Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway

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Fan, Yu [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Zhan, Qian [The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Xu, Hongying [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Li, Lili; Li, Chen [Cancer Epigenetics Laboratory, Department of Clinical Oncology, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong and CUHK Shenzhen Research Institute (Hong Kong); Xiao, Qian; Xiang, Shili; Hui, Tianli [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Xiang, Tingxiu, E-mail: larissaxiang@163.com [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Ren, Guosheng, E-mail: rengs726@126.com [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China)

2016-06-10

The KRAB–zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect on Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. -- Highlights: •Downregulated ZNF545 in MM tissues and cell lines and ectopic expression of ZNF545 suppresses tumor growth. •Tumor-specific methylation of ZNF545 represents an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. •ZNF545 exerts its tumor suppressive effects via transcriptional activating p53 pathway.

Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway

International Nuclear Information System (INIS)

Fan, Yu; Zhan, Qian; Xu, Hongying; Li, Lili; Li, Chen; Xiao, Qian; Xiang, Shili; Hui, Tianli; Xiang, Tingxiu; Ren, Guosheng

2016-01-01

The KRAB–zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect on Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. -- Highlights: •Downregulated ZNF545 in MM tissues and cell lines and ectopic expression of ZNF545 suppresses tumor growth. •Tumor-specific methylation of ZNF545 represents an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. •ZNF545 exerts its tumor suppressive effects via transcriptional activating p53 pathway.

Exome sequencing identifies ZNF644 mutations in high myopia.

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Yi Shi

2011-06-01

Full Text Available Myopia is the most common ocular disorder worldwide, and high myopia in particular is one of the leading causes of blindness. Genetic factors play a critical role in the development of myopia, especially high myopia. Recently, the exome sequencing approach has been successfully used for the disease gene identification of Mendelian disorders. Here we show a successful application of exome sequencing to identify a gene for an autosomal dominant disorder, and we have identified a gene potentially responsible for high myopia in a monogenic form. We captured exomes of two affected individuals from a Han Chinese family with high myopia and performed sequencing analysis by a second-generation sequencer with a mean coverage of 30× and sufficient depth to call variants at ∼97% of each targeted exome. The shared genetic variants of these two affected individuals in the family being studied were filtered against the 1000 Genomes Project and the dbSNP131 database. A mutation A672G in zinc finger protein 644 isoform 1 (ZNF644 was identified as being related to the phenotype of this family. After we performed sequencing analysis of the exons in the ZNF644 gene in 300 sporadic cases of high myopia, we identified an additional five mutations (I587V, R680G, C699Y, 3'UTR+12 C>G, and 3'UTR+592 G>A in 11 different patients. All these mutations were absent in 600 normal controls. The ZNF644 gene was expressed in human retinal and retinal pigment epithelium (RPE. Given that ZNF644 is predicted to be a transcription factor that may regulate genes involved in eye development, mutation may cause the axial elongation of eyeball found in high myopia patients. Our results suggest that ZNF644 might be a causal gene for high myopia in a monogenic form.

ZNF649, a novel Kruppel type zinc-finger protein, functions as a transcriptional suppressor

International Nuclear Information System (INIS)

Yang Hong; Yuan Wuzhou; Wang Ying; Zhu Chuanbing; Liu Bisheng; Wang Yuequn; Yang, Dan; Li Yongqing; Wang Canding; Wu Xiushan; Liu Mingyao

2005-01-01

Cardiac differentiation involves a cascade of coordinated gene expression that regulates cell proliferation and matrix protein formation in a defined temporo-spatial manner. Many of the KRAB-ZFPs are involved in cardiac development or cardiovascular diseases. Here we report the identification and characterization of a novel human zinc-finger gene named ZNF649. The cDNA of ZNF649 is 3176 bp, encoding a protein of 505 amino acids in the nuclei. Northern blot analysis indicates that ZNF649 is expressed in most of the examined human adult and embryonic tissues. ZNF649 is a transcription suppressor when fused to GAL-4 DNA-binding domain and cotransfected with VP-16. Overexpression of ZNF649 in COS-7 cells inhibits the transcriptional activities of SRE and AP-1. Deletion analysis with a series of truncated fusion proteins indicates that the KRAB motif is a basal repression domain when the truncated fusion proteins were assayed for the transcriptional activities of SRE and AP-1. These results suggest that ZNF649 protein may act as a transcriptional repressor in mitogen-activated protein kinase signaling pathway to mediate cellular functions

Spermatogenesis-related ring finger gene ZNF230 promoter: identification and functional analysis

DEFF Research Database (Denmark)

Xu, Wenming; Zhang, Sizhong; Qiu, Weimin

2009-01-01

reporter Plasmids. Overexpression and site-directed mutation test were used to characterize the cis-element. The results showed ZNF230 gene promoter to be GC rich and not contain a TATA box. Deletion analysis of the 5'-flanking region of ZNF230 in HEK293 cells indicated that the sequence encompassing from...... nt -131 to +152 has a basal transcriptional activity. Site-directed mutation test and mithramycin A treatment demonstrated that the ZNF230 promoter contained a functional Sp1 site. Overexpression of the Sox5 protein activated the promoter activity. A 312-bp fragment surrounding the transcription...

Identification of a novel zinc finger protein gene (ZNF298) in the GAP2 of human chromosome 21q

International Nuclear Information System (INIS)

Shibuya, Kazunori; Kudoh, Jun; Okui, Michiyo; Shimizu, Nobuyoshi

2005-01-01

We have isolated a novel zinc finger protein gene, designated ZNF298, as a candidate gene for a particular phenotype of Down syndrome or bipolar affective disorder (BPAD) which maps to human chromosome 21q22.3. ZNF298 gene consists of 25 exons spanning approximately 80 kb in a direction from the telomere to centromere. There are four kinds of transcripts that harbor three types of 3' UTR. These four transcripts (ZNF298a, ZNF298b, ZNF298c, and ZNF298d) contain putative open reading frames encoding 1178, 1198, 555, and 515 amino acids, respectively. ZNF298 gene was ubiquitously expressed in various tissues at very low level. The protein motif analysis revealed that ZNF298 proteins contain a SET [Su(var)3-9, Enhancer-of-zeste, Trithorax] domain, multiple C2H2-type zinc finger (ZnF C 2H2) domains, several nuclear localization signals (NLSs), and PEST sequences. Nuclear localization of ZNF298 protein was confirmed by transfection of expression vector of GFP-tagged protein into two human cell lines. Interestingly, this gene crosses over a clone gap (GAP2) remaining in the band 21q22.3. We obtained the DNA fragments corresponding to GAP2 using ZNF298 cDNA sequence as anchor primers for PCR and determined its genomic DNA sequence

ZNF804A Transcriptional Networks in Differentiating Neurons Derived from Induced Pluripotent Stem Cells of Human Origin.

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Jian Chen

Full Text Available ZNF804A (Zinc Finger Protein 804A has been identified as a candidate gene for schizophrenia (SZ, autism spectrum disorders (ASD, and bipolar disorder (BD in replicated genome wide association studies (GWAS and by copy number variation (CNV analysis. Although its function has not been well-characterized, ZNF804A contains a C2H2-type zinc-finger domain, suggesting that it has DNA binding properties, and consequently, a role in regulating gene expression. To further explore the role of ZNF804A on gene expression and its downstream targets, we used a gene knockdown (KD approach to reduce its expression in neural progenitor cells (NPCs derived from induced pluripotent stem cells (iPSCs. KD was accomplished by RNA interference (RNAi using lentiviral particles containing shRNAs that target ZNF804A mRNA. Stable transduced NPC lines were generated after puromycin selection. A control cell line expressing a random (scrambled shRNA was also generated. Neuronal differentiation was induced, RNA was harvested after 14 days and transcriptome analysis was carried out using RNA-seq. 1815 genes were found to be differentially expressed at a nominally significant level (p<0.05; 809 decreased in expression in the KD samples, while 1106 increased. Of these, 370 achieved genome wide significance (FDR<0.05; 125 were lower in the KD samples, 245 were higher. Pathway analysis showed that genes involved in interferon-signaling were enriched among those that were down-regulated in the KD samples. Correspondingly, ZNF804A KD was found to affect interferon-alpha 2 (IFNA2-mediated gene expression. The findings suggest that ZNF804A may affect a differentiating neuron's response to inflammatory cytokines, which is consistent with models of SZ and ASD that support a role for infectious disease, and/or autoimmunity in a subgroup of patients.

Zinc finger protein 219-like (ZNF219L) and Sox9a regulate synuclein-γ2 (sncgb) expression in the developing notochord of zebrafish.

