In all cultures only iturin A was identified. Among four iturin homologues (C13-16) produced by I'-1a strain, the highest relative contents of C16 variant (70-80%) were calculated for samples obtained from APE+P and CPE+P media. The obtained data indicate that the waste composition has an influence on both the types and amounts of biosurfactants produced by studied B. subtilis strains. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Handling of human short-chain acyl-CoA dehydrogenase (SCAD) variant proteins in transgenic mice
DEFF Research Database (Denmark)
Kragh, Peter M; Pedersen, Christina B; Schmidt, Stine P
2007-01-01
Abstract To investigate the in vivo handling of human short-chain acyl-CoA dehydrogenase (SCAD) variant proteins, three transgenic mouse lines were produced by pronuclear injection of cDNA encoding the wild-type, hSCAD-wt, and two disease causing folding variants hSCAD-319C > T and hSCAD-625G > A....... The transgenic mice were mated with an SCAD-deficient mouse strain (BALB/cByJ) and, in the second generation, three mouse lines were obtained without endogenous SCAD expression but harboring hSCAD-wt, hSCAD-319C > T, and hSCAD-625G > A transgenes, respectively. All three lines had expression of the transgene...... developed for any of the lines transgenic for the hSCAD folding variants. The indicated remarkable efficiency of the mouse protein quality control system in the degradation of SCAD folding variants should be further substantiated and investigated, since it might indicate ways to prevent disease...
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Tensile Strain Dependence of Critical Current for RHQ-Nb3Al Wires
Jin, Xinzhe; Oguro, Hidetoshi; Nakamoto, Tatsushi; Awaji, Satoshi; Ogitsu, Toru; Tsuchiya, Kiyosumi; Yamamoto, Akira; Kikuchi, Akihiro; Takeuchi, Takao
2011-01-01
KEK and NIMS have been jointly developing Nb3Al superconducting wire with a rapid heating and quenching (RHQ) method towards high field accelerator magnets in the Large Hadron Collider (LHC) luminosity upgrade. A15-type superconductors such as Nb3Al and Nb3Sn exhibit strain dependence with respect to their critical currents. Therefore, a thorough understanding of strain behavior is necessary for high field accelerator magnet development, which will be critical for the luminosity upgrade of th...
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ABCA7 rare variants and Alzheimer disease risk.
Le Guennec, Kilan; Nicolas, Gaël; Quenez, Olivier; Charbonnier, Camille; Wallon, David; Bellenguez, Céline; Grenier-Boley, Benjamin; Rousseau, Stéphane; Richard, Anne-Claire; Rovelet-Lecrux, Anne; Bacq, Delphine; Garnier, Jean-Guillaume; Olaso, Robert; Boland, Anne; Meyer, Vincent; Deleuze, Jean-François; Amouyel, Philippe; Munter, Hans Markus; Bourque, Guillaume; Lathrop, Mark; Frebourg, Thierry; Redon, Richard; Letenneur, Luc; Dartigues, Jean-François; Pasquier, Florence; Rollin-Sillaire, Adeline; Génin, Emmanuelle; Lambert, Jean-Charles; Hannequin, Didier; Campion, Dominique
2016-06-07
To study the association between ABCA7 rare coding variants and Alzheimer disease (AD) in a case-control setting. We conducted a whole exome analysis among 484 French patients with early-onset AD and 590 ethnically matched controls. After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of ABCA7 loss of function (LOF) and predicted damaging missense variants in cases (odds ratio [OR] 3.40, 95% confidence interval [CI] 1.68-7.35, p = 0.0002). Performing a meta-analysis with previously published data, we found that in a combined sample of 1,256 patients and 1,347 controls from France and Belgium, the OR was 2.81 (95% CI 1.89-4.20, p = 3.60 × 10(-7)). These results confirm that ABCA7 LOF variants are enriched in patients with AD and extend this finding to predicted damaging missense variants. © 2016 American Academy of Neurology.
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Shen, Bo; Damude, Howard G.; Everard, John D.; Booth, John R.
2016-01-01
Kinetically improved diacylglycerol acyltransferase (DGAT) variants were created to favorably alter carbon partitioning in soybean (Glycine max) seeds. Initially, variants of a type 1 DGAT from a high-oil, high-oleic acid plant seed, Corylus americana, were screened for high oil content in Saccharomyces cerevisiae. Nearly all DGAT variants examined from high-oil strains had increased affinity for oleoyl-CoA, with S0.5 values decreased as much as 4.7-fold compared with the wild-type value of 0.94 µm. Improved soybean DGAT variants were then designed to include amino acid substitutions observed in promising C. americana DGAT variants. The expression of soybean and C. americana DGAT variants in soybean somatic embryos resulted in oil contents as high as 10% and 12%, respectively, compared with only 5% and 7.6% oil achieved by overexpressing the corresponding wild-type DGATs. The affinity for oleoyl-CoA correlated strongly with oil content. The soybean DGAT variant that gave the greatest oil increase contained 14 amino acid substitutions out of a total of 504 (97% sequence identity with native). Seed-preferred expression of this soybean DGAT1 variant increased oil content of soybean seeds by an average of 3% (16% relative increase) in highly replicated, single-location field trials. The DGAT transgenes significantly reduced the soluble carbohydrate content of mature seeds and increased the seed protein content of some events. This study demonstrated that engineering of the native DGAT enzyme is an effective strategy to improve the oil content and value of soybeans. PMID:27208257
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Prevalence and genetic diversity of Bartonella strains in rodents from northwestern Mexico.
Rubio, André V; Ávila-Flores, Rafael; Osikowicz, Lynn M; Bai, Ying; Suzán, Gerardo; Kosoy, Michael Y
2014-12-01
Bartonella infections were investigated in wild rodents from northwestern Chihuahua, Mexico. A total of 489 rodents belonging to 14 species were surveyed in four areas. Bartonella bacteria were cultured from 50.1% of rodent samples (245/489). Infection rates ranged from 0% to 83.3% per rodent species, with no significant difference between sites except for Cynomys ludovicianus. Phylogenetic analyses of the citrate synthase gene (gltA) of the Bartonella isolates revealed 23 genetic variants (15 novel and 8 previously described), clustering into five phylogroups. Three phylogroups were associated with Bartonella vinsonii subsp. vinsonii, B. vinsonii subsp. arupensis, and B. washoensis, respectively. The other two phylogroups were not genetically related to any known Bartonella species. The genetic variants and phylogenetic groups exhibited a high degree of host specificity, mainly at the genus and family levels. This is the first study that describes the genetic diversity of Bartonella strains in wild rodents from Mexico. Considering that some variants found in this study are associated with Bartonella species that have been reported as zoonotic, more investigations are needed to further understand the ecology of Bartonella species in Mexican wildlife and their implications for human health.
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Some Routes in Forming C3Hn+ Ions and Deuterated Variants under Interstellar Conditions
International Nuclear Information System (INIS)
Savic, Igor; Gerlich, Dieter
2006-01-01
Laboratory experiments on hydrogenation and deuteration of C 3 + , C3H+ and C 3 H 2 + in collisions with H2 and HD have been performed from room temperature down to 15 K using a 22-pole ion-trap. At room temperature C 3 + reacts slowly with H2 but the reactivity increases with decreasing temperature. It has been shown that the association reaction C 3 + + H 2 → C 3 H 2 + + hν can compete with the exothermic reaction C 3 + + H 2 → C 3 H + + H. In collisions of C 3 + with HD, formation of C3D+ is slightly favored over C3H+ formation. A pronounced competition between various channels has been detected for deuterated variants of the C3H+ + H2 system. Most surprising is that formation of C3HD+ is over one hundred times faster then formation of C 3 H 2 + in collisions of C3H+ and HD. An tentative explanation is that the H-HD exchange takes place via an open-chain H2CCCH+ intermediate. Reactions of C 3 H 2 + and C 3 H 3 + with H2 are very slow. The formation of C3H2D+ or C 3 HD 2 + and finally C3HD via dissociative recombination has been discussed. The reaction C 3 H 3 + + HD → C 3 H 2 D + + H 2 can be ignored in astrochemical models since the reaction rate at 15 K is very small; however, quite efficient routes have been found starting from C 3 + and proceeding via deuterated C3H+ to C 3 H 2 + and C 3 H 3 + . The new reaction rate coefficients are recommended to be included in astrophysical databases. Nonetheless it is still unclear how to explain the large abundance of C3H2 and larger hydrocarbons and their deuterated variants observed in cold interstellar clouds
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Somatic cancer variant curation and harmonization through consensus minimum variant level data
Directory of Open Access Journals (Sweden)
Deborah I. Ritter
2016-11-01
Full Text Available Abstract Background To truly achieve personalized medicine in oncology, it is critical to catalog and curate cancer sequence variants for their clinical relevance. The Somatic Working Group (WG of the Clinical Genome Resource (ClinGen, in cooperation with ClinVar and multiple cancer variant curation stakeholders, has developed a consensus set of minimal variant level data (MVLD. MVLD is a framework of standardized data elements to curate cancer variants for clinical utility. With implementation of MVLD standards, and in a working partnership with ClinVar, we aim to streamline the somatic variant curation efforts in the community and reduce redundancy and time burden for the interpretation of cancer variants in clinical practice. Methods We developed MVLD through a consensus approach by i reviewing clinical actionability interpretations from institutions participating in the WG, ii conducting extensive literature search of clinical somatic interpretation schemas, and iii survey of cancer variant web portals. A forthcoming guideline on cancer variant interpretation, from the Association of Molecular Pathology (AMP, can be incorporated into MVLD. Results Along with harmonizing standardized terminology for allele interpretive and descriptive fields that are collected by many databases, the MVLD includes unique fields for cancer variants such as Biomarker Class, Therapeutic Context and Effect. In addition, MVLD includes recommendations for controlled semantics and ontologies. The Somatic WG is collaborating with ClinVar to evaluate MVLD use for somatic variant submissions. ClinVar is an open and centralized repository where sequencing laboratories can report summary-level variant data with clinical significance, and ClinVar accepts cancer variant data. Conclusions We expect the use of the MVLD to streamline clinical interpretation of cancer variants, enhance interoperability among multiple redundant curation efforts, and increase submission of
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Distribution of cytomegalovirus gN variants and associated clinical sequelae in infants.
Paradowska, Edyta; Jabłońska, Agnieszka; Studzińska, Mirosława; Suski, Patrycja; Kasztelewicz, Beata; Zawilińska, Barbara; Wiśniewska-Ligier, Małgorzata; Dzierżanowska-Fangrat, Katarzyna; Woźniakowska-Gęsicka, Teresa; Czech-Kowalska, Justyna; Lipka, Bożena; Kornacka, Maria; Pawlik, Dorota; Tomasik, Tomasz; Kosz-Vnenchak, Magdalena; Leśnikowski, Zbigniew J
2013-09-01
Human cytomegalovirus (HCMV) is the most widespread cause of congenital infection. The effects of various viral strains and viral loads on the infection outcome have been under debate. To determine the distribution of gN variants in HCMV strains isolated from children with congenital or postnatal infection and to establish the relationship between the viral genotype, the viral load, and the sequelae. The study population included congenitally HCMV-infected newborns and children with postnatal or unproven congenital HCMV infection. The genotyping was performed by RFLP analysis of PCR-amplified fragments, and the viral load was measured by quantitative real-time PCR. Our results demonstrated that the HCMV genotypes gN3b, gN4b, and gN4c were prevalent in the patients examined. There were no differences in the distributions of gN genotypes in the congenitally and postnatally infected children. Multiple HCMV strains were detected in both groups of children. A significant association between the HCMV gN4 genotype and the incidence of neurological disorders was observed (p=0.045). Our results suggest that the detection of the gN2 or the gN4 genotype may be indicative of serious manifestations in children. In contrast, the gN3b and the gN1 genotypes represent less pathogenic HCMV strains. The HCMV load in urine was significantly higher in children with congenital infection compared with children with postnatal infection. No correlation was found between the viral load and the genotype. Our results suggest that the gN genotype may be a virological marker of symptomatic HCMV infection in newborns. Copyright © 2013 Elsevier B.V. All rights reserved.
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Energy Technology Data Exchange (ETDEWEB)
Schultes, R.E.
Supplying 98% of the world's natural rubber, Hevea brasiliensis has transformed life around the world in only a century. This species - one of 10 in its genus - gives the best natural rubber, but much more remains to be studied concerning the numerous localized strains of the species. The British introduced to the orient seeds from the lower Amazon - representatives of a not superior ecotype of the species but, at that time a century ago, the only available germ plasm. The time for study of the intraspecific variants of H. brasiliensis and their use in programs of genetic manipulation of the genus is long overdue. But basic to this desired program is a clear taxonomic understanding of infraspecific variants, still awaiting evaluation. Although numerous taxonomic treatments of subspecific variants have been offered, there is little available to give genetic programs concrete information.
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Structural analysis of LaVO3 thin films under epitaxial strain
Directory of Open Access Journals (Sweden)
H. Meley
2018-04-01
Full Text Available Rare earth vanadate perovskites exhibit a phase diagram in which two different types of structural distortions coexist: the strongest, the rotation of the oxygen octahedra, comes from the small tolerance factor of the perovskite cell (t = 0.88 for LaVO3 and the smaller one comes from inter-site d-orbital interactions manifesting as a cooperative Jahn-Teller effect. Epitaxial strain acts on octahedral rotations and crystal field symmetry to alter this complex lattice-orbit coupling. In this study, LaVO3 thin film structures have been investigated by X-ray diffraction and scanning transmission electron microscopy. The analysis shows two different orientations of octahedral tilt patterns, as well as two distinct temperature behaviors, for compressive and tensile film strain states. Ab initio calculations capture the strain effect on the tilt pattern orientation in agreement with experimental data.
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Directory of Open Access Journals (Sweden)
Gonzalez Cezar Henrique
2004-01-01
Full Text Available Recently, electrical resistivity (ER measurements have been done during some thermomechanical tests in copper based shape memory alloys (SMA's. In this work, single crystals of Cu-based SMA's have been studied at different temperatures to analyse the relationship between stress (s and ER changes as a function of the strain (e. A good consistency between ER change values is observed in different experiments: thermal martensitic transformation, stress induced martensitic transformation and stress induced reorientation of martensite variants. During stress induced martensitic transformation (superelastic behaviour and stress induced reorientation of martensite variants, a linear relationship is obtained between ER and strain as well as the absence of hys teresis. In conclusion, the present results show a direct evidence of martensite electrical resistivity anisotropy.
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Directory of Open Access Journals (Sweden)
Khadija Khataby
2016-08-01
Three S1 gene hypervariable regions were studied and compared to the reference genotypes/serotypes that found emerging in African regions. This comparison was based on phylogenetic trees, nucleotide and amino-acid sequence analysis. It clearly appears that IBV variants reported in Africa, display a low genetic relationship between them and with the majority of the reference strains emerging in neighboring countries, except the case of variants from Libya and Egypt that show a high relatedness. Also the Massachusetts serotypes were the most prevalent co-circulating with both serotypes, Italy02 type in Morocco and Qx-like genotype in South part of the African continent. In order to control the IBV variants in African regions, an efficient vaccination strategy program should be implemented.
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Changes in classification of genetic variants in BRCA1 and BRCA2.
Kast, Karin; Wimberger, Pauline; Arnold, Norbert
2018-02-01
Classification of variants of unknown significance (VUS) in the breast cancer genes BRCA1 and BRCA2 changes with accumulating evidence for clinical relevance. In most cases down-staging towards neutral variants without clinical significance is possible. We searched the database of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) for changes in classification of genetic variants as an update to our earlier publication on genetic variants in the Centre of Dresden. Changes between 2015 and 2017 were recorded. In the group of variants of unclassified significance (VUS, Class 3, uncertain), only changes of classification towards neutral genetic variants were noted. In BRCA1, 25% of the Class 3 variants (n = 2/8) changed to Class 2 (likely benign) and Class 1 (benign). In BRCA2, in 50% of the Class 3 variants (n = 16/32), a change to Class 2 (n = 10/16) or Class 1 (n = 6/16) was observed. No change in classification was noted in Class 4 (likely pathogenic) and Class 5 (pathogenic) genetic variants in both genes. No up-staging from Class 1, Class 2 or Class 3 to more clinical significance was observed. All variants with a change in classification in our cohort were down-staged towards no clinical significance by a panel of experts of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). Prevention in families with Class 3 variants should be based on pedigree based risks and should not be guided by the presence of a VUS.
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Kikuchi, Wakako; Nakagomi, Toyoko; Gauchan, Punita; Agbemabiese, Chantal Ama; Noguchi, Atsuko; Nakagomi, Osamu; Takahashi, Tsutomu
2018-03-01
Equine-like G3P[8] rotavirus A strains with DS-1-like backbone genes have emerged since 2013. An equine-like RVA/Human-wt/JPN/15R429/2015/G3P[8] strain possessing I2-R2-C2-M2-A2-N2-T2-E2-H2 was detected in Japan in 2015. Its VP7 gene was ≥ 99.3% identical to those of equine-like G3P[4] strains detected in Japan, and the remaining 10 genes were 98.6-99.8% identical to G1P[8] double-gene reassortants detected in Japan, Thailand and the Philippines. Thus, 15R429 was likely generated through reassortment between the equine-like G3P[4] and G1P[8] reassortant strains. Notably, 15R429 was 98.5-99.8% identical across all 11 genes of the equine-like G3P[8] strains detected in Spain and Hungary in 2015.
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Absence of strong strain effects in behavioral analyses of Shank3-deficient mice
Directory of Open Access Journals (Sweden)
Elodie Drapeau
2014-06-01
Full Text Available Haploinsufficiency of SHANK3, caused by chromosomal abnormalities or mutations that disrupt one copy of the gene, leads to a neurodevelopmental syndrome called Phelan-McDermid syndrome, symptoms of which can include absent or delayed speech, intellectual disability, neurological changes and autism spectrum disorders. The SHANK3 protein forms a key structural part of the post-synaptic density. We previously generated and characterized mice with a targeted disruption of Shank3 in which exons coding for the ankyrin-repeat domain were deleted and expression of full-length Shank3 was disrupted. We documented specific deficits in synaptic function and plasticity, along with reduced reciprocal social interactions, in Shank3 heterozygous mice. Changes in phenotype owing to a mutation at a single locus are quite frequently modulated by other loci, most dramatically when the entire genetic background is changed. In mice, each strain of laboratory mouse represents a distinct genetic background and alterations in phenotype owing to gene knockout or transgenesis are frequently different across strains, which can lead to the identification of important modifier loci. We have investigated the effect of genetic background on phenotypes of Shank3 heterozygous, knockout and wild-type mice, using C57BL/6, 129SVE and FVB/Ntac strain backgrounds. We focused on observable behaviors with the goal of carrying out subsequent analyses to identify modifier loci. Surprisingly, there were very modest strain effects over a large battery of analyses. These results indicate that behavioral phenotypes associated with Shank3 haploinsufficiency are largely strain-independent.
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Directory of Open Access Journals (Sweden)
Mayumi Kamada
Full Text Available Bacillus subtilis is the main component in the fermentation of soybeans. To investigate the genetics of the soybean-fermenting B. subtilis strains and its relationship with the productivity of extracellular poly-γ-glutamic acid (γPGA, we sequenced the whole genome of eight B. subtilis stains isolated from non-salted fermented soybean foods in Southeast Asia. Assembled nucleotide sequences were compared with those of a natto (fermented soybean food starter strain B. subtilis BEST195 and the laboratory standard strain B. subtilis 168 that is incapable of γPGA production. Detected variants were investigated in terms of insertion sequences, biotin synthesis, production of subtilisin NAT, and regulatory genes for γPGA synthesis, which were related to fermentation process. Comparing genome sequences, we found that the strains that produce γPGA have a deletion in a protein that constitutes the flagellar basal body, and this deletion was not found in the non-producing strains. We further identified diversity in variants of the bio operon, which is responsible for the biotin auxotrophism of the natto starter strains. Phylogenetic analysis using multilocus sequencing typing revealed that the B. subtilis strains isolated from the non-salted fermented soybeans were not clustered together, while the natto-fermenting strains were tightly clustered; this analysis also suggested that the strain isolated from "Tua Nao" of Thailand traces a different evolutionary process from other strains.
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Strain dependent microstructural modifications of BiCrO{sub 3} epitaxial thin films
Energy Technology Data Exchange (ETDEWEB)
Kannan, Vijayanandhini, E-mail: kvnandhini@gmail.com [Max Planck Institute of Microstructure Physics, Weinberg 2, D-06120 Halle (Saale) (Germany); CNRS, University of Bordeaux, ICMCB, UPR 9048, F-33600 Pessac (France); Arredondo, Miryam; Johann, Florian; Hesse, Dietrich [Max Planck Institute of Microstructure Physics, Weinberg 2, D-06120 Halle (Saale) (Germany); Labrugere, Christine [CNRS, University of Bordeaux, ICMCB, UPR 9048, F-33600 Pessac (France); CeCaMA, University of Bordeaux, ICMCB, F-33600 Pessac (France); Maglione, Mario [CNRS, University of Bordeaux, ICMCB, UPR 9048, F-33600 Pessac (France); Vrejoiu, Ionela [Max Planck Institute of Microstructure Physics, Weinberg 2, D-06120 Halle (Saale) (Germany)
2013-10-31
Strain-dependent microstructural modifications were observed in epitaxial BiCrO{sub 3} (BCO) thin films fabricated on single crystalline substrates, utilizing pulsed laser deposition. The following conditions were employed to modify the epitaxial-strain: (i) in-plane tensile strain, BCO{sub STO} [BCO grown on buffered SrTiO{sub 3} (001)] and in-plane compressive strain, BCO{sub NGO} [BCO grown on buffered NdGaO{sub 3} (110)] and (ii) varying BCO film thickness. A combination of techniques like X-ray diffraction, X-ray photoelectron spectroscopy (XPS) and high resolution transmission electron microscopy (TEM) was used to analyse the epitaxial growth quality and the microstructure of BCO. Our studies revealed that in the case of BCO{sub STO}, a coherent interface with homogeneous orthorhombic phase is obtained only for BCO film with thicknesses, d < 50 nm. All the BCO{sub STO} films with d ≥ 50 nm were found to be strain-relaxed with an orthorhombic phase showing 1/2 <100> and 1/4 <101> satellite reflections, the latter oriented at 45° from orthorhombic diffraction spots. High angle annular dark field scanning TEM of these films strongly suggested that the satellite reflections, 1/2 <100> and 1/4 <101>, originate from the atomic stacking sequence changes (or “modulated structure”) as reported for polytypes, without altering the chemical composition. The unaltered stoichiometry was confirmed by estimating both valency of Bi and Cr cations by surface and in-depth XPS analysis as well as the stoichiometric ratio (1 Bi:1 Cr) using scanning TEM–energy dispersive X-ray analysis. In contrast, compressively strained BCO{sub NGO} films exhibited monoclinic symmetry without any structural modulations or interfacial defects, up to d ∼ 200 nm. Our results indicate that both the substrate-induced in-plane epitaxial strain and the BCO film thickness are the crucial parameters to stabilise a homogeneous BCO phase in an epitaxially grown film. - Highlights: • Phase pure
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Optimisation of 1.3 μm strained-layer semiconductor lasers
International Nuclear Information System (INIS)
Pacey, C.
1999-03-01
The objectives of the research undertaken have been to investigate the properties of semiconductor lasers operating at around 1.3 μm. The aim of the investigation is to suggest modifications which give rise to improved operating characteristics especially in the high temperature (approaching 85 deg. C) range. The investigation can be divided into 2 sections: a theoretical approach and an experimental section. The theoretical study examined the performance of compressively strained InGaAsP/InP multiple quantum-well lasers emitting at 1.3 μm. in order to investigate the important factors and trends in the threshold current density and differential gain with strain, well width and well number. Structures with a fixed compressive strain of 1% but variable well width, and also with a fixed well width but variable strain from 0% to 1.4% have been considered. It has been found that there is little benefit to having compressive strains greater than 1%. For structures with a fixed 1% compressive strain and unstrained barriers, an optimum structure for lowest threshold current density and a high differential gain has been found to consist of six 35 A quantum-wells. In addition, compensated strain (CS) structures with compressive wells and tensile barriers have been examined. It is shown that the conduction band offset can be significantly increased and the valence band offset reduced in such structures, to give band-offset ratios comparable with aluminium based 1.3 μm devices. The gain calculations performed suggest that there is little degradation in the threshold carrier density or differential gain due to these alterations in the band offsets; and hence a better laser performance is expected due to a reduction in thermal leakage currents due to the improved electron confinement. The experimental study concentrates on looking at certain key design parameters to investigate their effect on the laser performance. These design parameters range from the number of quantum
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Johnston, M. J. S.; Borcherdt, R. D.; Linde, A. T.
1986-10-01
Measurements of dilational earth strain in the frequency band 25-10-5 Hz have been made on a deep borehole strainmeter installed near the San Andreas fault. These data are used to determine seismic radiation fields during nuclear explosions, teleseisms, local earthquakes, and ground noise during seismically quiet times. Strains of less than 10-10 on these instruments can be clearly resolved at short periods (< 10 s) and are recorded with wide dynamic range digital recorders. This permits measurement of the static and dynamic strain variations in the near field of local earthquakes. Noise spectra for earth strain referenced to 1 (strain)2/Hz show that strain resolution decreases at about 10 dB per decade of frequency from -150 dB at 10-4 Hz to -223 dB at 10 Hz. Exact expressions are derived to relate the volumetric strain and displacement field for a homogeneous P wave in a general viscoelastic solid as observed on colocated dilatometers and seismometers. A rare near-field recording of strain and seismic velocity was obtained on May 26, 1984, from an earthquake (ML 3.2) at a hypocentral distance of 3.2 km near the San Andreas fault at San Juan Bautista, California. While the data indicate no precursory strain release at the 5 × 10-11 strain level, a coseismic strain release of 1.86 nanostrain was observed. This change in strain is consistent with that calculated from a simple dislocation model of the event. Ground displacement spectra, determined from the downhole strain data and instrument-corrected surface seismic data, suggest that source parameters estimated from surface recordings may be contaminated by amplification effects in near-surface low-velocity materials.
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Directory of Open Access Journals (Sweden)
MAHMOUD EL-HARIRI
2015-12-01
Full Text Available Glucose oxidase (GOx is the basic stone for many of biological industry worldwide. The improvement of GOx production basically depends on selection of hyper producer strain of Aspergillus niger. Selective isolation and screening for natural hyper producer strains of A. niger and sequence analysis of the GOD gene, which is responsible for production of the enzyme, are very effective approaches to investigate the naturally modified strains of A. niger with hyper productive capacity of GOx enzyme. The aims of the current study were selective isolation of naturally hyper GOx producing strains of A. niger and evaluation of their GOx activities under optimized parameters in the laboratory. Five wild Egyptian isolates of A. niger were screened for GOx and catalase activity using two types of modified basal liquid media. The GOx activity was evaluated by high throughout liquid phase system. The isolates showed a variable activity for GOx production ranged from 0 to 28.7 U.ml-1. One isolate coded Strain 7 was negative GOx producer on Vogel's broth medium in comparison to other isolates, while its GOx activity on Cazpek Dox was considered as positive (7.28 U.ml-1. It was concluded that GOx production is affected by three controllable factors – the basal media components, time of incubation, and the strain with its adaption to the media components. Also, the catalase activity was tested and it was produced with a different degree of variability, which may be reflected on GOx stability. GOD genes of these wild variant of A. niger were cloned and sequenced to determine intraspecies diversity of GOD between the wild variants. The comparison of isolated wild variants to other reference hyper GOx producer strains of A. niger was performed to determine if the GOD sequence analysis of these strains can be distinguished based on their GOx activity. This is the first report for isolation and detection of naturally A. niger hyper GOx-producer strains with
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Dealloyed Pt3Co nanoparticles with higher geometric strain for superior hydrogen evolution reaction
Saquib, Mohammad; Halder, Aditi
2018-06-01
In the present work, the effect of surface strain in the carbon supported Pt3Co dealloy catalyst towards hydrogen evolution reaction (HER) has been reported. Dealloying process is adopted to generate the geometric strain in Pt3Co/C alloy by preferential dissolution of non-noble metal (Co) from the alloy. The developed geometric strain has been estimated by different microstructural characterization techniques. Electrochemical studies showed that the highest current density for HER was obtained for Pt3Co/C dealloy catalyst and it was nearly 2 and 5 times higher than Pt3Co/C alloy and Pt/C respectively. Tafel slope for HER was improved from 49 (Pt/C) to 34 mV dec-1 (Pt3Co/C dealloy), indicating that the surface strain plays important role in the improvement of the catalytic activity of Pt3Co catalyst. The chronoamperometry data, LSV curves and ECSA values before and after chronoamperometry confirmed that Pt3Co/C dealloy catalyst was a stable as well as a durable electrocatalyst for HER.
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Directory of Open Access Journals (Sweden)
Salgado PC
2017-03-01
Full Text Available Patricia C Salgado,1 Fabiana DV Genvigir,1 Claudia R Felipe,2 Helio Tedesco-Silva Jr,2 Jose O Medina-Pestana,2 Sonia Q Doi,3 Mario H Hirata,1 Rosario DC Hirata1 1Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of Sao Paulo, 2Division of Nephrology, Hospital do Rim, Federal University of Sao Paulo, Sao Paulo, Brazil; 3School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA Background: The effects of genetic variants related to the pharmacodynamic mechanisms of immunosuppressive drugs on their therapeutic efficacy and safety have been poorly explored. This study was performed to investigate the influence of the PPP3CA c.249G>A variant on the clinical outcomes of kidney transplant recipients. Patients and methods: A total of 148 Brazilian patients received tacrolimus (TAC-based immunosuppressive therapy for 90 days post-kidney transplantation. The PPP3CA rs3730251 (c.249G>A polymorphism was determined by real-time polymerase chain reaction. Single-nucleotide polymorphism (SNP data for CYP3A5 rs776746 (CYP3A5*3C; g.6986A>G were used to eliminate the confounding effects of this variant. Results: The PPP3CA c.249G>A SNP did not influence early TAC exposure, renal function, or other laboratory parameters, including levels of urea, creatinine, glucose, and lipids, and blood counts. This variant also did not account for the cumulative incidence of biopsy-confirmed acute rejection or delayed graft function. Regarding adverse events, PPP3CA c.249A allele carriers initially had a 3.05-fold increased probability of treatment-induced blood and lymphatic system disorders compared with c.249GG genotype individuals (95% confidence interval: 1.10–8.48, p=0.032. However, this result was not maintained after adjusting for body weight and CYP3A5*3C SNP status (p=0.086. Conclusion: The PPP3CA c.249G>A variant does not influence the clinical outcomes of Brazilian patients in the
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Kim, Edward; Seftel, Allen; Goldfischer, Evan; Baygani, Simin; Burns, Patrick
2015-02-01
Phosphodiesterase type-5 inhibitors (PDE5Is) are first-line therapies for erectile dysfunction (ED). Sildenafil (SIL) and vardenafil (VAR) are approved for as-needed (PRN) dosing; tadalafil (TAD) is approved for both PRN and once-a-day (OaD) dosing for ED. Recent evidence suggests that TAD-OaD may be effective as therapy in men with an incomplete response to PRN-PDE5I therapy. This study evaluated whether TAD-OaD provides similar efficacy in men with ED who had previously demonstrated a partial response to PRN-PDE5I therapy. In this randomized, double-blind, placebo-controlled trial, men with a ≥3 month ED history received SIL 100 mg, TAD 20 mg, or VAR 20 mg during a 4 week open-label lead-in period. Those with International Index of Erectile Function - Erectile Function (IIEF-EF) domain scores TAD 2.5 mg up-titrated to 5 mg, TAD 5 mg, or placebo (PBO) OaD for 12 weeks. MAIN OUTCOME MEASURES obtained from patients treated with TAD-OaD were compared to PBO-treated patients. Additionally, results of treatment with TAD-OaD were compared to results obtained from 4 week PRN-PDE5I therapy to determine whether OaD and PRN regimens provided comparable efficacy. NCT01130532. International Index of Erectile Function (IIEF) domain scores; Sexual Encounter Profile (SEP) questions 2-5. Endpoint data was obtained from 590 men (391 TAD; 199 PBO). RESULTS for all IIEF and SEP measures were significantly better for TAD-OaD (p TAD 2.5 mg and TAD 5 mg OaD therapy were safe and generally well tolerated. Tadalafil once daily is a viable alternative to as-needed PDE5I therapy in men with ED. Key limitations include the lack of a PRN PDE5I study group during the double-blind period, and that many more patients took tadalafil than sildenafil or vardenafil during the PRN period.
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Balish, Amanda; Garten, Rebecca; Klimov, Alexander; Villanueva, Julie
2013-07-01
The performance of rapid influenza diagnostic tests (RIDTs) that detect influenza viral nucleoprotein (NP) antigen has been reported to be variable. Recent human infections with variant influenza A viruses that are circulating in pigs prompted the investigation of the analytical reactivity of RIDTs with these variant viruses. To determine analytical reactivity of seven FDA-cleared RIDTs with influenza A variant viruses in comparison with the reactivity with recently circulating seasonal influenza A viruses. Tenfold serial dilutions of cell culture-grown seasonal and variant influenza A viruses were prepared and tested in duplicate with seven RIDTs. All RIDTs evaluated in this study detected the seasonal influenza A(H3N2) virus, although detection limits varied among assays. All but one examined RIDT identified the influenza A(H1N1)pdm09 virus. However, only four of seven RIDTs detected all influenza A(H3N2)v, A(H1N2)v, and A(H1N1)v viruses. Reduced sensitivity of RIDTs to variant influenza viruses may be due to amino acid differences between the NP proteins of seasonal viruses and the NP proteins from viruses circulating in pigs. Clinicians should be aware of the limitations of RIDTs to detect influenza A variant viruses. Specimens from patients with influenza-like illness in whom H3N2v is suspected should be sent to public health laboratories for additional diagnostic testing. Published 2012. This article is a US Government work and is in the public domain in the USA.
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Competitive Dominance by a Bacteriocin-Producing Vibrio harveyi Strain.
Hoyt, P R; Sizemore, R K
1982-09-01
Vibrio (Beneckea) harveyi, a bioluminescent marine bacterium, has been shown to produce a bacteriocin-like substance the production of which is mediated by a plasmid. This substance is assumed to be proteinaceous because of its sensitivity to certain proteolytic enzymes. It is stable at low temperatures and can be concentrated by ammonium sulfate precipitation or negative-pressure dialysis. The molecular weight of the bacteriocin was determined to be 2.4 x 10 by molecular exclusion chromatography. Competition experiments indicated that bacteriocin-producing strains predominated over cured variants of the same strain in broth culture experiments. We studied several environmental parameters (pH, salinity, temperature, nutrient concentration) to determine their effects on the competitive advantage bestowed on a bacteriocin-producing strain. Under simulated free-living conditions, no competitive advantage attributable to bacteriocin production was observed. In a simulated enteric habitat, a bacteriocin-producing strain showed dramatic (>90%) inhibition of the sensitive strain within 24 h.
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Papadimitriou, Ioannis D; Lucia, Alejandro; Pitsiladis, Yannis P; Pushkarev, Vladimir P; Dyatlov, Dmitry A; Orekhov, Evgeniy F; Artioli, Guilherme G; Guilherme, João Paulo L F; Lancha, Antonio H; Ginevičienė, Valentina; Cieszczyk, Pawel; Maciejewska-Karlowska, Agnieszka; Sawczuk, Marek; Muniesa, Carlos A; Kouvatsi, Anastasia; Massidda, Myosotis; Calò, Carla Maria; Garton, Fleur; Houweling, Peter J; Wang, Guan; Austin, Krista; Druzhevskaya, Anastasiya M; Astratenkova, Irina V; Ahmetov, Ildus I; Bishop, David J; North, Kathryn N; Eynon, Nir
2016-04-13
To date, studies investigating the association between ACTN3 R577X and ACE I/D gene variants and elite sprint/power performance have been limited by small cohorts from mixed sport disciplines, without quantitative measures of performance. To examine the association between these variants and sprint time in elite athletes. We collected a total of 555 best personal 100-, 200-, and 400-m times of 346 elite sprinters in a large cohort of elite Caucasian or African origin sprinters from 10 different countries. Sprinters were genotyped for ACTN3 R577X and ACE ID variants. On average, male Caucasian sprinters with the ACTN3 577RR or the ACE DD genotype had faster best 200-m sprint time than their 577XX (21.19 ± 0.53 s vs. 21.86 ± 0.54 s, p = 0.016) and ACE II (21.33 ± 0.56 vs. 21.93 ± 0.67 sec, p = 0.004) counterparts and only one case of ACE II, and no cases of ACTN3 577XX, had a faster 200-m time than the 2012 London Olympics qualifying (vs. 12 qualified sprinters with 577RR or 577RX genotype). Caucasian sprinters with the ACE DD genotype had faster best 400-m sprint time than their ACE II counterparts (46.94 ± 1.19 s vs. 48.50 ± 1.07 s, p = 0.003). Using genetic models we found that the ACTN3 577R allele and ACE D allele dominant model account for 0.92 % and 1.48 % of sprint time variance, respectively. Despite sprint performance relying on many gene variants and environment, the % sprint time variance explained by ACE and ACTN3 is substantial at the elite level and might be the difference between a world record and only making the final.
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Directory of Open Access Journals (Sweden)
Régnier SA
2015-05-01
Full Text Available Stephane A Régnier,1 William Malcolm,2 Jennifer Haig,3 Weiguang Xue41Novartis Pharma AG, Basel, Switzerland; 2Novartis Pharmaceuticals UK Ltd, Frimley Business Park, UK; 3Optum, Burlington, ON, Canada; 4Optum, Uxbridge, UKBackground: Ranibizumab and aflibercept are alternative anti-vascular endothelial growth factor agents approved for the treatment of visual impairment (VI due to diabetic macular edema (DME.Objective: To estimate, from a UK healthcare perspective, the cost-effectiveness of ranibizumab 0.5 mg pro re nata (PRN and ranibizumab 0.5 mg treat and extend (T&E compared with aflibercept 2 mg every 8 weeks after five initial monthly doses (2q8 in the treatment of VI due to DME.Methods: A Markov model previously reviewed by the National Institute for Health and Care Excellence was used to simulate the long-term outcomes and costs of treating DME. Health states were defined by increments of ten letters in best-corrected visual acuity (BCVA, with a 3-month cycle length. Patients could gain (or lose a maximum of two health states between cycles. A 3-year treatment time frame and a lifetime horizon were used. Future costs and health outcomes were discounted at 3.5% per annum. Patient baseline characteristics and the efficacy of ranibizumab PRN were derived using data from the RESTORE study. The relative efficacies of ranibizumab PRN, ranibizumab T&E, and aflibercept were assessed with a network meta-analysis. Different utilities were assigned based on BCVA and whether the treated eye was the better- or the worse-seeing eye. Sensitivity analyses tested the robustness of the model.Results: Lifetime costs per patient of treating DME were £20,019 for ranibizumab PRN, £22,930 for ranibizumab T&E, and £25,859 for aflibercept 2q8. Ranibizumab was dominant over aflibercept, with an incremental gain of 0.05 quality-adjusted life-years (QALYs and cost savings of £5,841 (PRN and £2,930 (T&E compared with aflibercept. Ranibizumab PRN and
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Characterization of form variants of Xenorhabdus luminescens.
Gerritsen, L.J.M.; Raay, de G.; Smits, P.H.
1992-01-01
From Xenorhabdus luminescens XE-87.3 four variants were isolated. One, which produced a red pigment and antibiotics, was luminescent, and could take up dye from culture media, was considered the primary form (XE-red). A pink-pigmented variant (XE-pink) differed from the primary form only in
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Cingolani, Pablo; Platts, Adrian; Wang, Le Lily; Coon, Melissa; Nguyen, Tung; Wang, Luan; Land, Susan J; Lu, Xiangyi; Ruden, Douglas M
2012-01-01
We describe a new computer program, SnpEff, for rapidly categorizing the effects of variants in genome sequences. Once a genome is sequenced, SnpEff annotates variants based on their genomic locations and predicts coding effects. Annotated genomic locations include intronic, untranslated region, upstream, downstream, splice site, or intergenic regions. Coding effects such as synonymous or non-synonymous amino acid replacement, start codon gains or losses, stop codon gains or losses, or frame shifts can be predicted. Here the use of SnpEff is illustrated by annotating ~356,660 candidate SNPs in ~117 Mb unique sequences, representing a substitution rate of ~1/305 nucleotides, between the Drosophila melanogaster w(1118); iso-2; iso-3 strain and the reference y(1); cn(1) bw(1) sp(1) strain. We show that ~15,842 SNPs are synonymous and ~4,467 SNPs are non-synonymous (N/S ~0.28). The remaining SNPs are in other categories, such as stop codon gains (38 SNPs), stop codon losses (8 SNPs), and start codon gains (297 SNPs) in the 5'UTR. We found, as expected, that the SNP frequency is proportional to the recombination frequency (i.e., highest in the middle of chromosome arms). We also found that start-gain or stop-lost SNPs in Drosophila melanogaster often result in additions of N-terminal or C-terminal amino acids that are conserved in other Drosophila species. It appears that the 5' and 3' UTRs are reservoirs for genetic variations that changes the termini of proteins during evolution of the Drosophila genus. As genome sequencing is becoming inexpensive and routine, SnpEff enables rapid analyses of whole-genome sequencing data to be performed by an individual laboratory.
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Strain induced atomic structure at the Ir-doped LaAlO3/SrTiO3 interface.
Lee, M; Arras, R; Warot-Fonrose, B; Hungria, T; Lippmaa, M; Daimon, H; Casanove, M J
2017-11-01
The structure of Ir-doped LaAlO 3 /SrTiO 3 (001) interfaces was investigated on the atomic scale using probe-corrected transmission electron microscopy in high-angle annular dark-field scanning mode (HAADF-STEM) and electron energy loss spectroscopy (EELS), combined with first-principles calculations. We report the evolution of the strain state experimentally measured in a 5 unit-cell thick LaAlO 3 film as a function of the Ir concentration in the topmost SrTiO 3 layer. It is shown that the LaAlO 3 layers remain fully elastically strained up to 3% of Ir doping, whereas a higher doping level seems to promote strain relaxation through enhanced cationic interdiffusion. The observed differences between the energy loss near edge structure (ELNES) of Ti-L 2,3 and O-K edges at non-doped and Ir-doped interfaces are consistent with the location of the Ir dopants at the interface, up to 3% of Ir doping. These findings, supported by the results of density functional theory (DFT) calculations, provide strong evidence that the effect of dopant concentrations on the properties of this kind of interface should not be analyzed without obtaining essential information from the fine structural and chemical analysis of the grown structures.
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T3 Regulates a Human Macrophage-Derived TSH-β Splice Variant: Implications for Human Bone Biology.
Baliram, R; Latif, R; Morshed, S A; Zaidi, M; Davies, T F
2016-09-01
TSH and thyroid hormones (T3 and T4) are intimately involved in bone biology. We have previously reported the presence of a murine TSH-β splice variant (TSH-βv) expressed specifically in bone marrow-derived macrophages and that exerted an osteoprotective effect by inducing osteoblastogenesis. To extend this observation and its relevance to human bone biology, we set out to identify and characterize a TSH-β variant in human macrophages. Real-time PCR analyses using human TSH-β-specific primers identified a 364-bp product in macrophages, bone marrow, and peripheral blood mononuclear cells that was sequence verified and was homologous to a human TSH-βv previously reported. We then examined TSH-βv regulation using the THP-1 human monocyte cell line matured into macrophages. After 4 days, 46.1% of the THP-1 cells expressed the macrophage markers CD-14 and macrophage colony-stimulating factor and exhibited typical morphological characteristics of macrophages. Real-time PCR analyses of these cells treated in a dose-dependent manner with T3 showed a 14-fold induction of human TSH-βv mRNA and variant protein. Furthermore, these human TSH-βv-positive cells, induced by T3 exposure, had categorized into both M1 and M2 macrophage phenotypes as evidenced by the expression of macrophage colony-stimulating factor for M1 and CCL-22 for M2. These data indicate that in hyperthyroidism, bone marrow resident macrophages have the potential to exert enhanced osteoprotective effects by oversecreting human TSH-βv, which may exert its local osteoprotective role via osteoblast and osteoclast TSH receptors.
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Directory of Open Access Journals (Sweden)
Mengmeng Du
Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.
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Effects of pre- and postnatal litter size reduction on development and behavior of rat offspring.
Milković, K; Paunović, J; Joffe, J M
1976-07-01
Litter size was reduced to 2-5 rat pups either prenatally by unilateral maternal oviduct ligation (Group PRN) or postnatally by removing pups (Group PST). Normal size litters (8-10 pups) of sham ligated (SHM) and intact (CON) mothers served as controls. Weights at 30 days were increased by prenatal or postnatal reduction and reduced by prenatal stress (SHM); the sex difference in weight was most pronounced in PRN rats. At 75 days PRN rats were heaviest, with no differences between the other groups. Relative ovarian weights were reduced in PRN females and absolute testes weights increased in PST males. The PRN and SHM females had smaller relative adrenal weights than CON and PST females. Open-field activity was generally increased by prior avoidance conditioning and effects of treatments were found only in groups tested after avoidance-conditioning: PRN and SHM rats were more active than PST and CON rats, particularly on Days 1 (SHM) and 4 (SHM and PRN) of testing. Passive-avoidance behavior of PRN rats was also more susceptible to previous test experience: they emerged more slowly if they had prior open-field experience. The PST animals, in contrast, emerged more rapidly after prior test experience. Plasma corticosterone levels and shuttlebox conditioning and extinction were unaffected by treatments.
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Townley, Ryan A; Dawson, Elliot T; Drubach, Daniel A
2018-02-01
Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapid and fatal neurodegenerative disease defined by misfolded prion proteins accumulating in the brain. A minority of cases initially present with posterior cortical atrophy (PCA) phenotype, also known as Heidenhain variant or visual variant CJD. This case provides further evidence of sCJD presenting as PCA. The case also provides evidence for early DWI changes and cortical atrophy over 30 months before neurologic decline and subsequent death. The prolonged disease course correlates with prion protein codon 129 heterozygosity and coexistence of multiple prion strains.
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Effect of strain on voltage-controlled magnetism in BiFeO3-based heterostructures
Wang, J. J.; Hu, J. M.; Yang, T. N.; Feng, M.; Zhang, J. X.; Chen, L. Q.; Nan, C. W.
2014-01-01
Voltage-modulated magnetism in magnetic/BiFeO3 heterostructures can be driven by a combination of the intrinsic ferroelectric-antiferromagnetic coupling in BiFeO3 and the antiferromagnetic-ferromagnetic exchange interaction across the heterointerface. However, ferroelectric BiFeO3 film is also ferroelastic, thus it is possible to generate voltage-induced strain in BiFeO3 that could be applied onto the magnetic layer across the heterointerface and modulate magnetism through magnetoelastic coupling. Here, we investigated, using phase-field simulations, the role of strain in voltage-controlled magnetism for these BiFeO3-based heterostructures. It is predicted, under certain condition, coexistence of strain and exchange interaction will result in a pure voltage-driven 180° magnetization reversal in BiFeO3-based heterostructures. PMID:24686503
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Lu, Ling; Li, Chunhua; Yuan, Jie; Lu, Teng; Okamoto, Hiroaki; Murphy, Donald G
2013-03-01
We characterized the full-length genomes of five distinct hepatitis C virus (HCV)-3 isolates. These represent the first complete genomes for subtypes 3g and 3h, the second such genomes for 3k and 3i, and of one novel variant presently not assigned to a subtype. Each genome was determined from 18-25 overlapping fragments. They had lengths of 9579-9660 nt and each contained a single ORF encoding 3020-3025 aa. They were isolated from five patients residing in Canada; four were of Asian origin and one was of Somali origin. Phylogenetic analysis using 64 partial NS5B sequences differentiated 10 assigned subtypes, 3a-3i and 3k, and two additional lineages within genotype 3. From the data of this study, HCV-3 full-length sequences are now available for six of the assigned subtypes and one unassigned. Our findings should add insights to HCV evolutionary studies and clinical applications.
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Directory of Open Access Journals (Sweden)
Kozak Christine A
2009-10-01
Full Text Available Abstract Background The evolutionary interactions between retroviruses and their receptors result in adaptive selection of restriction variants that can allow natural populations to evade retrovirus infection. The mouse xenotropic/polytropic (X/PMV gammaretroviruses rely on the XPR1 cell surface receptor for entry into host cells, and polymorphic variants of this receptor have been identified in different rodent species. Results We screened a panel of X/PMVs for infectivity on rodent cells carrying 6 different XPR1 receptor variants. The X/PMVs included 5 well-characterized laboratory and wild mouse virus isolates as well as a novel cytopathic XMV-related virus, termed Cz524, isolated from an Eastern European wild mouse-derived strain, and XMRV, a xenotropic-like virus isolated from human prostate cancer. The 7 viruses define 6 distinct tropisms. Cz524 and another wild mouse isolate, CasE#1, have unique species tropisms. Among the PMVs, one Friend isolate is restricted by rat cells. Among the XMVs, two isolates, XMRV and AKR6, differ from other XMVs in their PMV-like restriction in hamster cells. We generated a set of Xpr1 mutants and chimeras, and identified critical amino acids in two extracellular loops (ECLs that mediate entry of these different viruses, including 3 residues in ECL3 that are involved in PMV entry (E500, T507, and V508 and can also influence infectivity by AKR6 and Cz524. Conclusion We used a set of natural variants and mutants of Xpr1 to define 6 distinct host range variants among naturally occurring X/PMVs (2 XMV variants, 2 PMVs, 2 different wild mouse variants. We identified critical amino acids in XPR1 that mediate entry of these viruses. These gammaretroviruses and their XPR1 receptor are thus highly functionally polymorphic, a consequence of the evolutionary pressures that favor both host resistance and virus escape mutants. This variation accounts for multiple naturally occurring virus resistance phenotypes and
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El Khoury, Louis; Ribbans, William J; Raleigh, Stuart M
2016-09-01
Variants within the MMP3 (rs679620) and TIMP2 (rs4789932) genes have been associated with the risk of Achilles tendon pathology (ATP) in populations from South Africa and Australia. This study aimed to determine whether these variants were associated with the risk of ATP in British Caucasians. We recruited 118 cases with ATP, including a subset of 25 individuals with Achilles tendon rupture (RUP) and 131 controls. DNA samples were isolated from saliva and genotyped using qPCR. For the TIMP2 rs4789932 variant we found a significant (p = 0.038) difference in the genotype distribution frequency between males with ATP (CC, 39.4%; CT, 43.7%; TT, 16.9%) compared to male controls (CC, 20.7%; CT, 59.8%; TT, 19.5%). We also observed a difference in the TIMP2 rs4789932 genotype distribution between males with rupture compared to male controls (p = 0.038). The MMP3 rs679620 GG genotype was found to be overrepresented in the Achilles tendon rupture (RUP) group (AA, 24.0%; AG, 32.0%; GG, 44.0%) compared to controls (AA, 26.7%; AG, 54.2%; GG, 19.1%). In conclusion, the CT genotype of the TIMP2 rs4789932 variant was associated with lower risk of ATP in males. Furthermore, while we revealed differences for both variants in genotype distribution between the RUP and control groups, the sample size of the RUP group was small and confirmation would be required in additional cohorts. Finally, although both the TIMP2 rs4789932 and MMP3 rs679620 variants tentatively associated with ATP, there were differences in the direction of association compared to earlier work.
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Development of intra-strain self-cloning procedure for breeding baker's yeast strains.
Nakagawa, Youji; Ogihara, Hiroyuki; Mochizuki, Chisato; Yamamura, Hideki; Iimura, Yuzuru; Hayakawa, Masayuki
2017-03-01
Previously reported self-cloning procedures for breeding of industrial yeast strains require DNA from other strains, plasmid DNA, or mutagenesis. Therefore, we aimed to construct a self-cloning baker's yeast strain that exhibits freeze tolerance via an improved self-cloning procedure. We first disrupted the URA3 gene of a prototrophic baker's yeast strain without the use of any marker gene, resulting in a Δura3 homozygous disruptant. Then, the URA3 gene of the parental baker's yeast strain was used as a selection marker to introduce the constitutive TDH3 promoter upstream of the PDE2 gene encoding high-affinity cyclic AMP phosphodiesterase. This self-cloning procedure was performed without using DNA from other Saccharomyces cerevisiae strains, plasmid DNA, or mutagenesis and was therefore designated an intra-strain self-cloning procedure. Using this self-cloning procedure, we succeeded in producing self-cloning baker's yeast strains that harbor the TDH3p-PDE2 gene heterozygously and homozygously, designated TDH3p-PDE2 hetero and TDH3p-PDE2 homo strains, respectively. These self-cloning strains expressed much higher levels of PDE2 mRNA than the parental strain and exhibited higher viability after freeze stress, as well as higher fermentation ability in frozen dough, when compared with the parental strain. The TDH3p-PDE2 homo strain was genetically more stable than the TDH3p-PDE2 hetero strain. These results indicate that both heterozygous and homozygous strains of self-cloning PDE2-overexpressing freeze-tolerant strains of industrial baker's yeast can be prepared using the intra-strain self-cloning procedure, and, from a practical viewpoint, the TDH3p-PDE2 homo strain constructed in this study is preferable to the TDH3p-PDE2 hetero strain for frozen dough baking. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
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Ho, Cynthia K. Y.; Welkers, Matthijs R. A.; Thomas, Xiomara V.; Sullivan, James C.; Kieffer, Tara L.; Reesink, Henk W.; Rebers, Sjoerd P. H.; de Jong, Menno D.; Schinkel, Janke; Molenkamp, Richard
2015-01-01
We compared 454 amplicon sequencing with clonal sequencing for the characterization of intra-host hepatitis C virus (HCV) NS3 variants. Clonal and 454 sequences were obtained from 12 patients enrolled in a clinical phase I study for telaprevir, an NS3-4a protease inhibitor. Thirty-nine datasets were
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Directory of Open Access Journals (Sweden)
Li Hui
2011-05-01
Full Text Available Abstract Background Synaptic genes, NLGN3 and NLGN4X, two homologous members of the neuroligin family, have been supposed as predisposition loci for autism spectrum disorders (ASDs, and defects of these two genes have been identified in a small fraction of individuals with ASDs. But no such rare variant in these two genes has as yet been adequately replicated in Chinese population and no common variant has been further investigated to be associated with ASDs. Methods 7 known ASDs-related rare variants in NLGN3 and NLGN4X genes were screened for replication of the initial findings and 12 intronic tagging single nucleotide polymorphisms (SNPs were genotyped for case-control association analysis in a total of 229 ASDs cases and 184 control individuals in a Chinese Han cohort, using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF mass spectrometry. Results We found that a common intronic variant, SNP rs4844285 in NLGN3 gene, and a specific 3-marker haplotype XA-XG-XT (rs11795613-rs4844285-rs4844286 containing this individual SNP were associated with ASDs and showed a male bias, even after correction for multiple testing (SNP allele: P = 0.048, haplotype:P = 0.032. Simultaneously, none of these 7 known rare mutation of NLGN3 and NLGN4X genes was identified, neither in our patients with ASDs nor controls, giving further evidence that these known rare variants might be not enriched in Chinese Han cohort. Conclusion The present study provides initial evidence that a common variant in NLGN3 gene may play a role in the etiology of ASDs among affected males in Chinese Han population, and further supports the hypothesis that defect of synapse might involvement in the pathophysiology of ASDs.
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Directory of Open Access Journals (Sweden)
David Metzgar
Full Text Available For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based or remarkably insensitive (antibody-based. Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A
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Metzgar, David; Myers, Christopher A; Russell, Kevin L; Faix, Dennis; Blair, Patrick J; Brown, Jason; Vo, Scott; Swayne, David E; Thomas, Colleen; Stenger, David A; Lin, Baochuan; Malanoski, Anthony P; Wang, Zheng; Blaney, Kate M; Long, Nina C; Schnur, Joel M; Saad, Magdi D; Borsuk, Lisa A; Lichanska, Agnieszka M; Lorence, Matthew C; Weslowski, Brian; Schafer, Klaus O; Tibbetts, Clark
2010-02-03
For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence
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Anisotropic strain relaxation in (Ba0.6Sr0.4)TiO3 epitaxial thin films
Simon, W. K.; Akdogan, E. K.; Safari, A.
2005-05-01
We have studied the evolution of anisotropic epitaxial strains in ⟨110⟩-oriented (Ba0.60Sr0.40)TiO3 paraelectric (m3m) thin films grown on orthorhombic (mm2) ⟨100⟩-oriented NdGaO3 by high-resolution x-ray diffractometry. All the six independent components of the three-dimensional strain tensor were measured in films with 25-1200-nm thickness, from which the principal stresses and strains were obtained. Pole figure analysis indicated that the epitaxial relations are [001]m3m‖[001]mm2 and [1¯10]m3m‖[010]mm2 in the plane of the film, and [110]m3m‖[100]mm2 along the growth direction. The dislocation system responsible for strain relief along [001] has been determined to be ∣b ∣(001)=3/4∣b∣. Strain relief along the [1¯10] direction, on the other hand, has been determined to be due to a coupled mechanism given by ∣b∣(1¯10)=∣b∣ and ∣b∣(1¯10)=√3 /4∣b∣. Critical thicknesses, as determined from nonlinear regression using the Matthews-Blakeslee equation, for misfit dislocation formation along [001] and [1¯10] direction were found to be 5 and 7 nm, respectively. The residual strain energy density was calculated as ˜2.9×106J/m3 at 25 nm, which was found to relax an order of magnitude by 200 nm. At 200 nm, the linear dislocation density along [001] and [1¯10] are ˜6.5×105 and ˜6×105cm-1, respectively. For films thicker than 600 nm, additional strain relief occurred through surface undulations, indicating that this secondary strain-relief mechanism is a volume effect that sets in upon cooling from the growth temperature.
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Simmons, Sheri L; Dibartolo, Genevieve; Denef, Vincent J; Goltsman, Daniela S Aliaga; Thelen, Michael P; Banfield, Jillian F
2008-07-22
Deeply sampled community genomic (metagenomic) datasets enable comprehensive analysis of heterogeneity in natural microbial populations. In this study, we used sequence data obtained from the dominant member of a low-diversity natural chemoautotrophic microbial community to determine how coexisting closely related individuals differ from each other in terms of gene sequence and gene content, and to uncover evidence of evolutionary processes that occur over short timescales. DNA sequence obtained from an acid mine drainage biofilm was reconstructed, taking into account the effects of strain variation, to generate a nearly complete genome tiling path for a Leptospirillum group II species closely related to L. ferriphilum (sampling depth approximately 20x). The population is dominated by one sequence type, yet we detected evidence for relatively abundant variants (>99.5% sequence identity to the dominant type) at multiple loci, and a few rare variants. Blocks of other Leptospirillum group II types ( approximately 94% sequence identity) have recombined into one or more variants. Variant blocks of both types are more numerous near the origin of replication. Heterogeneity in genetic potential within the population arises from localized variation in gene content, typically focused in integrated plasmid/phage-like regions. Some laterally transferred gene blocks encode physiologically important genes, including quorum-sensing genes of the LuxIR system. Overall, results suggest inter- and intrapopulation genetic exchange involving distinct parental genome types and implicate gain and loss of phage and plasmid genes in recent evolution of this Leptospirillum group II population. Population genetic analyses of single nucleotide polymorphisms indicate variation between closely related strains is not maintained by positive selection, suggesting that these regions do not represent adaptive differences between strains. Thus, the most likely explanation for the observed patterns of
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Directory of Open Access Journals (Sweden)
Sheri L Simmons
2008-07-01
Full Text Available Deeply sampled community genomic (metagenomic datasets enable comprehensive analysis of heterogeneity in natural microbial populations. In this study, we used sequence data obtained from the dominant member of a low-diversity natural chemoautotrophic microbial community to determine how coexisting closely related individuals differ from each other in terms of gene sequence and gene content, and to uncover evidence of evolutionary processes that occur over short timescales. DNA sequence obtained from an acid mine drainage biofilm was reconstructed, taking into account the effects of strain variation, to generate a nearly complete genome tiling path for a Leptospirillum group II species closely related to L. ferriphilum (sampling depth approximately 20x. The population is dominated by one sequence type, yet we detected evidence for relatively abundant variants (>99.5% sequence identity to the dominant type at multiple loci, and a few rare variants. Blocks of other Leptospirillum group II types ( approximately 94% sequence identity have recombined into one or more variants. Variant blocks of both types are more numerous near the origin of replication. Heterogeneity in genetic potential within the population arises from localized variation in gene content, typically focused in integrated plasmid/phage-like regions. Some laterally transferred gene blocks encode physiologically important genes, including quorum-sensing genes of the LuxIR system. Overall, results suggest inter- and intrapopulation genetic exchange involving distinct parental genome types and implicate gain and loss of phage and plasmid genes in recent evolution of this Leptospirillum group II population. Population genetic analyses of single nucleotide polymorphisms indicate variation between closely related strains is not maintained by positive selection, suggesting that these regions do not represent adaptive differences between strains. Thus, the most likely explanation for the
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International Nuclear Information System (INIS)
Ahn, T.-H.; Oh, C.-S.; Kim, D.H.; Oh, K.H.; Bei, H.; George, E.P.; Han, H.N.
2010-01-01
Strain-induced martensitic transformation of metastable austenite was investigated by nanoindentation of individual austenite grains in multi-phase steel. A cross-section prepared through one of these indented regions using focused ion beam milling was examined by transmission electron microscopy. The presence of martensite underneath the indent indicates that the pop-ins observed on the load-displacement curve during nanoindentation correspond to the onset of strain-induced martensitic transformation. The pop-ins can be understood as resulting from the selection of a favorable martensite variant during nanoindentation.
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Energy Technology Data Exchange (ETDEWEB)
Ahn, T.-H. [Seoul National University; Oh, C.-S. [Korean Institute of Materials Science; Kim, D. H. [Seoul National University; Oh, K. H. [Seoul National University; Bei, Hongbin [ORNL; George, Easo P [ORNL; Han, H. N. [Seoul National University
2010-01-01
Strain-induced martensitic transformation of metastable austenite was investigated by nanoindentation of individual austenite grains in multi-phase steel. A cross-section prepared through one of these indented regions using focused ion beam milling was examined by transmission electron microscopy. The presence of martensite underneath the indent indicates that the pop-ins observed on the load-displacement curve during nanoindentation correspond to the onset of strain-induced martensitic transformation. The pop-ins can be understood as resulting from the selection of a favorable martensite variant during nanoindentation.
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Glucose 6-phosphate dehydrogenase variants in Japan.
Miwa, S
1980-01-01
Fifty-four cases of glucose 6-phosphate dehydrogenase (G6PD) deficiency have so far been reported in Japan. Among them, 21 G6PD variants have been characterized. Nineteen out of the 21 variants were characterized in our laboratory and G6PD Heian and "Kyoto" by others. G6PD Tokyo, Tokushima, Ogikubo, Kurume, Fukushima, Yokohama, Yamaguchi, Wakayama, Akita, Heian and "Kyoto" were classified as Class 1, because all these cases showed chronic hemolytic anemia and severe enzyme deficiency. All these variants showed thermal instability. G6PD Mediterranean-like, Ogori, Gifu and Fukuoka were classified as Class 2, whereas G6PD Hofu, B(-) Chinese, Ube, Konan, Kamiube and Kiwa belonged to Class 3. All the 6 Class 3 variants were found as the results of the screening tests. The incidence of the deficiency in Japanese seems to be 0.1-0.5% but that of the cases which may slow drug-induced hemolysis would be much less. G6PD Ube and Konan appear to be relatively common in Japan.
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A genetic variant of the sperm-specific SLO3 K+ channel has altered pH and Ca2+ sensitivities.
Geng, Yanyan; Ferreira, Juan J; Dzikunu, Victor; Butler, Alice; Lybaert, Pascale; Yuan, Peng; Magleby, Karl L; Salkoff, Lawrence; Santi, Celia M
2017-05-26
To fertilize an oocyte, sperm must first undergo capacitation in which the sperm plasma membrane becomes hyperpolarized via activation of potassium (K + ) channels and resultant K + efflux. Sperm-specific SLO3 K + channels are responsible for these membrane potential changes critical for fertilization in mouse sperm, and they are only sensitive to pH i However, in human sperm, the major K + conductance is both Ca 2+ - and pH i -sensitive. It has been debated whether Ca 2+ -sensitive SLO1 channels substitute for human SLO3 (hSLO3) in human sperm or whether human SLO3 channels have acquired Ca 2+ sensitivity. Here we show that hSLO3 is rapidly evolving and reveal a natural structural variant with enhanced apparent Ca 2+ and pH sensitivities. This variant allele (C382R) alters an amino acid side chain at a principal interface between the intramembrane-gated pore and the cytoplasmic gating ring of the channel. Because the gating ring contains sensors to intracellular factors such as pH and Ca 2+ , the effectiveness of transduction between the gating ring and the pore domain appears to be enhanced. Our results suggest that sperm-specific genes can evolve rapidly and that natural genetic variation may have led to a SLO3 variant that differs from wild type in both pH and intracellular Ca 2+ sensitivities. Whether this physiological variation confers differences in fertility among males remains to be established. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
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Differential Expression Profile of ZFX Variants Discriminates Breast Cancer Subtypes
Pourkeramati, Fatemeh; Asadi, Malek Hossein; Shakeri, Shahryar; Farsinejad, Alireza
2018-05-13
ZFX is a transcriptional regulator in embryonic stem cells that plays an important role in pluripotency and self-renewal. ZFX is widely expressed in pluripotent stem cells and is down-regulated during differentiation of embryonic stem cells. ZFX has five different variants that encode three different protein isoforms. While several reports have determined the overexpression of ZFX in a variety of somatic cancers, the expression of ZFX-spliced variants in cancer cells is not well-understood. We investigated the expression of ZFX variants in a series of breast cancer tissues and cell lines using quantitative PCR. The expression of ZFX variant 1/3 was higher in tumor tissue compared to marginal tissue. In contrast, the ZFX variant 5 was down-regulated in tumor tissues. While the ZFX variant 1/3 and ZFX variant 5 expression significantly increased in low-grade tumors, ZFX variant 4 was strongly expressed in high-grade tumors and demonstrating lymphatic invasion. In addition, our result revealed a significant association between the HER2 status and the expression of ZFX-spliced variants. Our data suggest that the expression of ZFX-spliced transcripts varies between different types of breast cancer and may contribute to their tumorigenesis process. Hence, ZFX-spliced transcripts could be considered as novel tumor markers with a probable value in diagnosis, prognosis, and therapy of breast cancer.
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Mutagenesis at the ad-3A and ad-3B loci in haploid UV-sensitive strains of Neurospora crassa. Pt. 6
International Nuclear Information System (INIS)
De Serres, F.J.; Inoue, H.; Schuepbach, M.E.
1983-01-01
Genetic characterization of ad-3B mutants induced in wild-type and UV-sensitive strains has revealed qualitative differences between the spectra of genetic alterations at the molecular level. Ad-3B mutants induced in the two nucleotide excision-repair-deficient strains upr-1 and uvs-2 had significantly lower frequencies of nonpolarized complementation patterns and higher frequencies of noncomplementing mutants than ad-3B mutants induced in the wild-type strain in samples induced by either UV, #betta#-rays, 4NQO or MNNG. In these same samples ad-3B mutants induced in uvs-4, uvs-5 or uvs-6 did not differ significantly from those induced in the wild-type strain. After ICR-170 treatment, ad-3B mutants induced in the UV-sensitive strains did not differ significantly from those induced in wild-type. The comparisons in the present and previous studies demonstrate that the process of mutation-induction in the ad-3 region is under the control of other loci that not only alter mutant recovery quantitatively but also qualitatively. These data have important implications for comparative chemical mutagenesis, since the spectrum of genetic alterations produced by a given agent can be modified markedly as a result of defects in DNA repair. (orig./AJ)
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Strain Effect on Electronic Structure and Work Function in α-Fe2O3 Films
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Li Chen
2017-03-01
Full Text Available We investigate the electronic structure and work function modulation of α-Fe2O3 films by strain based on the density functional method. We find that the band gap of clean α-Fe2O3 films is a function of the strain and is influenced significantly by the element termination on the surface. The px and py orbitals keep close to Fermi level and account for a pronounced narrowing band gap under compressive strain, while unoccupied dz2 orbitals from conduction band minimum draw nearer to Fermi level and are responsible for the pronounced narrowing band gap under tensile strain. The spin polarized surface state, arising from localized dangling-bond states, is insensitive to strain, while the bulk band, especially for pz orbital, arising from extended Bloch states, is very sensitive to strain, which plays an important role for work function decreasing (increasing under compressive (tensile strain in Fe termination films. In particular, the work function in O terminated films is insensitive to strain because pz orbitals are less sensitive to strain than that of Fe termination films. Our findings confirm that the strain is an effective means to manipulate electronic structures and corrosion potential.
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José L Santos
Full Text Available INTRODUCTION: The melanocortin system plays an important role in energy homeostasis. Mice genetically deficient in the melanocortin-3 receptor gene have a normal body weight with increased body fat, mild hypophagia compared to wild-type mice. In humans, Thr6Lys and Val81Ile variants of the melanocortin-3 receptor gene (MC3R have been associated with childhood obesity, higher BMI Z-score and elevated body fat percentage compared to non-carriers. The aim of this study is to assess the association in adults between allelic variants of MC3R with weight loss induced by energy-restricted diets. SUBJECTS AND METHODS: This research is based on the NUGENOB study, a trial conducted to assess weight loss during a 10-week dietary intervention involving two different hypo-energetic (high-fat and low-fat diets. A total of 760 obese patients were genotyped for 10 single nucleotide polymorphisms covering the single exon of MC3R gene and its flanking regions, including the missense variants Thr6Lys and Val81Ile. Linear mixed models and haplotype-based analysis were carried out to assess the potential association between genetic polymorphisms and differential weight loss, fat mass loss, waist change and resting energy expenditure changes. RESULTS: No differences in drop-out rate were found by MC3R genotypes. The rs6014646 polymorphism was significantly associated with weight loss using co-dominant (p = 0.04 and dominant models (p = 0.03. These p-values were not statistically significant after strict control for multiple testing. Haplotype-based multivariate analysis using permutations showed that rs3827103-rs1543873 (p = 0.06, rs6014646-rs6024730 (p = 0.05 and rs3746619-rs3827103 (p = 0.10 displayed near-statistical significant results in relation to weight loss. No other significant associations or gene*diet interactions were detected for weight loss, fat mass loss, waist change and resting energy expenditure changes. CONCLUSION: The study
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Transcriptomes of Frankia sp. strain CcI3 in growth transitions
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Bickhart Derek M
2011-08-01
Full Text Available Abstract Background Frankia sp. strains are actinobacteria that form N2-fixing root nodules on angiosperms. Several reference genome sequences are available enabling transcriptome studies in Frankia sp. Genomes from Frankia sp. strains differ markedly in size, a consequence proposed to be associated with a high number of indigenous transposases, more than 200 of which are found in Frankia sp. strain CcI3 used in this study. Because Frankia exhibits a high degree of cell heterogeneity as a consequence of its mycelial growth pattern, its transcriptome is likely to be quite sensitive to culture age. This study focuses on the behavior of the Frankia sp. strain CcI3 transcriptome as a function of nitrogen source and culture age. Results To study global transcription in Frankia sp. CcI3 grown under different conditions, complete transcriptomes were determined using high throughput RNA deep sequencing. Samples varied by time (five days vs. three days and by culture conditions (NH4+ added vs. N2 fixing. Assembly of millions of reads revealed more diversity of gene expression between five-day and three-day old cultures than between three day old cultures differing in nitrogen sources. Heat map analysis organized genes into groups that were expressed or repressed under the various conditions compared to median expression values. Twenty-one SNPs common to all three transcriptome samples were detected indicating culture heterogeneity in this slow-growing organism. Significantly higher expression of transposase ORFs was found in the five-day and N2-fixing cultures, suggesting that N starvation and culture aging provide conditions for on-going genome modification. Transposases have previously been proposed to participate in the creating the large number of gene duplication or deletion in host strains. Subsequent RT-qPCR experiments confirmed predicted elevated transposase expression levels indicated by the mRNA-seq data. Conclusions The overall pattern of
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Directory of Open Access Journals (Sweden)
Richard M Harvey
Full Text Available Streptococcus pneumoniae is the world's leading cause of pneumonia, bacteremia, meningitis and otitis media. A major pneumococcal virulence factor is the cholesterol-dependent cytolysin, which has the defining property of forming pores in cholesterol-containing membranes. In recent times a clinically significant and internationally successful serotype 1 ST306 clone has been found to express a non-cytolytic variant of Ply (Ply306. However, while the pneumococcus is a naturally transformable organism, strains of the ST306 clonal group have to date been virtually impossible to transform, severely restricting efforts to understand the role of non-cytolytic Ply in the success of this clone. In this study isogenic Ply mutants were constructed in the D39 background and for the first time in the ST306 background (A0229467 to enable direct comparisons between Ply variants for their impact on the immune response in a macrophage-like cell line. Strains that expressed cytolytic Ply were found to induce a significant increase in IL-1β release from macrophage-like cells compared to the non-cytolytic and Ply-deficient strains in a background-independent manner, confirming the requirement for pore formation in the Ply-dependent activation of the NLRP3 inflammasome. However, cytolytic activity in the D39 background was found to induce increased expression of the genes encoding GM-CSF (CSF2, p19 subunit of IL-23 (IL23A and IFNβ (IFNB1 compared to non-cytolytic and Ply-deficient D39 mutants, but had no effect in the A0229467 background. The impact of Ply on the immune response to the pneumococcus is highly dependent on the strain background, thus emphasising the importance of the interaction between specific virulence factors and other components of the genetic background of this organism.