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Lien, Huang-Wei; Yang, Chung-Hsiang; Cheng, Chia-Hsiung; Liao, Yung-Feng; Han, Yu-San; Huang, Chang-Jen

2013-12-13

Zebrafish synuclein-γ2 (sncgb) has been reported to be expressed specifically in the notochord. However, the mechanism by which the sncgb gene promoter is regulated has not been described. In this paper, we demonstrate that Zinc finger protein 219-like (ZNF219L) and sox9a are involved in the regulation of sncgb gene expression. Furthermore, we observed that over-expression of both ZNF219L and Sox9a resulted in increased sncgb expression. In addition, ZNF219L is physically associated with Sox9a, and simultaneous morpholino knockdown of znf219L and sox9a caused a synergistic decrease of sncgb expression in the notochord. Taken together, our results reveal that coordination of ZNF219L with Sox9a is involved in the regulation of notochord-specific expression of sncgb. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

ZNF804A risk allele is associated with relatively intact gray matter volume in patients with schizophrenia.

LENUS (Irish Health Repository)

Donohoe, Gary

2011-02-01

ZNF804A rs1344706 is the first genetic risk variant to achieve genome wide significance for psychosis. Following earlier evidence that patients carrying the ZNF804A risk allele had relatively spared memory function compared to patient non-carriers, we investigated whether ZNF804A was also associated with variation in brain volume. In a sample of 70 patients and 38 healthy participants we used voxel based morphometry to compare homozygous (AA) carriers of the ZNF804A risk allele to heterozygous and homozygous (AC\\/CC) non-carriers for both whole brain volume and specific regions implicated in earlier ZNF804A studies-the dorsolateral pre-frontal cortex, the hippocampus, and the amygdala. For patients, but not for controls, we found that homozygous \\'AA\\' risk carriers had relatively larger gray matter volumes than heterozygous\\/homozygous non-carriers (AC\\/CC), particularly for hippocampal volumes. These data are consistent with our earlier behavioral data and suggest that ZNF804A is delineating a schizophrenia subtype characterized by relatively intact brain volume. Establishing if this represents a discrete molecular pathogenesis with consequences for nosology and treatment will be an important next step in understanding ZNF084A\\'s role in illness risk.

Probing the (110)-Oriented plane of rutile ZnF2: A DFT investigation

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Tamijani, Ali Abbaspour; Ebrahimiaqda, Elham

2017-12-01

For many years, rutile-like crystals have given rise to pronounced enthusiasm amongst mineralogists. In this context, rutile-type ZnF2 has found numerous applications across a variety of disciplines, ranging from material sciences to optoelectronics. Surprisingly, very limited literature is concerned with the molecular adsorption on ZnF2 surfaces and related energetics. Additionally, surface probing with small particles is a well-entrenched technique to analyze the interfacial properties. In this regard, small organic species are valuable picks. In the present work, we have employed electronic structure calculations to simulate the adsorption of methane, chloroform, pyrrole, benzene, naphthalene, anthracene, tetracene and pentacene at the (110) plane of rutile ZnF2. Dispersion-corrected DFT method was chosen to predict the binding energies and structures of molecule-adsorbed surfaces. Interestingly, a linear proportionality relationship was found between the binding energies of aromatic adsorbates and their respective molecular lengths. By applying this relationship, we were able to predict the adsorption energy of pentacene on ZnF2 to within 2% of our DFT-based result.

High expression of ZNF703 independent of amplification indicates worse prognosis in patients with luminal B breast cancer

International Nuclear Information System (INIS)

Reynisdottir, Inga; Arason, Adalgeir; Einarsdottir, Berglind O; Gunnarsson, Haukur; Staaf, Johan; Vallon-Christersson, Johan; Jonsson, Goran; Ringnér, Markus; Agnarsson, Bjarni A; Olafsdottir, Kristrun; Fagerholm, Rainer; Einarsdottir, Thorbjorg; Johannesdottir, Gudrun; Johannsson, Oskar Thor; Nevanlinna, Heli; Borg, Ake; Barkardottir, Rosa Bjork

2013-01-01

Amplification of 8p12-p11 is relatively common in breast cancer and several genes within the region have been suggested to affect breast tumor progression. The aim of the study was to map the amplified 8p12-p11 region in a large set of breast tumors in an effort to identify the genetic driver and to explore its impact on tumor progression and prognosis. Copy number alterations (CNAs) were mapped in 359 tumors, and gene expression data from 577 tumors (359 tumors included) were correlated with CNA, clinical–pathological factors, and protein expression (39 tumors). 8p12-p11 was amplified in 11.4% of tumors. The smallest region of amplification harbored one full-length gene, ZNF703. ZNF703 mRNA expression was significantly higher in estrogen receptor (ER)-positive than ER-negative tumors (P = 2 × 10 −16 ), a reflection of high expression in luminal tumors. Forty-eight percent of tumors with ZNF703 amplification were luminal B tumors in which the best correlation between DNA copy number and mRNA was seen (P = 1.2 × 10 −7 ) as well as correlation between mRNA and protein expression (P = 0.02). High ZNF703 mRNA correlated with poor survival in patients with ER-positive luminal B tumors (log rank P = 0.04). Furthermore, high ZNF703 mRNA expression correlated with poor outcome in patients with ZNF703 copy number neutral, ER-positive, luminal B tumors (log rank P = 0.004). The results support ZNF703 as the driver gene of the 8p12 amplification and suggest that independent of amplification, high expression of the gene affects prognosis in luminal B tumors. Our mapping of 8p12-p11 and analyses of ZNF703 mRNA and protein expression in breast tumors support ZNF703 as an oncogene in luminal B tumors. High ZNF703 expression, independent of the amplification, correlated with worse prognosis for the breast cancer patients with ER-positive luminal tumors, particularly of the luminal B subtype

Novel Variants in ZNF34 and Other Brain-Expressed Transcription Factors are Shared Among Early-Onset MDD Relatives

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Subaran, Ryan L.; Odgerel, Zagaa; Swaminathan, Rajeswari; Glatt, Charles E.; Weissman, Myrna M.

2018-01-01

There are no known genetic variants with large effects on susceptibility to major depressive disorder (MDD). Although one proposed study approach is to increase sensitivity by increasing sample sizes, another is to focus on families with multiple affected individuals to identify genes with rare or novel variants with strong effects. Choosing the family-based approach, we performed whole-exome analysis on affected individuals (n = 12) across five MDD families, each with at least five affected individuals, early onset, and prepubertal diagnoses. We identified 67 genes where novel deleterious variants were shared among affected relatives. Gene ontology analysis shows that of these 67 genes, 18 encode transcriptional regulators, eight of which are expressed in the human brain, including four KRAB-A box-containing Zn2+ finger repressors. One of these, ZNF34, has been reported as being associated with bipolar disorder and as differentially expressed in bipolar disorder patients compared to healthy controls. We found a novel variant—encoding a non-conservative P17R substitution in the conserved repressor domain of ZNF34 protein—segregating completely with MDD in all available individuals in the family in which it was discovered. Further analysis showed a common ZNF34 coding indel segregating with MDD in a separate family, possibly indicating the presence of an unobserved, linked, rare variant in that particular family. Our results indicate that genes encoding transcription factors expressed in the brain might be an important group of MDD candidate genes and that rare variants in ZNF34 might contribute to susceptibility to MDD and perhaps other affective disorders. PMID:26823146

The ZNF75 zinc finger gene subfamily: Isolation and mapping of the four members in humans and great apes

Energy Technology Data Exchange (ETDEWEB)

Villa, A.; Strina, D.; Frattini, A. [Consiglio Nazionale delle Ricerche, Milan (Italy)] [and others

1996-07-15

We have previously reported the characterization of the human ZNF75 gene located on Xq26, which has only limited homology (less than 65%) to other ZF genes in the databases. Here, we describe three human zinc finger genes with 86 to 95% homology to ZNF75 at the nucleotide level, which represent all the members of the human ZNF75 subfamily. One of these, ZNF75B, is a pseudogene mapped to chromosome 12q13. The other two, ZNF75A and ZNF75C, maintain on ORF in the sequenced region, and at least the latter is expressed in the U937 cell line. They were mapped to chromosomes 16 and 11, respectively. All these genes are conserved in chimpanzees, gorillas, and orangutans. The ZNF75B homologue is a pseudogene in all three great apes, and in chimpanzee it is located on chromosome 10 (phylogenetic XII), at p13 (corresponding to the human 12q13). The chimpanzee homologue of ZNF75 is also located on the Xq26 chromosome, in the same region, as detected by in situ hybridization. As expected, nucleotide changes were clearly more abundant between human and organutan than between human and chimpanzee or gorilla homologues. Members of the same class were more similar to each other than to the other homologues within the same species. This suggests that the duplication and/or retrotranscription events occurred in a common ancestor long before great ape speciation. This, together with the existance of at least two genes in cows and horses, suggests a relatively high conservation of this gene family. 20 refs., 5 figs., 1 tab.