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Bai, Y.; Kosoy, M.Y.; Cully, J.F.; Bala, T.; Ray, C.; Collinge, S.K.
2007-01-01
Rodent-associated Bartonella species are generally host-specific parasites in North America. Here evidence that Bartonella species can 'jump' between host species is presented. Northern grasshopper mice and other rodents were trapped in the western USA. A study of Bartonella infection in grasshopper mice demonstrated a high prevalence that varied from 25% to 90% by location. Bartonella infection was detected in other rodent species with a high prevalence as well. Sequence analyses of gltA identified 29 Bartonella variants in rodents, 10 of which were obtained from grasshopper mice. Among these 10, only six variants were specific to grasshopper mice, whereas four were identical to variants specific to deer mice or 13-lined ground squirrels. Fourteen of 90 sequenced isolates obtained from grasshopper mice were strains found more commonly in other rodent species and were apparently acquired from these animals. The ecological behavior of grasshopper mice may explain the occurrence of Bartonella strains in occasional hosts. The observed rate at which Bartonella jumps from a donor host species to the grasshopper mouse was directly proportional to a metric of donor host density and to the prevalence of Bartonella in the donor host, and inversely proportional to the same parameters for the grasshopper mouse. ?? 2007 Federation of European Microbiological Societies.
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Identifying genetic variants that affect viability in large cohorts.
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Hakhamanesh Mostafavi
2017-09-01
Full Text Available A number of open questions in human evolutionary genetics would become tractable if we were able to directly measure evolutionary fitness. As a step towards this goal, we developed a method to examine whether individual genetic variants, or sets of genetic variants, currently influence viability. The approach consists in testing whether the frequency of an allele varies across ages, accounting for variation in ancestry. We applied it to the Genetic Epidemiology Research on Adult Health and Aging (GERA cohort and to the parents of participants in the UK Biobank. Across the genome, we found only a few common variants with large effects on age-specific mortality: tagging the APOE ε4 allele and near CHRNA3. These results suggest that when large, even late-onset effects are kept at low frequency by purifying selection. Testing viability effects of sets of genetic variants that jointly influence 1 of 42 traits, we detected a number of strong signals. In participants of the UK Biobank of British ancestry, we found that variants that delay puberty timing are associated with a longer parental life span (P~6.2 × 10-6 for fathers and P~2.0 × 10-3 for mothers, consistent with epidemiological studies. Similarly, variants associated with later age at first birth are associated with a longer maternal life span (P~1.4 × 10-3. Signals are also observed for variants influencing cholesterol levels, risk of coronary artery disease (CAD, body mass index, as well as risk of asthma. These signals exhibit consistent effects in the GERA cohort and among participants of the UK Biobank of non-British ancestry. We also found marked differences between males and females, most notably at the CHRNA3 locus, and variants associated with risk of CAD and cholesterol levels. Beyond our findings, the analysis serves as a proof of principle for how upcoming biomedical data sets can be used to learn about selection effects in contemporary humans.
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Kvannli, Line; Krohn, Jørgen
2017-11-01
To evaluate the visual outcome after transitioning from a pro re nata (PRN) intravitreal injection regimen to a treat-and-extend (TAE) regimen for patients with neovascular age-related macular degeneration (AMD). A retrospective review of patients who were switched from a PRN regimen with intravitreal injections of bevacizumab, ranibizumab or aflibercept to a TAE regimen. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and type of medication used at baseline, at the time of changing treatment regimen and at the end of the study were analysed. Twenty-one eyes of 21 patients met the inclusion criteria. Prior to the switch, the patients received a mean of 13.8 injections (median, 10; range, 3-39 injections) with the PRN regimen for 44 months (range, 3-100 months), which improved the visual acuity in five patients (24%). After a mean of 6.1 injections (median, 5; range, 3-14 injections) with the TAE regimen over 8 months (range, 2-16 months), the visual acuity improved in 12 patients (57%). The improvement in visual acuity during treatment with the TAE regimen was statistically significant (p = 0.005). The proportion of patients with a visual acuity of 0.2 or better was significantly higher after treatment with the TAE regimen than after treatment with the PRN regimen (p = 0.048). No significant differences in CRT were found between the two treatment regimens. Even after prolonged treatment and a high number of intravitreal injections, switching AMD patients from a PRN regimen to a strict TAE regimen significantly improves visual acuity. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
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Directory of Open Access Journals (Sweden)
Faten GORSANE
2010-09-01
Full Text Available Tunisian pomegranate Hop stunt viroid (HSVd variants are described. Dot-blot hybridization, S-Page, and reverse transcription polymerase chain reaction (RT-PCR of RNA extracts from infected tissues were carried out. Results obtained by these techniques were confirmed by cDNA sequencing. The genetic diversity among the Tunisian variants was investigated, which also involved analysis of sequences of previously described HSVd variants from Tunisian citrus var. clementine and fig, and from fruit trees from other Mediterranean countries. Phylogenetic analysis showed that Tunisian pomegranate HSVd variants were clustered into two groups: a cachexia strain within the citrus type group and a recombinant citrus-plum type group. Results also showed a high haplotype diversity which was not related either to the host or to the geographical origin. Selective neutrality and genetic network tests suggest that the HSVd isolates have spread rapidly.
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Studies on a morphologically distinct colchicine-resistance variant of Entamoeba sp.
Injeyan, H; Huebner, E; Meerovitch, E
1979-05-01
Colchicine has a temperature-dependent cytotoxic effect on Entamoeba sp. (Laredo isolate) that is most apparent when the drug is applied during the initiation of cultures at a concentration of 7.5 mM or higher. Continued transfer of cultures in medium containing progressively increasing concentrations of colchicine has resulted in a variant that grows prolifically in the presence of colchicine (7.5 mM) with a generation time comparable to that of the parent stock, Comparison of a number of parameters of the 2 variants revealed that colchicine resistance was accompanied by a change in cell shape, a reduced membrane permeability, which could partially be overcome by the addition of dimethyl sulfoxide (DMSO), and a reduced tolerance to osmotic stress. However, the parent strain and resistant variant were equally susceptible to cycloheximide and puromycin suggesting that the acquired colchicine resistance may not be explained on the basis of an entirely unspecific generalized reduced ability for drug uptake. Colchicine resistance and altered structure were found to be stable over a long period of time. The possible interdependence of these 2 parameters and their relation to cell motility in Entamoeba sp. are discussed.
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De Vleeschauwer, Annebel; Qiu, Yu; Van Reeth, Kristien
2015-05-11
The human A/Port Chalmers/1/73 (H3N2) influenza virus strain, the supposed ancestor of European H3N2 swine influenza viruses (SIVs), was used in most commercial SIV vaccines in Europe until recently. If manufacturers want to update vaccine strains, they have to perform laborious intratracheal (IT) challenge experiments and demonstrate reduced virus titres in the lungs of vaccinated pigs. We aimed to examine (a) the ability of a Port Chalmers/73-based commercial vaccine to induce cross-protection against a contemporary European H3N2 SIV and serologic cross-reaction against H3N2 SIVs from Europe and North America and (b) the validity of intranasal (IN) challenge and virus titrations of nasal swabs as alternatives for IT challenge and titrations of lung tissue in vaccine potency tests. Pigs were vaccinated with Suvaxyn Flu(®) and challenged by the IT or IN route with sw/Gent/172/08. Post-vaccination sera were examined in haemagglutination-inhibition assays against vaccine and challenge strains and additional H3N2 SIVs from Europe and North America, including an H3N2 variant virus. Tissues of the respiratory tract and nasal swabs were collected 3 days post challenge (DPCh) and from 0-7 DPCh, respectively, and examined by virus titration. Two vaccinations consistently induced cross-reactive antibodies against European H3N2 SIVs from 1998-2012, but minimal or undetectable antibody titres against North American viruses. Challenge virus titres in the lungs, trachea and nasal mucosa of the vaccinated pigs were significantly reduced after both IT and IN challenge. Yet the reduction of virus titres and nasal shedding was greater after IT challenge. The Port Chalmers/73-based vaccine still offered protection against a European H3N2 SIV isolated 35 years later and with only 86.9% amino acid homology in its HA1, but it is unlikely to protect against H3N2 SIVs that are endemic in North America. We use our data to reflect on vaccine strain updates and on the vaccine potency test
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Backer, Julie De; Braverman, Alan C
2018-05-01
Predominant cardiovascular manifestations in the spectrum of Heritable Thoracic Aortic Disease include by default aortic root aneurysms- and dissections, which may be associated with aortic valve disease. Mitral- and tricuspid valve prolapse are other commonly recognized features. Myocardial disease, characterized by heart failure and/or malignant arrhythmias has been reported in humans and in animal models harboring pathogenic variants in the Fibrillin1 gene. Description of clinical history of three cases from one family in Ghent (Belgium) and one family in St. Louis (US). We report on three cases from two families presenting end-stage heart failure (in two) and lethal arrhythmias associated with moderate left ventricular dilatation (in one). All three cases harbor a pathogenic variant in the SMAD3 gene, known to cause aneurysm osteoarthritis syndrome, Loeys-Dietz syndrome type 3 or isolated Heritable Thoracic Aortic Disease. These unusual presentations warrant awareness for myocardial disease in patients harboring pathogenic variants in genes causing Heritable Thoracic Aortic Disease and indicate the need for prospective studies in larger cohorts. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
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Alonso, Carla Andrea; Mora, Azucena; Díaz, Dafne; Blanco, Miguel; González-Barrio, David; Ruiz-Fons, Francisco; Simón, Carmen; Blanco, Jorge; Torres, Carmen
2017-08-01
Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC) strains are food-borne pathogens associated with acute diarrhea. Haemolytic-uremic syndrome (HUS) is often a complication of STEC infection. In order to examine the occurrence, serotypes, virulence and antimicrobial-resistance profiles of STEC and EPEC in wildlife, 326 faecal E. coli strains from 304 clinically healthy animals were analyzed. For this approach stx 1 , stx 2 and eae genes, as well as accessory virulence determinants (ehx, hlyA, saa, tia, bfp, subAB) were PCR-screened and sequenced. Serotyping was performed employing all available O (O1-O185) and H (H1-H56) antisera. Genetic diversity was analyzed by XbaI-PFGE and phylotyping. Thirteen STEC (4.3%) and 10 EPEC (3.3%) were identified among 12 deer, 3 mouflon, 6 wild boars and 2 birds. Nine STEC showed seropathotypes B (O145:[H28]) and C (O22:H8, O128:[H2]) associated with HUS, and D (O110:H28, O146:H21, O146:[H28], ONT:H8) associated with human diarrhea. Although most isolates harbored stx 2b and stx 1c variants, stx 2a and stx 1a (related with severe disease) were also detected. Additionally, the eae gene was present in one stx 2a -positive O145:[H28] STEC from a deer and 11 STEC harbored subAB genes (mainly the subAB 2 variant). EPEC isolates showed 7 different intimin variants (β1, β2, γ1, ε1, ζ1, ι1-A, κ). Interestingly, the O49:[H10] eae-κ EPEC isolated from a wild boar was bfpA-positive showing a combination of serotype/virulence profile previously detected among human clinical tEPEC. Based on present results, wild ruminants, wild boars and to a lesser extent birds would be carriers of potentially pathogenic STEC and EPEC strains. Copyright © 2017 Elsevier B.V. All rights reserved.
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Variant Selection during Alpha Precipitation in Titanium Alloys: A Simulation Study
Shi, Rongpei
Variant selection of alpha phase during its precipitation from beta matrix plays a key role in determining transformation texture and final mechanical properties of alpha/beta and beta titanium alloys. In this study we develop a three-dimensional quantitative phase field model (PFM) to predict variant selection and microstructure evolution during beta to alpha transformation in polycrystalline Ti-6Al-4V under the influence of different processing variables. The model links its inputs directly to thermodynamic and mobility databases, and incorporates crystallography of BCC to HCP transformation, elastic anisotropy, defects within semi-coherent alpha/beta interfaces and elastic inhomogeneities among different beta grains. In particular, microstructure and transformation texture evolution are treated simultaneously via orientation distribution function (ODF) modeling of alpha/beta two-phase microstructure in beta polycrystalline obtained by PFM. It is found that, for a given undercooling, the development of transformation texture of the alpha phase due to variant selection during precipitation depends on both externally applied stress or strain, initial texture state of parent beta sample and internal stress generated by the precipitation reaction itself. Moreover, the growth of pre-existing widmanstatten alpha precipitates is accompanied by selective nucleation and growth of secondary alpha plates of preferred variants. We further develop a crystallographic model based on the ideal Burgers orientation relationship (BOR) between GBalpha and one of the two adjacent beta grains to investigate how a prior beta grain boundary contributes to variant selection of grain boundary allotriomorph (GBalpha). The model is able to predict all possible special beta grain boundaries where GBalpha is able to maintain BOR with two neighboring grain. In particular, the model has been used to evaluate the validity of all current empirical variant selection rules to obtain more insight of
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New genetic variants of influenza A(H1N1)pdm09 detected in Cuba during 2011-2013.
Arencibia, Amely; Acosta, Belsy; Muné, Mayra; Valdés, Odalys; Fernandez, Leandro; Medina, Isel; Savón, Clara; Oropesa, Suset; Gonzalez, Grehete; Roque, Rosmery; Gonzalez, Guelsys; Hernández, Bárbara; Goyenechea, Angel; Piñón, Alexander
2015-06-01
Influenza A(H1N1)pdm09 virus has evolved continually since its emergence in 2009. For influenza virus strains, genetic changes occurring in HA1 domain of the hemagglutinin cause the emergence of new variants. The aim of our study is to establish genetic associations between 35 A(H1N1)pdm09 viruses circulating in Cuba in 2011-2012 and 2012-2013 seasons, and A/California/07/2009 strain recommended by WHO as the H1N1 component of the influenza vaccine. The phylogenetic analysis revealed the circulation of clades 3, 6A, 6B, 6C and 7. Mutations were detected in the antigenic site or in the receptor-binding domains of HA1 segment, including S174P, S179N, K180Q, S202T, S220T and R222K. Substitutions S174P, S179N, K180Q and R222K were detected in Cuban strains for the first time. Copyright © 2015 Elsevier B.V. All rights reserved.
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Genomic diversity of Bombyx mori nucleopolyhedrovirus strains.
Xu, Yi-Peng; Cheng, Ruo-Lin; Xi, Yu; Zhang, Chuan-Xi
2013-07-01
Bombyx mori nucleopolyhedrovirus (BmNPV) is a baculovirus that selectively infects the domestic silkworm. In this study, six BmNPV strains were compared at the whole genome level. We found that the number of bro genes and the composition of the homologous regions (hrs) are the two primary areas of divergence within these genomes. When we compared the ORFs of these BmNPV variants, we noticed a high degree of sequence divergence in the ORFs that are not baculovirus core genes. This result is consistent with the results derived from phylogenetic trees and evolutionary pressure analyses of these ORFs, indicating that ORFs that are not core genes likely play important roles in the evolution of BmNPV strains. The evolutionary relationships of these BmNPV strains might be explained by their geographic origins or those of their hosts. In addition, the total number of hr palindromes seems to affect viral DNA replication in Bm5 cells. Copyright © 2013 Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
Bester Rachelle
2012-09-01
Full Text Available Abstract Background Grapevine leafroll-associated virus 3 (GLRaV-3 is the main contributing agent of leafroll disease worldwide. Four of the six GLRaV-3 variant groups known have been found in South Africa, but their individual contribution to leafroll disease is unknown. In order to study the pathogenesis of leafroll disease, a sensitive and accurate diagnostic assay is required that can detect different variant groups of GLRaV-3. Methods In this study, a one-step real-time RT-PCR, followed by high-resolution melting (HRM curve analysis for the simultaneous detection and identification of GLRaV-3 variants of groups I, II, III and VI, was developed. A melting point confidence interval for each variant group was calculated to include at least 90% of all melting points observed. A multiplex RT-PCR protocol was developed to these four variant groups in order to assess the efficacy of the real-time RT-PCR HRM assay. Results A universal primer set for GLRaV-3 targeting the heat shock protein 70 homologue (Hsp70h gene of GLRaV-3 was designed that is able to detect GLRaV-3 variant groups I, II, III and VI and differentiate between them with high-resolution melting curve analysis. The real-time RT-PCR HRM and the multiplex RT-PCR were optimized using 121 GLRaV-3 positive samples. Due to a considerable variation in melting profile observed within each GLRaV-3 group, a confidence interval of above 90% was calculated for each variant group, based on the range and distribution of melting points. The intervals of groups I and II could not be distinguished and a 95% joint confidence interval was calculated for simultaneous detection of group I and II variants. An additional primer pair targeting GLRaV-3 ORF1a was developed that can be used in a subsequent real-time RT-PCR HRM to differentiate between variants of groups I and II. Additionally, the multiplex RT-PCR successfully validated 94.64% of the infections detected with the real-time RT-PCR HRM
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DEFF Research Database (Denmark)
Herrero-Fresno, Ana; Zachariasen, Camilla; Hansen, Monica Hegstad
2016-01-01
of treatment, and apramycin treatment resulted in significantly higher counts compared to the non-treated group. This represents the first demonstration of how antimicrobial treatment affects spread of resistant bacteria in pig production. The use of apramycin may lead to enhanced spread of gentamicin-resistant......The effect of apramycin treatment on transfer and selection of an Escherichia coli strain (E. coli 912) in the intestine of pigs was analyzed through an in vivo experiment. The strain was sequenced and assigned to the sequence type ST101 and serotype O11. It carried resistance genes to apramycin......-treated (pen 3), along with a non-inoculated control group (pen 1). Two pigs of pen 2 and 3 were inoculated intragastrically with a rifampicin resistant variant of the strain. Apramycin treatment in pen 2 was initiated immediately after inoculation. Strain colonization was assessed in the feces from all pigs...
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International Nuclear Information System (INIS)
Horiuchi, Rie; Akimoto, Takayuki; Hong, Zhang; Ushida, Takashi
2012-01-01
Mechanical strain has been reported to affect the proliferation/differentiation of many cell types; however, the effects of mechanotransduction on self-renewal as well as pluripotency of embryonic stem (ES) cells remains unknown. To investigate the effects of mechanical strain on mouse ES cell fate, we examined the expression of Nanog, which is an essential regulator of self-renewal and pluripotency as well as Nanog-associated intracellular signaling during uniaxial cyclic mechanical strain. The mouse ES cell line, CCE was plated onto elastic membranes, and we applied 10% strain at 0.17 Hz. The expression of Nanog was reduced during ES cell differentiation in response to the withdrawal of leukemia inhibitory factor (LIF); however, two days of cyclic mechanical strain attenuated this reduction of Nanog expression. On the other hand, the cyclic mechanical strain promoted PI3K-Akt signaling, which is reported as an upstream of Nanog transcription. The cyclic mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor wortmannin. Furthermore, cytochalasin D, an inhibitor of actin polymerization, also inhibited the mechanical strain-induced increase in phospho-Akt. These findings imply that mechanical force plays a role in regulating Nanog expression in ES cells through the actin cytoskeleton-PI3K-Akt signaling. -- Highlights: ► The expression of Nanog, which is an essential regulator of “stemness” was reduced during embryonic stem (ES) cell differentiation. ► Cyclic mechanical strain attenuated the reduction of Nanog expression. ► Cyclic mechanical strain promoted PI3K-Akt signaling and mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor and an inhibitor of actin polymerization.
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Directory of Open Access Journals (Sweden)
Ankita Srivastava
2016-01-01
Full Text Available Roles of nutrients and other environmental variables in development of cyanobacterial bloom and its toxicity are complex and not well understood. We have monitored the photoautotrophic growth, total microcystin concentration, and microcystins synthetase gene (mcyA expression in lab-grown strains of Microcystis NIES 843 (reference strain, KW (Wangsong Reservoir, South Korea, and Durgakund (Varanasi, India under different nutrient regimes (nitrogen, phosphorus, and boron. Higher level of nitrogen and boron resulted in increased growth (avg. 5 and 6.5 Chl a mg/L, resp., total microcystin concentrations (avg. 1.185 and 7.153 mg/L, resp., and mcyA transcript but its expression was not directly correlated with total microcystin concentrations in the target strains. Interestingly, Durgakund strain had much lower microcystin content and lacked microcystin-YR variant over NIES 843 and KW. It is inferred that microcystin concentration and its variants are strain specific. We have also examined the heterotrophic bacteria associated with cyanobacterial bloom in Durgakund Pond and Wangsong Reservoir which were found to be enriched in Alpha-, Beta-, and Gammaproteobacteria and that could influence the bloom dynamics.
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DEFF Research Database (Denmark)
Nazipi, Seven; Stødkilde-Jørgensen, Kristian; Scavenius, Carsten
2017-01-01
Hyaluronic acid (HA) and other glycosaminoglycans are extracellular matrix components in the human epidermis and dermis. One of the most prevalent skin microorganisms, Propionibacterium acnes, possesses HA-degrading activity, possibly conferred by the enzyme hyaluronate lyase (HYL). In this study......, we identified the HYL of P. acnes and investigated the genotypic and phenotypic characteristics. Investigations include the generation of a P. acneshyl knockout mutant and HYL activity assays to determine the substrate range and formed products. We found that P. acnes employs two distinct variants...... of the observed differences between P. acnes phylotype IA and IB/II strains. Whereas type IA strains are primarily found on the skin surface and associated with acne vulgaris, type IB/II strains are more often associated with soft and deep tissue infections, which would require elaborate tissue invasion...
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Reinoso-Pozo, Yaritza; Del Rincón-Castro, Ma Cristina; Ibarra, Jorge E
2016-09-01
The LBIT-1200 strain of Bacillus thuringiensis was recently isolated from soil, and showed a 6.4 and 9.5 increase in toxicity, against Manduca sexta and Trichoplusia ni, respectively, compared to HD-73. However, LBIT-1200 was still highly similar to HD-73, including the production of bipyramidal crystals containing only one protein of ∼130 000 kDa, its flagellin gene sequence related to the kurstaki serotype, plasmid and RepPCR patterns similar to HD-73, no production of β-exotoxin and no presence of VIP genes. Sequencing of its cry gene showed the presence of a cry1Ac-type gene with four amino acid differences, including two amino acid replacements in domain III, compared to Cry1Ac1, which may explain its higher toxicity. In conclusion, the LBIT-1200 strain is a variant of the HD-73 strain but shows a much higher toxicity, which makes this new strain an important candidate to be developed as a bioinsecticide, once it passes other tests, throughout its biotechnological development. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Directory of Open Access Journals (Sweden)
Dilhan Kuru
2011-09-01
Full Text Available Objective: The Philadelphia (Ph chromosome, consisting of the t(9;22(q34;q11 translocation, is observed in ~90% of patients with chronic myeloid leukemia (CML. Variant Ph translocations are observed in 5%-10% of CML patients. In variant translocations 3 and possibly more chromosomes are involved. Herein we report 6 CML patients with variant Ph translocations.Materials and Methods: Bone marrow samples were examined using conventional cytogenetic meth ods. Fluorescence in situ hybridization (FISH with whole-chromosome paints and BCR-ABL 1D probes were used to confirm and/or complement the findings, and identify rearrangements beyond the resolution of conventional cytogenetic methods. Results: Variant Ph translocations in the 6 patients were as follows: t(7;22(p22;q11, t(9;22;15(q34;q11;q22, t(15;22(p11;q11, t(1;9;22;3(q24;q34;q11;q21, t(12;22(p13;q11, and t(4;8;9;22(q11;q13;q34;q11.Conclusion: Among the patients, 3 had simple and 3 had complex variant Ph translocations. Two of the presented cases had variant Ph chromosomes not previously described, 1 of which had a new complex Ph translocation involving chromosomes 1, 3, 9, 22, and t(1;9;22;3(q24;q34;q11;q21 apart from a clone with a classical Ph, and the other case had variant Ph translocation with chromosomes 4, 8, 9, and 22, and t(4;8;9;22(q11;q13;q34;q11 full complex translocation. Number of studies reported that some patients with variant Ph translocation were poor responders to imatinib. All of our patients with variant Ph translocations had suboptimal responses to imatinib, denoting a poor prognosis also. Variant Ph translocations may be important as they are associated with prognosis and therapy for CML patients.
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Growth of strained, ferroelectric NaNbO{sub 3} thin films by pulsed laser deposition
Energy Technology Data Exchange (ETDEWEB)
Sellmann, Jan; Schwarzkopf, Jutta; Duk, Andreas; Kwasniewski, Albert; Schmidbauer, Martin; Fornari, Roberto [IKZ, Berlin (Germany)
2012-07-01
Due to its promising ferro-/piezoelectric properties and high Curie temperature NaNbO{sub 3} has attracted much attention. In contrast to bulk crystals, thin epitaxial films may incorporate and maintain a certain compressive or tensile lattice strain, depending on the used substrate/film combination. This deformation of the crystal lattice is known to strongly influence the ferroelectric properties of perovskites. In the case of NaNbO{sub 3} compressive strain is achieved in films deposited on NdGaO{sub 3} and SrTiO{sub 3} substrates while deposition on DyScO{sub 3} and TbScO{sub 3} leads to tensile in-plane strain. In order to characterize and practically apply the ferroelectric films, it is necessary to embed them in a capacitor structure for which we use pseudomorphically grown SrRuO{sub 3} as bottom electrodes. We report on the deposition of SrRuO{sub 3} and NaNbO{sub 3} single layers on SrTiO{sub 3}, DyScO{sub 3}, TbScO{sub 3} and NbGaO{sub 3} substrates by means of pulsed laser deposition. By adjusting the substrate temperature, the oxygen partial pressure and the laser frequency we have successfully deposited smooth, strained, single phase NaNbO{sub 3} thin films. Investigations of the films by atomic force microscopy and high resolution X-ray diffraction reveal the dependence of the surface morphology and the incorporated lattice strain on the deposition parameters and the lattice mismatch, respectively. All films exhibit piezoelectric properties, as proven by piezoresponse force microscopy.
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Toxic cyanobacteria strains isolated from blooms in the Guadiana River (southwestern Spain
Directory of Open Access Journals (Sweden)
ISABEL M MORENO
2004-01-01
Full Text Available This paper describes the occurrence of toxic cyanobacteria along the Guadiana River over its course between Mérida and Badajoz (Extremadura, Spain. Water sampling for phytoplankton quantification and toxin analysis was carried out regularly between 1999 and 2001 in six different locations, including two shallow, slow-flowing river sites, two streamed river sites and two drinking water reservoirs. The cyanobacterial community differed significantly between these locations, especially during the summer. The predominant genera were Microcystis, Oscillatoria, Aphanizomenon and Anabaena. Using an ELISA assay the total microcystin contents of natural water samples from the most eutrophic locations ranged from 0.10 _ 21.86 mg mcyst-LR equivalent·L-1 in Valdelacalzada and 0.10-11.3 µg mcyst-LR equivalent·L-1 in Vitonogales, and a seasonal variation of toxin content was observed. The amount of microcystins produced by each strain was determined by ELISA assay and the detection and identification of microcystin variants of three toxic strains of Microcystis aeruginosa was performed by high performance liquid chromatography (HPLC. The analysis of microcystins of the cultured strains revealed that toxin production was variable among different strains of M. aeruginosa isolated either from different blooms or from the same bloom.
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Energy Technology Data Exchange (ETDEWEB)
Lu, Yafeng [Walther-Meissner-Institut, Bayerische Akademie der Wissenschaften, Walther-Meissner Str. 8, 85748 Garching (Germany); Northwest Institute for Nonferrous Metal Research, P.O. Box 51, Xi' an, Shaanxi 710016 (China); Klein, J.; Herbstritt, F.; Philipp, J.B.; Marx, A.; Alff, L.; Gross, R. [Walther-Meissner-Institut, Bayerische Akademie der Wissenschaften, Walther-Meissner Str. 8, 85748 Garching (Germany); Zhang, H. [Engineering Center of Electronic Information Materials and Devices, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054 (China)
2005-07-01
We have prepared high quality, coherently strained La{sub 2/3}Ca{sub 1/3}MnO{sub 3}/SrTiO{sub 3} superlattices with different modulation periods by laser molecular beam epitaxy on (001) SrTiO{sub 3} and NdGaO{sub 3} substrates. A detailed structural characterization was performed by high-angle X-ray diffraction (HAXRD) and low-angle X-ray reflectivity (LAXRR). All superlattices are very flat, show excellent structural coherence and very small mosaic spread (0.02 ). The in-plane coherency strain was varied by changing the thickness ratio of the constituent layers allowing for a systematic variation of the resulting tetragonal distortion of LCMO. The c-axis lattice parameter of LCMO could be continuously changed from 3.87 Aa to 3.79 Aa. The interface roughness was analyzed by offset low-angle X-ray reflectivity and low-angle rocking curve measurements. It was found to be of the order of one unit cell with a significant part of the roughness being vertically correlated. The strain induced tetragonal distortion of LCMO was found to cause strong reduction of the paramagnetic to ferromagnetic transition temperature from about 260 to 120 K and an increase of resistivity. The transport properties in the paramagnetic regime could be well described by a small polaron hopping model. The lattice distortions were found to result in a significant increase of the polaron trapping energy. Our results show that coherently strain superlattices are an interesting model system for the systematic study of the effect of lattice distortions on the magnetic and electronic properties of the doped manganites. (copyright 2005 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)
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Yoo, Gilsung; Kim, Juwon; Yoon, Kap Joon; Lee, Jong-Han
2018-04-17
Transferrin is the major plasma transport protein for iron. We aimed to investigate the characteristics of transferrin variant by carbohydrate-deficient transferrin (CDT) test using capillary zone electrophoresis. We retrospectively analyzed the CDT tests of 2449 patients from March 2009 to May 2017 at a tertiary hospital in Korea. CDT was quantified using a Capillarys 2 system (Sebia, Lisses, France) by capillary zone electrophoresis. The characteristics of variant transferrin patterns using electropherogram of CDT tests were analyzed. Seventy-seven (3.1%) patients were classified as variant transferrin. Mean age of these patients was 51.8 years, and the male-to-female ratio was 3.5:1. The most common variants were the BC variants (n = 37), followed by the CD variants (n = 27), unclear patterns (n = 7), BD variants (n = 3), CC variants (n = 2), misclassification (n = 1). In the variant Tf group, the most common disease was alcoholic liver cirrhosis (n = 22, 28.6%), followed by the toxic effects of substances (n = 17, 22.1%), and mental and behavioral disorders attributable to alcohol (n = 11, 14.3%). Nonvariant group showed a predominance of the toxic substance effects (n = 880, 37.1%), a personal history of suicide attempts (n = 634, 26.7%), and mental and behavioral disorders due to alcohol (n = 336, 14.2%). We analyzed the basic characteristics of variant transferrin by CDT tests using capillary zone electrophoresis. The prevalence of variant transferrin was 3.1% of the study subjects. Male patients, alcohol abusers, and liver cirrhosis patients predominated in the variant transferrin population. Further prospective studies are warranted to elucidate variant transferrin in clinical practice. © 2018 Wiley Periodicals, Inc.
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DFT+DMFT study of strain and interface effects in LaTiO{sub 3} and LaVO{sub 3}
Energy Technology Data Exchange (ETDEWEB)
Dymkowski, Krzysztof; Sclauzero, Gabriele; Ederer, Claude [Materials Theory, ETH Zurich (Switzerland)
2015-07-01
Metal-insulator transitions in thin films of early transition metal correlated oxides are linked to both epitaxial strain and electronic reconstruction at the film/substrate interface. We separately address these two key factors for LaTiO{sub 3} and LaVO{sub 3} through density functional theory plus dynamical mean-field theory (DFT+DMFT). We find that mere epitaxial strain suffices to induce an insulator-to-metal transition in LaTiO{sub 3}, but not in LaVO{sub 3}, in agreement with recent experiments. We show that this difference can be explained by the combined effect of strain-induced changes in the crystal field splitting of t{sub 2g} orbitals and different orbital filling in these two materials. The role of the interface is investigated through DFT+DMFT simulations of LaVO{sub 3}/SrTiO{sub 3} heterostructures with varying superlattice periodicities and substrate terminations. Our aim is to assess whether the metallicity observed at the LaVO3/SrTiO3 interface could be driven by pure electronic reconstruction effects, rather than structural or stoichiometric reasons (such as, e.g., O-related defects).
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Arishima, Taichi; Sasaki, Shinji; Isobe, Tomohiro; Ikebata, Yoshihisa; Shimbara, Shinichi; Ikeda, Shogo; Kawashima, Keisuke; Suzuki, Yutaka; Watanabe, Manabu; Sugano, Sumio; Mizoshita, Kazunori; Sugimoto, Yoshikazu
2017-12-06
Repeat breeding, which is defined as cattle failure to conceive after three or more inseminations in the absence of clinical abnormalities, is a substantial problem in cattle breeding. To identify maternal genetic variants of repeat breeding in Japanese Black cattle, we selected 29 repeat-breeding heifers that failed to conceive following embryo transfer (ET) and conducted a genome-wide association study (GWAS) using the traits. We found that a single-nucleotide polymorphism (SNP; g.92,377,635A > G) in the upstream region of the FOXP3 gene on the X chromosome was highly associated with repeat breeding and failure to conceive following ET (P = 1.51 × 10 -14 ). FOXP3 is a master gene for differentiation of regulatory T (T reg ) cells that function in pregnancy maintenance. Reporter assay results revealed that the activity of the FOXP3 promoter was lower in reporter constructs with the risk-allele than in those with the non-risk-allele by approximately 0.68 fold. These findings suggest that the variant in the upstream region of FOXP3 with the risk-allele decreased FOXP3 transcription, which in turn, could reduce the number of maternal T reg cells and lead to infertility. The frequency of the risk-allele in repeat-breeding heifers is more than that in cows, suggesting that the risk-allele could be associated with infertility in repeat-breeding heifers. This GWAS identified a maternal variant in the upstream region of FOXP3 that was associated with infertility in repeat-breeding Japanese Black cattle that failed to conceive using ET. The variant affected the level of FOXP3 mRNA expression. Thus, the results suggest that the risk-allele could serve as a useful marker to reduce and eliminate animals with inferior fertility in Japanese Black cattle.
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Antonic, Vlado; Stojadinovic, Alexander; Zhang, Binxue; Izadjoo, Mina J; Alavi, Mohammad
2013-01-01
Staphyloxanthin is a virulence factor which protects Staphylococcus aureus in stress conditions. We isolated two pigment variants of S. aureus and one strain of Pseudomonas aeruginosa from a single wound infection. S. aureus variants displayed white and yellow colony phenotypes. The sequence of the operons for staphyloxanthin synthesis indicated that coding and promoter regions were identical between the two pigment variants. Quorum sensing controls pigment synthesis in some bacteria. It is also shown that P. aeruginosa quorum-sensing molecules affect S. aureus transcription. We explored whether the co-infecting P. aeruginosa can affect pigment production in the white S. aureus variant. In co-culture experiments between the white variants and a selected number of Gram-positive and Gram-negative bacteria, only P. aeruginosa induced pigment production in the white variant. Gene expression analysis of the white variant did not indicate upregulation of the crtM and other genes known to be involved in pigment production (sigB, sarA, farnesyl pyrophosphate synthase gene [FPP-synthase], hfq). In contrast, transcription of the catalase gene was significantly upregulated after co-culture. P. aeruginosa-induced pigment synthesis and catalase upregulation correlated with increased resistance to polymyxin B, hydrogen peroxide, and the intracellular environment of macrophages. Our data indicate the presence of silent but functional staphyloxanthin synthesis machinery in a white phenotypic variant of S. aureus which is activated by a co-infecting P. aeruginosa via inter-species communication. Another S. aureus virulence factor, catalase is also induced by this co-infecting bacterium. The resulting phenotypic changes are directly correlated with resistance of the white variant to stressful conditions.
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Auction based spectrum management of cognitive radio networks
DEFF Research Database (Denmark)
Chang, H. B.; Chen, K.-C.; Prasad, Ramjee
2009-01-01
(PS-MSs), and we therefore construct a cognitive radio network (CRN) consisting of a PRN with multiple CR-MSs. We propose a spectrum management policy framework such that CR-MSs can compete in utilization of the PRN spectrum bands available to opportunistic transmission of CR-MSs by Vickrey auction...... to the PRN, the overall spectrum utilization, the profit of the service provider, the spectrum access opportunity of the CR-MSs are increased to achieve cowin situation for every party in cognitive radio networks.......Cognitive radio (CR) technology is considered as an effective solution to enhance overall spectrum efficiency, especially primary radio network (PRN) typically having relatively low spectrum utilization. However, to realize CR concept, it is essential to provide enough incentives to PRN and extra...
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Krishnamoorthy, Soumya; Rajan, Roopa; Banerjee, Moinak; Kumar, Hardeep; Sarma, Gangadhara; Krishnan, Syam; Sarma, Sankara; Kishore, Asha
2016-09-01
Impulse control disorders (ICD) are reported to occur at variable frequencies in different ethnic groups. Genetic vulnerability is suspected to underlie the individual risk for ICD. We investigated whether the allelic variants of dopamine (DRD3), glutamate (GRIN2B) and serotonin (HTR2A) receptors are linked to ICD in Indian Parkinson's disease (PD) patients. We conducted a prospective, case-control study which included PD patients (70 with ICD, 100 without ICD categorized after direct psychiatric interview of patient and caregiver) and 285 healthy controls. Single nucleotide polymorphism (SNP) variants of DRD3 p.S9G (rs6280), GRIN2B c.2664C>T (rs1806201) and HTR2A c.102T>C (rs6313) were genotyped. Multivariate regression analysis revealed that DRD3 p.Ser9Gly (rs6280) heterozygous variant CT (OR = 2.22, 95% CI: 1.03-4.86, p = 0.041), higher daily Levodopa equivalent doses (LED) of drugs (for 100 mg LED, OR = 1.14, 95% CI: 1.01-1.29, p = 0.041), current dopamine agonist but not Levodopa use (OR = 2.16, 95% CI: 1.03-4.55, p = 0.042) and age of onset of motor symptoms under 50 years (OR 2.09, 95% CI: 1.05-4.18, p = 0.035) were independently associated with ICD. DRD3 p.Ser9Gly (rs6280) CT genotype is associated with ICD in Indian PD patients and this association is novel. Enhanced D3 receptor affinity due to gain-of-function conferred by the glycine residues could impair reward-risk assessment in the mesolimbic system and contribute to development of impulsive behaviour, in carriers of this genotype. Copyright © 2016. Published by Elsevier Ltd.
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Burke, Eileen G; Gold, Brian; Hoang, Trish T; Raines, Ronald T; Schomaker, Jennifer M
2017-06-14
The ability to achieve predictable control over the polarization of strained cycloalkynes can influence their behavior in subsequent reactions, providing opportunities to increase both rate and chemoselectivity. A series of new heterocyclic strained cyclooctynes containing a sulfamate backbone (SNO-OCTs) were prepared under mild conditions by employing ring expansions of silylated methyleneaziridines. SNO-OCT derivative 8 outpaced even a difluorinated cyclooctyne in a 1,3-dipolar cycloaddition with benzylazide. The various orbital interactions of the propargylic and homopropargylic heteroatoms in SNO-OCT were explored both experimentally and computationally. The inclusion of these heteroatoms had a positive impact on stability and reactivity, where electronic effects could be utilized to relieve ring strain. The choice of the heteroatom combinations in various SNO-OCTs significantly affected the alkyne geometries, thus illustrating a new strategy for modulating strain via remote substituents. Additionally, this unique heteroatom activation was capable of accelerating the rate of reaction of SNO-OCT with diazoacetamide over azidoacetamide, opening the possibility of further method development in the context of chemoselective, bioorthogonal labeling.
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Directory of Open Access Journals (Sweden)
Masaaki Kanai
2010-07-01
Full Text Available Tryptophan 2,3-dioxygenase (TDO is a first and rate-limiting enzyme for the kynurenine pathway of tryptophan metabolism. Using Tdo-/-mice, we have recently shown that TDO plays a pivotal role in systemic tryptophan metabolism and brain serotonin synthesis as well as emotional status and adult neurogenesis. However, the expression of TDO in the brain has not yet been well characterized, in contrast to its predominant expression in the liver. To further examine the possible role of local TDO in the brain, we quantified the levels of tdo mRNA in various nervous tissues, using Northern blot and quantitative real-time RT-PCR. Higher levels of tdo mRNA expression were detected in the cerebellum and hippocampus. We also identified two novel variants of the tdo gene, termed tdo variant1 and variant2, in the brain. Similar to the known TDO form (TDO full-form, tetramer formation and enzymatic activity were obtained when these variant forms were expressed in vitro. While quantitative real-time RT-PCR revealed that the tissue distribution of these variants was similar to that of tdo full-form, the expression patterns of these variants during early postnatal development in the hippocampus and cerebellum differed. Our findings indicate that in addition to hepatic TDO, TDO and its variants in the brain might function in the developing and adult nervous system. Given the previously reported associations of tdo gene polymorphisms in the patients with autism and Tourette syndrome, the expression of TDO in the brain suggests the possible influence of TDO on psychiatric status. Potential functions of TDOs in the cerebellum, hippocampus and cerebral cortex under physiological and pathological conditions are discussed.
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Energy Technology Data Exchange (ETDEWEB)
Horiuchi, Rie [Division of Regenerative Medical Engineering, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033 (Japan); Akimoto, Takayuki, E-mail: akimoto@m.u-tokyo.ac.jp [Division of Regenerative Medical Engineering, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033 (Japan); Institute for Biomedical Engineering, Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Waseda-tsurumaki, Shinjuku, Tokyo 162-0041 (Japan); Hong, Zhang [Institute for Biomedical Engineering, Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Waseda-tsurumaki, Shinjuku, Tokyo 162-0041 (Japan); Ushida, Takashi [Division of Regenerative Medical Engineering, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033 (Japan)
2012-08-15
Mechanical strain has been reported to affect the proliferation/differentiation of many cell types; however, the effects of mechanotransduction on self-renewal as well as pluripotency of embryonic stem (ES) cells remains unknown. To investigate the effects of mechanical strain on mouse ES cell fate, we examined the expression of Nanog, which is an essential regulator of self-renewal and pluripotency as well as Nanog-associated intracellular signaling during uniaxial cyclic mechanical strain. The mouse ES cell line, CCE was plated onto elastic membranes, and we applied 10% strain at 0.17 Hz. The expression of Nanog was reduced during ES cell differentiation in response to the withdrawal of leukemia inhibitory factor (LIF); however, two days of cyclic mechanical strain attenuated this reduction of Nanog expression. On the other hand, the cyclic mechanical strain promoted PI3K-Akt signaling, which is reported as an upstream of Nanog transcription. The cyclic mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor wortmannin. Furthermore, cytochalasin D, an inhibitor of actin polymerization, also inhibited the mechanical strain-induced increase in phospho-Akt. These findings imply that mechanical force plays a role in regulating Nanog expression in ES cells through the actin cytoskeleton-PI3K-Akt signaling. -- Highlights: Black-Right-Pointing-Pointer The expression of Nanog, which is an essential regulator of 'stemness' was reduced during embryonic stem (ES) cell differentiation. Black-Right-Pointing-Pointer Cyclic mechanical strain attenuated the reduction of Nanog expression. Black-Right-Pointing-Pointer Cyclic mechanical strain promoted PI3K-Akt signaling and mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor and an inhibitor of actin polymerization.
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Energy Technology Data Exchange (ETDEWEB)
Velden, Yme U. van der; Kleibeuker, Wendy; Harwig, Alex; Klaver, Bep; Siteur-van Rijnstra, Esther; Frankin, Esmay; Berkhout, Ben; Das, Atze T., E-mail: a.t.das@amc.uva.nl
2016-01-15
Conditionally replicating HIV-1 variants that can be switched on and off at will are attractive tools for HIV research. We previously developed a genetically modified HIV-1 variant that replicates exclusively when doxycycline (dox) is administered. The nef gene in this HIV-rtTA variant was replaced with the gene encoding the dox-dependent rtTA transcriptional activator. Because loss of Nef expression compromises virus replication in primary cells and precludes studies on Nef function, we tested different approaches to restore Nef production in HIV-rtTA. Strategies that involved translation via an EMCV or synthetic internal ribosome entry site (IRES) failed because these elements were incompatible with efficient virus replication. Fusion protein approaches with the FMDV 2A peptide and human ubiquitin were successful and resulted in genetically-stable Nef-expressing HIV-rtTA strains that replicate more efficiently in primary T-cells and human immune system (HIS) mice than Nef-deficient variants, thus confirming the positive effect of Nef on in vivo virus replication. - Highlights: • Different approaches to encode additional proteins in the HIV-1 genome were tested. • IRES translation elements are incompatible with efficient HIV-1 replication. • Ubiquitin and 2A fusion protein approaches allow efficient HIV-1 replication. • Doxycycline-controlled HIV-1 variants that encode all viral proteins were developed. • Nef stimulates HIV-rtTA replication in primary cells and human immune system mice.
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[Hemoglobin variants in Colombian patients referred to discard hemoglobinopathies].
Romero-Sánchez, Consuelo; Gómez Gutiérrez, Alberto; Duarte, Yurani; Amazo, Constanza; Manosalva, Clara; Chila M, Lorena; Casas-Gómez, María Consuelo; Briceño Balcázar, Ignacio
2015-10-01
Oxygen transport is altered in hemoglobinopathies. To study the distribution of hemoglobinopathies in Andean subjects without African ancestry. We analyzed blood samples of 1,407 subjects aged 18 to 59 years (58% females), living in the central Andean region of Colombia, referred to discard hemoglobinopathies. The frequency and type of hemoglobinopathy was established by capillary and agarose gel electrophoresis. The frequency of hemoglobinopathies was 34.5% and higher among females. The structural variants found were: AS-heterozygous hemoglobin (8.1%), homozygous SS (3.7%), heterozygous SC (2.2%), AC heterozygotes (0.5%) and heterozygous AE (0.3%). Quantitative variants found were Hb A-Beta thalassemia (13.91%) and Hb H (0.06%), Beta-thalassemia heterozygotes C (0.88%), S-Beta thalassemia heterozygotes (6.07%) and compound heterozygous SC/Beta thalassemia (0.25%), with a persistence of fetal hemoglobin 0. Composite thalassemia was also found in 31%. All techniques showed good correlation and capillary electrophoresis demonstrated a greater detection of hemoglobin variants. The frequency of hemoglobin variants in the analyzed population was high, which is an important public health indicator. The most common hemoglobin variant was HbA/Increased structural Hb A2 and the mos frequent structural hemoglobinopathy was sickle cell trait. Capillary electrophoresis can discern any Hb variants present in the population.
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Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A.
Ji, Rong; Lee, Clement M; Gonzales, Linda W; Yang, Yi; Aksoy, Mark O; Wang, Ping; Brailoiu, Eugen; Dun, Nae; Hurford, Matthew T; Kelsen, Steven G
2008-06-01
Chemokine receptors control several fundamental cellular processes in both hematopoietic and structural cells, including directed cell movement, i.e., chemotaxis, cell differentiation, and proliferation. We have previously demonstrated that CXCR3, the chemokine receptor expressed by Th1/Tc1 inflammatory cells present in the lung, is also expressed by human airway epithelial cells. In airway epithelial cells, activation of CXCR3 induces airway epithelial cell movement and proliferation, processes that underlie lung repair. The present study examined the expression and function of CXCR3 in human alveolar type II pneumocytes, whose destruction causes emphysema. CXCR3 was present in human fetal and adult type II pneumocytes as assessed by immunocytochemistry, immunohistochemistry, and Western blotting. CXCR3-A and -B splice variant mRNA was present constitutively in cultured type II cells, but levels of CXCR3-B greatly exceeded CXCR3-A mRNA. In cultured type II cells, I-TAC, IP-10, and Mig induced chemotaxis. Overexpression of CXCR3-A in the A549 pneumocyte cell line produced robust chemotactic responses to I-TAC and IP-10. In contrast, I-TAC did not induce chemotactic responses in CXCR3-B and mock-transfected cells. Finally, I-TAC increased cytosolic Ca(2+) and activated the extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B kinases only in CXCR3-A-transfected cells. These data indicate that the CXCR3 receptor is expressed by human type II pneumocytes, and the CXCR3-A splice variant mediates chemotactic responses possibly through Ca(2+) activation of both mitogen-activated protein kinase and PI 3-kinase signaling pathways. Expression of CXCR3 in alveolar epithelial cells may be important in pneumocyte repair from injury.
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Y-type urethral duplication with posterior perineal fistula: A new variant
Directory of Open Access Journals (Sweden)
Sandesh V Parelkar
2017-05-01
Full Text Available 13 months old boy presented with constipation and straining during micturition with poor urinary stream and voiding of urine per rectum. Perineal examination revealed posterior perineal fistula. Voiding cysto-urethrogram showed bilateral vesicoureteral reflux with bladder diverticuli, normal dorsal urethra and dye going from urethra to rectum suggestive of Y type urethral duplication. Under stoma cover, he underwent excision of posterior perineal fistula with accessory ventral urethra and anorectoplasty was done. At present patient is passing urine in good stream without straining. The uniqueness of our case is the presence of Y type of urethral duplication with normal calibre dorsal urethra and presence of posterior perineal fistula. Therefore, we consider our case to be an unusual variant of Y type of urethral duplication that has not been described before.
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Electrophoretic variation in low molecular weight lens crystallins from inbred strains of rats.
Donner, M E; Skow, L C; Kunz, H W; Gill, T J
1985-10-01
Analysis of rat lens soluble proteins by analytical isoelectric focusing detected two inherited electrophoretic differences in low molecular weight (LM) crystallins from inbred strains of rats (Rattus norvegicus). The polymorphic lens crystallins were shown to be similar to a genetically variant LM crystallin, LEN-1, previously described in mice (Mus musculus) and encoded on chromosome 1, at a locus linked to Pep-3 (dipeptidase). Linkage analysis demonstrated that the rat crystallin locus was loosely linked to Pep-3 at a recombination distance of 38 +/- 4.5 U. These data suggest the conservation of a large chromosomal region during the evolution of Rodentia and support the hypothesis that the gamma-crystallins are evolving more rapidly than alpha- or beta-crystallins.
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Associations between Mycobacterium tuberculosis Strains and Phenotypes
Brown, Timothy; Nikolayevskyy, Vladyslav; Velji, Preya
2010-01-01
To inform development of tuberculosis (TB) control strategies, we characterized a total of 2,261 Mycobacterium tuberculosis complex isolates by using multiple phenotypic and molecular markers, including polymorphisms in repetitive sequences (spoligotyping and variable-number tandem repeats [VNTRs]) and large sequence and single-nucleotide polymorphisms. The Beijing family was strongly associated with multidrug resistance (p = 0.0001), and VNTR allelic variants showed strong associations with spoligotyping families: >5 copies at exact tandem repeat (ETR) A, >2 at mycobacterial interspersed repetitive unit 24, and >3 at ETR-B associated with the East African–Indian and M. bovis strains. All M. tuberculosis isolates were differentiated into 4 major lineages, and a maximum parsimony tree was constructed suggesting a more complex phylogeny for M. africanum. These findings can be used as a model of pathogen global diversity. PMID:20113558
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Exploring strain-promoted 1,3-dipolar cycloadditions of end functionalized polymers
Ledin, Petr A; Kolishetti, Nagesh; Hudlikar, Manish S; Boons, Geert-Jan
2014-01-01
Strain-promoted 1,3-dipolar cycloaddition of cyclooctynes with 1,3-dipoles such as azides, nitrones, and nitrile oxides, are of interest for the functionalization of polymers. In this study, we have explored the use of a 4-dibenzocyclooctynol (DIBO)-containing chain transfer agent in reversible
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Low-field magnetoresistance anisotropy in strained ultrathin Pr0.67Sr0.33MnO3 films
International Nuclear Information System (INIS)
Wang, H.S.; Li, Q.
1999-01-01
The authors have studied the anisotropic low-field magnetoresistance (LFMR) in ultrathin Pr 0.67 sr 0.33 MnO 3 (PSMO) films epitaxially grown on LaAlO 3 (LAO), STiO 3 (STO), and NdGaO 3 (NGO) substrates which impose compressive, tensile, and nearly-zero strains in the films. The compressively-strained films show a very large negative LFMR in a perpendicular magnetic field and a much smaller MR in a parallel field, while the tensile-strain films show positive LFMR in a perpendicular field and negative MR in a parallel field. The results are interpreted based on the strain-induced magnetic anisotropy
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Directory of Open Access Journals (Sweden)
Tracy Russell P
2011-03-01
Full Text Available Abstract Background Genetic risk factors might improve prediction of coronary events. Several variants at chromosome 9p21.3 have been widely reported to be associated with coronary heart disease (CHD in prospective and case-control studies. A variant of KIF6 (719Arg has also been reported to be associated with increased risk of CHD in large prospective studies, but not in case-control studies. We asked whether the addition of genetic information (the 9p21.3 or KIF6 variants or a well-established non-genetic risk factor (C-reactive protein [CRP] can improve risk prediction by the Framingham Risk Score (FRS in the Cardiovascular Health Study (CHS--a prospective observational study of risk factors for cardiovascular disease among > 5,000 participants aged 65 or older. Methods Improvement of risk prediction was assessed by change in the area under the receiver-operator characteristic curve (AUC and by net reclassification improvement (NRI. Results Among white participants the FRS was improved by addition of KIF6 719Arg carrier status among men as assessed by the AUC (from 0.581 to 0.596, P = 0.03 but not by NRI (NRI = 0.027, P = 0.32. Adding both CRP and 719Arg carrier status to the FRS improved risk prediction by the AUC (0.608, P = 0.02 and NRI (0.093, P = 0.008 in men, but not women (P ≥ 0.24. Conclusions While none of these risk markers individually or in combination improved risk prediction among women, a combination of KIF6 719Arg carrier status and CRP levels modestly improved risk prediction among white men; although this improvement is not significant after multiple-testing correction. These observations should be investigated in other prospective studies.
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Enhanced photovoltaic currents in strained Fe-doped LiNbO{sub 3} films
Energy Technology Data Exchange (ETDEWEB)
Inoue, Ryotaro [Division of Physics, Institute of Liberal Education, School of Medicine, Nihon University, 31-10, Ooyaguchi-kamicho, Itabashi-ku, Tokyo 173-8601 (Japan); Takahashi, Shusuke; Kitanaka, Yuuki; Oguchi, Takeshi; Noguchi, Yuji; Miyayama, Masaru [Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8654 (Japan)
2015-12-15
We investigate the impact of strain on photovoltaic current (J{sub z}) characteristics for iron-doped LiNbO{sub 3} (Fe-LN) under visible light illumination by thin-film experiments. The J{sub z} values are demonstrated to be dramatically enhanced for the film with a tensile strain along the P{sub s} direction, which is over 500 times as large as that of the bulk (strain-free) Fe-LN crystals. Density functional theory (DFT) calculations show that the tensile strain increases an off-center displacement of Fe{sup 2+} that is opposite to the P{sub s} direction. Our experimental and DFT study demonstrates that the control of the lattice strain is effective in enhancing the photovoltaic effect in the Fe-LN system. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)
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Directory of Open Access Journals (Sweden)
Fabíola Gomes de Carvalho
2005-12-01
Full Text Available O cultivo sucessivo de soja inoculada numa mesma área proporcionou a adaptação de uma população de rizóbios, que podem não ser tão eficientes quanto à capacidade de fixação de N2, mas apresentam alta competitividade, dificultando a introdução de novas estirpes mais eficientes. Com a finalidade de avaliar o desempenho simbiótico (eficiência e competitividade de variantes espontâneos isolados de estirpes de B. japonicum (SEMIA 5079 e SEMIA 5080 e B. elkanii (SEMIA 587 e SEMIA 5019, realizou-se um experimento em casa de vegetação onde os variantes foram inoculados isoladamente e em diferentes combinações entre os variantes e uma estirpe comprovadamente mais competitiva (SEMIA 587 ou SEMIA 5019 a partir da adição de inóculos mistos (1/1; v/v no cultivar de soja BR-16. Por meio da avaliação das variáveis analisadas (nodulação, produção de matéria de seca da parte aérea, N total acumulado na parte aérea e ocupação nodular, foi possível constatar que o determinante da maior eficiência em tratamentos co-inoculados não foi a ocupação nodular de determinada estirpe ou variante presente no inóculo, mas, sim, o tipo de interação (sinérgica ou antagônica predominante no tratamento co-inoculado e que é possível selecionar variantes eficientes e competitivos para a cultura da soja a partir de estirpes parentais que já apresentam características desejáveis para utilização em inoculantes comerciais.The continuous cultivation of inoculated soybean in the same area can determine the soil colonization with a rhizobia population presenting low nitrogen fixation effectiveness. This fact can be a problem for the establishment of a more effective population. A greenhouse experiment was carried out to evaluate the symbiotic effectiveness and competitiveness of spontaneous mutants isolated from B. japonicum (SEMIA 5079 and SEMIA 5080 and B. elkanii (SEMIA 587 and SEMIA 5019 strains. The soybean biovar BR 16 was
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Electrical Transport and Magnetoresistance Properties of Tensile-Strained CaMnO3 Thin Films
Ullery, Dustin; Lawson, Bridget; Zimmerman, William; Neubauer, Samuel; Chaudhry, Adeel; Hart, Cacie; Yong, Grace; Smolyaninova, Vera; Kolagani, Rajeswari
We will present our studies of the electrical transport and magnetoresistance properties of tensile strained CaMnO3 thin films. We observe that the resistivity decreases significantly as the film thickness decreases which is opposite to what is observed in thin films of hole doped manganites. The decrease in resistivity is more pronounced in the films on (100) SrTiO3, with resistivity of the thinnest films being about 3 orders of magnitude lower than that of bulk CaMnO3. Structural changes accompanying resistivity changes cannot be fully explained as due to tensile strain, and indicate the presence of oxygen vacancies. These results also suggest a coupling between tensile strain and oxygen deficiency, consistent with predictions from models based on density functional theory calculations. We observe a change in resistance under the application of moderate magnetic field. Experiments are underway to understand the origin of the magnetoresistance and its possible relation to the tensile strain effects. We acknowledge support from: Towson Office of University Undergraduate Research, Fisher Endowment Grant and Undergraduate Research Grants from the Fisher College of Science and Mathematics, and Seed Funding Grant from the School of Emerging technologies.
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Costantino, Angela; Coppola, Nicola; Spada, Enea; Bruni, Roberto; Taffon, Stefania; Equestre, Michele; Marcantonio, Cinzia; Sagnelli, Caterina; Dell'Isola, Chiara; Tosone, Grazia; Mascolo, Silvia; Sagnelli, Evangelista; Ciccaglione, Anna Rita
2017-11-01
In Italy, the incidence of hepatitis A has progressively declined over the last 30 years, though not homogeneously throughout the country. In Campania, Southern Italy, high annual incidence rates have been reported and several periodic outbreaks have occurred. To investigate the phylogenetic and epidemiologic relationships among HAV strains circulating in Campania over the period 1997-2015, 87 hepatitis A cases were investigated. The most frequent risk factor was the consumption of raw/undercooked shellfish (75/87, 86.2%). During 1997-2002 most viral strains were subtype IA (16/23, 70%); the phylogenetic pattern suggests that the incidence peaks observed in 2000-2001 had likely been caused by multiple strains. During a large 2004 outbreak, almost all viral variants were subtype IB (38/41, 93%); most of them (22/38, 58%) were recognized to be one of two main strains (differing for just a single nucleotide), the remaining sequences were strictly related variants. In 2014/2015, only IA strains were observed; two phylogenetically related but distinct strains were responsible, respectively, for a small cluster in 2014 and an outbreak in 2015. In each outbreak, several strains unrelated to those responsible for most cases were detected in a minority of patients, documenting a background of sporadic cases occurring even in the course of outbreaks; some of them proved to be identical to strains detected 11-14 years previously. Overall, the data suggest that several related and unrelated HAV strains have endemically circulated over the last 15 years in Campania, with some strains gaining epidemic transmission likely because of a local combination of multiple factors, including inadequate waste water purification and dietary habits. © 2017 Wiley Periodicals, Inc.
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Variant in GALNT3 Gene Linked with Reduced Coronary Artery Disease Risk in Chinese Population.
Guo, Liwei; Li, Duan; Li, Mengting; Li, Lin; Huang, Yanmei
2017-07-01
Our previous study found expression of GALNT3 gene was reduced in coronary artery disease (CAD) patients, and it contributed to endothelial injury by regulating apoptosis and matrix metalloproteinase (MMP) expression. GALNT3 gene may be a potential target for future therapeutic intervention of CAD. However, none reports linking the GALNT3 gene to susceptibility of CAD. This study investigated the variant associations of GALNT3 gene and CAD. Thirteen single nucleotide polymorphism (SNP) in and around the GALNT3 gene were tagged and analyzed in CAD patients (n = 1515) and control individuals (n = 5019), and the SNPs with CAD were tested with multiple logistic regression analysis in an additive genetic model (with one degree of freedom) after adjusting for age and sex. Expression of GALNT3 gene was detected by real-time PCR and Western blot. Luciferase reporter assays were used to detect the allele-specific effect of rs4621175 on transcriptional activity. Two GALNT3 markers, rs13427924 and rs4621175, were significantly associated with CAD (odds ratio [OR] = 0.87, p = 1.01 × 10 -3 and OR = 0.75, p = 2.51 × 10 -4 , respectively), and the risk A allele of rs4621175 was associated with lower GALNT3 expression in both mRNA and protein level; also, A allele showed decreased reporter activity. In addition, we found the level of GALNT3 negatively correlated with MMP-2 gene expression. This study identified GALNT3 as a novel gene that rendered patients susceptible to CAD, and the A allele of a disease-associated variant rs4621175 linked reduced CAD risk through decreased GALNT3 expression. These results confirmed the role of GALNT3 gene in CAD and provided new insights into the genetic regulation of the GALNT3 gene with respect to the pathogenesis of CAD.
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Bock, Gabriella; Gebhart, Mathias; Scharinger, Anja; Jangsangthong, Wanchana; Busquet, Perrine; Poggiani, Chiara; Sartori, Simone; Mangoni, Matteo E; Sinnegger-Brauns, Martina J; Herzig, Stefan; Striessnig, Jörg; Koschak, Alexandra
2011-12-09
An intramolecular interaction between a distal (DCRD) and a proximal regulatory domain (PCRD) within the C terminus of long Ca(v)1.3 L-type Ca(2+) channels (Ca(v)1.3(L)) is a major determinant of their voltage- and Ca(2+)-dependent gating kinetics. Removal of these regulatory domains by alternative splicing generates Ca(v)1.3(42A) channels that activate at a more negative voltage range and exhibit more pronounced Ca(2+)-dependent inactivation. Here we describe the discovery of a novel short splice variant (Ca(v)1.3(43S)) that is expressed at high levels in the brain but not in the heart. It lacks the DCRD but, in contrast to Ca(v)1.3(42A), still contains PCRD. When expressed together with α2δ1 and β3 subunits in tsA-201 cells, Ca(v)1.3(43S) also activated at more negative voltages like Ca(v)1.3(42A) but Ca(2+)-dependent inactivation was less pronounced. Single channel recordings revealed much higher channel open probabilities for both short splice variants as compared with Ca(v)1.3(L). The presence of the proximal C terminus in Ca(v)1.3(43S) channels preserved their modulation by distal C terminus-containing Ca(v)1.3- and Ca(v)1.2-derived C-terminal peptides. Removal of the C-terminal modulation by alternative splicing also induced a faster decay of Ca(2+) influx during electrical activities mimicking trains of neuronal action potentials. Our findings extend the spectrum of functionally diverse Ca(v)1.3 L-type channels produced by tissue-specific alternative splicing. This diversity may help to fine tune Ca(2+) channel signaling and, in the case of short variants lacking a functional C-terminal modulation, prevent excessive Ca(2+) accumulation during burst firing in neurons. This may be especially important in neurons that are affected by Ca(2+)-induced neurodegenerative processes.
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Directory of Open Access Journals (Sweden)
Dorthe S Bille
Full Text Available Two meta-analyses of genome-wide association studies (GWAS have suggested that four variants: rs2605100 in lysophospholipase-like 1 (LYPLAL1, rs10146997 in neuroxin 3 (NRXN3, rs545854 in methionine sulfoxide reductase A (MSRA, and rs987237 in transcription factor activating enhancer-binding protein 2 beta (TFAP2B associate with measures of central obesity. To elucidate potential underlying phenotypes we aimed to investigate whether these variants associated with: 1 quantitative metabolic traits, 2 anthropometric measures (waist circumference (WC, waist-hip ratio, and BMI, or 3 type 2 diabetes, and central and general overweight and obesity.The four variants were genotyped in Danish individuals using KASPar®. Quantitative metabolic traits were examined in a population-based sample (n = 6,038 and WC and BMI were furthermore analyzed in a combined study sample (n = 13,507. Case-control studies of diabetes and adiposity included 15,326 individuals. The major G-allele of LYPLAL1 rs2605100 associated with increased fasting serum triglyceride concentrations (per allele effect (β = 3%(1;5(95%CI, p(additive = 2.7×10(-3, an association driven by the male gender (p(interaction = 0.02. The same allele associated with increased fasting serum insulin concentrations (β = 3%(1;5, p(additive = 2.5×10(-3 and increased insulin resistance (HOMA-IR (β = 4%(1;6, p(additive = 1.5×10(-3. The minor G-allele of rs10146997 in NRXN3 associated with increased WC among women (β = 0.55cm (0.20;0.89, p(additive = 1.7×10(-3, p(interaction = 1.0×10(-3, but showed no associations with obesity related metabolic traits. The MSRA rs545854 and TFAP2B rs987237 showed nominal associations with central obesity; however, no underlying metabolic phenotypes became obvious, when investigating quantitative metabolic traits. None of the variants influenced the prevalence of type 2 diabetes.We demonstrate that several of the central
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Directory of Open Access Journals (Sweden)
Simon D Rees
Full Text Available BACKGROUND: The Meta-Analysis of Glucose and Insulin related traits Consortium (MAGIC recently identified 16 loci robustly associated with fasting glucose, some of which were also associated with type 2 diabetes. The purpose of our study was to explore the role of these variants in South Asian populations of Punjabi ancestry, originating predominantly from the District of Mirpur, Pakistan. METHODOLOGY/PRINCIPAL FINDINGS: Sixteen single nucleotide polymorphisms (SNPs were genotyped in 1678 subjects with type 2 diabetes and 1584 normoglycaemic controls from two Punjabi populations; one resident in the UK and one indigenous to the District of Mirpur. In the normoglycaemic controls investigated for fasting glucose associations, 12 of 16 SNPs displayed β values with the same direction of effect as that seen in European studies, although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose (β = 0.063 [95% CI: 0.013, 0.113] p = 0.015. Of interest, the MTNR1B rs10830963 SNP displayed a negative β value for fasting glucose in our study; this effect size was significantly lower than that seen in Europeans (p = 1.29×10(-4. In addition to previously reported type 2 diabetes risk variants in TCF7L2 and SLC30A8, SNPs in ADCY5 (rs11708067 and GLIS3 (rs7034200 displayed evidence for association with type 2 diabetes, with odds ratios of 1.23 (95% CI: 1.09, 1.39; p = 9.1×10(-4 and 1.16 (95% CI: 1.05, 1.29; p = 3.49×10(-3 respectively. CONCLUSIONS/SIGNIFICANCE: Although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose in our study, the finding that 12 out of 16 SNPs displayed a direction of effect consistent with European studies suggests that a number of these variants may contribute to fasting glucose variation in individuals of South Asian ancestry. We also provide evidence for the first time in South Asians that alleles of SNPs in GLIS3 and ADCY5 may confer risk of type 2 diabetes.
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Matthew, Ashley N; Zephyr, Jacqueto; Hill, Caitlin J; Jahangir, Muhammad; Newton, Alicia; Petropoulos, Christos J; Huang, Wei; Kurt-Yilmaz, Nese; Schiffer, Celia A; Ali, Akbar
2017-07-13
A substrate envelope-guided design strategy is reported for improving the resistance profile of HCV NS3/4A protease inhibitors. Analogues of 5172-mcP1P3 were designed by incorporating diverse quinoxalines at the P2 position that predominantly interact with the invariant catalytic triad of the protease. Exploration of structure-activity relationships showed that inhibitors with small hydrophobic substituents at the 3-position of P2 quinoxaline maintain better potency against drug resistant variants, likely due to reduced interactions with residues in the S2 subsite. In contrast, inhibitors with larger groups at this position were highly susceptible to mutations at Arg155, Ala156, and Asp168. Excitingly, several inhibitors exhibited exceptional potency profiles with EC 50 values ≤5 nM against major drug resistant HCV variants. These findings support that inhibitors designed to interact with evolutionarily constrained regions of the protease, while avoiding interactions with residues not essential for substrate recognition, are less likely to be susceptible to drug resistance.
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Directory of Open Access Journals (Sweden)
Fei-Feng Li
Full Text Available Nodal/TGF signaling pathway has an important effect at early stages of differentiation of human embryonic stem cells in directing them to develop into different embryonic lineages. SMAD3 is a key intracellular messenger regulating factor in the Nodal/TGF signaling pathway, playing important roles in embryonic and, particularly, cardiovascular system development. The aim of this work was to find evidence on whether SMAD3 variations might be associated with ventricular septal defects (VSD or other congenital heart diseases (CHD.We sequenced the SMAD3 gene for 372 Chinese Han CHD patients including 176 VSD patients and evaluated SNP rs2289263, which is located before the 5'UTR sequence of the gene. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 13.0. The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE.Three heterozygous variants in SMAD3 gene, rs2289263, rs35874463 and rs17228212, were identified. Statistical analyses showed that the rs2289263 variant located before the 5'UTR sequence of SMAD3 gene was associated with the risk of VSD (P value=0.013 <0.05.The SNP rs2289263 in the SMAD3 gene is associated with VSD in Chinese Han populations.