Activation of transcriptional activities of AP-1 and SRE by a new zinc-finger protein ZNF641

International Nuclear Information System (INIS)

Qi Xingzhu; Li Yongqing; Xiao Jing; Yuan Wuzhou; Yan Yan; Wang Yuequn; Liang Shuyuan; Zhu Chuanbing; Chen Yingduan; Liu Mingyao; Wu Xiushan

2006-01-01

Mitogen-activated protein kinases (MAPKs) are evolutionarily conserved enzymes in cell signal transduction connecting cell-surface receptors to critical regulatory targets within cells and control cell survival, adaptation, and proliferation. Previous studies revealed that zinc-finger proteins are involved in the regulation of the MAPK signaling pathways. Here, we report the identification and characterization of a novel human zinc-finger protein, ZNF641. The cDNA of ZNF641 is 4.9 kb, encoding 438 amino acids in the nucleus. The protein is highly conserved in evolution across different vertebrate species from mouse to human. Northern blot analysis indicates that ZNF641 is expressed in most of the examined human tissues, with a high level in skeletal muscle. Overexpression of pCMV-Tag2B-ZNF641 in the COS-7 cells activates the transcriptional activities of AP-1 and SRE. Deletion analysis indicates that the linker between KRAB box and C 2 H 2 -type zinc-fingers represents the basal activation domain. These results suggest that ZNF641 may be a positive regulator in MAPK-mediated signaling pathways that lead to the activation of AP-1 and SRE

ZNF328, a novel human zinc-finger protein, suppresses transcriptional activities of SRE and AP-1

International Nuclear Information System (INIS)

Ou Ying; Wang Shenqiu; Cai Zhenyu; Wang Yuequn; Wang Canding; Li Yongqing; Li Fang; Yuan Wuzhou; Liu Bisheng; Wu Xiushan; Liu Mingyao

2005-01-01

The zinc finger proteins containing the Kruppel-associated box domain (KRAB-ZFPs) are the single largest class of transcription factors in human genome. Many of the KRAB-ZFPs are involved in cardiac development or cardiovascular diseases. Here, we have identified a novel human KRAB zinc finger gene, named ZNF328, from the human fetal heart cDNA library. The complete sequence of ZNF328 cDNA contains a 2376-bp open reading frame (ORF) and encodes a 792 amino acid protein with an N-terminal KRAB domain and classical zinc finger C 2 H 2 motifs in the C-terminus. Northern blot analysis indicates that the protein is expressed in most of the examined human adult and embryonic tissues. ZNF328 is a transcription suppressor when fused to Gal-4 DNA-binding domain and cotransfected with VP-16. Overexpression of ZNF328 in COS-7 cells inhibits the transcriptional activities of SRE and AP-1. Deletion analysis with a series of truncated fusion proteins indicates that the KRAB motif is a basal repression domain when cotransfected with VP-16. Similar results were obtained when the truncated fusion proteins were assayed for the transcriptional activities of SRE and AP-1. These results suggest that ZNF328 protein may act as a transcriptional repressor in mitogen-activated protein kinase (MAPK) signaling pathway to mediate cellular functions

Elevated ZNF703 Protein Expression Is an Independent Unfavorable Prognostic Factor for Survival of the Patients with Head and Neck Squamous Cell Carcinoma

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Hang Yang

2015-01-01

Full Text Available Aim. Data from The Cancer Genome Atlas (TCGA show that the ZNF703 gene amplifies and overexpresses in head and neck squamous cell carcinomas (HNSCC. However, the clinical relevance of this observation in HNSCC is unclear. The purpose of this study was to clarify the expression of ZNF703 protein and its prognostic effect on HNSCC. Methods. Two hundred ten HNSCC patients from Sun Yat-Sen University Cancer Center with complete survival follow-up were included in this study. Tumor samples from primary sites were collected. The expression of the ZNF703 protein was tested by immunohistochemistry (IHC. Results. The high expression of ZNF703 in HNSCC tumor tissues was significantly higher than that of the matched noncancerous tissues (48.6% versus 11.6%, P<0.001. ZNF703 overexpression was correlated with tumor position (laryngeal carcinoma and recurrence (all P<0.05. Multivariate analysis revealed that ZNF703 protein overexpression was an independent prognostic factor (P=0.022, hazard ratio = 1.635, 95% CI 1.073–2.493 in HNSCC patients. Conclusion. ZNF703 overexpression is associated with adverse prognosis in HNSCC, which might be a novel biomarker of HNSCC.

Genetic variations in the CLNK gene and ZNF518B gene are associated with gout in case-control sample sets.

Science.gov (United States)

Jin, Tian-Bo; Ren, Yongchao; Shi, Xugang; Jiri, Mutu; He, Na; Feng, Tian; Yuan, Dongya; Kang, Longli

2015-07-01

A genome-wide association study of gout in European populations identified 12 genetic variants strongly associated with risk of gout, but it is unknown whether these variants are also associated with gout risk in Chinese populations. A total of 145 patients with gout and 310 healthy control patients were recruited for a case-control association study. Twelve SNPs of CLNK and ZNF518B gene were genotyped, and association analysis was performed. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the association. Overall, we found four risk alleles for gout in patients: the allele "G" of rs2041215 and rs1686947 in the CLNK gene by dominant model (OR 1.66; 95 % CI 1.04-2.63; p = 0.031) (OR 2.19; 95 % CI 1.38-3.46; p = 0.001) and additive model (OR 1.39; 95 % CI 1.00-1.93; p = 0.049) (OR 1.67; 95 % CI 1.19-2.32; p = 0.003), respectively, and the allele "A" of rs10938799 and rs10016022 in ZNF518B gene by recessive model (OR 4.66; 95 % CI 1.44-15.09; p = 0.008) (OR 4.54; 95 % CI 1.23-16.76; p = 0.020). Further haplotype analysis showed that the TCATTCTGA haplotype of CLNK was more frequent among patients with gout (adjusted OR 0.48; 95 % CI 0.24-0.95; p = 0.036). Additionally, polymorphisms of rs2041215, rs10938799, and rs17467273 were also correlated with clinical pathological parameters. This study provides evidence for gout susceptibility genes, CLNK and ZNF518B, in a Chinese population, which may have potential as diagnostic and prognostic marker for gout patients.

The schizophrenia risk gene ZNF804A influences the antipsychotic response of positive schizophrenia symptoms

OpenAIRE

Mössner, R; Schumacher, A; Wagner, M; Lennertz, L; Steinbrecher, A; Quednow, Boris B; Rujescu, D; Rietschel, M; Maier, W

2012-01-01

Genetic factors determining the response to antipsychotic treatment in schizophrenia are poorly understood. A new schizophrenia susceptibility gene, the zinc-finger gene ZNF804A, has recently been identified. To assess the pharmacogenetic importance of this gene, we treated 144 schizophrenia patients and assessed the response of positive and negative symptoms by PANSS. Patients homozygous for the ZNF804A risk allele for schizophrenia (rs1344706 AA) showed poorer improvement of positive sympto...

Sphingosine-1-phosphate induces human endothelial VEGF and MMP-2 production via transcription factor ZNF580: Novel insights into angiogenesis

Energy Technology Data Exchange (ETDEWEB)

Sun, Hui-Yan, E-mail: shy35309@sohu.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China); Wei, Shu-Ping, E-mail: weishuping_83@163.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China); Xu, Rui-Cheng, E-mail: xu_rc@sohu.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China); Xu, Peng-Xiao, E-mail: xupengxiao1228@sina.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China); Zhang, Wen-Cheng, E-mail: wenchengzhang@yahoo.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China)

2010-05-07

Sphingosine-1-phosphate (S1P)-induced migration and proliferation of endothelial cells are critical for angiogenesis. C2H2-zinc finger (ZNF) proteins usually play an essential role in altering gene expression and regulating the angiogenesis. The aim of this study is to investigate whether a novel human C2H2-zinc finger gene ZNF580 (Gene ID: 51157) is involved in the migration and proliferation of endothelial cells stimulated by S1P. Our study shows that EAhy926 endothelial cells express S1P1, S1P3 and S1P5 receptors. Furthermore, S1P upregulates both ZNF580 mRNA and protein levels in a concentration- and time-dependent manner. SB203580, the specific inhibitor of the p38 mitogen-activated protein kinase (p38 MAPK) pathway, blocks the S1P-induced upregulation of ZNF580. Moreover, overexpression/downexpression of ZNF580 in EAhy926 cells leads to the enhancement/decrease of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) expression as well as the migration and proliferation of EAhy926 endothelial cells. These results elucidate the important role that ZNF580 plays in the process of migration and proliferation of endothelial cells, which provides a foundation for a novel approach to regulate angiogenesis.