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Strain measurement of abdominal aortic aneurysm with real-time 3D ultrasound speckle tracking.
Bihari, P; Shelke, A; Nwe, T H; Mularczyk, M; Nelson, K; Schmandra, T; Knez, P; Schmitz-Rixen, T
2013-04-01
Abdominal aortic aneurysm rupture is caused by mechanical vascular tissue failure. Although mechanical properties within the aneurysm vary, currently available ultrasound methods assess only one cross-sectional segment of the aorta. This study aims to establish real-time 3-dimensional (3D) speckle tracking ultrasound to explore local displacement and strain parameters of the whole abdominal aortic aneurysm. Validation was performed on a silicone aneurysm model, perfused in a pulsatile artificial circulatory system. Wall motion of the silicone model was measured simultaneously with a commercial real-time 3D speckle tracking ultrasound system and either with laser-scan micrometry or with video photogrammetry. After validation, 3D ultrasound data were collected from abdominal aortic aneurysms of five patients and displacement and strain parameters were analysed. Displacement parameters measured in vitro by 3D ultrasound and laser scan micrometer or video analysis were significantly correlated at pulse pressures between 40 and 80 mmHg. Strong local differences in displacement and strain were identified within the aortic aneurysms of patients. Local wall strain of the whole abdominal aortic aneurysm can be analysed in vivo with real-time 3D ultrasound speckle tracking imaging, offering the prospect of individual non-invasive rupture risk analysis of abdominal aortic aneurysms. Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
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Enhanced Proton Conductivity in Y-Doped BaZrO3 via Strain Engineering.
Fluri, Aline; Marcolongo, Aris; Roddatis, Vladimir; Wokaun, Alexander; Pergolesi, Daniele; Marzari, Nicola; Lippert, Thomas
2017-12-01
The effects of stress-induced lattice distortions (strain) on the conductivity of Y-doped BaZrO 3 , a high-temperature proton conductor with key technological applications for sustainable electrochemical energy conversion, are studied. Highly ordered epitaxial thin films are grown in different strain states while monitoring the stress generation and evolution in situ. Enhanced proton conductivity due to lower activation energies is discovered under controlled conditions of tensile strain. In particular, a twofold increased conductivity is measured at 200 °C along a 0.7% tensile strained lattice. This is at variance with conclusions coming from force-field simulations or the static calculations of diffusion barriers. Here, extensive first-principles molecular dynamic simulations of proton diffusivity in the proton-trapping regime are therefore performed and found to agree with the experiments. The simulations highlight that compressive strain confines protons in planes parallel to the substrate, while tensile strain boosts diffusivity in the perpendicular direction, with the net result that the overall conductivity is enhanced. It is indeed the presence of the dopant and the proton-trapping effect that makes tensile strain favorable for proton conduction.
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Major enhancement of the thermoelectric performance in Pr/Nb-doped SrTiO3 under strain
Amin, B.
2013-07-16
The electronic structure and thermoelectric properties of strained (biaxially and uniaxially) Sr0.95Pr0.05TiO3 and SrTi0.95Nb0.05O3 are investigated in the temperature range from 300 K to 1200 K. Substitutions of Pr at the Sr site and Nb at the Ti site generate n-type doping and thus improve the thermoelectric performance as compared to pristine SrTiO3. Further enhancement is achieved by the application of strain, for example, of the Seebeck coefficient by 21% for Sr0.95Pr0.05TiO3 and 10% for SrTi0.95Nb0.05O3 at room temperature in the case of 5% biaxial strain. At 1200 K, we predict figures of merit of 0.58 and 0.55 for 2.5% biaxially strained Sr0.95Pr0.05TiO3 and SrTi0.95Nb0.05O3 , respectively, which are the highest values reported for rare earth doped SrTiO3.
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DEFF Research Database (Denmark)
Herrero-Fresno, Ana; Zachariasen, Camilla; Hansen, Monica Hegstad
2016-01-01
. E. coli 912 was shown to spread to non-inoculated pigs in both groups. The selective effect did not persist beyond 3 days post-treatment, and the strain was not detected from this time point in pen 2. We demonstrated that E. coli 912 was able to spread between pigs in the same pen irrespective....../gentamicin, sulphonamide, tetracycline, hygromycin B, β-lactams and streptomycin [aac(3)-IV, sul2, tet(X), aph(4), bla TEM-1 and strA/B], with all but tet(X) located on the same conjugative plasmid. Nineteen pigs were randomly allocated into two inoculation groups, one treated with apramycin (pen 2) and one non......-treated (pen 3), along with a non-inoculated control group (pen 1). Two pigs of pen 2 and 3 were inoculated intragastrically with a rifampicin resistant variant of the strain. Apramycin treatment in pen 2 was initiated immediately after inoculation. Strain colonization was assessed in the feces from all pigs...
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Zhang, Yanping; Liu, Changjun; Yan, Fuhai; Liu, Ailing; Cheng, Yun; Li, Zhijie; Sun, Guorong; Lv, Hongchao; Wang, Xiaomei
2017-08-24
Gallid herpesvirus 2 (GaHV-2) continuously evolves, which reduces the effectiveness of existing vaccines. To construct new GaHV-2 candidate vaccines, LMS, which is a virulent GaHV-2 field strain isolated from diseased chicken flocks in Southwest China in 2007, was modified such that both copies of its meq oncogene were partially deleted. The resulting virus, i.e., rMSΔmeq, was characterized using PCR and sequencing. To evaluate the safety and protective efficacy of rMSΔmeq, specific pathogen-free (SPF) chickens were inoculated with 2000 plaque forming units (pfu) and 20,000pfu of rMSΔmeq immediately after hatching. All birds grew well during the experimental period, and none of the challenged chickens developed Marek's disease-associated lymphoma. In addition, the rMSΔmeq- and CVI988/Rispens-vaccinated SPF chickens were challenged with 1000 pfu and 5000 pfu of the representative virulent GaHV-2 Md5 strain and 1000 pfu of the variant GaHV-2 strains LCC or LTS. The results showed that the rMSΔmeq strain provided complete protection, which was similar to that provided by the CVI988/Rispens vaccine (protective index (PI) of 95.5) when challenged with a conventional dose of the Md5 strain. However, rMSΔmeq provided a PI of 90.9 when challenged with 5000 pfu of the Md5 strain, which was significantly higher than that provided by the CVI988/Rispens vaccine (54.5). rMSΔmeq provided a PI of 86.4 against LCC, which was equal to that provided by the CVI988/Rispens vaccine (81.8). In addition, rMSΔmeq provided a PI of 100 against LTS, which was significantly higher than that provided by the CVI988/Rispens vaccine (68.2). Altogether, the rMSΔmeq virus provided efficient protection against representative and variant GaHV-2 strains. In conclusion, the rMSΔmeq virus is a safe and effective vaccine candidate for the prevention of Marek's disease and is effective against the Chinese variant GaHV-2 strains. Copyright © 2017. Published by Elsevier Ltd.
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Kaur, G; Singh, T P; Malik, R K
2013-01-01
Antilisterial efficiency of three bacteriocins, viz, Nisin, Pediocin 34 and Enterocin FH99 was tested individually and in combination against Listeria mononcytogenes ATCC 53135. A greater antibacterial effect was observed when the bacteriocins were combined in pairs, indicating that the use of more than one LAB bacteriocin in combination have a higher antibacterial action than when used individually. Variants of Listeria monocytogenes ATCC 53135 resistant to Nisin, Pediocin 34 and Enterocin FH99 were developed. Bacteriocin cross-resistance of wild type and their corresponding resistant variants were assessed and results showed that resistance to a bacteriocin may extend to other bacteriocins within the same class. Resistance to Pediocin 34 conferred cross resistance to Enterocin FH 99 but not to Nisin. Similarly resistance to Enterocin FH99 conferred cross resistance to Pediocin 34 but not to Nisin. Also, the sensitivity of Nisin, Pediocin 34 and Enterocin FH99 resistant variants of Listeria monocytogenes to low pH, salt, sodium nitrite, and potassium sorbate was assayed in broth and compared to the parental wild-type strain. The Nisin, Pediocin 34 and Enterocin FH99 resistant variants did not have intrinsic resistance to low pH, sodium chloride, potassium sorbate, or sodium nitrite. In no case were the bacteriocin resistant Listeria monocytogenes variants examined were more resistant to inhibitors than the parental strains.
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Directory of Open Access Journals (Sweden)
G. Kaur
2013-01-01
Full Text Available Antilisterial efficiency of three bacteriocins, viz, Nisin, Pediocin 34 and Enterocin FH99 was tested individually and in combination against Listeria mononcytogenes ATCC 53135. A greater antibacterial effect was observed when the bacteriocins were combined in pairs, indicating that the use of more than one LAB bacteriocin in combination have a higher antibacterial action than when used individually. Variants of Listeria monocytogenes ATCC 53135 resistant to Nisin, Pediocin 34 and Enterocin FH99 were developed. Bacteriocin cross-resistance of wild type and their corresponding resistant variants were assessed and results showed that resistance to a bacteriocin may extend to other bacteriocins within the same class. Resistance to Pediocin 34 conferred cross resistance to Enterocin FH 99 but not to Nisin. Similarly resistance to Enterocin FH99 conferred cross resistance to Pediocin 34 but not to Nisin. Also, the sensitivity of Nisin, Pediocin 34 and Enterocin FH99 resistant variants of Listeria monocytogenes to low pH, salt, sodium nitrite, and potassium sorbate was assayed in broth and compared to the parental wild-type strain. The Nisin, Pediocin 34 and Enterocin FH99 resistant variants did not have intrinsic resistance to low pH, sodium chloride, potassium sorbate, or sodium nitrite. In no case were the bacteriocin resistant Listeria monocytogenes variants examined were more resistant to inhibitors than the parental strains.
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Cubillos, Francisco A; Brice, Claire; Molinet, Jennifer; Tisné, Sebastién; Abarca, Valentina; Tapia, Sebastián M; Oporto, Christian; García, Verónica; Liti, Gianni; Martínez, Claudio
2017-06-07
Saccharomyces cerevisiae is responsible for wine must fermentation. In this process, nitrogen represents a limiting nutrient and its scarcity results in important economic losses for the wine industry. Yeast isolates use different strategies to grow in poor nitrogen environments and their genomic plasticity enables adaptation to multiple habitats through improvements in nitrogen consumption. Here, we used a highly recombinant S. cerevisiae multi-parent population (SGRP-4X) derived from the intercross of four parental strains of different origins to identify new genetic variants responsible for nitrogen consumption differences during wine fermentation. Analysis of 165 fully sequenced F12 segregants allowed us to map 26 QTL in narrow intervals for 14 amino acid sources and ammonium, the majority of which represent genomic regions previously unmapped for these traits. To complement this strategy, we performed Bulk segregant RNA-seq (BSR-seq) analysis in segregants exhibiting extremely high and low ammonium consumption levels. This identified several QTL overlapping differentially expressed genes and refined the gene candidate search. Based on these approaches, we were able to validate ARO1 , PDC1 , CPS1 , ASI2 , LYP1 , and ALP1 allelic variants underlying nitrogen consumption differences between strains, providing evidence of many genes with small phenotypic effects. Altogether, these variants significantly shape yeast nitrogen consumption with important implications for evolution, ecological, and quantitative genomics. Copyright © 2017 Cubillos et al.
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Directory of Open Access Journals (Sweden)
Francisco A. Cubillos
2017-06-01
Full Text Available Saccharomyces cerevisiae is responsible for wine must fermentation. In this process, nitrogen represents a limiting nutrient and its scarcity results in important economic losses for the wine industry. Yeast isolates use different strategies to grow in poor nitrogen environments and their genomic plasticity enables adaptation to multiple habitats through improvements in nitrogen consumption. Here, we used a highly recombinant S. cerevisiae multi-parent population (SGRP-4X derived from the intercross of four parental strains of different origins to identify new genetic variants responsible for nitrogen consumption differences during wine fermentation. Analysis of 165 fully sequenced F12 segregants allowed us to map 26 QTL in narrow intervals for 14 amino acid sources and ammonium, the majority of which represent genomic regions previously unmapped for these traits. To complement this strategy, we performed Bulk segregant RNA-seq (BSR-seq analysis in segregants exhibiting extremely high and low ammonium consumption levels. This identified several QTL overlapping differentially expressed genes and refined the gene candidate search. Based on these approaches, we were able to validate ARO1, PDC1, CPS1, ASI2, LYP1, and ALP1 allelic variants underlying nitrogen consumption differences between strains, providing evidence of many genes with small phenotypic effects. Altogether, these variants significantly shape yeast nitrogen consumption with important implications for evolution, ecological, and quantitative genomics.
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Electrophoretic variants of blood proteins in Japanese, 7
International Nuclear Information System (INIS)
Satoh, Chiyoko; Takahashi, Norio; Kimura, Yasukazu; Miura, Akiko; Kaneko, Junko; Fujita, Mikio; Toyama, Kyoko.
1986-11-01
A total of 16,835 children, of whom 11,737 are unrelated, from Hiroshima and Nagasaki were examined for erythrocyte cytoplasmic glutamate-oxaloacetate transaminase (GOT1) by starch gel electrophoresis. A variant allele named GOT1*2HR1 which seems to be identical with GOT1*2 was encountered in polymorphic frequency. Five kinds of rare variants, 3NG1, 4NG1, 5NG1, 6HR1, and 7NG1 were encountered in a total of 109 children. Except for 7NG1 for which complete family study was unable, family studies confirmed the genetic nature of these rare variants, since for all instances in which both parents could be examined, one of the parents exhibited the same variant as that of their child. Thermostability profiles of these six variants were normal. The enzyme activities of five were decreased, while the value of one was normal compared to that of GOT1 1. (author)
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Understanding Strain-Induced Phase Transformations in BiFeO3 Thin Films.
Dixit, Hemant; Beekman, Christianne; Schlepütz, Christian M; Siemons, Wolter; Yang, Yongsoo; Senabulya, Nancy; Clarke, Roy; Chi, Miaofang; Christen, Hans M; Cooper, Valentino R
2015-08-01
Experiments demonstrate that under large epitaxial strain a coexisting striped phase emerges in BiFeO 3 thin films, which comprises a tetragonal-like ( T ') and an intermediate S ' polymorph. It exhibits a relatively large piezoelectric response when switching between the coexisting phase and a uniform T ' phase. This strain-induced phase transformation is investigated through a synergistic combination of first-principles theory and experiments. The results show that the S ' phase is energetically very close to the T ' phase, but is structurally similar to the bulk rhombohedral ( R ) phase. By fully characterizing the intermediate S ' polymorph, it is demonstrated that the flat energy landscape resulting in the absence of an energy barrier between the T ' and S ' phases fosters the above-mentioned reversible phase transformation. This ability to readily transform between the S ' and T ' polymorphs, which have very different octahedral rotation patterns and c / a ratios, is crucial to the enhanced piezoelectricity in strained BiFeO 3 films. Additionally, a blueshift in the band gap when moving from R to S ' to T ' is observed. These results emphasize the importance of strain engineering for tuning electromechanical responses or, creating unique energy harvesting photonic structures, in oxide thin film architectures.
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Bock, Gabriella; Gebhart, Mathias; Scharinger, Anja; Jangsangthong, Wanchana; Busquet, Perrine; Poggiani, Chiara; Sartori, Simone; Mangoni, Matteo E.; Sinnegger-Brauns, Martina J.; Herzig, Stefan; Striessnig, Jörg; Koschak, Alexandra
2011-01-01
An intramolecular interaction between a distal (DCRD) and a proximal regulatory domain (PCRD) within the C terminus of long Cav1.3 L-type Ca2+ channels (Cav1.3L) is a major determinant of their voltage- and Ca2+-dependent gating kinetics. Removal of these regulatory domains by alternative splicing generates Cav1.342A channels that activate at a more negative voltage range and exhibit more pronounced Ca2+-dependent inactivation. Here we describe the discovery of a novel short splice variant (Cav1.343S) that is expressed at high levels in the brain but not in the heart. It lacks the DCRD but, in contrast to Cav1.342A, still contains PCRD. When expressed together with α2δ1 and β3 subunits in tsA-201 cells, Cav1.343S also activated at more negative voltages like Cav1.342A but Ca2+-dependent inactivation was less pronounced. Single channel recordings revealed much higher channel open probabilities for both short splice variants as compared with Cav1.3L. The presence of the proximal C terminus in Cav1.343S channels preserved their modulation by distal C terminus-containing Cav1.3- and Cav1.2-derived C-terminal peptides. Removal of the C-terminal modulation by alternative splicing also induced a faster decay of Ca2+ influx during electrical activities mimicking trains of neuronal action potentials. Our findings extend the spectrum of functionally diverse Cav1.3 L-type channels produced by tissue-specific alternative splicing. This diversity may help to fine tune Ca2+ channel signaling and, in the case of short variants lacking a functional C-terminal modulation, prevent excessive Ca2+ accumulation during burst firing in neurons. This may be especially important in neurons that are affected by Ca2+-induced neurodegenerative processes. PMID:21998310
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Directory of Open Access Journals (Sweden)
Marcus Ho-yin Wong
2016-10-01
Full Text Available This study reports the complete sequence of pE80, a conjugative IncFII plasmid recovered from an E. coli strain isolated from chicken meat. This plasmid harbors multiple resistance determinants including oqxAB, fosA3, blaCTX-M-55 and blaTEM-1, and is a close variant of the recently reported p42-2 element, which was recovered from E. coli of veterinary source. Recovery of pE80 constitutes evidence that evolution or genetic re-arrangement of IncFII type plasmids residing in animal-borne organisms is an active event, which involves acquisition and integration of foreign resistance elements into the plasmid backbone. Dissemination of these plasmids may further compromise the effectiveness of current antimicrobial strategies.
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Directory of Open Access Journals (Sweden)
Masaaki Kanai
2010-01-01
Full Text Available Tryptophan 2,3-dioxygenase (TDO is a first and rate-limiting enzyme for the kynurenine pathway of tryptophan metabolism. Using Tdo −/− mice, we have recently shown that TDO plays a pivotal role in systemic tryptophan metabolism and brain serotonin synthesis as well as emotional status and adult neurogenesis. However, the expression of TDO in the brain has not yet been well characterized, in contrast to its predominant expression in the liver. To further examine the possible role of local TDO in the brain, we quantified the levels of tdo mRNA in various nervous tissues, using Northern blot and quantitative real-time RT-PCR. Higher levels of tdo mRNA expression were detected in the cerebellum and hippocampus. We also identified two novel variants of the tdo gene, termed tdo variant1 and variant2, in the brain. Similar to the known TDO form (TDO full-form, tetramer formation and enzymatic activity were obtained when these variant forms were expressed in vitro . While quantitative real-time RT-PCR revealed that the tissue distribution of these variants was similar to that of tdo full-form, the expression patterns of these variants during early postnatal development in the hippocampus and cerebellum differed. Our findings indicate that in addition to hepatic TDO, TDO and its variants in the brain might function in the developing and adult nervous system. Given the previously reported associations of tdo gene polymorphisms in the patients with autism and Tourette syndrome, the expression of TDO in the brain suggests the possible influence of TDO on psychiatric status. Potential functions of TDOs in the cerebellum, hippocampus and cerebral cortex under physiological and pathological conditions are discussed.
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Reimann, S; Grattepanche, F; Baggenstos, C; Rezzonico, E; Berger, B; Arigoni, F; Lacroix, C
2010-06-01
An efficient screening method for selection of Bifidobacterium longum strains resistant to spray drying and storage was developed based on randomly amplified polymorphic DNA (RAPD) for identification of the best survivors in mixed strains bacterial preparations. Three different primers were used to generate RAPD profiles of 22 B. longum strains. All strains were distinguished according to their RAPD profiles except for the strain NCC2705 and its H(2)O(2) resistant derivative variant. The 22 strains were grouped in 3 batches of 7, 7 and 8 strains and subjected to spray drying and storage at 30 and 37 °C under anaerobic conditions. Batch survival rates after spray drying reached 17.1±4.4%. Strains showing the highest prevalence and/or resistance to storage at 37 °C were selected from individual batches for subsequent spray drying and storage testing. After 67 days of storage, NCC572 was identified as the dominant strain in powder. The stability of strain NCC572 was confirmed by performing single spray drying and storage tests. Out of 22 B. longum strains, a robust strain was identified by combining RAPD with a simultaneous screening test for survival under spray drying and storage. The method allowed a fast screening of B. longum strains in mixture for resistance to spray drying and storage compared to traditional screening procedures carried out with individual strains, in the same conditions. This approach could be applied to other stress conditions.
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Ali, Sikander; Nawaz, Wajeeha
2016-08-01
The present research work is concerned with the biotransformation of L-tyrosine to dopamine (DA) by calcium alginate entrapped conidiospores of a mutant strain of Aspergillus oryzae. Different strains of A. oryzae were isolated from soil. Out of 13 isolated strains, isolate-2 (I-2) was found to be a better DA producer. The wild-type I-2 was chemically improved by treating it with different concentrations of ethyl methyl sulfonate (EMS). Among seven mutant variants, EMS-6 exhibiting maximal DA activity of 43 μg/ml was selected. The strain was further exposed with L-cysteine HCl to make it resistant against diversion and environmental stress. The conidiospores of selected mutant variant A. oryzae EMS-6 strain were entrapped in calcium alginate beads. Different parameters for immobilization were investigated. The activity was further improved from 44 to 62 μg/ml under optimized conditions (1.5 % sodium alginate, 2 ml inoculum, and 2 mm bead size). The best resistant mutant variable exhibited over threefold increase in DA activity (62 μg/ml) than did wild-type I-2 (21 μg/ml) in the reaction mixture. From the results presented in the study, it was observed that high titers of DA activity in vitro could effectively be achieved by the EMS-induced mutagenesis of filamentous fungus culture used.
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Functional characterization of 3-ketosteroid 9α-hydroxylases in Rhodococcus ruber strain chol-4.
Guevara, Govinda; Heras, Laura Fernández de Las; Perera, Julián; Llorens, Juana María Navarro
2017-09-01
The 3-Ketosteroid-9α-Hydroxylase, also known as KshAB [androsta-1,4-diene-3,17-dione, NADH:oxygen oxidoreductase (9α-hydroxylating); EC 1.14.13.142)], is a key enzyme in the general scheme of the bacterial steroid catabolism in combination with a 3-ketosteroid-Δ 1 -dehydrogenase activity (KstD), being both responsible of the steroid nucleus (rings A/B) breakage. KshAB initiates the opening of the steroid ring by the 9α-hydroxylation of the C9 carbon of 4-ene-3-oxosteroids (e.g. AD) or 1,4-diene-3-oxosteroids (e.g. ADD), transforming them into 9α-hydroxy-4-androsten-3,17-dione (9OHAD) or 9α-hydroxy-1,4-androstadiene-3,17-dione (9OHADD), respectively. The redundancy of these enzymes in the actinobacterial genomes results in a serious difficulty for metabolic engineering this catabolic pathway to obtain intermediates of industrial interest. In this work, we have identified three homologous kshA genes and one kshB gen in different genomic regions of R. ruber strain Chol-4. We present a set of data that helps to understand their specific roles in this strain, including: i) description of the KshAB enzymes ii) construction and characterization of ΔkshB and single, double and triple ΔkshA mutants in R. ruber iii) growth studies of the above strains on different substrates and iv) genetic complementation and biotransformation assays with those strains. Our results show that KshA2 isoform is needed for the degradation of steroid substrates with short side chain, while KshA3 works on those molecules with longer side chains. KshA1 is a more versatile enzyme related to the cholic acid catabolism, although it also collaborates with KshA2 or KshA3 activities in the catabolism of steroids. Accordingly to what it is described for other Rhodococcus strains, our results also suggest that the side chain degradation is KshAB-independent. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Czech Academy of Sciences Publication Activity Database
Růžek, Daniel; Štěrba, Ján; Kopecký, Jan; Grubhoffer, Libor
2006-01-01
Roč. 50, č. 4 (2006), s. 277-278 ISSN 0001-723X R&D Projects: GA ČR(CZ) GA524/06/1479 Grant - others:Grant Agency of the University of South Bohemia(CZ) 35/2005/P-BF Institutional research plan: CEZ:AV0Z60220518 Keywords : TBE virus * Langat virus * Hy-HK attenuated variant Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 0.788, year: 2006
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Identification of microcystins from three collection strains of Microcystis aeruginosa
International Nuclear Information System (INIS)
Campo, Francisca F. del; Ouahid, Youness
2010-01-01
Microcystins (MCs) are toxic cyclic heptapeptides produced by various cyanobacteria genera, especially Microcystis. We identified 10 out of 12 MCs produced by three Microcystis aeruginosa strains from cyanobacteria collections, UTEX 2666, UTEX 2670 and UAM 1303, by using two analytical methods: Matrix-assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF/MS) and HPLC Photodiode Array Detector coupled to a hybrid Quadrupole Time of Flight Mass Spectrometry (HPLC-PDA-QTOF/MS). MALDI-TOF/MS failed to detect non-polar MCs, such as MC-LY and MC-LW. HPLC-QTOF/MS permitted the accurate identification of most MCs present in methanolic extracts. Besides, three new MCs, namely: [D-Glu(OCH 3 ) 6 , D-Asp 3 ] MC-LAba, MC-YL and MC-YM were detected by HPLC-QTOF/MS. - Three new microcystin variants identified by HPLC-QTOF/MS.
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Epitaxial strain and its relaxation at the LaAlO{sub 3}/SrTiO{sub 3} interface
Energy Technology Data Exchange (ETDEWEB)
Liu, Guozhen, E-mail: guozhen.liu@hotmail.com [Department of Physics, Temple University, Philadelphia, Pennsylvania 19122 (United States); Research Center for Solid State Physics and Materials, School of Mathematics and Physics, Suzhou University of Science and Technology, Suzhou 215009 (China); Lei, Qingyu; Wolak, Matthäus A.; Xi, Xiaoxing [Department of Physics, Temple University, Philadelphia, Pennsylvania 19122 (United States); Li, Qun [Department of Materials Science and Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802 (United States); State Key Laboratory for Strength and Vibration of Mechanical Structures, School of Aerospace, Xi' an Jiaotong University, Xi' an 710049 (China); Chen, Long-Qing [Department of Materials Science and Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802 (United States); Winkler, Christopher; Sloppy, Jennifer; Taheri, Mitra L. [Department of Materials Science and Engineering, Drexel University, Philadelphia, Pennsylvania 19104 (United States)
2016-08-28
A series of LaAlO{sub 3} thin films with different thicknesses were deposited by pulsed laser deposition at temperatures from 720 °C to 800 °C. The results from grazing incidence x-ray diffraction and reciprocal space mapping indicate that a thin layer of LaAlO{sub 3} adjacent to the SrTiO{sub 3} substrate remains almost coherently strained to the substrate, while the top layer starts to relax quickly above a certain critical thickness, followed by a gradual relaxation at larger film thickness when they are grown at lower temperatures. The atomic force microscopy results show that the fast relaxation is accompanied by the formation of cracks on the film surface. This can be ascribed to the larger energy release rate when compared with the resistance of LaAlO{sub 3} to cracking, according to calculations from the Griffith fracture theory. For films grown at 720 °C, a drop in sheet resistance by two orders of magnitude is observed when the top layer starts to relax, indicating a relationship between the strain and the conductivity of the two-dimensional electron gas at the LaAlO{sub 3}/SrTiO{sub 3} interface. The strain engineered by growth temperature provides a useful tool for the manipulation of the electronic properties of oxide heterointerfaces.
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Fatigue and strain effects in NbTi, Nb3Sn, and V2(Hf, Zr) multifilamentary superconductors
International Nuclear Information System (INIS)
Kuroda, T.; Wada, H.; Tachikawa, K.
1988-01-01
The effects of cyclic strain on critical current were studied in NbTi, bronze processed Nb 3 Sn, and composite diffusion processed V 2 (Hf,Zr) multifilamentary wires. No appreciable changes in critical current were found in NbTi wires until just prior to fatigue-induced fracture. Critical current degradation was also not observed in Nb 3 Sn or V 2 (Hf,Zr) as long as the wires were strained below the reversible limit strain. For strains beyond this limit strain the critical current was first degraded by an increasing number of cycles and then remained constant after a certain cycle number was passed
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Energy Technology Data Exchange (ETDEWEB)
Tan, X. L.; Chen, F.; Chen, P. F.; Xu, H. R.; Chen, B. B.; Jin, F.; Gao, G. Y.; Wu, W. B., E-mail: wuwb@ustc.edu.cn [Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, and High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230026 (China)
2014-10-15
We investigate the strain relaxation and surface morphology of epitaxial SrTiO{sub 3} (STO) films grown on (001){sub O} and (110){sub O} planes of orthorhombic NdGaO{sub 3} (NGO), and (001) plane of cubic (LaAlO{sub 3}){sub 0.3}(Sr{sub 2}AlTaO{sub 6}){sub 0.7} (LSAT) substrates. Although the average lattice mismatches are similar, strikingly regular crosshatched surface patterns can be found on STO/NGO(001){sub O}[(110){sub O}] films, contrary to the uniform surface of STO/LSAT(001). Based on the orientation and thickness dependent patterns and high-resolution x-ray diffractions, we ascribe the crosshatch morphology to the anisotropic strain relaxation with possibly the 60° misfit dislocation formation and lateral surface step flow in STO/NGO films, while an isotropic strain relaxation in STO/LSAT. Further, we show that the crosshatched STO/NGO(110){sub O} surface could be utilized as a template to modify the magnetotransport properties of epitaxial La{sub 0.6}Ca{sub 0.4}MnO{sub 3} films. This study highlights the crucial role of symmetry mismatch in determining the surface morphology of the perovskite oxide films, in addition to their epitaxial strain states, and offers a different route for designing and fabricating functional perovskite-oxide devices.
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International Nuclear Information System (INIS)
Hu, Sixia; Wang, Haibo; Dong, Yongqi; Hong, Bing; He, Hao; Bao, Jun; Huang, Haoliang; Yang, Yuanjun; Luo, Zhenlin; Yang, Mengmeng; Gao, Chen
2014-01-01
Large scale electronic phase separation (EPS) between ferromagnetic metallic and charge-ordered insulating phases in La 5/8-y Pr y Ca 3/8 MnO 3 (y = 0.3) (LPCMO) is very sensitive to the structural changes. This work investigates the effects of post-annealing on the strain states and electrical transport properties of LPCMO films epitaxially grown on (001) pc SrTiO 3 (tensile strain), LaAlO 3 (compressive strain) and NdGaO 3 (near-zero strain) substrates. Before annealing, all the films are coherent-epitaxial and insulating through the measured temperature range. Obvious change of film lattice is observed during the post-annealing: the in-plane strain in LPCMO/LAO varies from −1.5% to −0.1% while that in LPCMO/STO changes from 1.6% to 1.3%, and the lattice of LPCMO/NGO keeps constant because of the good lattice-match between LPCMO and NGO. Consequently, the varied film strain leads to the emergence of metal-insulator transitions (MIT) and shift of the critical transition temperature in the electrical transport. These results demonstrate that lattice-mismatch combined with post-annealing is an effective approach to tune strain in epitaxial LPCMO films, and thus to control the EPS and MIT in the films
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Re-Ranking Sequencing Variants in the Post-GWAS Era for Accurate Causal Variant Identification
Faye, Laura L.; Machiela, Mitchell J.; Kraft, Peter; Bull, Shelley B.; Sun, Lei
2013-01-01
Next generation sequencing has dramatically increased our ability to localize disease-causing variants by providing base-pair level information at costs increasingly feasible for the large sample sizes required to detect complex-trait associations. Yet, identification of causal variants within an established region of association remains a challenge. Counter-intuitively, certain factors that increase power to detect an associated region can decrease power to localize the causal variant. First, combining GWAS with imputation or low coverage sequencing to achieve the large sample sizes required for high power can have the unintended effect of producing differential genotyping error among SNPs. This tends to bias the relative evidence for association toward better genotyped SNPs. Second, re-use of GWAS data for fine-mapping exploits previous findings to ensure genome-wide significance in GWAS-associated regions. However, using GWAS findings to inform fine-mapping analysis can bias evidence away from the causal SNP toward the tag SNP and SNPs in high LD with the tag. Together these factors can reduce power to localize the causal SNP by more than half. Other strategies commonly employed to increase power to detect association, namely increasing sample size and using higher density genotyping arrays, can, in certain common scenarios, actually exacerbate these effects and further decrease power to localize causal variants. We develop a re-ranking procedure that accounts for these adverse effects and substantially improves the accuracy of causal SNP identification, often doubling the probability that the causal SNP is top-ranked. Application to the NCI BPC3 aggressive prostate cancer GWAS with imputation meta-analysis identified a new top SNP at 2 of 3 associated loci and several additional possible causal SNPs at these loci that may have otherwise been overlooked. This method is simple to implement using R scripts provided on the author's website. PMID:23950724
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Analysing the dhaT gene in Colombian Clostridium sp. (Clostridia 1,3-propanediol-producing strains
Directory of Open Access Journals (Sweden)
Diana Milena Quilaguy-Ayure
2010-04-01
Full Text Available To analyze the dhaT gene, one of the genes responsible for the 1,3-propanediol (1,3-PD production, in two native Clostridiumstrains. Materials and methods: The dhaT gene was amplified by Polimerase Chain Reaction with specific primers designed fromClostridium butyricum VPI1718 operon. Bioinformatics tools like BLASTN, ORF finder, BLASTP and ClustalW were used to determinethe identity of the sequence and to assign a function. Results: DNA amplification products were obtained from Colombian Clostridium sp.native strains (IBUN 13A and IBUN 158B and the Clostridium butyricum DSM 2478 strain, which were sequenced. According to thebioinformatics analysis of the above sequences, a high degree of similarity was found with the dhaT gene of different bacterial species. Thehighest percentage of identity was obtained with the Clostridium butyricum VPI 1718 strain. Conclusion: knowledge of the physicalstructure of the 1,3-PD operon in native strains opens the way for developing genetic and metabolic engineering strategies for improvingprocesses productivity.
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Strain Distribution of Au and Ag Nanoparticles Embedded in Al2O3 Thin Film
Directory of Open Access Journals (Sweden)
Honghua Huang
2014-01-01
Full Text Available Au and Ag nanoparticles embedded in amorphous Al2O3 matrix are fabricated by the pulsed laser deposition (PLD method and rapid thermal annealing (RTA technique, which are confirmed by the experimental high-resolution transmission electron microscope (HRTEM results, respectively. The strain distribution of Au and Ag nanoparticles embedded in the Al2O3 matrix is investigated by the finite-element (FE calculations. The simulation results clearly indicate that both the Au and Ag nanoparticles incur compressive strain by the Al2O3 matrix. However, the compressive strain existing on the Au nanoparticle is much weaker than that on the Ag nanoparticle. This phenomenon can be attributed to the reason that Young’s modulus of Au is larger than that of Ag. This different strain distribution of Au and Ag nanoparticles in the same host matrix may have a significant influence on the technological potential applications of the Au-Ag alloy nanoparticles.
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Li, Lixiang; Li, Kun; Wang, Kai; Chen, Chao; Gao, Chao; Ma, Cuiqing; Xu, Ping
2014-10-01
In this study, a thermophilic Bacillus licheniformis strain X10 was newly isolated for 2,3-butanediol (2,3-BD) production from lignocellulosic hydrolysate. Strain X10 could utilize glucose and xylose simultaneously without carbon catabolite repression. In addition, strain X10 possesses high tolerance to fermentation inhibitors including furfural, vanillin, formic acid, and acetic acid. In a fed-batch fermentation, 74.0g/L of 2,3-BD was obtained from corn stover hydrolysate, with a productivity of 2.1g/Lh and a yield of 94.6%. Thus, this thermophilic B. licheniformis strain is a candidate for the development of efficient industrial production of 2,3-BD from corn stover hydrolysate. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Bui, Long M G; Kidd, Stephen P
2015-12-01
A key to persistent and recurrent Staphylococcus aureus infections is its ability to adapt to diverse and toxic conditions. This ability includes a switch into a biofilm or to the quasi-dormant Small Colony Variant (SCV). The development and molecular attributes of SCVs have been difficult to study due to their rapid reversion to their parental cell-type. We recently described the unique induction of a matrix-embedded and stable SCV cell-type in a clinical S. aureus strain (WCH-SK2) by growing the cells with limiting conditions for a prolonged timeframe. Here we further study their characteristics. They possessed an increased viability in the presence of antibiotics compared to their non-SCV form. Their stability implied that there had been genetic changes; we therefore determined both the genome sequence of WCH-SK2 and its stable SCV form at a single base resolution, employing Single Molecular Real-Time (SMRT) sequencing that enabled the methylome to also be determined. The genetic features of WCH-SK2 have been identified; the SCCmec type, the pathogenicity and genetic islands and virulence factors. The genetic changes that had occurred in the stable SCV form were identified; most notably being in MgrA, a global regulator, and RsbU, a phosphoserine phosphatase within the regulatory pathway of the sigma factor SigB. There was a shift in the methylomes of the non-SCV and stable SCV forms. We have also shown a similar induction of this cell-type in other S. aureus strains and performed a genetic comparison to these and other S. aureus genomes. We additionally map RNAseq data to the WCH-SK2 genome in a transcriptomic analysis of the parental, SCV and stable SCV cells. The results from this study represent the unique identification of a suite of epigenetic, genetic and transcriptional factors that are implicated in the switch in S. aureus to its persistent SCV form. Copyright © 2015 Elsevier B.V. All rights reserved.
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Strain-induced oxygen vacancies in ultrathin epitaxial CaMnO3 films
Chandrasena, Ravini; Yang, Weibing; Lei, Qingyu; Delgado-Jaime, Mario; de Groot, Frank; Arenholz, Elke; Kobayashi, Keisuke; Aschauer, Ulrich; Spaldin, Nicola; Xi, Xiaoxing; Gray, Alexander
Dynamic control of strain-induced ionic defects in transition-metal oxides is considered to be an exciting new avenue towards creating materials with novel electronic, magnetic and structural properties. Here we use atomic layer-by-layer laser molecular beam epitaxy to synthesize high-quality ultrathin single-crystalline CaMnO3 films with systematically varying coherent tensile strain. We then utilize a combination of high-resolution soft x-ray absorption spectroscopy and bulk-sensitive hard x-ray photoemission spectroscopy in conjunction with first-principles theory and core-hole multiplet calculations to establish a direct link between the coherent in-plane strain and the oxygen-vacancy content. We show that the oxygen vacancies are highly mobile, which necessitates an in-situ-grown capping layer in order to preserve the original strain-induced oxygen-vacancy content. Our findings open the door for designing and controlling new ionically active properties in strongly-correlated transition-metal oxides.
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Zhao, Zhanqin; Wang, Chen; Xue, Yun; Ding, Ke; Zhang, Chunjie; Cheng, Xiangchao; Li, Yinju; Liu, Yichen; Wu, Tingcai
2010-09-01
In this study we showed the immunogenicity and protective efficacy of five pertactin recombinants against Bordetella bronchiseptica (Bb) challenge. The complete coding sequence (2040 bp) of the prn gene (PRN) and its fragments,5'-terminal 1173 bp fragment (PN),3'-terminal 867 bp fragment (PC), two copies of region I (654 bp; PR I) in PN, and 2 copies of region II (678 bp; PR II) in PC, were separately cloned into the prokaryotic expression vector pGEX-KG, and expressed in the Eschierichia coli BL21 (DE3) using induction by isopropyl-beta-D-thiogalactopyranoside. The recombinant proteins were named GST-PRN, GST-PN, GST-PC, GST-2PR I and GST-2PR II. All five recombinant proteins showed immunological reactivity in the Western-blot analysis. Mice, immunized subcutaneously with two doses of the purified proteins mixed with an equal volume of Freund's adjuvant,produced robust PRN-specific IgG antibody levels. When challenged, 6 of 9 mice in GST-2PR I group and all 9 mice in the other groups survived intranasal challenge with three times the 50% lethal dose (LD50) of virulent Bb HH0809. After challenge with 10 LD50 7/9,3/9,6/9,1/10 and 6/10 of the mice survived. Furthermore, complete protection against intraperitoneal (i.p.) challenge with 10 LD50 of HH0809 was observed in mice that were injected i.p. with 0.5 ml rabbit anti-GST-PRN, GST-PN,GST-PC or GST-2PR II serum. Only 1 of 10 mice survived in the group of mice that received anti-GST-2PR I, and no survivors were noted in the group of mice that received PRN-absorbed rabbit antiserum (0/5). In this study,we showed that all of five pertactin recombinants had differential immunogenicity and protective efficacy against Bb challenge. Mice immunized with GST-PC had better survival against fatal Bb challenge than did those immunized with GST-PN. In addition, GST-2PR II and GST-2PR I provided the similar results These data may have implications for the development of safe and efficacious subunit vaccines for the prevention of
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Aramberri, H.; Muñoz, M. C.
2017-05-01
We investigate the effects of strain on the topological order of the Bi2Se3 family of topological insulators by ab initio first-principles methods. Strain can induce a topological phase transition and we present the phase diagram for the 3D topological insulators, Bi2Te3 , Sb2Te3 , Bi2Se3 , and Sb2Se3 , under combined uniaxial and biaxial strain. Their phase diagram is universal and shows metallic and insulating phases, both topologically trivial and nontrivial. In particular, uniaxial tension can drive the four compounds into a topologically trivial insulating phase. We propose a Sb2Te3/Bi2Te3 heterojunction in which a strain-induced topological interface state arises in the common gap of this normal insulator-topological insulator heterojunction. Unexpectedly, the interface state is confined in the topologically trivial subsystem and is physically protected from ambient impurities. It can be switched on or off by means of uniaxial strain and therefore Sb2Te3 /Bi2Te3 heterojunctions provide a topological system which hosts tunable robust helical interface states with promising spintronic applications.
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Hsu, Vivian M; Wes, Ari M; Tahiri, Youssef; Cornman-Homonoff, Joshua; Percec, Ivona
2014-09-01
The aim of this study is to evaluate and quantify dynamic soft-tissue strain in the human face using real-time 3-dimensional imaging technology. Thirteen subjects (8 women, 5 men) between the ages of 18 and 70 were imaged using a dual-camera system and 3-dimensional optical analysis (ARAMIS, Trilion Quality Systems, Pa.). Each subject was imaged at rest and with the following facial expressions: (1) smile, (2) laughter, (3) surprise, (4) anger, (5) grimace, and (6) pursed lips. The facial strains defining stretch and compression were computed for each subject and compared. The areas of greatest strain were localized to the midface and lower face for all expressions. Subjects over the age of 40 had a statistically significant increase in stretch in the perioral region while lip pursing compared with subjects under the age of 40 (58.4% vs 33.8%, P = 0.015). When specific components of lip pursing were analyzed, there was a significantly greater degree of stretch in the nasolabial fold region in subjects over 40 compared with those under 40 (61.6% vs 32.9%, P = 0.007). Furthermore, we observed a greater degree of asymmetry of strain in the nasolabial fold region in the older age group (18.4% vs 5.4%, P = 0.03). This pilot study illustrates that the face can be objectively and quantitatively evaluated using dynamic major strain analysis. The technology of 3-dimensional optical imaging can be used to advance our understanding of facial soft-tissue dynamics and the effects of animation on facial strain over time.
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Functional analysis of four naturally occurring variants of human constitutive androstane receptor.
Ikeda, Shinobu; Kurose, Kouichi; Jinno, Hideto; Sai, Kimie; Ozawa, Shogo; Hasegawa, Ryuichi; Komamura, Kazuo; Kotake, Takeshi; Morishita, Hideki; Kamakura, Shiro; Kitakaze, Masafumi; Tomoike, Hitonobu; Tamura, Tomohide; Yamamoto, Noboru; Kunitoh, Hideo; Yamada, Yasuhide; Ohe, Yuichiro; Shimada, Yasuhiro; Shirao, Kuniaki; Kubota, Kaoru; Minami, Hironobu; Ohtsu, Atsushi; Yoshida, Teruhiko; Saijo, Nagahiro; Saito, Yoshiro; Sawada, Jun-ichi
2005-01-01
The human constitutive androstane receptor (CAR, NR1I3) is a member of the orphan nuclear receptor superfamily that plays an important role in the control of drug metabolism and disposition. In this study, we sequenced all the coding exons of the NR1I3 gene for 334 Japanese subjects. We identified three novel single nucleotide polymorphisms (SNPs) that induce non-synonymous alterations of amino acids (His246Arg, Leu308Pro, and Asn323Ser) residing in the ligand-binding domain of CAR, in addition to the Val133Gly variant, which was another CAR variant identified in our previous study. We performed functional analysis of these four naturally occurring CAR variants in COS-7 cells using a CYP3A4 promoter/enhancer reporter gene that includes the CAR responsive elements. The His246Arg variant caused marked reductions in both transactivation of the reporter gene and in the response to 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO), which is a human CAR-specific agonist. The transactivation ability of the Leu308Pro variant was also significantly decreased, but its responsiveness to CITCO was not abrogated. The transactivation ability and CITCO response of the Val133Gly and Asn323Ser variants did not change as compared to the wild-type CAR. These data suggest that the His246Arg and Leu308Pro variants, especially His246Arg, may influence the expression of drug-metabolizing enzymes and transporters that are transactivated by CAR.
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DEFF Research Database (Denmark)
Christensen, Henrik; Angen, Øystein; Olsen, John E.
2004-01-01
Strains deviating in key phenotypic characters, mainly isolated from cases of bovine pneumonia in five European countries, were genotyped in order to examine their genotypic relationship with Pasteurella multocida. Twenty-two strains of Pasteurella avium biovar 2, including variants in indole, xy...
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Rosdahl Brems, Mathias; Paaske, Jens; Lunde, Anders Mathias; Willatzen, Morten
2018-05-01
Based on group theoretical arguments we derive the most general Hamiltonian for the Bi2Se3-class of materials including terms to third order in the wave vector, first order in electric and magnetic fields, first order in strain and first order in both strain and wave vector. We determine analytically the effects of strain on the electronic structure of Bi2Se3. For the most experimentally relevant surface termination we analytically derive the surface state (SS) spectrum, revealing an anisotropic Dirac cone with elliptical constant energy contours giving rise to a direction-dependent group velocity. The spin-momentum locking of strained Bi2Se3 is shown to be modified. Hence, strain control can be used to manipulate the spin degree of freedom via the spin–orbit coupling. We show that for a thin film of Bi2Se3 the SS band gap induced by coupling between the opposite surfaces changes opposite to the bulk band gap under strain. Tuning the SS band gap by strain, gives new possibilities for the experimental investigation of the thickness dependent gap and optimization of optical properties relevant for, e.g., photodetector and energy harvesting applications. We finally derive analytical expressions for the effective mass tensor of the Bi2Se3 class of materials as a function of strain and electric field.
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International Nuclear Information System (INIS)
Jin Xinzhe; Nakamoto, Tatsushi; Tsuchiya, Kiyosumi; Ogitsu, Toru; Yamamoto, Akira; Ito, Takayoshi; Harjo, Stefanus; Kikuchi, Akihiro; Takeuchi, Takao; Hemmi, Tsutomu
2012-01-01
We prepared three types of non-Cu RHQ-Nb 3 Al wire sample with different matrix structures: an all-Ta matrix, a composite matrix of Nb and Ta with a Ta inter-filament, and an all-Nb matrix. Neutron diffraction patterns of the wire samples were measured at room temperature in the J-PARC ‘TAKUMI’. To obtain the residual strains of the materials, we estimated the lattice constant a by multi-peak analysis in the wires. A powder sample of each wire was measured, where the powder was considered to be strain free. The grain size of all the powder samples was below 0.02 mm. For the wire sample with the all-Nb matrix, we also obtained the lattice spacing d by a single-peak analysis. The residual strains of the Nb 3 Al filament were estimated from the two analysis results and were compared. The resulting residual strains obtained from the multi-peak analysis showed a good accuracy with small standard deviation. The multi-peak analysis results for the residual strains of the Nb 3 Al filaments in the three samples (without Cu plating) were all tensile residual strain in the axial direction, of 0.12%, 0.12%, and 0.05% for the all-Ta matrix, the composite matrix, and the all-Nb matrix, respectively. The difference in the residual strain of the Nb 3 Al filament between the composite and all-Nb matrix samples indicates that the type of inter-filament material shows a great effect on the residual strain. In this paper, we report the method of measurement, method of analysis, and results for the residual strain in the three types of non-Cu RHQ-Nb 3 Al wires. (paper)
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Effect of strain on the martensitic phase transition in superconducting Nb3Sn
International Nuclear Information System (INIS)
Hoard, R.W.; Scanlan, R.M.; Smith, G.S.; Farrell, C.L.
1980-01-01
The connection between the cubic-to-tetragonal martensitic phase transformation and the phenomenon of superconductivity in A15 compounds is being investigated. The degradation of the critical parameters, such as T/sub c/, H/sub c2/, and J/sub c/, with mechanical straining is of particular interest. Low-temperature x-ray diffraction experiments are performed on Nb 3 Sn ribbons (with the bronze layers etched off) mounted on copper and indium sample stages. The cryostat used is unique in that it has a vacuum mechanical insert which allows the superconductor to be placed under both compressive and tensile strains while at low temperatures. Preliminary results indicate that the martensitic phase transition temperature, T/sub m/, increases with compressive strains. Other effects of strain on tetragonal phase production are also discussed
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Directory of Open Access Journals (Sweden)
Kristoffer T Bæk
Full Text Available Staphylococcus aureus strains of the 8325 lineage, especially 8325-4 and derivatives lacking prophage, have been used extensively for decades of research. We report herein the results of our deep sequence analysis of strain 8325-4. Assignment of sequence variants compared with the reference strain 8325 (NRS77/PS47 required correction of errors in the 8325 reference genome, and reassessment of variation previously attributed to chemical mutagenesis of the restriction-defective RN4220. Using an extensive strain pedigree analysis, we discovered that 8325-4 contains 16 single nucleotide polymorphisms (SNP arising prior to the construction of RN4220. We identified 5 indels in 8325-4 compared with 8325. Three indels correspond to expected Φ11, 12, 13 excisions, one indel is explained by a sequence assembly artifact, and the final indel (Δ63bp in the spa-sarS intergenic region is common to only a sub-lineage of 8325-4 strains including SH1000. This deletion was found to significantly decrease (75% steady state sarS but not spa transcript levels in post-exponential phase. The sub-lineage 8325-4 was also found to harbor 4 additional SNPs. We also found large sequence variation between 8325, 8325-4 and RN4220 in a cluster of repetitive hypothetical proteins (SA0282 homologs near the Ess secretion cluster. The overall 8325-4 SNP set results in 17 alterations within coding sequences. Remarkably, we discovered that all tested strains of the 8325-4 lineage lack phenol soluble modulin α3 (PSMα3, a virulence determinant implicated in neutrophil chemotaxis, biofilm architecture and surface spreading. Collectively, our results clarify and define the 8325-4 pedigree and reveal clear evidence that mutations existing throughout all branches of this lineage, including the widely used RN6390 and SH1000 strains, could conceivably impact virulence regulation.
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International Nuclear Information System (INIS)
Pan, Deshun; Liu, Bing; Jin, Xiaobao; Zhu, Jiayong
2012-01-01
Highlights: ► This study confirms the role of IL-7δ5 in breast cancer cell proliferation. ► IL-7δ5 promotes breast cancer cell proliferation and cell cycle progression. ► IL-7δ5 promotes cell proliferation via activation of PI3K/Akt pathway. -- Abstract: Various tumor cells express interleukin 7 (IL-7) and IL-7 variants. IL-7 has been confirmed to stimulate solid tumor cell proliferation. However, the effect of IL-7 variants on tumor cell proliferation remains unclear. In this study, we evaluated the role of IL-7δ5 (an IL-7 variant lacking exon 5) on proliferation and cell cycle progression of human MDA-MB-231 and MCF-7 breast cancer cells. The results showed that IL-7δ5 promoted cell proliferation and cell cycle progression from G1 phase to G2/M phase, associated with upregulation of cyclin D1 expression and the downregulation of p27 kip1 expression. Mechanistically, we found that IL-7δ5 induced the activation of Akt. Inhibition of PI3K/Akt pathway by LY294002 reversed the proliferation and cell cycle progression of MDA-MB-231 and MCF-7 cells induced by IL-7δ5. In conclusion, our findings demonstrate that IL-7δ5 variant induces human breast cancer cell proliferation and cell cycle progression via activation of PI3K/Akt pathway. Thus, IL-7δ5 may be a potential target for human breast cancer therapeutics intervention.
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Novel image analysis methods for quantification of in situ 3-D tendon cell and matrix strain.
Fung, Ashley K; Paredes, J J; Andarawis-Puri, Nelly
2018-01-23
Macroscopic tendon loads modulate the cellular microenvironment leading to biological outcomes such as degeneration or repair. Previous studies have shown that damage accumulation and the phases of tendon healing are marked by significant changes in the extracellular matrix, but it remains unknown how mechanical forces of the extracellular matrix are translated to mechanotransduction pathways that ultimately drive the biological response. Our overarching hypothesis is that the unique relationship between extracellular matrix strain and cell deformation will dictate biological outcomes, prompting the need for quantitative methods to characterize the local strain environment. While 2-D methods have successfully calculated matrix strain and cell deformation, 3-D methods are necessary to capture the increased complexity that can arise due to high levels of anisotropy and out-of-plane motion, particularly in the disorganized, highly cellular, injured state. In this study, we validated the use of digital volume correlation methods to quantify 3-D matrix strain using images of naïve tendon cells, the collagen fiber matrix, and injured tendon cells. Additionally, naïve tendon cell images were used to develop novel methods for 3-D cell deformation and 3-D cell-matrix strain, which is defined as a quantitative measure of the relationship between matrix strain and cell deformation. The results support that these methods can be used to detect strains with high accuracy and can be further extended to an in vivo setting for observing temporal changes in cell and matrix mechanics during degeneration and healing. Copyright © 2017. Published by Elsevier Ltd.
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Strain tuning of optical properties in Bi2Se3
DEFF Research Database (Denmark)
Jensen, Mathias Rosdahl; Mørk, Jesper; Willatzen, Morten
2017-01-01
Based on symmetry principles we determine the most general Hamiltonian for the low energy physics of Bi2Se3, including contributions due to a static electric field and strain. The full three-dimensional model is projected into the surface states at k= 0, giving an effective two-dimensional Hamilt...
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Substrate-induced strain effects on Pr0.6Ca0.4MnO3 films
International Nuclear Information System (INIS)
Nelson, C S; Hill, J P; Gibbs, Doon; Rajeswari, M; Biswas, A; Shinde, S; Greene, R L; Venkatesan, T; Millis, A J; Yokaichiya, F; Giles, C; Casa, D; Venkataraman, C T; Gog, T
2004-01-01
We report the characterization of the crystal structure, low-temperature charge and orbital ordering, transport and magnetization of Pr 0.6 Ca 0.4 MnO 3 films grown on LaAlO 3 , NdGaO 3 and SrTiO 3 substrates, which provide compressive (LaAlO 3 ) and tensile (NdGaO 3 and SrTiO 3 ) strain. The films are observed to exhibit different crystallographic symmetries from the bulk material and the low-temperature ordering is found to be more robust under compressive as opposed to tensile strain. In fact, bulk-like charge and orbital ordering is not observed in the film grown on NdGaO 3 , which is the substrate that provides the least amount of measured, but tensile, strain. This result suggests the importance of the role played by the Mn-O--Mn bond angles in the formation of charge and orbital ordering at low temperatures. Finally, in the film grown on LaAlO 3 , a connection between the lattice distortion associated with orbital ordering and the magnetization is reported
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Sivley, R Michael; Sheehan, Jonathan H; Kropski, Jonathan A; Cogan, Joy; Blackwell, Timothy S; Phillips, John A; Bush, William S; Meiler, Jens; Capra, John A
2018-01-23
Next-generation sequencing of individuals with genetic diseases often detects candidate rare variants in numerous genes, but determining which are causal remains challenging. We hypothesized that the spatial distribution of missense variants in protein structures contains information about function and pathogenicity that can help prioritize variants of unknown significance (VUS) and elucidate the structural mechanisms leading to disease. To illustrate this approach in a clinical application, we analyzed 13 candidate missense variants in regulator of telomere elongation helicase 1 (RTEL1) identified in patients with Familial Interstitial Pneumonia (FIP). We curated pathogenic and neutral RTEL1 variants from the literature and public databases. We then used homology modeling to construct a 3D structural model of RTEL1 and mapped known variants into this structure. We next developed a pathogenicity prediction algorithm based on proximity to known disease causing and neutral variants and evaluated its performance with leave-one-out cross-validation. We further validated our predictions with segregation analyses, telomere lengths, and mutagenesis data from the homologous XPD protein. Our algorithm for classifying RTEL1 VUS based on spatial proximity to pathogenic and neutral variation accurately distinguished 7 known pathogenic from 29 neutral variants (ROC AUC = 0.85) in the N-terminal domains of RTEL1. Pathogenic proximity scores were also significantly correlated with effects on ATPase activity (Pearson r = -0.65, p = 0.0004) in XPD, a related helicase. Applying the algorithm to 13 VUS identified from sequencing of RTEL1 from patients predicted five out of six disease-segregating VUS to be pathogenic. We provide structural hypotheses regarding how these mutations may disrupt RTEL1 ATPase and helicase function. Spatial analysis of missense variation accurately classified candidate VUS in RTEL1 and suggests how such variants cause disease. Incorporating
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Product Variant Master as a Means to Handle Variant Design
DEFF Research Database (Denmark)
Hildre, Hans Petter; Mortensen, Niels Henrik; Andreasen, Mogens Myrup
1996-01-01
be implemented in the CAD system I-DEAS. A precondition for high degree of computer support is identification of a product variant master from which new variants can be derived. This class platform defines how a product build up fit certain production methods and rules governing determination of modules...
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Characterization of Acinetobacter baumannii strain PS3 in degradation of food emulsifiers
Nguyen, Ngoc Tuan; Tran, Tuyet Nhung; Ha, Thi Bich Ngoc
2018-04-01
Strain SP3 revealed the abilty to utilizes emulsifier which is widely used in the preparation of drugs, vaccines, food, cosmetics and skin care products as its sole carbon and energy source. Generation time ranges from 1.4 to 2.1 h on the polysorbate family. Strain was identified as Acinetobacter baumannii based on 16S rRNA gene and it could dispose 27 % polysorbate 80 within a day. The proposed mechanism for polysorbate utilization belongs to the β-oxidation.
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An exponential scaling law for the strain dependence of the Nb3Sn critical current density
International Nuclear Information System (INIS)
Bordini, B; Alknes, P; Bottura, L; Rossi, L; Valentinis, D
2013-01-01
The critical current density of the Nb 3 Sn superconductor is strongly dependent on the strain applied to the material. In order to investigate this dependence, it is a common practice to measure the critical current of Nb 3 Sn strands for different values of applied axial strain. In the literature, several models have been proposed to describe these experimental data in the reversible strain region. All these models are capable of fitting the measurement results in the strain region where data are collected, but tend to predict unphysical trends outside the range of data, and especially for large strain values. In this paper we present a model of a new strain function, together with the results obtained by applying the new scaling law on relevant datasets. The data analyzed consisted of the critical current measurements at 4.2 K that were carried out under applied axial strain at Durham University and the University of Geneva on different strand types. With respect to the previous models proposed, the new scaling function does not present problems at large strain values, has a lower number of fitting parameters (only two instead of three or four), and is very stable, so that, starting from few experimental points, it can estimate quite accurately the strand behavior in a strain region where there are no data. A relationship is shown between the proposed strain function and the elastic strain energy, and an analogy is drawn with the exponential form of the McMillan equation for the critical temperature. (paper)
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Energy Technology Data Exchange (ETDEWEB)
Fujii, Ichiro, E-mail: ifujii@rins.ryukoku.ac.jp [Department of Materials Chemistry, Ryukoku University, Otsu, Shiga 520-2194 (Japan); Iizuka, Ryo; Ueno, Shintaro; Nakashima, Kouichi; Wada, Satoshi [Interdisciplinary Graduate School of Medical and Engineering, University of Yamanashi, Kofu, Yamanashi 400-8510 (Japan); Nakahira, Yuki; Sunada, Yuya; Magome, Eisuke; Moriyoshi, Chikako; Kuroiwa, Yoshihiro [Department of Physical Science, Hiroshima University, Higashihiroshima, Hiroshima 739-8526 (Japan)
2016-04-25
Contributions to the piezoelectric response in pseudocubic 0.3BaTiO{sub 3}-0.1Bi(Mg{sub 1/2}Ti{sub 1/2})O{sub 3}-0.6BiFeO{sub 3} ceramics were investigated by synchrotron X-ray diffraction under electric fields. All of the lattice strain determined from the 110, 111, and 200 pseudocubic diffraction peaks showed similar lattice strain hysteresis that was comparable to the bulk butterfly-like strain curve. It was suggested that the hysteresis of the lattice strain and the lack of anisotropy were related to the complex domain structure and the phase boundary composition.
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Schotte, Peter; Dewerte, Isabelle; De Groeve, Manu; De Keyser, Saskia; De Brabandere, Veronique; Stanssens, Patrick
2016-06-07
Over the last few decades the methylotrophic yeast Pichia pastoris has become a popular host for a wide range of products such as vaccines and therapeutic proteins. Several P. pastoris engineered strains and mutants have been developed to improve the performance of the expression system. Yield and quality of a recombinant product are important parameters to monitor during the host selection and development process but little information is published regarding quality differences of a product produced by different P. pastoris strains. We compared titer and quality of several Nanobodies(®) produced in wild type and Mut(S) strains. Titer in fed-batch fermentation was comparable between all strains for each Nanobody but a significant difference in quality was observed. Nanobodies expressed in Mut(S) strains contained a product variant with a Δ-16 Da mass difference that was not observed in wild type strains. This variant showed substitution of methionine residues due to misincorporation of O-methyl-L-homoserine, also called methoxine. Methoxine is likely synthesized by the enzymatic action of O-acetyl homoserine sulfhydrylase and we confirmed that Nanobodies produced in the corresponding knock-out strain contained no methoxine variants. We could show the incorporation of methoxine during biosynthesis by its addition to the culture medium. We showed that misincorporation of methoxine occurs particularly in P. pastoris Mut(S) strains. This reduction in product quality could outweigh the advantages of using Mut strains, such as lower oxygen and methanol demand, heat formation and in some cases improved expression. Methoxine incorporation in recombinant proteins is likely to occur when an excess of methanol is present during fermentation but can be avoided when the methanol feed rate protocol is carefully designed.
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Temperature dependence of microstructure and strain evolution in strained ZnO films on Al2O3(0001)
International Nuclear Information System (INIS)
Kim, In-Woo; Lee, Kyu-Mann
2008-01-01
We have studied the temperature dependence of the growth mode and microstructure evolution in highly mismatched sputter-grown ZnO/Al 2 O 3 (0001) heteroepitaxial films. The growth mode was studied by real-time synchrotron x-ray scattering. We find that the growth mode changes from a two-dimensional (2D) layer to a 3D island in the early growth stage with temperature (300-600 deg. C), in sharp contrast to the reported transition from three dimensions to two dimensions in metal-organic vapor phase epitaxy. At around 400 deg. C intermediate 2D platelets nucleate in the early stage, which act as nucleation cores of 3D islands and transform to a misaligned state during further growth. Meanwhile, at high temperature (above 500 deg. C), the spinel structure of ZnAl 2 O 4 grows in the early stage, and it undergoes a transition to wurtzite-ZnO (w-ZnO) with thickness. The spinel formation is presumably driven by high temperature and large incident energy of impacting atoms during sputtering. The results of the strain evolution as functions of temperature and thickness during growth suggest that the surface diffusion is a major factor determining the microstructural properties in the strained ZnO/Al 2 O 3 (0001) heteroepitaxy
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DEFF Research Database (Denmark)
Brems, Mathias Rosdahl; Paaske, Jens; Lunde, Anders Mathias
2018-01-01
Based on group theoretical arguments we derive the most general Hamiltonian for the Bi2Se3-class of materials including terms to third order in the wave vector, first order in electric and magnetic fields, first order in strain and first order in both strain and wave vector. We determine analytic......Based on group theoretical arguments we derive the most general Hamiltonian for the Bi2Se3-class of materials including terms to third order in the wave vector, first order in electric and magnetic fields, first order in strain and first order in both strain and wave vector. We determine...... for the effective mass tensor of the Bi2Se3 class of materials as a function of strain and electric field....
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Recent advances in echocardiography: strain and strain rate imaging [version 1; referees: 3 approved
Directory of Open Access Journals (Sweden)
Oana Mirea
2016-04-01
Full Text Available Deformation imaging by echocardiography is a well-established research tool which has been gaining interest from clinical cardiologists since the introduction of speckle tracking. Post-processing of echo images to analyze deformation has become readily available at the fingertips of the user. New parameters such as global longitudinal strain have been shown to provide added diagnostic value, and ongoing efforts of the imaging societies and industry aimed at harmonizing methods will improve the technique further. This review focuses on recent advances in the field of echocardiographic strain and strain rate imaging, and provides an overview on its current and potential future clinical applications.
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Multiferroic Properties of o-LuMnO3 Controlled by b-Axis Strain
Windsor, Y. W.; Huang, S. W.; Hu, Y.; Rettig, L.; Alberca, A.; Shimamoto, K.; Scagnoli, V.; Lippert, T.; Schneider, C. W.; Staub, U.
2014-10-01
Strain is a leading candidate for controlling magnetoelectric coupling in multiferroics. Here, we use x-ray diffraction to study the coupling between magnetic order and structural distortion in epitaxial films of the orthorhombic (o-) perovskite LuMnO3. An antiferromagnetic spin canting in the E-type magnetic structure is shown to be related to the ferroelectrically induced structural distortion and to a change in the magnetic propagation vector. By comparing films of different orientations and thicknesses, these quantities are found to be controlled by b-axis strain. It is shown that compressive strain destabilizes the commensurate E-type structure and reduces its accompanying ferroelectric distortion.
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Chemical strain engineering of magnetism in PrVO3 thin films
Prellier, Wilfrid; Copie, Olivier; Varignon, Julien; Rotella, Helene; Steciuk, Gwladys; Boullay, Philippe; Pautrat, Alain; David, Adrian; Mercey, Bernard; Ghosez, Philippe
Transition metal oxides having a perovskite structure present a wide range of functional properties ranging from insulator-to-metal, ferroelectricity, colossal magnetoresistance, high-temperature superconductivity and multiferroicity. Such systems are generally characterized by strong electronic correlations, complex phase diagrams and competing ground states. In addition, small perturbation induced by external stimuli (electric or magnetic field, temperature, strain, pressure..) may change structure, and ultimately modify the physical properties. Here, we synthetize an orthorhombic perovskite praseodymium vanadate (PrVO3), which is grown on strontium titanate substrate. We show that the control of the content of oxygen vacancies, the so-called chemical strain, can indeed result in unexpected properties. We further demonstrate that the Néel temperature can be tuned using the same substrate in agreement with first-principles calculations, and demonstrate that monitoring the concentration of oxygen vacancies through the oxygen partial pressure or the growth temperature can produce a substantial macroscopic tensile strain of a few percents.
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la Torre, David De; Mafla, Eulalia; Puga, Byron; Erazo, Linda; Astolfi-Ferreira, Claudete; Ferreira, Antonio Piantino
2018-04-01
The objective of this study was to determine the presence of the variants of canine parvovirus (CPV)-2 in the city of Quito, Ecuador, due to the high domestic and street-type canine population, and to identify possible mutations at a genetic level that could be causing structural changes in the virus with a consequent influence on the immune response of the hosts. Thirty-five stool samples from different puppies with characteristic signs of the disease and positives for CPV through immunochromatography kits were collected from different veterinarian clinics of the city. Polymerase chain reaction and DNA sequencing were used to determine the mutations in residue 426 of the VP2 gene, which determines the variants of CPV-2; in addition, four samples were chosen for complete sequencing of the VP2 gene to identify all possible mutations in the circulating strains in this region of the country. The results revealed the presence of the three variants of CPV-2 with a prevalence of 57.1% (20/35) for CPV-2a, 8.5% (3/35) for CPV-2b, and 34.3% (12/35) for CPV-2c. In addition, complete sequencing of the VP2 gene showed amino acid substitutions in residues 87, 101, 139, 219, 297, 300, 305, 322, 324, 375, 386, 426, 440, and 514 of the three Ecuadorian variants when compared with the original CPV-2 sequence. This study describes the detection of CPV variants in the city of Quito, Ecuador. Variants of CPV-2 (2a, 2b, and 2c) have been reported in South America, and there are cases in Ecuador where CVP-2 is affecting even vaccinated puppies.
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Xu, Chang; Nezami Ranjbar, Mohammad R; Wu, Zhong; DiCarlo, John; Wang, Yexun
2017-01-03
Detection of DNA mutations at very low allele fractions with high accuracy will significantly improve the effectiveness of precision medicine for cancer patients. To achieve this goal through next generation sequencing, researchers need a detection method that 1) captures rare mutation-containing DNA fragments efficiently in the mix of abundant wild-type DNA; 2) sequences the DNA library extensively to deep coverage; and 3) distinguishes low level true variants from amplification and sequencing errors with high accuracy. Targeted enrichment using PCR primers provides researchers with a convenient way to achieve deep sequencing for a small, yet most relevant region using benchtop sequencers. Molecular barcoding (or indexing) provides a unique solution for reducing sequencing artifacts analytically. Although different molecular barcoding schemes have been reported in recent literature, most variant calling has been done on limited targets, using simple custom scripts. The analytical performance of barcode-aware variant calling can be significantly improved by incorporating advanced statistical models. We present here a highly efficient, simple and scalable enrichment protocol that integrates molecular barcodes in multiplex PCR amplification. In addition, we developed smCounter, an open source, generic, barcode-aware variant caller based on a Bayesian probabilistic model. smCounter was optimized and benchmarked on two independent read sets with SNVs and indels at 5 and 1% allele fractions. Variants were called with very good sensitivity and specificity within coding regions. We demonstrated that we can accurately detect somatic mutations with allele fractions as low as 1% in coding regions using our enrichment protocol and variant caller.
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Clinical and microbiologic characteristics of tcdA-negative variant clostridium difficile infections
Directory of Open Access Journals (Sweden)
Kim Jieun
2012-05-01
Full Text Available Abstract Background The tcdA-negative variant (A-B+ of Clostridium difficile is prevalent in East Asian countries. However, the risk factors and clinical characteristics of A-B+C. difficile infections (CDI are not clearly documented. The objective of this study was to investigate these characteristics. Methods From September 2008 through January 2010, the clinical characteristics, medication history and treatment outcomes of CDI patients were recorded prospectively. Toxin characterization and antibiotic susceptibility tests were performed on stool isolates of C. difficile. Results During the study period, we identified 22 cases of CDI caused by tcdA-negative tcdB-positive (A-B+ strains and 105 cases caused by tcdA-positive tcdB-positive (A+B+ strains. There was no significant difference in disease severity or clinical characteristics between the two groups. Previous use of clindamycin and young age were identified as significant risk factors for the acquisition of A-B+ CDI (OR = 4.738, 95% CI 1.48–15.157, p = 0.009 and OR = 0.966, 95% CI 0.935–0.998, p = 0.038, respectively in logistic regression. Rates of resistance to clindamycin were 100% and 69.6% in the A-B+ and A+B+ isolates, respectively (p = 0.006, and the ermB gene was identified in 17 of 21 A-B+ isolates (81%. Resistance to moxifloxacin was also more frequent in the A-B+ than in the A+B+ isolates (95.2% vs. 63.7%, p = 0.004. Conclusions The clinical course of A-B+ CDI is not different from that of A+B+ CDI. Clindamycin use is a significant risk factor for the acquisition of tcdA-negative variant strains.