Sphingosine-1-phosphate induces human endothelial VEGF and MMP-2 production via transcription factor ZNF580: Novel insights into angiogenesis

International Nuclear Information System (INIS)

Sun, Hui-Yan; Wei, Shu-Ping; Xu, Rui-Cheng; Xu, Peng-Xiao; Zhang, Wen-Cheng

2010-01-01

Sphingosine-1-phosphate (S1P)-induced migration and proliferation of endothelial cells are critical for angiogenesis. C2H2-zinc finger (ZNF) proteins usually play an essential role in altering gene expression and regulating the angiogenesis. The aim of this study is to investigate whether a novel human C2H2-zinc finger gene ZNF580 (Gene ID: 51157) is involved in the migration and proliferation of endothelial cells stimulated by S1P. Our study shows that EAhy926 endothelial cells express S1P1, S1P3 and S1P5 receptors. Furthermore, S1P upregulates both ZNF580 mRNA and protein levels in a concentration- and time-dependent manner. SB203580, the specific inhibitor of the p38 mitogen-activated protein kinase (p38 MAPK) pathway, blocks the S1P-induced upregulation of ZNF580. Moreover, overexpression/downexpression of ZNF580 in EAhy926 cells leads to the enhancement/decrease of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) expression as well as the migration and proliferation of EAhy926 endothelial cells. These results elucidate the important role that ZNF580 plays in the process of migration and proliferation of endothelial cells, which provides a foundation for a novel approach to regulate angiogenesis.

The Rat Homolog of the Schizophrenia Susceptibility Gene ZNF804A Is Highly Expressed during Brain Development, Particularly in Growth Cones.

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Katja Hvid Hinna

Full Text Available A single nucleotide polymorphism in the ZNF804A gene, rs1344706, is associated with schizophrenia. The polymorphism has been suggested to alter fetal expression of ZNF804A. It has also been reported to be associated with altered cortical functioning and neural connectivity in the brain. Since developmental mechanisms are suggested in the pathophysiology for schizophrenia, expression of Zfp804A, the rat homolog of ZNF804A, was investigated in the developing rat brain. We found that expression of Zfp804A in most brain regions is developmentally regulated and peaks around birth, where after it decreases towards adult levels. This time point is developmentally the equivalent to the second trimester of fetal development in humans. An exception to this expression pattern is the hippocampus where the expression of Zfp804A appears to increase again in the adult brain. Using laser capture and quantitative PCR we found that Zfp804A mRNA expression in the adult rat hippocampus is highest in the CA1 sub region, where the overall firing rates of neurons is higher than in the CA3 region. In cultured cortical neurons Zfp804A mRNA expression peaked at day 4 and then decreased. The ZFP804A protein expression was therefore investigated with immunochemistry in such cultures. Interestingly, before day 4, the protein is mostly found in the perinuclear region of the cell but at day 4, ZFP804A was instead found throughout the cell and particularly in the growth cones. In conclusion we demonstrate that Zfp804A increases in the rat brain at the time of birth, coinciding with neuronal differentiation. We also show that ZFP804A is localized to growth cones of growing neurites. These data implicate ZFP804A in growth cone function and neurite elongation. The polymorphism rs1344706 lowers expression of ZNF804A during prenatal brain development. This may affect ZNF804A's role in cone function and neurite elongation leading to synaptic deficits and altered neural connectivity.

Downregulation of ZNF132 in prostate cancer is associated with aberrant promoter hypermethylation and poor prognosis

DEFF Research Database (Denmark)

Abildgaard, Mette Opstrup; Borre, Michael; Mørck Mortensen, Martin

2012-01-01

This study investigates the expression and biomarker potential of zinc finger protein 132 (ZNF132) in prostate cancer (PC) by transcriptional profiling and immunohistochemical analysis of tissue microarrays, including tumor specimens from 615 radical prostatectomy (RP) patients and 199...... conservatively treated patients. Primary clinical endpoints were time to PSA recurrence and cancer-specific death, respectively. Compared to normal prostate epithelial cells from men without PC, ZNF132 transcript levels were significantly reduced in PC cells from patients with localized PC and further...... immunoreactivity was significantly associated with high Gleason score and advanced T stage in both PC patient cohorts. By univariate analysis, no/weak ZNF132 staining was a significant adverse predictor of PSA recurrence after RP (p = 0.024) and cancer-specific death following conservative treatment (p = 0...

High-throughput cell-based screening reveals a role for ZNF131 as a repressor of ERalpha signaling

Directory of Open Access Journals (Sweden)

Du Peige

2008-10-01

Full Text Available Abstract Background Estrogen receptor α (ERα is a transcription factor whose activity is affected by multiple regulatory cofactors. In an effort to identify the human genes involved in the regulation of ERα, we constructed a high-throughput, cell-based, functional screening platform by linking a response element (ERE with a reporter gene. This allowed the cellular activity of ERα, in cells cotransfected with the candidate gene, to be quantified in the presence or absence of its cognate ligand E2. Results From a library of 570 human cDNA clones, we identified zinc finger protein 131 (ZNF131 as a repressor of ERα mediated transactivation. ZNF131 is a typical member of the BTB/POZ family of transcription factors, and shows both ubiquitous expression and a high degree of sequence conservation. The luciferase reporter gene assay revealed that ZNF131 inhibits ligand-dependent transactivation by ERα in a dose-dependent manner. Electrophoretic mobility shift assay clearly demonstrated that the interaction between ZNF131 and ERα interrupts or prevents ERα binding to the estrogen response element (ERE. In addition, ZNF131 was able to suppress the expression of pS2, an ERα target gene. Conclusion We suggest that the functional screening platform we constructed can be applied for high-throughput genomic screening candidate ERα-related genes. This in turn may provide new insights into the underlying molecular mechanisms of ERα regulation in mammalian cells.

A CGG-repeat expansion mutation in ZNF713 causes FRA7A: association with autistic spectrum disorder in two families.

Science.gov (United States)

Metsu, Sofie; Rainger, Jacqueline K; Debacker, Kim; Bernhard, Birgitta; Rooms, Liesbeth; Grafodatskaya, Daria; Weksberg, Rosanna; Fombonne, Eric; Taylor, Martin S; Scherer, Stephen W; Kooy, R Frank; FitzPatrick, David R

2014-11-01

We report de novo occurrence of the 7p11.2 folate-sensitive fragile site FRA7A in a male with an autistic spectrum disorder (ASD) due to a CGG-repeat expansion mutation (∼450 repeats) in a 5' intron of ZNF713. This expanded allele showed hypermethylation of the adjacent CpG island with reduced ZNF713 expression observed in a proband-derived lymphoblastoid cell line (LCL). His unaffected mother carried an unmethylated premutation (85 repeats). This CGG-repeat showed length polymorphism in control samples (five to 22 repeats). In a second unrelated family, three siblings with ASD and their unaffected father were found to carry FRA7A premutations, which were partially or mosaically methylated. In one of the affected siblings, mitotic instability of the premutation was observed. ZNF713 expression in LCLs in this family was increased in three of these four premutation carriers. A firm link cannot yet be established between ASD and the repeat expansion mutation but plausible pathogenic mechanisms are discussed. © 2014 WILEY PERIODICALS, INC.

An X-linked homologue of the autosomal inprinted gene ZNF127 escapes X inactivation

Energy Technology Data Exchange (ETDEWEB)

Longstreet, M.; Nicholls, R.D.; Willard, H.F. [Case Western Reserve Univ., Cleveland, OH (United States)] [and others

1994-09-01

The ZNF127 gene has been shown to be subject to parental imprinting in both humans and the mouse and maps to within the Prader-Willi/Angelman Syndrome critical region on chromosome 15. We have cloned two X-linked related loci, one of which, ZNFXp is a transcribed gene while the other, ZNFXq, is an untranscribed pseudogene. ZNFXp is 83.6% identical to ZNFXq and 65.4% identical to ZNF127 over 1.4 kb of open reading frame they share in common, Like ZNF127, the predicted protein sequence of ZNFXp contains a C{sub 3}HC{sub 4} zinc finger domain and C{sub 3}H zinc finger-like motifs. Whereas ZNF127 has three C{sub 3}H motifs, ZNFXp has four. A strong CpG island is located within 1 kb 5{prime} of the predicted amino terminus of ZNFXp. Expression of ZNFXp has been detected from mouse/human somatic cell hybrids containing either an active (n=2) or an inactive (n=4) chromosome, and thus escapes X inactivation. Probes made from the 3{prime} UTR of ZNFXp detect a number of related loci in both human and murine DNA, none of which is the ZNF127 locus on chromosome 15. None of the detectable murine bands shows dosage differences between males and females as would be expected for X-linked loci. This raises the possibility that ZNFXp inserted into the human X chromosome after its divergence from a common ancestor with the murine X. We have mapped ZNFXp to Xp11.4 by Southern blotting and PCR of hybrid DNAs and by fluorescence in situ hybridization (FISH). ZNFXq maps within the X Inactivation Center (XIC) region on Xq13.2, approximately 300 kb distal to the XIST gene. We find it intriguing, and perhaps significant, that two members of this gene family are subject to epigenetic regulation -- one autosomal imprinting, and the other escape from X inactivation. These results could imply an evolutionary and mechanistic relationship between these two processes.

Moessbauer spectroscopy at the 93.3 KeV gamma transition at Zn-67

International Nuclear Information System (INIS)

Forster, A.

1981-01-01

This work presents the result of a Moessbauer effect study at the zinc-67 isotope. The 93.3 KeV gamma transition has the highest energy resolution of all accessible Moessbauer transitions. Source and absorber we cooled down to 4.2 K. The aim of the examination was 1) development of a method for solid state physical measuring of Moessbauer-resonances with high resolution and 2) to test this method to study the hfs parameters for ZnO, ZnS, ZnSe, ZnTe and ZnF 2 . (KHF)

ZNF322, a novel human C2H2 Krueppel-like zinc-finger protein, regulates transcriptional activation in MAPK signaling pathways

International Nuclear Information System (INIS)

Li Yongqing; Wang Yuequn; Zhang Caibo; Yuan Wuzhou; Wang Jun; Zhu Chuanbing; Chen Lei; Huang Wen; Zeng Weiqi; Wu Xiushan; Liu Mingyao

2004-01-01

Cardiac differentiation involves a cascade of coordinated gene expression that regulates cell proliferation and matrix protein formation in a defined temporal-spatial manner. The C 2 H 2 zinc finger-containing transcription factors have been implicated as critical regulators of multiple cardiac-expressed genes and are important for human heart development and diseases. Here we have identified and characterized a novel zinc-finger gene named ZNF322 using degenerated primers from a human embryo heart cDNA library. The gene contains four exons and spans 23.2 kb in chromosome 6p22.1 region, and transcribes a 2.7 kb mRNA that encodes a protein with 402 amino acid residues. The predicted protein contains 9 tandem C 2 H 2 -type zinc-finger motifs. Northern blot analysis shows that ZNF322 is expressed in every human tissue examined at adult stage and during embryonic developmental stages from 80 days to 24 weeks. When overexpressed in COS-7 cells, ZNF322-EGFP fusion protein is detected in the nucleus and cytoplasm. Reporter gene assays show that ZNF322 is a transcriptional activator. Furthermore, overexpression of ZNF322 in COS-7 cells activates the transcriptional activity of SRE and AP-1. Together, these results suggest that ZNF322 is a member of the zinc-finger transcription factor family and may act as a positive regulator in gene transcription mediated by the MAPK signaling pathways

The genome-wide associated candidate gene ZNF804A and psychosis-proneness: Evidence of sex-modulated association.

Directory of Open Access Journals (Sweden)

Marta de Castro-Catala

Full Text Available The Zinc finger protein 804A (ZNF804A is a promising candidate gene for schizophrenia and the broader psychosis phenotype that emerged from genome-wide association studies. It is related to neurodevelopment and associated to severe symptoms of schizophrenia and alterations in brain structure, as well as positive schizotypal personality traits in non-clinical samples. Moreover, a female-specific association has been observed between ZNF804A and schizophrenia.The present study examined the association of two ZNF804A polymorphisms (rs1344706 and rs7597593 with the positive dimension of schizotypy and psychotic-like experiences in a sample of 808 non-clinical subjects. Additionally, we wanted to explore whether the sexual differences reported in schizophrenia are also present in psychosis-proneness.Our results showed an association between rs7597593 and both schizotypy and psychotic-like experiences. These associations were driven by females, such those carrying the C allele had higher scores in the positive dimension of both variables compared to TT allele homozygotes.The findings of the present study support the inclusion of ZNF804 variability in studies of the vulnerability for the development of psychopathology in non-clinical samples and consideration of sex as a moderator of this association.

SLC2A9 and ZNF518B polymorphisms correlate with gout-related metabolic indices in Chinese Tibetan populations.

Science.gov (United States)

Zhang, X Y; Geng, T T; Liu, L J; Yuan, D Y; Feng, T; Kang, L L; Jin, T B; Chen, C

2015-08-19

Current evidence suggests that heredity and metabolic syndrome contribute to gout progression. SLC2A9 and ZNF518B may play a role in gout progression in different populations, but no studies have focused on the Tibetan Chinese population. In this study, we determined whether variations in these 2 genes were correlated with gout-related indices in Chinese-Tibetan gout patients. We detected 6 single nucleotide polymorphisms in SLC2A9 and ZNF518B in 319 Chinese Tibetan gout patients. One-way analysis of variance was used to evaluate the polymorphisms' effects on gout based on mean serum levels of metabolism indicators. Polymorphisms in SLC2A9 and ZNF518B affected multiple risk factors related to gout development. Significant differences in serum triglyceride levels and high-density lipoprotein-cholesterol level were detected between different genotypic groups with SLC2A9 polymorphisms rs13129697 (P = 0.022), rs4447863 (P = 0.018), and rs1014290 (P = 0.045). Similarly in ZNF518B, rs3217 (P = 0.016) and rs10016022 (P = 0.046) were associated with high creatinine and glucose levels, respectively. This study is the first to investigate and identify positive correlations between SLC2A9 and ZNF518B gene polymorphisms and metabolic indices in Tibetan gout patients. We found significant evidence indicating that genetic polymorphisms affect gout-related factors in Chinese Tibetan populations.

Hypoxia-inducible factors regulate pluripotency factor expression by ZNF217- and ALKBH5-mediated modulation of RNA methylation in breast cancer cells.

Science.gov (United States)

Zhang, Chuanzhao; Zhi, Wanqing Iris; Lu, Haiquan; Samanta, Debangshu; Chen, Ivan; Gabrielson, Edward; Semenza, Gregg L

2016-10-04

Exposure of breast cancer cells to hypoxia increases the percentage of breast cancer stem cells (BCSCs), which are required for tumor initiation and metastasis, and this response is dependent on the activity of hypoxia-inducible factors (HIFs). We previously reported that exposure of breast cancer cells to hypoxia induces the ALKBH5-mediated demethylation of N6-methyladenosine (m6A) in NANOG mRNA leading to increased expression of NANOG, which is a pluripotency factor that promotes BCSC specification. Here we report that exposure of breast cancer cells to hypoxia also induces ZNF217-dependent inhibition of m6A methylation of mRNAs encoding NANOG and KLF4, which is another pluripotency factor that mediates BCSC specification. Although hypoxia induced the BCSC phenotype in all breast-cancer cell lines analyzed, it did so through variable induction of pluripotency factors and ALKBH5 or ZNF217. However, in every breast cancer line, the hypoxic induction of pluripotency factor and ALKBH5 or ZNF217 expression was HIF-dependent. Immunohistochemistry revealed that expression of HIF-1α and ALKBH5 was concordant in all human breast cancer biopsies analyzed. ALKBH5 knockdown in MDA-MB-231 breast cancer cells significantly decreased metastasis from breast to lungs in immunodeficient mice. Thus, HIFs stimulate pluripotency factor expression and BCSC specification by negative regulation of RNA methylation.

GSTT1 copy number gain and ZNF overexpression are predictors of poor response to imatinib in gastrointestinal stromal tumors.

Directory of Open Access Journals (Sweden)

Eui Jin Lee

Full Text Available Oncogenic mutations in gastrointestinal stromal tumors (GISTs predict prognosis and therapeutic responses to imatinib. In wild-type GISTs, the tumor-initiating events are still unknown, and wild-type GISTs are resistant to imatinib therapy. We performed an association study between copy number alterations (CNAs identified from array CGH and gene expression analyses results for four wild-type GISTs and an imatinib-resistant PDGFRA D842V mutant GIST, and compared the results to those obtained from 27 GISTs with KIT mutations. All wild-type GISTs had multiple CNAs, and CNAs in 1p and 22q that harbor the SDHB and GSTT1 genes, respectively, correlated well with expression levels of these genes. mRNA expression levels of all SDH gene subunits were significantly lower (P≤0.041, whereas mRNA expression levels of VEGF (P=0.025, IGF1R (P=0.026, and ZNFs (P<0.05 were significantly higher in GISTs with wild-type/PDGFRA D842V mutations than GISTs with KIT mutations. qRT-PCR validation of the GSTT1 results in this cohort and 11 additional malignant GISTs showed a significant increase in the frequency of GSTT1 CN gain and increased mRNA expression of GSTT1 in wild-type/PDGFRA D842V GISTs than KIT-mutant GISTs (P=0.033. Surprisingly, all four malignant GISTs with KIT exon 11 deletion mutations with primary resistance to imatinib had an increased GSTT1 CN and mRNA expression level of GSTT1. Increased mRNA expression of GSTT1 and ZNF could be predictors of a poor response to imatinib. Our integrative approach reveals that for patients with wild-type (or imatinib-resistant GISTs, attempts to target VEGFRs and IGF1R may be reasonable options.