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Stress-strain effects in alumina-Cu reinforced Nb3Sn wires fabricated by the tube process
International Nuclear Information System (INIS)
Murase, Satoru; Nakayama, Shigeo; Masegi, Tamaki; Koyanagi, Kei; Nomura, Shunji; Shiga, Noriyuki; Kobayashi, Norio; Watanabe, Kazuo.
1997-01-01
In order to fabricate a large-bore, high-field magnet which achieves a low coil weight and volume, a high strength compound superconducting wire is required. For those demands we have developed the reinforced Nb 3 Sn wire using alumina dispersion strengthened copper (alumina-Cu) as a reinforcement material and the tube process of the Nb 3 Sn wire fabrication. The ductility study of the composites which consisted of the reinforcement, Nb tube, Cu, and Cu clad Sn brought a 1 km long alumina-Cu reinforced Nb 3 Sn wire successfully. Using fabricated wires measurements and evaluations of critical current density as parameters of magnetic field, tensile stress, tensile strain, and transverse compressive stress, and those of stress-strain curves at 4.2 K were performed. They showed superior performance such as high 0.3% proof stress (240 MPa at 0.3% strain) and high maximum tolerance stress (320 MPa) which were two times as large as those of conventional Cu matrix Nb 3 Sn wire. The strain sensitivity parameters were obtained for the reinforced Nb 3 Sn wire and the Cu matrix one using the scaling law. Residual stress of the component materials caused by cooling down to 4.2 K from heat-treatment temperature was calculated using equivalent Young's modulus, equivalent yield strength, thermal expansion coefficient and other mechanical parameters. Calculated stress-strain curves at 4.2 K for the reinforced Nb 3 Sn wire and the Cu matrix one based on calculation of residual stress, had good agreement with the experimental values. (author)
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Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits
DEFF Research Database (Denmark)
Chami, Nathalie; Chen, Ming-Huei; Slater, Andrew J
2016-01-01
array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p
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Samuelsen, Orjan; Haukland, Hanne Husom; Kahl, Barbara C; von Eiff, Christof; Proctor, Richard A; Ulvatne, Hilde; Sandvik, Kjersti; Vorland, Lars H
2005-12-01
To determine whether Staphylococcus aureus small colony variants (SCVs) are resistant to the antimicrobial peptide lactoferricin B. To assess if deficiency in transmembrane potential, a common characteristic of SCVs that are haemin- or menadione-auxotrophs, affects the uptake of the peptide into the bacterial cytoplasm. A broth microdilution technique was used for susceptibility testing to determine the MIC of lactoferricin B for SCVs with three different auxotrophisms (haemin, menadione or thymidine) and their isogenic parent strains. Both clinical isolates and genetically defined mutants were used. The internalization of lactoferricin B in a hemB mutant and the respective parent strain was studied using transmission electron microscopy and immunogold labelling. All SCVs showed reduced susceptibility to lactoferricin B irrespective of their auxotrophy compared with their isogenic parent strains. The MIC for all SCVs was >256 mg/L, whereas the MICs for the parent strains ranged from 16-256 mg/L. Surprisingly, the hemB mutant contained significantly more lactoferricin B intracellularly than the respective parent strain. The resistance mechanism of SCVs towards the antimicrobial peptide lactoferricin B is presumably caused by the metabolic changes present in SCVs rather than by a changed transmembrane potential of SCVs or reduced uptake of the peptide.
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Biochemical characterization of the GM2 gangliosidosis B1 variant
Directory of Open Access Journals (Sweden)
Tutor J.C.
2004-01-01
Full Text Available The deficiency of the A isoenzyme of ß-hexosaminidase (Hex produced by different mutations of the gene that codes for the alpha subunit (Tay-Sachs disease has two variants with enzymological differences: the B variant consists of the absence of Hex A isoenzyme and the B1 variant produces an inactive Hex A isoenzyme for the hydrolysis of the GM2 ganglioside and synthetic substrates with negative charge. In contrast to the early childhood form of the B variant, the B1 variant appears at a later clinical stage (3 to 7 years of age with neurodegenerative symptoms leading to the death of the patient in the second decade of life. The most frequent mutation responsible for the GM2 gangliosidosis B1 variant is R178H, which has a widespread geographic and ethnic distribution. The highest incidence has been described in Portugal, which has been suggested as the point of origin of this mutation. Biochemical characterization of this lysosomal disease is carried out using negatively charged synthetic alpha subunit-specific sulfated substrates, since Hex A isoenzyme heat-inactivation assays are not applicable. However, the determination of the apparent activation energy of Hex using the neutral substrate 3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-ß-D-glucosaminide, may offer a valid alternative. The presence of an alpha subunit in the alphaß heterodimer Hex A means that its activation energy (41.8 kJ/mol is significantly lower than that of the ßß homodimer Hex B (75.1 kJ/mol; however, as mutation inactivates the alpha subunit, the Hex A of the B1 variant presents an activation energy that is similar to that of the Hex B isoenzyme.
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Strain dependent magnetocaloric effect in La0.67Sr0.33MnO3 thin-films
Directory of Open Access Journals (Sweden)
V. Suresh Kumar
2013-05-01
Full Text Available The strain dependent magnetocaloric properties of La0.67Sr0.33MnO3 thin films deposited on three different substrates (001 LaAlO3 (LAO, (001 SrTiO3 (STO, and (001 La0.3Sr0.7Al0.65Ta0.35O9 (LSAT have been investigated under low magnetic fields and around magnetic phase transition temperatures. Compared to bulk samples, we observe a remarkable decrease in the ferromagnetic transition temperature that is close to room temperature, closely matched isothermal magnetic entropy change and relative cooling power values in tensile strained La0.67Sr0.33MnO3 films. The epitaxial strain plays a significant role in tuning the peak position of isothermal magnetic entropy change towards room temperature with improved cooling capacity.
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Liu, Kewei; Sakurai, Makoto; Aono, Masakazu
2012-12-07
The humidity sensitivity of a single β-Ga(2) O(3) /amorphous SnO(2) core/shell microribbon on a flexible substrate is enhanced by the application of tensile strain and increases linearly with the strain. The strain-induced enhancement originates from the increase in the effective surface area where water molecules are adsorbed. This strain dependence of humidity sensitivity can be used to monitor the external strain. The strain sensing of the microribbon device under various amounts of mechanical loading shows excellent reliability and reproducibility with a gauge factor of -41. The flexible device has high potential to detect both humidity and strain at room temperature. These findings and the mechanism involved are expected to pave the way for new flexible strain and multifunctional sensors. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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THE INFLUENCE OF CULTURE MEDIA ON ACETIC FERMENTATION WITH SELECTED Acetobacter STRAINS
Directory of Open Access Journals (Sweden)
MARIA CRISTIANA GARNAI
2012-06-01
Full Text Available We have systematically followed the efficiency of acetic fermentation, by cultivating 14 Acetobacter strains (previously isolated and identified, within a medium obtain out of ethanol and acetic acid, in various proportions, and utilizing corn extract (CE as a nutrient. The purpose of the research was to determine the resistance of the studied Acetobacter strains related to the composition of the cultivation media (acidity and alcohol content of the medium, as well as following the dynamics of the acetic fermentation by calculating the practical yield. The research led to optimal variants which may be industrially exploited in order to obtain vinegar.
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Bergval, Indra; Coll, Francesc; Schuitema, Anja; de Ronde, Hans; Mallard, Kim; Pain, Arnab; McNerney, Ruth; Clark, Taane G.; Anthony, Richard M.
2015-01-01
We studied genomic variation in a previously selected collection of isogenic Mycobacterium tuberculosis laboratory strains subjected to one or two rounds of antibiotic selection. Whole genome sequencing analysis identified eleven single, unique mutations (four synonymous, six non-synonymous, one intergenic), in addition to drug resistance-conferring mutations, that were fixed in the genomes of six monoresistant strains. Eight loci, present as minority variants (five non-synonymous, three synonymous) in the genome of the susceptible parent strain, became fixed in the genomes of multiple daughter strains. None of these mutations are known to be involved with drug resistance. Our results confirm previously observed genomic stability for M. tuberculosis, although the parent strain had accumulated allelic variants at multiple locations in an antibiotic-free in vitro environment. It is therefore likely to assume that these so-called hitchhiking mutations were co-selected and fixed in multiple daughter strains during antibiotic selection. The presence of multiple allelic variations, accumulated under non-selective conditions, which become fixed during subsequent selective steps, deserves attention. The wider availability of 'deep' sequencing methods could help to detect multiple bacterial (sub)populations within patients with high resolution and would therefore be useful in assisting in the detailed investigation of transmission chains.
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Bergval, Indra
2015-01-09
We studied genomic variation in a previously selected collection of isogenic Mycobacterium tuberculosis laboratory strains subjected to one or two rounds of antibiotic selection. Whole genome sequencing analysis identified eleven single, unique mutations (four synonymous, six non-synonymous, one intergenic), in addition to drug resistance-conferring mutations, that were fixed in the genomes of six monoresistant strains. Eight loci, present as minority variants (five non-synonymous, three synonymous) in the genome of the susceptible parent strain, became fixed in the genomes of multiple daughter strains. None of these mutations are known to be involved with drug resistance. Our results confirm previously observed genomic stability for M. tuberculosis, although the parent strain had accumulated allelic variants at multiple locations in an antibiotic-free in vitro environment. It is therefore likely to assume that these so-called hitchhiking mutations were co-selected and fixed in multiple daughter strains during antibiotic selection. The presence of multiple allelic variations, accumulated under non-selective conditions, which become fixed during subsequent selective steps, deserves attention. The wider availability of \\'deep\\' sequencing methods could help to detect multiple bacterial (sub)populations within patients with high resolution and would therefore be useful in assisting in the detailed investigation of transmission chains.
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Wang, Jing; Long, Cheng; Zhang, Haijun; Zhang, Yanan; Wang, Hao; Yue, Hongyuan; Wang, Xiaocui; Wu, Shugeng; Qi, Guanghai
2016-01-01
Genetic variant T329S in flavin-containing monooxygenase 3 (FMO3) impairs trimethylamine (TMA) metabolism in birds. The TMA metabolism that under complex genetic and dietary regulation, closely linked to cardiovascular disease risk. We determined whether the genetic defects in TMA metabolism may change other metabolic traits in birds, determined whether the genetic effects depend on diets, and to identify genes or gene pathways that underlie the metabolic alteration induced by genetic and die...
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Fog, Amura Francesca; Kvalvaag, Gunnar; Engedal, Knut; Straand, Jørund
2017-12-01
We describe the drug-related problems (DRPs) identified during medication reviews (MRs) and the changes in drug utilization after MRs at nursing homes in Oslo, Norway. We explored predictors for the observed changes. Observational before-after study. Forty-one nursing homes. MRs performed by multidisciplinary teams during November 2011 to February 2014. In all, 2465 long-term care patients. DRPs identified by explicit criteria (STOPP/START and NORGEP) and drug-drug interaction database; interventions to resolve DRPs; drug use changes after MR. A total of 6158 DRPs were identified, an average of 2.6 DRPs/patient, 2.0 for regular and 0.6 for pro re nata (prn) drugs. Of these patients, 17.3% had no DRPs. The remaining 82.7% of the patients had on average 3.0 DRPs/patient. Use of unnecessary drugs (43.5%), excess dosing (12.5%) and lack of monitoring of the drug use (11%) were the most frequent DRPs. Opioids and psychotropic drugs were involved in 34.4% of all DRPs. The mean number of drugs decreased after the MR from 6.8 to 6.3 for regular drugs and from 3.0 to 2.6 for prn drugs. Patients with DRPs experienced a decrease of 1.1 drugs after MR (0.5 for regular and 0.6 for prn drugs). The reduction was most pronounced for the regular use of antipsychotics, antidepressants, hypnotics/sedatives, diuretics, antithrombotic agents, antacid drugs; and for prn use of anxiolytics, opioids, hypnotics/sedatives, metoclopramide and NSAIDs. The medication review resulted in less drug use, especially opioids and psychotropic drugs.
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IL10 low-frequency variants in Behçet's disease patients.
Matos, Mafalda; Xavier, Joana M; Abrantes, Patrícia; Sousa, Inês; Rei, Nádia; Davatchi, Fereydoun; Shahram, Farhad; Jesus, Gorete; Barcelos, Filipe; Vedes, Joana; Salgado, Manuel; Abdollahi, Bahar Sadeghi; Nadji, Abdolhadi; Moraes-Fontes, Maria Francisca; Shafiee, Niloofar Mojarad; Ghaderibarmi, Fahmida; Vaz Patto, José; Crespo, Jorge; Oliveira, Sofia A
2017-05-01
To explain the missing heritability after the genome-wide association studies era, sequencing studies allow the identification of low-frequency variants with a stronger effect on disease risk. Common variants in the interleukin 10 gene (IL10) have been consistently associated with Behçet's disease (BD) and the goal of this study is to investigate the role of low-frequency IL10 variants in BD susceptibility. To identify IL10 low-frequency variants, a discovery group of 50 Portuguese BD patients were Sanger-sequenced in a 7.7 kb genomic region encompassing the complete IL10 gene, 0.9 kb upstream and 2 kb downstream, and two conserved regions in the putative promoter. To assess if the novel variants are BD- and/or Portuguese-specific, they were assayed in an additional group of BD patients (26 Portuguese and 964 Iranian) and controls (104 Portuguese and 823 Iranian). Rare IL10 coding variants were not detected in BD patients, but we identified 28 known single nucleotide polymorphisms with minor allele frequencies ranging from 0.010 to 0.390, and five novel non-coding variants in five heterozygous cases. ss836185595, located in the IL10 3' untranslated region, was also detected in one Iranian control individual and therefore is not specific to BD. The remaining novel IL10 variants (ss836185596 and ss836185602 in intron 3, ss836185598 and ss836185604 in the putative promoter region) were not found in the replication dataset. This study highlights the importance of screening the whole gene and regulatory regions when searching for novel variants associated with complex diseases, and the need to develop bioinformatics tools to predict the functional impact of non-coding variants and statistical tests which incorporate these predictions. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.
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International Nuclear Information System (INIS)
Quadri, Mohammad I.; Al-Sheikh, Iman H.
2001-01-01
Hairy cell leukaemia variant is a very rare chronic lymphoproliferative disorder and is closely related to hairy cell leukemia. We hereby describe a case of hairy cell leukaemia variant for the first time in Saudi Arabia. An elderly Saudi man presented with pallor, massive splenomegaly, and moderate hepatomegaly. Hemoglobin was 7.7 g/dl, Platelets were 134 x109/l and white blood count was 140x10 9/l with 97% being abnormal lymphoid cells with cytoplasmic projections. The morphology, cytochemistry, and immunophenotype of the lymphoid cells were classical of hairy cell leukaemia variant. The bone marrow was easily aspirated and findings were consistent with hairy cell leukaemia variant. (author)
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Deletion mutant defines DQ beta variants with DR4 positive DQw3 positive haplotypes
International Nuclear Information System (INIS)
Nepom, B.S.; Kim, S.J.; Nepom, G.T.
1986-01-01
We describe the production of an HLA deletion mutation by radiation mutagenesis of a DR4- and DQw3-homozygous, Dw4- and Dw14-heterozygous cell line designed to analyze polymorphisms associated with DR4 and DQw3. Southern blot analysis confirms a deletion of class I and class II genes on one haplotype. Variation in DQ beta alleles associated with DQw3 was previously described by characteristic RFLP patterns for a DQ beta bene. One pattern, which correlated precisely with A-10-83 monoclonal antibody reactivity (TA10), defined an allele which we call DQ''3.1''. The mutant cell line has lost the polymorphic bands on Southern blots corresponding to the DQ''3.1'' allele, while the intact Dw14 haplotype retains the alternate allele at DQ beta which is DQw-3 positive. TA10-negative. These data demonstrate the segregation of two DQw3 positive DQ beta allelic variants, both associated with DR4, which can be distinguished on the basis of both RFLP and monoclonal antibody reactivity
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Indian Academy of Sciences (India)
Administrator
2017-11-03
Nov 3, 2017 ... Chairperson: M M Sarin, Physical Research laboratory, Ahmedabad. 1200–1220 Shailesh Nayak, Ministry of Earth Sciences, New Delhi. Towards the understanding of triggered earthquakes. 1225–1245 Gobinda Majumder, Tata Institute of Fundamental Research, Mumbai. A journey to the discovery of ...
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Differences in Shiga toxin and phage production among stx2g-positive STEC strains
Directory of Open Access Journals (Sweden)
Claudia Viviana Granobles Velandia
2012-06-01
Full Text Available Shigatoxigenic E. coli (STEC are characterized by the production of Shiga toxins (Stx encoded by temperate bacteriophages. Stx production is linked to the induction of the phage lytic cycle. Several stx variants have been described and differentially associated with the risk of developing severe illness.The variant named stx2g was first identified in a STEC strain isolated from the faeces of healthy cattle. Analysis of stx2g-positive strains isolated from humans, animals and environmental sources have shown that they have a close relationship. In this study, stx2g-positive STEC isolated from cattle were analyzed for phage and Stx production, with the aim to relate the results to differences observed in cytotoxicity.The presence of inducible phages was assessed by analyzing the bacterial growth/lysis curves and also by plaque assay. Bacterial growth curves in the absence of induction were similar for all isolates, however, notably differed among induced cultures. The two strains that clearly evidenced bacteriolysis under this condition also showed higher phage titers in plaque assays. However, only the phage plaques produced by one of these strains (FB 62 hybridized with a stx2-probe. Furthermore, the production of Stx was evaluated by EIA and Western immunoblotting in overnight supernatants. By EIA, we detected Stx only in supernatants of FB 62, with a higher signal with induced than in uninduced cultures. By immunoblotting, Stx2 could be detected after induction in all stx2g-positive isolates, but with lower amounts of Stx2B subunit in those supernatants where phages could not be detected.Taking into account all the results, several differences could be found among stx2g-positive strains. The strain with the highest cytotoxic titer showed higher levels of stx2-phages and toxin production by EIA, and the opposite was observed for strains that previously showed low cytotoxic titers, confirming that in stx2g-positive strains Stx production is
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[Clinico-pathogenetic variants of chronic gastritis].
Chernin, V V; Dzhulaĭ, G S
2004-01-01
To evaluate specific features of the course of chronic gastritis (CG), morphofunctional condition of gastric mucosa, vegetative regulation, adrenergic and cholinergic shifts, histamine metabolism and effects of exogenic and endogenic risk factors in CG patients; to study clinicopathogenetic variants of CG. A total of 311 CG patients aged from 16 to 72 years were studied. They were divided into three groups by their gastric mucosa condition. The control group consisted of 30 healthy donors. The following parameters were studied: visual and histological condition of gastric mucosa, total acidity, the levels of free hydrochloric acid, pepsin, bioelectric gastric activity, general autonomic tonicity, cholinesterase activity. Three clinicopathogenetic variants of the disease have been identified. Variant 1 was characterized by a recurrent course, subjective manifestation of the disease only in exacerbation, surface (primarily antral) mucosal affection, normal or enhanced secretory and motor functions of the stomach, adequate reaction of acid production to caffeine and histamine stimulation, parasympathicotonia, absolute hyperhistaminemia, relative hypoacetylcholinemia, subnormal urinary excretion of adrenalin. Variant 2 manifested with rare recurrences, longer and more severe exacerbations, frequent spontaneous and provoked aggravations, moderate focal atrophy of the mucosa, secretory insufficiency with adequate reaction to histamine and minor to caffeine stimuli, hypomotor gastric dyskinesia, vegetative eutonia, normohistaminemia, absolute hypoacetylcholinemia, subnormal urinary excretion of noradrenaline. Variant 3 runs without definite remissions and exacerbations, with continuous abdominal pain and dyspepsia, frequent spontaneous aggravations, marked extended mucosal atrophy with secretory insufficiency up to achlorhydria, no stimulation of acid production in response to caffeine and histamine, gastric hypomotility, sympathicotonia, absolute hypohistaminemia
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Directory of Open Access Journals (Sweden)
Stella De Nicola
Full Text Available BACKGROUND AND AIMS: The PNPLA3 I148M sequence variant favors hepatic lipid accumulation and confers susceptibility to hepatic fibrosis and hepatocellular carcinoma. The aim of this study was to estimate the effect size of homozygosity for the PNPLA3 I148M variant (148M/M on the fibrosis progression rate (FPR and the interaction with age at infection in chronic hepatitis C (CHC. METHODS: FPR was estimated in a prospective cohort of 247 CHC patients without alcohol intake and diabetes, with careful estimation of age at infection and determination of fibrosis stage by Ishak score. RESULTS: Older age at infection was the strongest determinant of FPR (p<0.0001. PNPLA3 148M/M was associated with faster FPR in individuals infected at older age (above the median, 21 years; -0.64±0.2, n = 8 vs. -0.95±0.3, n = 166 log10 FPR respectively; p = 0.001; confirmed for lower age thresholds, p<0.05, but not in those infected at younger age (p = ns. The negative impact of PNPLA3 148M/M on fibrosis progression was more marked in subjects at risk of altered hepatic lipid metabolism (those with grade 2-3 steatosis, genotype 3, and overweight; p<0.05. At multivariate analysis, PNPLA3 148M/M was associated with FPR (incremental effect 0.08±0.03 log10 fibrosis unit per year; p = 0.022, independently of several confounders, and there was a significant interaction between 148M/M and older age at infection (p = 0.025. The association between 148M/M and FPR remained significant even after adjustment for steatosis severity (p = 0.032. CONCLUSIONS: We observed an interaction between homozygosity for the PNPLA3 I148M variant and age at infection in determining fibrosis progression in CHC patients.
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Andreevskaia, S N; Chernousova, L N; Smirnova, T G; Larionova, E E; Kuz'min, A V
2006-01-01
The investigation was carried out on 134 M. tuberculosis isolated from 134 patients treated at the Central Research Institute of Tuberculosis, Russian Academy of Medical Sciences. The patients were divided into 2 groups: 1) those who were natives of Moscow and the Moscow Region (MR patients); 2) those who were migrants to the Moscow Region from Azerbaijan, Daghestan, Chechnya, Ingushetia, Karachai-Cherkessia, North Ossetia (the Caucasian Region) (CR patients) who had fallen in the place of birth. Genotyping by the polymorphism of lengths of the restriction fragments containing the insertion sequence IS6110 revealed a genetic diversity of M. tuberculosis strains. The examined M. tuberculosis strains belonged to 13 genotypic families. The W and AI families were prevalent. The family W M. tuberculosis strains isolated from the Caucasians were highly clustered, as confirmed by the overwhelming predominance of the strain variant W148 (19.7%). The spectrum of the strain variants of the W family, and those of the AI family in particular, greatly differed in MR and CR patients. Only one strain variant AI12 occurring both in MR and CR patients was detected. A study of the transmission activity coefficient (TAC) of the families W and AI indicated that the transmission activity of W strains was significantly higher than that of M. tuberculosis strains of the AI family. A comparative analysis of the TAC of M. tuberculosis strains of the AI family demonstrated that the transmission activity of the strains of this family was identical no matter where a patient had fallen ill (1.59 and 1.41% in the Moscow and Caucasian Regions, respectively). Unlike M. tuberculosis strains of the AI family, the TAC of W strains isolated from the patients infected in the Moscow Region (28.17 and 19.05%, respectively), which suggests the more intensive transmission of the pathogen M. tuberculosis of the W family in the Caucasian Region.
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Zhang, Chi; Tian, Jun; Ren, Jun; Wang, Zhongwen
2017-01-26
Aiming to develop efficient and general strategies for construction of complex and diverse polycyclic skeletons, we have successfully developed [4+3]IMPC (intramolecular parallel cycloaddition) of cyclopropane 1,1-diesters with [3]dendralenes. With a combination of the [4+3]IMPC and subsequent [4+n] cycloadditions, trans-[5.3.0]decane skeleton and its corresponding structurally complex and diverse polycyclic variants could be constructed efficiently. This novel [4+3] cycloaddition reaction mode of donor-acceptor cyclopropanes proceeds as a result of the ring-strain relief of a trans-[3.3.0]octane. We strongly believe that the developed methods will demonstrate potential applications in natural products synthesis and drug discovery. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic
DEFF Research Database (Denmark)
Ahlborn, Lise B; Dandanell, Mette; Steffensen, Ane Y
2015-01-01
by functional analysis at the protein level. Results from a validated mini-gene splicing assay indicated that nine BRCA1 variants resulted in splicing aberrations leading to truncated transcripts and thus can be considered pathogenic (c.4987A>T/p.Met1663Leu, c.4988T>A/p.Met1663Lys, c.5072C>T/p.Thr1691Ile, c......Pathogenic germline mutations in the BRCA1 gene predispose carriers to early onset breast and ovarian cancer. Clinical genetic screening of BRCA1 often reveals variants with uncertain clinical significance, complicating patient and family management. Therefore, functional examinations are urgently...... needed to classify whether these uncertain variants are pathogenic or benign. In this study, we investigated 14 BRCA1 variants by in silico splicing analysis and mini-gene splicing assay. All 14 alterations were missense variants located within the BRCT domain of BRCA1 and had previously been examined...
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Marandino, Ana; Tomás, Gonzalo; Panzera, Yanina; Greif, Gonzalo; Parodi-Talice, Adriana; Hernández, Martín; Techera, Claudia; Hernández, Diego; Pérez, Ruben
2017-10-01
Infectious bronchitis virus (Gammacoronavirus, Coronaviridae) is a genetically variable RNA virus that causes one of the most persistent respiratory diseases in poultry. The virus is classified in genotypes and lineages with different epidemiological relevance. Two lineages of the GI genotype (11 and 16) have been widely circulating for decades in South America. GI-11 is an exclusive South American lineage while the GI-16 lineage is distributed in Asia, Europe and South America. Here, we obtained the whole genome of two Uruguayan strains of the GI-11 and GI-16 lineages using Illumina high-throughput sequencing. The strains here sequenced are the first obtained in South America for the infectious bronchitis virus and provide new insights into the origin, spreading and evolution of viral variants. The complete genome of the GI-11 and GI-16 strains have 27,621 and 27,638 nucleotides, respectively, and possess the same genomic organization. Phylogenetic incongruence analysis reveals that both strains have a mosaic genome that arose by recombination between Euro Asiatic strains of the GI-16 lineage and ancestral South American GI-11 viruses. The recombination occurred in South America and produced two viral variants that have retained the full-length S1 sequences of the parental lineages but are extremely similar in the rest of their genomes. These recombinant virus have been extraordinary successful, persisting in the continent for several years with a notorious wide geographic distribution. Our findings reveal a singular viral dynamics and emphasize the importance of complete genomic characterization to understand the emergence and evolutionary history of viral variants. Copyright © 2017 Elsevier B.V. All rights reserved.
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Beutin, Lothar; Miko, Angelika; Krause, Gladys; Pries, Karin; Haby, Sabine; Steege, Katja; Albrecht, Nadine
2007-08-01
We examined 219 Shiga toxin-producing Escherichia coli (STEC) strains from meat, milk, and cheese samples collected in Germany between 2005 and 2006. All strains were investigated for their serotypes and for genetic variants of Shiga toxins 1 and 2 (Stx1 and Stx2). stx(1) or variant genes were detected in 88 (40.2%) strains and stx(2) and variants in 177 (80.8%) strains. Typing of stx genes was performed by stx-specific PCRs and by analysis of restriction fragment length polymorphisms (RFLP) of PCR products. Major genotypes of the Stx1 (stx(1), stx(1c), and stx(1d)) and the Stx2 (stx(2), stx(2d), stx(2-O118), stx(2e), and stx(2g)) families were detected, and multiple types of stx genes coexisted frequently in STEC strains. Only 1.8% of the STEC strains from food belonged to the classical enterohemorrhagic E. coli (EHEC) types O26:H11, O103:H2, and O157:H7, and only 5.0% of the STEC strains from food were positive for the eae gene, which is a virulence trait of classical EHEC. In contrast, 95 (43.4%) of the food-borne STEC strains carried stx(2) and/or mucus-activatable stx(2d) genes, an indicator for potential high virulence of STEC for humans. Most of these strains belonged to serotypes associated with severe illness in humans, such as O22:H8, O91:H21, O113:H21, O174:H2, and O174:H21. stx(2) and stx(2d) STEC strains were found frequently in milk and beef products. Other stx types were associated more frequently with pork (stx(2e)), lamb, and wildlife meat (stx(1c)). The combination of serotyping and stx genotyping was found useful for identification and for assignment of food-borne STEC to groups with potential lower and higher levels of virulence for humans.
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Strain in epitaxial high-index Bi{sub 2}Se{sub 3}(221) films grown by molecular-beam epitaxy
Energy Technology Data Exchange (ETDEWEB)
Li, Bin [Physics Department, The University of Hong Kong, Pokfulam Road (Hong Kong); Chen, Weiguang [College of Physics and Electronic Engineering, Henan Normal University, Xinxiang, Henan 453007 (China); School of Physics and Electronic Engineering, Zhengzhou Normal University, Zhengzhou, Henan 450044 (China); Guo, Xin; Ho, Wingkin [Physics Department, The University of Hong Kong, Pokfulam Road (Hong Kong); Dai, Xianqi [College of Physics and Electronic Engineering, Henan Normal University, Xinxiang, Henan 453007 (China); School of Physics and Electronic Engineering, Zhengzhou Normal University, Zhengzhou, Henan 450044 (China); Jia, Jinfeng [Key Laboratory of Artificial Structures and Quantum Control (Ministry of Education), Collaborative Innovation Center of Advanced Microstructures, Department of Physics and Astronomy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240 (China); Xie, Maohai, E-mail: mhxie@hku.hk [Physics Department, The University of Hong Kong, Pokfulam Road (Hong Kong)
2017-02-28
Highlights: • High-index, off c-axis, Bi{sub 2}Se{sub 3} has been grown by molecular beam epitaxy on In{sub 2}Se{sub 3}. • A retarded strain relaxation process in such high-index Bi{sub 2}Se{sub 3} is observed, enabling experimentally probe strain effect on topological insulators. • It has been shown by calculation that the Dirac electrons participate in chemical bonding at the heterointerface. - Abstract: High-index Bi{sub 2}Se{sub 3}(221) film has been grown on In{sub 2}Se{sub 3}-buffered GaAs(001), in which a much retarded strain relaxation dynamics is recorded. The slow strain-relaxation process of in epitaxial Bi{sub 2}Se{sub 3}(221) can be attributed to the layered structure of Bi{sub 2}Se{sub 3} crystal, where the epifilm grown along [221] is like a pile of weakly-coupled quintuple layer slabs stacked side-by-side on substrate. Finally, we reveal strong chemical bonding at the interface of Bi{sub 2}Se{sub 3} and In{sub 2}Se{sub 3} by plotting differential charge contour calculated by first-principle method. This study points to the feasibility of achieving strained TIs for manipulating the properties of topological systems.
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Basak, Anup; Levitas, Valery I.
2018-04-01
A thermodynamically consistent, novel multiphase phase field approach for stress- and temperature-induced martensitic phase transformations at finite strains and with interfacial stresses has been developed. The model considers a single order parameter to describe the austenite↔martensitic transformations, and another N order parameters describing N variants and constrained to a plane in an N-dimensional order parameter space. In the free energy model coexistence of three or more phases at a single material point (multiphase junction), and deviation of each variant-variant transformation path from a straight line have been penalized. Some shortcomings of the existing models are resolved. Three different kinematic models (KMs) for the transformation deformation gradient tensors are assumed: (i) In KM-I the transformation deformation gradient tensor is a linear function of the Bain tensors for the variants. (ii) In KM-II the natural logarithms of the transformation deformation gradient is taken as a linear combination of the natural logarithm of the Bain tensors multiplied with the interpolation functions. (iii) In KM-III it is derived using the twinning equation from the crystallographic theory. The instability criteria for all the phase transformations have been derived for all the kinematic models, and their comparative study is presented. A large strain finite element procedure has been developed and used for studying the evolution of some complex microstructures in nanoscale samples under various loading conditions. Also, the stresses within variant-variant boundaries, the sample size effect, effect of penalizing the triple junctions, and twinned microstructures have been studied. The present approach can be extended for studying grain growth, solidifications, para↔ferro electric transformations, and diffusive phase transformations.
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International Nuclear Information System (INIS)
Contreras-Paredes, Adriana; Cruz-Hernandez, Erick de la; Martinez-Ramirez, Imelda; Duenas-Gonzalez, Alfonso; Lizano, Marcela
2009-01-01
Intra-type genome variations of high risk Human papillomavirus (HPV) have been associated with a differential threat for cervical cancer development. In this work, the effect of HPV18 E6 isolates in Akt/PKB and Mitogen-associated protein kinase (MAPKs) signaling pathways and its implication in cell proliferation were analyzed. E6 from HPV types 16 and 18 are able to bind and promote degradation of Human disc large (hDlg). Our results show that E6 variants differentially modulate hDlg degradation, rebounding in levels of activated PTEN and PKB. HPV18 E6 variants are also able to upregulate phospho-PI3K protein, strongly correlating with activated MAPKs and cell proliferation. Data was supported by the effect of E6 silencing in HPV18-containing HeLa cells, as well as hDlg silencing in the tested cells. Results suggest that HPV18 intra-type variations may derive in differential abilities to activate cell-signaling pathways such as Akt/PKB and MAPKs, directly involved in cell survival and proliferation
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DEFF Research Database (Denmark)
Glubb, Dylan M; Maranian, Mel J; Michailidou, Kyriaki
2015-01-01
evidence of association of a further 173 variants (iCHAV2) containing three subsets with a range of effects (the strongest was rs113317823 [pcond = 1.61 × 10(-5)]) and five variants composing iCHAV3 (lead rs11949391; ER(+): OR = 0.90, 95% CI = 0.87-0.93, pcond = 1.4 × 10(-4)). Twenty-six percent......CHAV2a], and rs17432750 [iCHAV3]) increased MAP3K1 transcriptional activity. Chromatin immunoprecipitation analysis revealed diminished GATA3 binding to the minor (cancer-protective) allele of rs17432750, indicating a mechanism for its action. We propose that the cancer risk alleles act to increase MAP3...
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International Nuclear Information System (INIS)
Oliver, E.C.; Mori, T.; Daymond, M.R.; Withers, P.J.