A novel zinc finger protein 219-like (ZNF219L) is involved in the regulation of collagen type 2 alpha 1a (col2a1a) gene expression in zebrafish notochord.

Science.gov (United States)

Lien, Huang-Wei; Yang, Chung-Hsiang; Cheng, Chia-Hsiung; Hung, Chin-Chun; Liao, Wei-Hao; Hwang, Pung-Pung; Han, Yu-San; Huang, Chang-Jen

2013-01-01

The notochord is required for body plan patterning in vertebrates, and defects in notochord development during embryogenesis can lead to diseases affecting the adult. It is therefore important to elucidate the gene regulatory mechanism underlying notochord formation. In this study, we cloned the zebrafish zinc finger 219-like (ZNF219L) based on mammalian ZNF219, which contains nine C2H2-type zinc finger domains. Through whole-mount in situ hybridization, we found that znf219L mRNA is mainly expressed in the zebrafish midbrain-hindbrain boundary, hindbrain, and notochord during development. The znf219L morpholino knockdown caused partial abnormal notochord phenotype and reduced expression of endogenous col2a1a in the notochord specifically. In addition, ZNF219L could recognize binding sites with GGGGG motifs and trigger augmented activity of the col2a1a promoter in a luciferase assay. Furthermore, in vitro binding experiments revealed that ZNF219L recognizes the GGGGG motifs in the promoter region of the zebrafish col2a1a gene through its sixth and ninth zinc finger domains. Taken together, our results reveal that ZNF219L is involved in regulating the expression of col2a1a in zebrafish notochord specifically.

[Effect of transcription activity regulated by VNTR-ZNF and -14C/T variants in the promoter region of ATP-binding cassette transporter 1 in HepG2 cells].

Science.gov (United States)

Gao, Shenxia; Zhao, Lili; Zhang, Ying; Mao, Yongmin

2016-10-01

To explore the effect of VNTR-ZNF and -14C/T variants of the promoter region of the ABCA1 gene on the transcription activity of genes in vitro. The recombinants were constructed by ligating DNA fragment containing VNTR-ZNF ACCCC inserted/deleted allele with or without -14C/T substitution fragments with a PGL2-basic vector containing luciferase reporter gene. The recombinants were then transfected into HepG2 cells using the cationic lipid method. After 48 h, transfected cells were collected and used to detect the luciferase activity. Luciferase activity of PGL2-ZNF-ACCCCDel was greater than that of PGL2-ZNF-ACCCCIns. Luciferase activity of PGL2-ZNFDel-14C was greater than that of PGL2-ZNFDel-14T, PGL2-ZNFIns-14C, PGL2-ZNFIns-14T. Compared with the insertion type, the ACCCC-deleted type of VNTR-ZNF can significantly enhance the transcription activity of ABCA1. And co-transfection of -14 C allele can further enhance this activity.

ZNF143 protein is an important regulator of the myeloid transcription factor C/EBP

Czech Academy of Sciences Publication Activity Database

Gonzalez, D.; Luyten, A.; Bartholdy, B.; Zhou, Q.; Kardošová, Miroslava; Ebralidze, A.; Swanson, K.D.; Radomska, H.S.; Zhang, P.; Kobayashi, S.S.; Welner, R.S.; Levantini, E.; Steidl, U.; Chong, G.; Collombet, S.; Choi, M.H.; Friedman, A.D.; Scott, L.M.; Alberich-Jorda, Meritxell; Tenen, D.G.

2017-01-01

Roč. 292, č. 46 (2017), s. 18924-18936 ISSN 0021-9258 Institutional support: RVO:68378050 Keywords : CCAAT-enhancer-binding protein * gene regulation * hematopoiesis * promoter * transcription factor * EBPalpha * ZNF143 Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 4.125, year: 2016

Zinc finger protein 598 inhibits cell survival by promoting UV-induced apoptosis.

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Yang, Qiaohong; Gupta, Romi

2018-01-19

UV is one of the major causes of DNA damage induced apoptosis. However, cancer cells adopt alternative mechanisms to evade UV-induced apoptosis. To identify factors that protect cancer cells from UV-induced apoptosis, we performed a genome wide short-hairpin RNA (shRNA) screen, which identified Zinc finger protein 598 (ZNF598) as a key regulator of UV-induced apoptosis. Here, we show that UV irradiation transcriptionally upregulates ZNF598 expression. Additionally, ZNF598 knockdown in cancer cells inhibited UV-induced apoptosis. In our study, we observe that ELK1 mRNA level as well as phosphorylated ELK1 levels was up regulated upon UV irradiation, which was necessary for UV irradiation induced upregulation of ZNF598. Cells expressing ELK1 shRNA were also resistant to UV-induced apoptosis, and phenocopy ZNF598 knockdown. Upon further investigation, we found that ZNF598 knockdown inhibits UV-induced apoptotic gene expression, which matches with decrease in percentage of annexin V positive cell. Similarly, ectopic expression of ZNF598 promoted apoptotic gene expression and also increased annexin V positive cells. Collectively, these results demonstrate that ZNF598 is a UV irradiation regulated gene and its loss results in resistance to UV-induced apoptosis.

Recurrent deletion of ZNF630 at Xp11.23 is not associated with mental retardation

DEFF Research Database (Denmark)

Lugtenberg, Dorien; Zangrande-Vieira, Luiz; Kirchhoff, Maria

2010-01-01

12 ZNF630 deletions in a total of 1,562 male patients with mental retardation from Brazil, USA, Australia, and Europe. The breakpoints were analyzed in 10 families, and in all cases they were located within two segmental duplications that share more than 99% sequence identity, indicating...

Enhancing caries resistance with a short-pulsed CO2 9.3-μm laser: a laboratory study (Conference Presentation)

Science.gov (United States)

Rechmann, Peter; Rechmann, Beate M.; Groves, William H.; Le, Charles; Rapozo-Hilo, Marcia L.; Featherstone, John D. B.

2016-02-01

The objective of this laboratory study was to test whether irradiation with a new 9.3µm microsecond short-pulsed CO2-laser enhances enamel caries resistance with and without additional fluoride applications. 101 human enamel samples were divided into 7 groups. Each group was treated with different laser parameters (Carbon-dioxide laser, wavelength 9.3µm, 43Hz pulse-repetition rate, pulse duration between 3μs to 7μs (1.5mJ/pulse to 2.9mJ/pulse). Using a pH-cycling model and cross-sectional microhardness testing determined the mean relative mineral loss delta Z (∆Z) for each group. The pH-cycling was performed with or without additional fluoride. The CO2 9.3μm short-pulsed laser energy rendered enamel caries resistant with and without additional fluoride use.

Effector-driven marker development and cloning of resistance genes against Phytophthora infestans in potato breeding clone SW93-1015

DEFF Research Database (Denmark)

Lenman, Marit; Ali, Ashfaq; Mühlenbock, Per

2016-01-01

different P. infestans effectors, containing the conserved motif RXLR (for Arg, any amino acid, Leu, Arg), revealed a specific response to Avr2, which suggests that SW93-1015 might contain a functional homolog of the R2 resistance gene. We cloned eight R2 gene homologs from SW93-1015, whereof seven have...

A genome-wide RNAi screen identifies novel targets of neratinib resistance leading to identification of potential drug resistant genetic markers.

Science.gov (United States)

Seyhan, Attila A; Varadarajan, Usha; Choe, Sung; Liu, Wei; Ryan, Terence E

2012-04-01

Neratinib (HKI-272) is a small molecule tyrosine kinase inhibitor of the ErbB receptor family currently in Phase III clinical trials. Despite its efficacy, the mechanism of potential cellular resistance to neratinib and genes involved with it remains unknown. We have used a pool-based lentiviral genome-wide functional RNAi screen combined with a lethal dose of neratinib to discover chemoresistant interactions with neratinib. Our screen has identified a collection of genes whose inhibition by RNAi led to neratinib resistance including genes involved in oncogenesis (e.g. RAB33A, RAB6A and BCL2L14), transcription factors (e.g. FOXP4, TFEC, ZNF), cellular ion transport (e.g. CLIC3, TRAPPC2P1, P2RX2), protein ubiquitination (e.g. UBL5), cell cycle (e.g. CCNF), and genes known to interact with breast cancer-associated genes (e.g. CCNF, FOXP4, TFEC, several ZNF factors, GNA13, IGFBP1, PMEPA1, SOX5, RAB33A, RAB6A, FXR1, DDO, TFEC, OLFM2). The identification of novel mediators of cellular resistance to neratinib could lead to the identification of new or neoadjuvant drug targets. Their use as patient or treatment selection biomarkers could make the application of anti-ErbB therapeutics more clinically effective.

Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway

NARCIS (Netherlands)

Nicodemus, Kristin K.; Hargreaves, April; Morris, Derek; Anney, Richard; Gill, Michael; Corvin, Aiden; Donohoe, Gary; Ripke, Stephan; Sanders, Alan R.; Kendler, Kenneth S.; Levinson, Douglas F.; Sklar, Pamela; Holmans, Peter A.; Lin, Dan-Yu; Duan, Jubao; Ophoff, Roel A.; Andreassen, Ole A.; Scolnick, Edward; Cichon, Sven; St Clair, David; Gurling, Hugh; Werge, Thomas; Rujescu, Dan; Blackwood, Douglas H. R.; Pato, Carlos N.; Malhotra, Anil K.; Purcell, Shaun; Dudbridge, Frank; Neale, Benjamin M.; Rossin, Lizzy; Visscher, Peter M.; Posthuma, Danielle; Ruderfer, Douglas M.; Fanous, Ayman; Stefansson, Hreinn; Steinberg, Stacy; Mowry, Bryan J.; Golimbet, Vera; de Hert, Marc; Jönsson, Erik G.; Bitter, István; Pietiläinen, Olli P. H.; Collier, David A.; Tosato, Sarah; Agartz, Ingrid; Albus, Margot; Alexander, Madeline; Amdur, Richard L.; de Haan, Lieuwe; Linszen, Don H.

2014-01-01

We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative

Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway.

NARCIS (Netherlands)

Nicodemus, K.K.; Hargreaves, A.; Morris, D.; Anney, R.; Gill, M.; Corvin, A.; Posthuma, D.; Donohoe, G.

2014-01-01

IMPORTANCE We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the

Ampicillin-Resistant Non-β-Lactamase-Producing Haemophilus influenzae in Spain: Recent Emergence of Clonal Isolates with Increased Resistance to Cefotaxime and Cefixime▿

Science.gov (United States)

García-Cobos, Silvia; Campos, José; Lázaro, Edurne; Román, Federico; Cercenado, Emilia; García-Rey, César; Pérez-Vázquez, María; Oteo, Jesús; de Abajo, Francisco

2007-01-01

The sequence of the ftsI gene encoding the transpeptidase domain of penicillin-binding protein 3 (PBP 3) was determined for 354 nonconsecutive Haemophilus influenzae isolates from Spain; 17.8% of them were ampicillin susceptible, 56% were β-lactamase nonproducing ampicillin resistant (BLNAR), 15.8% were β-lactamase producers and ampicillin resistant, and 10.4% displayed both resistance mechanisms. The ftsI gene sequences had 28 different mutation patterns and amino acid substitutions at 23 positions. Some 93.2% of the BLNAR strains had amino acid substitutions at the Lys-Thr-Gly (KTG) motif, the two most common being Asn526 to Lys (83.9%) and Arg517 to His (9.3%). Amino acid substitutions at positions 377, 385, and 389, which conferred cefotaxime and cefixime MICs 10 to 60 times higher than those of susceptible strains, were found for the first time in Europe. In 72 isolates for which the repressor acrR gene of the AcrAB efflux pump was sequenced, numerous amino acid substitutions were found. Eight isolates with ampicillin MICs of 0.25 to 2 μg/ml showed changes that predicted the early termination of the acrR reading frame. Pulsed-field gel electrophoresis analysis demonstrated that most BLNAR strains were genetically diverse, although clonal dissemination was detected in a group of isolates presenting with increased resistance to cefotaxime and cefixime. Background antibiotic use at the community level revealed a marked trend toward increased amoxicillin-clavulanic acid consumption. BLNAR H. influenzae strains have arisen by vertical and horizontal spread and have evolved to adapt rapidly to the increased selective pressures posed by the use of oral penicillins and cephalosporins. PMID:17470649

Expanding the range of ZNF804A variants conferring risk of psychosis

DEFF Research Database (Denmark)

Steinberg, S; Mors, O; Børglum, A D

2011-01-01

. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 × 10-7, and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 × 10-8. In this study, using 5164 schizophrenia cases and 20¿709 controls, we replicated the association......A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P

Relationship of ZNF423 and CTSO with breast cancer risk in two randomised tamoxifen prevention trials.

Science.gov (United States)

Brentnall, Adam R; Cuzick, Jack; Byers, Helen; Segal, Corrinne; Reuter, Caroline; Detre, Simone; Sestak, Ivana; Howell, Anthony; Powles, Trevor J; Newman, William G; Dowsett, Mitchell

2016-08-01

A case-control study from two randomised breast cancer prevention trials of tamoxifen and raloxifene (P-1 and P-2) identified single-nucleotide polymorphisms (SNPs) in or near genes ZNF423 and CTSO as factors which predict which women will derive most anti-cancer benefit from selective oestrogen receptor modulator (SERM) therapy. In this article, we further examine this question using blood samples from two randomised tamoxifen prevention trials: the International Breast Cancer Intervention Study I (IBIS-I) and the Royal Marsden trial (Marsden). A nested case-control study was designed with 2:1 matching in IBIS-I and 1:1 matching in Marsden. The OncoArray was used for genotyping and included two SNPs previously identified (rs8060157 in ZNF423 and rs10030044 near CTSO), and 102 further SNPs within the same regions. Overall, there were 369 cases and 662 controls, with 148 cases and 268 controls from the tamoxifen arms. Odds ratios were estimated by conditional logistic regression, with Wald 95 % confidence intervals. In the tamoxifen arms, the per-allele odds ratio for rs8060157 was 0.99 (95 %CI 0.73-1.34) and 1.00 (95 %CI 0.76-1.33) for rs10030044. In the placebo arm, the odds ratio was 1.10 (95 %CI 0.87-1.40) for rs8060157 and 1.01 (95 %CI 0.79-1.29) for rs10030044. There was no evidence to suggest that other SNPs in the surrounding regions of these SNPs might predict response to tamoxifen. Results from these two prevention trials do not support the earlier findings. rs8060157 in ZNF423 and rs10030044 near CTSO do not appear to predict response to tamoxifen.

Genome-wide discovered psychosis-risk gene ZNF804A impacts on white matter microstructure in health, schizophrenia and bipolar disorder

Directory of Open Access Journals (Sweden)

Emma-Jane Mallas

2016-02-01

Full Text Available Background. Schizophrenia (SZ and bipolar disorder (BD have both been associated with reduced microstructural white matter integrity using, as a proxy, fractional anisotropy (FA detected using diffusion tensor imaging (DTI. Genetic susceptibility for both illnesses has also been positively correlated in recent genome-wide association studies with allele A (adenine of single nucleotide polymorphism (SNP rs1344706 of the ZNF804A gene. However, little is known about how the genomic linkage disequilibrium region tagged by this SNP impacts on the brain to increase risk for psychosis. This study aimed to assess the impact of this risk variant on FA in patients with SZ, in those with BD and in healthy controls. Methods. 230 individuals were genotyped for the rs1344706 SNP and underwent DTI. We used tract-based spatial statistics (TBSS followed by an analysis of variance, with threshold-free cluster enhancement (TFCE, to assess underlying effects of genotype, diagnosis and their interaction, on FA. Results. As predicted, statistically significant reductions in FA across a widely distributed brain network (p < 0.05, TFCE-corrected were positively associated both with a diagnosis of SZ or BD and with the double (homozygous presence of the ZNF804A rs1344706 risk variant (A. The main effect of genotype was medium (d = 0.48 in a 44,054-voxel cluster and the effect in the SZ group alone was large (d = 1.01 in a 51,260-voxel cluster, with no significant effects in BD or controls, in isolation. No areas under a significant diagnosis by genotype interaction were found. Discussion. We provide the first evidence in a predominantly Caucasian clinical sample, of an association between ZNF804A rs1344706 A-homozygosity and reduced FA, both irrespective of diagnosis and particularly in SZ (in overlapping brain areas. This suggests that the previously observed involvement of this genomic region in psychosis susceptibility, and in impaired functional connectivity, may be

Novel loci associated with increased risk of sudden cardiac death in the context of coronary artery disease.

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Adriana Huertas-Vazquez

Full Text Available Recent genome-wide association studies (GWAS have identified novel loci associated with sudden cardiac death (SCD. Despite this progress, identified DNA variants account for a relatively small portion of overall SCD risk, suggesting that additional loci contributing to SCD susceptibility await discovery. The objective of this study was to identify novel DNA variation associated with SCD in the context of coronary artery disease (CAD.Using the MetaboChip custom array we conducted a case-control association analysis of 119,117 SNPs in 948 SCD cases (with underlying CAD from the Oregon Sudden Unexpected Death Study (Oregon-SUDS and 3,050 controls with CAD from the Wellcome Trust Case-Control Consortium (WTCCC. Two newly identified loci were significantly associated with increased risk of SCD after correction for multiple comparisons at: rs6730157 in the RAB3GAP1 gene on chromosome 2 (P = 4.93×10(-12, OR = 1.60 and rs2077316 in the ZNF365 gene on chromosome 10 (P = 3.64×10(-8, OR = 2.41.Our findings suggest that RAB3GAP1 and ZNF365 are relevant candidate genes for SCD and will contribute to the mechanistic understanding of SCD susceptibility.