2003-01-01
Neutron diffraction spectra were recorded during tensile testing of Fe-30.5 at.% Pd shape memory alloy at temperatures above M s and below M f . Peak intensity changes indicate that the application of tensile stress to initially fully austenitic material results in the preferential martensitic transformation of grains oriented with austenite parallel to the tensile axis. Tensile stress applied to initially fully martensitic material causes the greatest extent of reorientation in those variants oriented with martensite lying parallel to the tensile axis. These results are interpreted using a simple elasticity-based theory. Additionally, diffraction peak shifts provide information on the development of lattice strain in differently oriented grain families during loading. This indicates that above M s the alloy exhibits high single crystal elastic anisotropy. Below M f the apparent stiffnesses of different grain families suggest that axially compressive internal stresses develop in those grain families in which most variant reorientation occurs. These stresses act to reverse the variant changes upon subsequent unloading
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Following of erosive wash of soil in variants with different intercrops
Directory of Open Access Journals (Sweden)
Barbora Badalíková
2010-01-01
Full Text Available In a pilot experiment established in a sugar beet growing region the erosive washing away of soil was studied in the years 2006 to 2008. The area is located at an altitude of 246 m with the long-term mean precipitation of 500 mm and the mean annual temperature of 8.4 °C. The soils are classified as Chernozem, moderately heavy, loamy, with a good supply of nutrients, humus content of 2.30 % and an alkaline soil reaction. Slope gradient is 12 %, exposition is NE. To study the role of intercrops in erosion control, three variants were established after the harvest of the main crop, two variants with different intercrops and one (control with no intercrop. These were Variant 1 with Secale cereale L. var. multicaule METZG. ex ALEF., a non-freezing intercrop, Variant 2 with cluster mallow (Malva verticillata L., a freezing intercrop, and a control variant with no intercrop. In Variant 1 Secale cereale L. var. multicaule was desiccated with the herbicide Roundup in early spring. All the variants involved maize as the main crop. In variants 1 and 2, maize was sown in intercrop residues after seedbed preparation by Vario and a compactor. In Variant 3 maize was sown after conventional seedbed preparation. For assessment of soil conditions soil samples were taken to determine soil physical and chemical properties and water content in the soil. Soil loss by erosion was determined using specially-designed pockets. Erosive washing away of soil was monitored during the entire growing season of maize. The variants in which intercrops were used were found very effective in soil erosion control. In Variant 3 (control without surface crop residues, the washing away of soil was recorded with each heavy torrential rain. During the all years the total amount of soil loss by erosion in this treatment was 2.25 t . ha−1.
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Octahedral rotations in strained LaAlO3/SrTiO3 (001 heterostructures
Directory of Open Access Journals (Sweden)
T. T. Fister
2014-02-01
Full Text Available Many complex oxides display an array of structural instabilities often tied to altered electronic behavior. For oxide heterostructures, several different interfacial effects can dramatically change the nature of these instabilities. Here, we investigate LaAlO3/SrTiO3 (001 heterostructures using synchrotron x-ray scattering. We find that when cooling from high temperature, LaAlO3 transforms from the Pm3¯m to the Imma phase due to strain. Furthermore, the first 4 unit cells of the film adjacent to the substrate exhibit a gradient in rotation angle that can couple with polar displacements in films thinner than that necessary for 2D electron gas formation.
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van den Broek, M; Bolat, I; Nijkamp, J F; Ramos, E; Luttik, M A H; Koopman, F; Geertman, J M; de Ridder, D; Pronk, J T; Daran, J-M
2015-09-01
Lager brewing strains of Saccharomyces pastorianus are natural interspecific hybrids originating from the spontaneous hybridization of Saccharomyces cerevisiae and Saccharomyces eubayanus. Over the past 500 years, S. pastorianus has been domesticated to become one of the most important industrial microorganisms. Production of lager-type beers requires a set of essential phenotypes, including the ability to ferment maltose and maltotriose at low temperature, the production of flavors and aromas, and the ability to flocculate. Understanding of the molecular basis of complex brewing-related phenotypic traits is a prerequisite for rational strain improvement. While genome sequences have been reported, the variability and dynamics of S. pastorianus genomes have not been investigated in detail. Here, using deep sequencing and chromosome copy number analysis, we showed that S. pastorianus strain CBS1483 exhibited extensive aneuploidy. This was confirmed by quantitative PCR and by flow cytometry. As a direct consequence of this aneuploidy, a massive number of sequence variants was identified, leading to at least 1,800 additional protein variants in S. pastorianus CBS1483. Analysis of eight additional S. pastorianus strains revealed that the previously defined group I strains showed comparable karyotypes, while group II strains showed large interstrain karyotypic variability. Comparison of three strains with nearly identical genome sequences revealed substantial chromosome copy number variation, which may contribute to strain-specific phenotypic traits. The observed variability of lager yeast genomes demonstrates that systematic linking of genotype to phenotype requires a three-dimensional genome analysis encompassing physical chromosomal structures, the copy number of individual chromosomes or chromosomal regions, and the allelic variation of copies of individual genes. Copyright © 2015, van den Broek et al.
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Hu, Dongfang; Zhang, Zhendong; Lv, Lin; Xiao, Yihong; Qu, Yajin; Ma, Haiying; Niu, Yujuan; Wang, Guangwen; Liu, Sidang
2015-09-01
An epidemic that mainly endangered 3-7-day-old piglets struck many farms in Shandong Province, China in 2013 and caused heavy losses. To identify the pathogenesis, the type of lesions, and the causative agent, systemic examinations were performed. Autopsy showed multiple lesions, including necrotic foci of the spleen and liver, punctate hemorrhage of the renal cortex, and interstitial pneumonia. Histological examinations showed typical nonsuppurative encephalitis, necrotic lymphocytes, and reticuloendothelial cells in lymphatic tissues, as well as eosinophilic inclusion bodies in the nuclei of reticuloendothelial cells, necrotic foci in liver cells, and hemorrhagic glomeruli. The average seroprevalence rate of field pseudorabies virus (PRV; Suid herpesvirus 1) of a representative farm tested by enzyme-linked immunosorbent assay was 46%, indicating that the PRV infectious pressure was quite severe especially among gilts, young multiparous sows, boars, and growing-finishing pigs. The glycoprotein E (gE) gene of PRV was detected in 8 of 10 clinical samples, and the virus in the positive samples induced obvious cytopathic effects. An immunoperoxidase monolayer assay showed that PRV antigens were distributed both in the nucleoli and cytoplasm of infected cells. Sequencing and phylogenetic analysis of the gE gene showed that the strain isolated herein, TaiAn SD 2013, was highly similar to previously isolated strains, especially those isolated in northern China in 2013, and was closely related to other isolates from Asia. Evidence confirmed that the variant PRV was the etiologic agent of this epidemic, suggesting that the Bartha-K61 vaccine does not provide complete protection against PRV infection. Further challenge tests are ongoing to investigate the virulence of variant PRV. © 2015 The Author(s).
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Directory of Open Access Journals (Sweden)
Camila Appolinário
2015-09-01
Full Text Available Rabies virus (RABV isolated from different mammals seems to have unique characteristics that influence the outcome of infection. RABV circulates in nature and is maintained by reservoirs that are responsible for the persistence of the disease for almost 4000 years. Considering the different pattern of pathogenicity of RABV strains in naturally and experimentally infected animals, the aim of this study was to analyze the characteristics of RABV variants isolated from the main Brazilian reservoirs, being related to a dog (variant 2, Desmodus rotundus (variant 3, crab eating fox, marmoset, and Myotis spp. Viral replication in brain tissue of experimentally infected mouse was evaluated by two laboratory techniques and the results were compared to clinical evolution from five RABV variants. The presence of the RABV was investigated in brain samples by fluorescent antibody test (FAT and real time polymerase chain reaction (qRT-PCR for quantification of rabies virus nucleoprotein gene (N gene. Virus replication is not correlated with clinical signs and evolution. The pattern of FAT is associated with RABV replication levels. Virus isolates from crab eating fox and marmoset had a longer evolution period and higher survival rate suggesting that the evolution period may contribute to the outcome. RABV virus variants had independent characteristics that determine the clinical evolution and survival of the infected mice.
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Metselaar, Karin I; Abee, Tjakko; Zwietering, Marcel H; den Besten, Heidy M W
2016-09-01
Listeria monocytogenes exhibits a heterogeneous response upon stress exposure which can be partially attributed to the presence of stable stress-resistant variants. This study aimed to evaluate the impact of the presence of stress-resistant variants of Listeria monocytogenes and their corresponding trade-offs on population composition under different environmental conditions. A set of stress robustness and growth parameters of the wild type (WT) and an rpsU deletion variant was obtained and used to model their growth behavior under combined mild stress conditions and to model their kinetics under single- and mixed-strain conditions in a simulated food chain. Growth predictions for the WT and the rpsU deletion variant matched the experimental data generally well, although some deviations from the predictions were observed. The data highlighted the influence of the environmental conditions on the ratio between the WT and variant. Prediction of performance in the simulated food chain proved to be challenging. The trend of faster growth and lower stress robustness for the WT than for the rpsU variant in the different steps of the chain was confirmed, but especially for the inactivation steps and the time needed to resume growth after an inactivation step, the experimental data deviated from the model predictions. This report provides insights into the conditions which can select for stress-resistant variants in industrial settings and discusses their potential persistence in food processing environments. Listeria monocytogenes exhibits a heterogeneous stress response which can partially be attributed to the presence of genetic variants. These stress-resistant variants survive better under severe conditions but have, on the other hand, a reduced growth rate. To date, the ecological behavior and potential impact of the presence of stress-resistant variants is not fully understood. In this study, we quantitatively assessed growth and inactivation behavior of wild-type L
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Directory of Open Access Journals (Sweden)
T. B. Sentsova
2017-01-01
Full Text Available To study the immune manifestations of the interferon-lambda 3 genepolymorphism in chronic viral hepatitis C, 110 Russian children (54 girls and 56 boys with chronic HCV infection aged from 3 to 17 years were examined. All children were on combined therapy (pegylated interferon + ribavirin. It was found that among the studied polymorphic variants of the IFN-λ 3 gene in children with chronic HCV infection, T allele of the marker rs12979860 is associated with infection and chronization of HCV. The T/T rs12979860 genotype of the IFN-λ3 gene is unfavorable for the course of chronic HCV infection due to low levels of activated T-lymphocytes, intactness of the proinflammatory cytokines TNF-α, IL-6, IL-1α, and interferon-γ inducible protein IP-10. The revealed relation of the polymorphic variants of C/C + C/T locus rs12979860 of INF-λ3 gene with the expression of activated T-lymphocytes discloses the protective nature of these genotypes to the development of chronic HCV infection in children.
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Heterozygous RTEL1 variants in bone marrow failure and myeloid neoplasms.
Marsh, Judith C W; Gutierrez-Rodrigues, Fernanda; Cooper, James; Jiang, Jie; Gandhi, Shreyans; Kajigaya, Sachiko; Feng, Xingmin; Ibanez, Maria Del Pilar F; Donaires, Flávia S; Lopes da Silva, João P; Li, Zejuan; Das, Soma; Ibanez, Maria; Smith, Alexander E; Lea, Nicholas; Best, Steven; Ireland, Robin; Kulasekararaj, Austin G; McLornan, Donal P; Pagliuca, Anthony; Callebaut, Isabelle; Young, Neal S; Calado, Rodrigo T; Townsley, Danielle M; Mufti, Ghulam J
2018-01-09
Biallelic germline mutations in RTEL1 (regulator of telomere elongation helicase 1) result in pathologic telomere erosion and cause dyskeratosis congenita. However, the role of RTEL1 mutations in other bone marrow failure (BMF) syndromes and myeloid neoplasms, and the contribution of monoallelic RTEL1 mutations to disease development are not well defined. We screened 516 patients for germline mutations in telomere-associated genes by next-generation sequencing in 2 independent cohorts; one constituting unselected patients with idiopathic BMF, unexplained cytopenia, or myeloid neoplasms (n = 457) and a second cohort comprising selected patients on the basis of the suspicion of constitutional/familial BMF (n = 59). Twenty-three RTEL1 variants were identified in 27 unrelated patients from both cohorts: 7 variants were likely pathogenic, 13 were of uncertain significance, and 3 were likely benign. Likely pathogenic RTEL1 variants were identified in 9 unrelated patients (7 heterozygous and 2 biallelic). Most patients were suspected to have constitutional BMF, which included aplastic anemia (AA), unexplained cytopenia, hypoplastic myelodysplastic syndrome, and macrocytosis with hypocellular bone marrow. In the other 18 patients, RTEL1 variants were likely benign or of uncertain significance. Telomeres were short in 21 patients (78%), and 3' telomeric overhangs were significantly eroded in 4. In summary, heterozygous RTEL1 variants were associated with marrow failure, and telomere length measurement alone may not identify patients with telomere dysfunction carrying RTEL1 variants. Pathogenicity assessment of heterozygous RTEL1 variants relied on a combination of clinical, computational, and functional data required to avoid misinterpretation of common variants.
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Strain driven anisotropic magnetoresistance in antiferromagnetic La$_{0.4}$Sr$_{0.6}$MnO$_{3}$
Wong, A. T.; Beekman, C.; Guo, H.; Siemons, W.; Gai, Z.; Arenholz, E.; Takamura, Y.; Ward, T. Z.
2014-01-01
We investigate the effects of strain on antiferromagnetic (AFM) single crystal thin films of La 1-x Sr x MnO 3 (x = 0.6). Nominally unstrained samples have strong magnetoresistance with anisotropic magnetoresistances (AMR) of up to 8%. Compressive strain suppresses magnetoresistance but generates AMR values of up to 63%. Tensile strain presents the only case of a metal-insulator transition and demonstrates a previously unreported AMR behavior. In all three cases, we find evidence of magnetic...
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Hasing, Maria E.; Preiksaitis, Jutta K.; Tellier, Raymond; Honish, Lance; Senthilselvan, Ambikaipakan; Pang, Xiaoli L.
2013-01-01
The public health impact of the emergence of new norovirus (NoV) strains is uncertain. A biennial pattern of alternating quiescent and epidemic levels of NoV outbreak activity associated with the emergence of new GII.4 variants was observed in Alberta, Canada, between July 2000 and June 2008. In this study, NoV genogroup I (GI) and GII strains isolated from 710 outbreak specimens in Alberta between July 2008 and January 2013 were characterized to update historical data. The seasonality and annual variation in NoV outbreak burden were analyzed over a 10-year period (July 2002 to June 2012). We found that GII.4-2006b had persisted as the predominant variant over three observation periods (July 2006 to June 2009) during which the biennial NoV outbreak pattern continued. The emergence of GII.4-2010 (winter 2009) was not associated with increased outbreak activity, and outbreak activity between July 2009 and June 2012 when GII.4-2010 predominated (67.5 to 97.7%) did not follow a biennial pattern. GII.4-2012 first emerged in Alberta in September 2011 and became predominant in observation period July 2012 to June 2013. NoV GI, relatively rare in past years, had a higher activity level (37.3%) as represented by GI.6 and GI.7 in the winter of 2012 to 2013. A higher proportion of GI outbreaks occurred in non-health care facility settings compared to GII. Our study suggests that factors other than new variants emergence contribute to the levels of NoV outbreak activity in Alberta. PMID:23637302
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Bancerz-Kisiel, Agata; Szczerba-Turek, Anna; Platt-Samoraj, Aleksandra; Michalczyk, Maria; Szweda, Wojciech
2017-03-01
Y. enterocolitica is the causative agent of yersiniosis. The objective of the article was a study of single nucleotide polymorphism in the ystB gene of Y. enterocolitica strains isolated from various wild animal species. High-resolution melting (HRM) analysis was applied to identify single nucleotide polymorphism (SNP) of ystB gene fragments of 88 Y. enterocolitica biotype 1A strains isolated from wild boar, roe deer, red deer and wild ducks. HRM analysis revealed 14 different melting profiles - 4 of them were defined as regular genotypes (G1, G2, G3, G4), whereas 10 as variations. 24 of the examined Y. enterocolitica strains were classified as G1, 18 strains as a G2, 21 strains as a G3, and 15 strains as a G4. Nucleotide sequences classified as G1 revealed 100% similarity with the Y. enterocolitica D88145.1 sequence (NCBI). Analysis of G2 revealed one point mutation - transition T111A. One mutation was also found in G3, but SNP was placed in a different gene region - transition G193A. Two SNPs - transitions G92C and T111A - were identified in G4. Direct sequencing of 10 variations revealed 5 new variants of the ystB nucleotide sequence: V1 - transition G129A (3 strains); V2 - transitions T111A and G193A (2 strains); V3 - transitions C118T and G193A (1 strain); V4 - transitions C141A and G193A (2 strains); and V5 characterized by 19 SNPs: G83A, T93A, A109G, G114T, C116T, A123G, T134C, T142G, T144C, A150C, G162A, T165G, T170G, T174A, T177G, G178A, A179G, A184G and G193A (2 strains). The predominant genotype in isolates from wild ducks was G1; in red deer G2; in wild boar G3; in roe deer G1 and G4. The proposed HRM method could be used to analyze Y. enterocolitica biotype 1A strains isolated from different sources, including humans.
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Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis.
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Nada Abdelmagid
Full Text Available Herpes simplex encephalitis (HSE is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats with the asymptomatic infection of BN (Brown Norway. Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains, displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus named Hse6 towards the end of chromosome 4 (160.89-174Mb containing the Vwf (von Willebrand factor gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism. Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008 after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.
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Behzad, Somayeh
2017-11-01
Recently, a new two-dimensional (2D) material, the 2D BC3 crystal, has been synthesized. Here, the mechanical control of the electro-optical properties of monolayer and bilayer BC3 by applying the biaxial strain is investigated. The electronic structure calculations showed that the strain-free monolayer and bilayer BC3 are indirect band-gap semiconductors with band gap of 0.62 and 0.29 eV, respectively, where the conduction band minimum (CBM) is at the M point whereas the valence band maximum (VBM) is at the Γ point. The doubly degenerated bands in the monolayer BC3 are splitted in the bilayer BC3 due to the interlayer interactions. Both monolayer and bilayer BC3 remain indirect gap semiconductor under biaxial tensile strain and their band gaps increases with strain. On the other hand, by increasing the magnitude of tensile strain, the optical spectra shift to the lower energies and the static dielectric constant increases. These findings suggest the potential of strain-engineered 2D BC3 in electronic and optoelectronic device applications.
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Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA.
Schrader, Kasmintan A; Cheng, Donavan T; Joseph, Vijai; Prasad, Meera; Walsh, Michael; Zehir, Ahmet; Ni, Ai; Thomas, Tinu; Benayed, Ryma; Ashraf, Asad; Lincoln, Annie; Arcila, Maria; Stadler, Zsofia; Solit, David; Hyman, David M; Hyman, David; Zhang, Liying; Klimstra, David; Ladanyi, Marc; Offit, Kenneth; Berger, Michael; Robson, Mark
2016-01-01
Tumor genetic sequencing identifies potentially targetable genetic alterations with therapeutic implications. Analysis has concentrated on detecting tumor-specific variants, but recognition of germline variants may prove valuable as well. To estimate the burden of germline variants identified through routine clinical tumor sequencing. Patients with advanced cancer diagnoses eligible for studies of targeted agents at Memorial Sloan Kettering Cancer Center are offered tumor-normal sequencing with MSK-IMPACT, a 341-gene panel. We surveyed the germline variants seen in 187 overlapping genes with Mendelian disease associations in 1566 patients who had undergone tumor profiling between March and October 2014. The number of presumed pathogenic germline variants (PPGVs) and variants of uncertain significance per person in 187 genes associated with single-gene disorders and the proportions of individuals with PPGVs in clinically relevant gene subsets, in genes consistent with known tumor phenotypes, and in genes with evidence of second somatic hits in their tumors. The mean age of the 1566 patients was 58 years, and 54% were women. Presumed pathogenic germline variants in known Mendelian disease-associated genes were identified in 246 of 1566 patients (15.7%; 95% CI, 14.0%-17.6%), including 198 individuals with mutations in genes associated with cancer susceptibility. Germline findings in cancer susceptibility genes were concordant with the individual's cancer type in only 81 of 198 cases (40.9%; 95% CI, 34.3%-47.9%). In individuals with PPGVs retained in the tumor, somatic alteration of the other allele was seen in 39 of 182 cases (21.4%; 95% CI, 16.1%-28.0%), of which 13 cases did not show a known correlation of the germline mutation and a known syndrome. Mutations in non-cancer-related Mendelian disease genes were seen in 55 of 1566 cases (3.5%; 95% CI, 27.1%-45.4%). Almost every individual had more than 1 variant of uncertain significance (1565 of 1566 patients; 99
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Rodríguez-López, Pedro; Puga, Carmen H; Orgaz, Belén; Cabo, Marta L
2017-09-01
This work presents the assessment of the effectivity of a pronase (PRN)-benzalkonium chloride (BAC) sequential treatment in removing Listeria monocytogenes-Escherichia coli dual-species biofilms grown on stainless steel (SS) using fluorescence microscopy and plate count assays. The effects of PRN-BAC on the occupied area (OA) by undamaged cells in 168 h dual-species samples were determined using a first-order factorial design. Empirical equations significantly (r 2 = 0.927) described a negative individual effect of BAC and a negative interactive effect of PRN-BAC achieving OA reductions up to 46%. After treatment, high numbers of remaining attached and released viable and cultivable E. coli cells were detected in PRN-BAC combinations when low BAC concentrations were used. Therefore, at appropriate BAC doses, in addition to biofilm removal, sequential application of PRN and BAC represents an appealing strategy for pathogen control on SS surfaces while hindering the dispersion of live cells into the environment.
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Energy Technology Data Exchange (ETDEWEB)
Himcinschi, Cameliu, E-mail: himcinsc@physik.tu-freiberg.de; Talkenberger, Andreas; Kortus, Jens [TU Bergakademie Freiberg, Institute of Theoretical Physics, 09596 Freiberg (Germany); Guo, Er-Jia [Institute of Physics, Martin-Luther-University Halle-Wittenberg, 06099 Halle (Germany); Institute for Metallic Materials, IFW Dresden, 01069 Dresden (Germany); Quantum Condensed Matter Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830 (United States); Dörr, Kathrin [Institute of Physics, Martin-Luther-University Halle-Wittenberg, 06099 Halle (Germany); Institute for Metallic Materials, IFW Dresden, 01069 Dresden (Germany)
2016-01-25
BiFeO{sub 3} epitaxial thin films were deposited on piezoelectric 0.72Pb(Mg{sub 1/3}Nb{sub 2/3})O{sub 3}-0.28PbTiO{sub 3} (PMN-PT) substrates with a conductive buffer layer (La{sub 0.7}Sr{sub 0.3}MnO{sub 3} or SrRuO{sub 3}) using pulsed laser deposition. The calibration of the strain values induced by the electric field applied on the piezoelectric PMN-PT substrates was realised using X-Ray diffraction measurements. The method of piezoelectrically induced strain allows one to directly obtain a quantitative correlation between the strain and the shift of the Raman-active phonons. This is a prerequisite for making Raman scattering a strong tool to probe the strain coupling in multiferroic nanostructures. Using the Poisson's number for BiFeO{sub 3}, one can determine the volume change induced by strain, and therefore the Grüneisen parameters for specific phonon modes.
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An 18 case outbreak of variant H3N2 influenza A occurred during 2016 after exposure to influenza-infected swine at seven agricultural fairs. Sixteen cases were infected with a reassortant between 2010-2011 human seasonal H3N2 strains and viruses endemic in North American swine, a viral lineage incre...
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Essghaier, Badiaa; Hedi, Abdeljabbar; Bajji, Mohammed; Jijakli, Haissam; Boudabous, Abdellatif; Sadfi-Zouaoui, Najla
2012-01-01
A new chitinase produced by the moderately halophilic bacterium Virgibacillus marismortui strain M3- 23 was identified and characterized. Distinguishable characteristics of high activity and stability at different pH, temperatures and salinity of M3-23 chitinase are reported. Analysis of the catalytic domain sequence from the enzyme highlighted its relationship to glycosyl hydrolase family 18. Comparison of the deduced chitinase sequence from strain M3-23 to known chitinases from Bacillus spe...
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Banks, David J; Porcella, Stephen F; Barbian, Kent D; Beres, Stephen B; Philips, Lauren E; Voyich, Jovanka M; DeLeo, Frank R; Martin, Judith M; Somerville, Greg A; Musser, James M
2004-08-15
We describe the genome sequence of a macrolide-resistant strain (MGAS10394) of serotype M6 group A Streptococcus (GAS). The genome is 1,900,156 bp in length, and 8 prophage-like elements or remnants compose 12.4% of the chromosome. A 8.3-kb prophage remnant encodes the SpeA4 variant of streptococcal pyrogenic exotoxin A. The genome of strain MGAS10394 contains a chimeric genetic element composed of prophage genes and a transposon encoding the mefA gene conferring macrolide resistance. This chimeric element also has a gene encoding a novel surface-exposed protein (designated "R6 protein"), with an LPKTG cell-anchor motif located at the carboxyterminus. Surface expression of this protein was confirmed by flow cytometry. Humans with GAS pharyngitis caused by serotype M6 strains had antibody against the R6 protein present in convalescent, but not acute, serum samples. Our studies add to the theme that GAS prophage-encoded extracellular proteins contribute to host-pathogen interactions in a strain-specific fashion.
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Genetic Diversity of Tick-Borne Rickettsial Pathogens; Insights Gained from Distant Strains
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Sebastián Aguilar Pierlé
2014-01-01
Full Text Available The ability to capture genetic variation with unprecedented resolution improves our understanding of bacterial populations and their ability to cause disease. The goal of the pathogenomics era is to define genetic diversity that results in disease. Despite the economic losses caused by vector-borne bacteria in the Order Rickettsiales, little is known about the genetic variants responsible for observed phenotypes. The tick-transmitted rickettsial pathogen Anaplasma marginale infects cattle in tropical and subtropical regions worldwide, including Australia. Genomic analysis of North American A. marginale strains reveals a closed core genome defined by high levels of Single Nucleotide Polymorphisms (SNPs. Here we report the first genome sequences and comparative analysis for Australian strains that differ in virulence and transmissibility. A list of genetic differences that segregate with phenotype was evaluated for the ability to distinguish the attenuated strain from virulent field strains. Phylogenetic analyses of the Australian strains revealed a marked evolutionary distance from all previously sequenced strains. SNP analysis showed a strikingly reduced genetic diversity between these strains, with the smallest number of SNPs detected between any two A. marginale strains. The low diversity between these phenotypically distinct bacteria presents a unique opportunity to identify the genetic determinants of virulence and transmission.
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Genotyping Fanconi anemia patients from Serbia reveals three novel FANCD2 variants
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Filipović-Tričković Jelena
2017-01-01
Full Text Available Fanconi anemia is rare inherited disease characterized by wide spectrum of congenital anomalies, progressive pancytopenia, and predisposition to hematological malignancies and solid tumors. Molecular genetic analysis of mutations in FANC genes is of a great importance for diagnosis confirmation, prenatal and carrier testing, as well as for prediction of chemotherapy outcome and disease complications. In this study we performed screening of frequently affected regions of FANCD2 gene for sequence variants in six unrelated FA-D2 patients in Serbia. This is the first molecular analysis of FANCD2 gene in Serbian FA-D2 patients. A total of 10 sequence variants were detected, one in homozygous, and nine in heterozygous state. Two variants were found within exons, and eight within introns, in deep intronic regions. In-silico analysis showed that among all detected variants one exon variant and three intron variants might have impact on splicing mechanism. Heterozygous variants found in intron 3, c.206-246delG; exon 26, c.2396 C>A and intron 28, c.2715+573 C>T were not previously reported. In-silico analysis revealed that among them, two (intron 3, c.206-246 delG and exon 26, c.2396 C>A could be novel disease-causing mutations. Many variants were found in more than one patient, including those unreported, indicating their possible ethnic association. Great number of variants in some patients suggests their non-random emergence in Fanconi anemia pathway. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 173046
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Directory of Open Access Journals (Sweden)
Vivian M. Hsu, MD
2014-09-01
Conclusions: This pilot study illustrates that the face can be objectively and quantitatively evaluated using dynamic major strain analysis. The technology of 3-dimensional optical imaging can be used to advance our understanding of facial soft-tissue dynamics and the effects of animation on facial strain over time.
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Zhang, Rong; Xu, Xingjian; Chen, Wenli; Huang, Qiaoyun
2016-02-01
A multifunctional Pseudomonas putida X3 strain was successfully engineered by introducing methyl parathion (MP)-degrading gene and enhanced green fluorescent protein (EGFP) gene in P. putida X4 (CCTCC: 209319). In liquid cultures, the engineered X3 strain utilized MP as sole carbon source for growth and degraded 100 mg L(-1) of MP within 24 h; however, this strain did not further metabolize p-nitrophenol (PNP), an intermediate metabolite of MP. No discrepancy in minimum inhibitory concentrations (MICs) to cadmium (Cd), copper (Cu), zinc (Zn), and cobalt (Co) was observed between the engineered X3 strain and its host strain. The inoculated X3 strain accelerated MP degradation in different polluted soil microcosms with 100 mg MP kg(-1) dry soil and/or 5 mg Cd kg(-1) dry soil; MP was completely eliminated within 40 h. However, the presence of Cd in the early stage of remediation slightly delayed MP degradation. The application of X3 strain in Cd-contaminated soil strongly affected the distribution of Cd fractions and immobilized Cd by reducing bioavailable Cd concentrations with lower soluble/exchangeable Cd and organic-bound Cd. The inoculated X3 strain also colonized and proliferated in various contaminated microcosms. Our results suggested that the engineered X3 strain is a potential bioremediation agent showing competitive advantage in complex contaminated environments.
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Pulled hamstring muscle; Sprain - hamstring ... There are 3 levels of hamstring strains: Grade 1 -- mild muscle strain or pull Grade 2 -- partial muscle tear Grade 3 -- complete muscle tear Recovery time depends ...
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DEFF Research Database (Denmark)
Brems, Mathias Rosdahl; Paaske, Jens; Lunde, Anders Mathias
2018-01-01
velocity. The spin-momentum locking of strained Bi2Se3 is shown to be modified. Hence, strain control can be used to manipulate the spin degree of freedom via the spin–orbit coupling. We show that for a thin film of Bi2Se3 the SS band gap induced by coupling between the opposite surfaces changes opposite...... to the bulk band gap under strain. Tuning the SS band gap by strain, gives new possibilities for the experimental investigation of the thickness dependent gap and optimization of optical properties relevant for, e.g., photodetector and energy harvesting applications. We finally derive analytical expressions...... analytically the effects of strain on the electronic structure of Bi2Se3. For the most experimentally relevant surface termination we analytically derive the surface state (SS) spectrum, revealing an anisotropic Dirac cone with elliptical constant energy contours giving rise to a direction-dependent group...
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International Nuclear Information System (INIS)
Moretta, A.; Poggi, A.; Olive, D.; Bottino, C.; Fortis, C.; Pantaleo, G.; Moretta, L.
1987-01-01
A clone of the interleukin 2-producing Jurkat leukemia cell line termed JA3 (surface phenotype, T3 + , Ti + , T44 + , T11 + , T40 + ) has been used to induce and select cell variants lacking surface molecules involved in T-cell activation. Following 200 rad of γ-radiation (1 rad = 0.01 Gy), cells were treated with monoclonal antibodies (mAbs) directed to T3, Ti, T44, or T11 antigen and complement. After growth of the residual cells in culture, negative cells were cloned under limiting conditions. Depending on the specificity of the mAb used for the immunoselection, three groups of variants were obtained. (i) The use of mAbs directed to T3 or Ti resulted in cell variants that expressed the T3 - Ti - T44 + Leu1 + T11 + T40 + 4F2 + HLA class I + surface phenotype. (ii) Immunoselection with anti-T44 mAb resulted in 2 variants that shared the T3 - Ti - T44 - Leu1 - T11 - T40 - 4F2 - HLA class I + phenotype. (iii) Cell treatment with anti-T11 mAb resulted in 15 variants characterized by the lack of T11 antigen expression and of all the other T-cell-specific surface antigens. Therefore, it appears that the different sets of JA3 cell variants, like T cells at discrete stages of intrathymic differentiation, may follow a coordinated expression of surface differentiation antigens. Analysis of the functional responsiveness of the three distinct groups of JA3 cell variants to different stimuli showed that all produced interleukin 2 in response to A23187 calcium ionophore plus phorbol 12-myristate 13-acetate
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Microcystis aeruginos strain [D-Leu1] Mcyst-LR producer, from Buenos Aires province, Argentina
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Lorena Rosso
2014-04-01
Full Text Available Objective: To show the toxicological and phylogenetic characterization of a native Microcystis aeruginosa (M. aeruginosa strain (named CAAT 2005-3 isolated from a water body of Buenos Aires province, Argentine. Methods: A M. aeruginosa strain was isolated from the drainage canal of the sewage treatment in the town of Pila, Buenos Aires province, Argentina and acclimated to laboratory conditions. The amplification of cpcBA-IGS Phcocyanin (PC, intergenic spacer and flanking regions was carried out in order to build a phylogenetic tree. An exactive/orbitrap mass spectrometer equipped with an electrospray ionization source (Thermo Fisher Scientific, Bremen, Germany was used for the LC/ESI-HRMS microcystins analysis. The number of cell/mL and [D-Leu1] Mcyst-LR production obtained as a function of time was modelled using the Gompertz equation. Results: The phylogenetic analysis showed that the sequence clustered with others M. aeruginosa sequences obtained from NCBI. The first Argentinian strain of M. aeruginosa (CAAT 2005-3 growing under culture conditions maintains the typical colonial architecture of M. aeruginosa with profuse mucilage. M. aeruginosa CAAT 2005-3 expresses a toxin variant, that was identified by LC-HRMS/Orbitrapas as [D-Leu1] microcystin-LR ([M+H]+=1 037.8 m/z. Conclusions: [D-Leu1] microcystin-LR has been also detected in M. aeruginosa samples from Canada, Brazil and Argentina. This work provides the basis for technological development and production of analytical standards of toxins present in our region.
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Genetic homogeneity of Clostridium botulinum type A1 strains with unique toxin gene clusters.
Raphael, Brian H; Luquez, Carolina; McCroskey, Loretta M; Joseph, Lavin A; Jacobson, Mark J; Johnson, Eric A; Maslanka, Susan E; Andreadis, Joanne D
2008-07-01
A group of five clonally related Clostridium botulinum type A strains isolated from different sources over a period of nearly 40 years harbored several conserved genetic properties. These strains contained a variant bont/A1 with five nucleotide polymorphisms compared to the gene in C. botulinum strain ATCC 3502. The strains also had a common toxin gene cluster composition (ha-/orfX+) similar to that associated with bont/A in type A strains containing an unexpressed bont/B [termed A(B) strains]. However, bont/B was not identified in the strains examined. Comparative genomic hybridization demonstrated identical genomic content among the strains relative to C. botulinum strain ATCC 3502. In addition, microarray data demonstrated the absence of several genes flanking the toxin gene cluster among the ha-/orfX+ A1 strains, suggesting the presence of genomic rearrangements with respect to this region compared to the C. botulinum ATCC 3502 strain. All five strains were shown to have identical flaA variable region nucleotide sequences. The pulsed-field gel electrophoresis patterns of the strains were indistinguishable when digested with SmaI, and a shift in the size of at least one band was observed in a single strain when digested with XhoI. These results demonstrate surprising genomic homogeneity among a cluster of unique C. botulinum type A strains of diverse origin.
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Geisinger, Edward; Chen, John; Novick, Richard P
2012-06-01
Agr is an autoinducing, quorum-sensing system that functions in many Gram-positive species and is best characterized in the pathogen Staphylococcus aureus, in which it is a global regulator of virulence gene expression. Allelic variations in the agr genes have resulted in the emergence of four quorum-sensing specificity groups in S. aureus, which correlate with different strain pathotypes. The basis for these predilections is unclear but is hypothesized to involve the phenomenon of quorum-sensing interference between strains of different agr groups, which may drive S. aureus strain isolation and divergence. Whether properties intrinsic to each agr allele directly influence virulence phenotypes within S. aureus is unknown. In this study, we examined group-specific differences in agr autoinduction and virulence gene regulation by utilizing congenic strains, each harboring a unique S. aureus agr allele, enabling a dissection of agr locus-dependent versus genotype-dependent effects on quorum-sensing dynamics and virulence factor production. Employing a reporter fusion to the principal agr promoter, P3, we observed allele-dependent differences in the timing and magnitude of agr activation. These differences were mediated by polymorphisms within the agrBDCA genes and translated to significant variations in the expression of a key transcriptional regulator, Rot, and of several important exoproteins and surface factors involved in pathogenesis. This work uncovers the contribution of divergent quorum-sensing alleles to variant expression of virulence determinants within a bacterial species.