No effect of schizophrenia risk genes MIR137, TCF4, and ZNF804A on macroscopic brain structure

NARCIS (Netherlands)

Cousijn, H.; Eissing, M.; Fernandez, G.S.E.; Fisher, S.E.; Franke, B.; Zwiers, M.P.; Harrison, P.J.; Arias Vasquez, A.

2014-01-01

Single nucleotide polymorphisms (SNPs) within the MIR137, TCF4, and ZNF804A genes show genome-wide association to schizophrenia. However, the biological basis for the associations is unknown. Here, we tested the effects of these genes on brain structure in 1300 healthy adults. Using volumetry and

Antibiotic resistance increases with local temperature

Science.gov (United States)

MacFadden, Derek R.; McGough, Sarah F.; Fisman, David; Santillana, Mauricio; Brownstein, John S.

2018-06-01

Bacteria that cause infections in humans can develop or acquire resistance to antibiotics commonly used against them1,2. Antimicrobial resistance (in bacteria and other microbes) causes significant morbidity worldwide, and some estimates indicate the attributable mortality could reach up to 10 million by 20502-4. Antibiotic resistance in bacteria is believed to develop largely under the selective pressure of antibiotic use; however, other factors may contribute to population level increases in antibiotic resistance1,2. We explored the role of climate (temperature) and additional factors on the distribution of antibiotic resistance across the United States, and here we show that increasing local temperature as well as population density are associated with increasing antibiotic resistance (percent resistant) in common pathogens. We found that an increase in temperature of 10 °C across regions was associated with an increases in antibiotic resistance of 4.2%, 2.2%, and 2.7% for the common pathogens Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. The associations between temperature and antibiotic resistance in this ecological study are consistent across most classes of antibiotics and pathogens and may be strengthening over time. These findings suggest that current forecasts of the burden of antibiotic resistance could be significant underestimates in the face of a growing population and climate change4.

Electromigration early resistance increase measurements

NARCIS (Netherlands)

Niehof, J.; Flinn, P.A.; Maloney, T.J.

1993-01-01

An early resistance change measurement set-up, using an AC bridge technique, has been developed, and measurements have been performed. Large sample-to-sample variations occur. The characteristic time for the resistance change curve is shorter for resistance increase (under current stress) than for

Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder

NARCIS (Netherlands)

Williams, H.J.; Norton, N.; Dwyer, S.; Moskvina, V.; Nikolov, I.; Carroll, L.; Georgieva, L.; Williams, N.M.; Morris, D.W.; Quinn, E.M.; Giegling, I.; Ikeda, M.; Wood, J.; Lencz, T.; Hultman, C.; Lichtenstein, P.; Thiselton, D.; Maher, B.S.; Malhotra, A.K.; Riley, B.; Kendler, K.S.; Gill, M.; Sullivan, P.; Sklar, P.; Purcell, S.; Nimgaonkar, V.L.; Kirov, G.; Holmans, P.; Corvin, A.; Rujescu, D.; Craddock, N.; Owen, M.J.; O'Donovan, M.C.; GROUP investigators, [No Value

2011-01-01

A recent genome-wide association study (GWAS) reported evidence for association between rs1344706 within ZNF804A (encoding zinc-finger protein 804A) and schizophrenia (P = 1.61 x 10(-7)), and stronger evidence when the phenotype was broadened to include bipolar disorder (P = 9.96 x 10(-9)). In this

Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans

DEFF Research Database (Denmark)

Mangino, Massimo; Hwang, Shih-Jen; Spector, Timothy D

2012-01-01

(-8)). We also identified two novel genomic regions associated with LTL variation that map near a conserved telomere maintenance complex component 1 (CTC1; rs3027234, P = 3.6 × 10(-8)) on chromosome17p13.1 and zinc finger protein 676 (ZNF676; rs412658, P = 3.3 × 10(-8)) on 19p12. The minor allele of rs...

Interaction of the regulatory subunit of the cAMP-dependent protein kinase with PATZ1 (ZNF278)

International Nuclear Information System (INIS)

Yang, Weng-Lang; Ravatn, Roald; Kudoh, Kazuya; Alabanza, Leah; Chin, Khew-Voon

2010-01-01

The effects of cAMP in cell are predominantly mediated by the cAMP-dependent protein kinase (PKA), which is composed of two genetically distinct subunits, catalytic (C) and regulatory (R), forming a tetrameric holoenzyme R 2 C 2 . The only known function for the R subunit is that of inhibiting the activity of the C subunit kinase. It has been shown that overexpression of RIα, but not the C subunit kinase, is associated with neoplastic transformation. In addition, it has also been demonstrated that mutation in the RIα, but not the C subunit is associated with increased resistance to the DNA-damaging anticancer drug cisplatin, thus suggesting that the RIα subunit of PKA may have functions independent of the kinase. We show here that the RIα subunit interacts with a BTB/POZ domain zinc-finger transcription factor, PATZ1 (ZNF278), and co-expression with RIα results in its sequestration in the cytoplasm. The cytoplasmic/nuclear translocation is inducible by cAMP. C-terminus deletion abolishes PATZ1 interaction with RIα and results in its localization in the nucleus. PATZ1 transactivates the cMyc promoter and the presence of cAMP and co-expression with RIα modulates its transactivation. Moreover, PATZ1 is aberrantly expressed in cancer. Taken together, our results showed a potentially novel mechanism of cAMP signaling mediated through the interaction of RIα with PATZ1 that is independent of the kinase activity of PKA, and the aberrant expression of PATZ1 in cancer point to its role in cell growth regulation.

Increasing Incidence of Linezolid-Intermediate or -Resistant, Vancomycin-Resistant Enterococcus faecium Strains Parallels Increasing Linezolid Consumption▿

OpenAIRE

Scheetz, Marc H.; Knechtel, Stephanie A.; Malczynski, Michael; Postelnick, Michael J.; Qi, Chao

2008-01-01

Clinical enterococcal resistance to linezolid is defined by the presence of the G2576T mutation. We evaluated the incidence of genetically proven linezolid resistance among vancomycin-resistant Enterococcus faecium strains and linezolid consumption for a possible association. A relationship was found (r2 = 0.73, P = 0.03) and predicts increasing resistance with current trends of linezolid use.

A Functional Link between the Histone Demethylase PHF8 and the Transcription Factor ZNF711 in X-Linked Mental Retardation

DEFF Research Database (Denmark)

Kleine-Kohlbrecher, Daniela; Christensen, Jesper; Vandamme, Julien

2010-01-01

X-linked mental retardation (XLMR) is an inherited disorder that mostly affects males and is caused by mutations in genes located on the X chromosome. Here, we show that the XLMR protein PHF8 and a C. elegans homolog F29B9.2 catalyze demethylation of di- and monomethylated lysine 9 of histone H3 (H......3K9me2/me1). The PHD domain of PHF8 binds to H3K4me3 and colocalizes with H3K4me3 at transcription initiation sites. Furthermore, PHF8 interacts with another XMLR protein, ZNF711, which binds to a subset of PHF8 target genes, including the XLMR gene JARID1C. Of interest, the C. elegans PHF8 homolog...... is highly expressed in neurons, and mutant animals show impaired locomotion. Taken together, our results functionally link the XLMR gene PHF8 to two other XLMR genes, ZNF711 and JARID1C, indicating that MR genes may be functionally linked in pathways, causing the complex phenotypes observed in patients...

Increased platelet expression of glycoprotein IIIa following aspirin treatment in aspirin-resistant but not aspirin-sensitive subjects

Science.gov (United States)

Floyd, Christopher N; Goodman, Timothy; Becker, Silke; Chen, Nan; Mustafa, Agnesa; Schofield, Emma; Campbell, James; Ward, Malcolm; Sharma, Pankaj; Ferro, Albert

2014-01-01

Aims Aspirin is widely used as an anti-platelet agent for cardiovascular prophylaxis. Despite aspirin treatment, many patients experience recurrent thrombotic events, and aspirin resistance may contribute to this. We examined the prevalence of aspirin resistance in a healthy population, and investigated whether the platelet proteome differed in aspirin-resistant subjects. Methods Ninety-three healthy subjects received aspirin 300 mg daily for 28 days. Before and at the end of treatment, urine was taken to determine 11-dehydrothromboxane B2, and blood was taken to measure arachidonic acid (AA)-induced aggregation of platelet-rich plasma and to interrogate the platelet proteome by mass spectrometric analysis with further confirmation of findings using Western blotting. Results In two of the 93 subjects, neither AA-induced aggregation nor urinary 11-dehydrothromboxane B2 was effectively suppressed by aspirin, despite measurable plasma salicylate concentrations, suggesting the presence of true aspirin resistance. Despite no detectable differences in the platelet proteome at baseline, following aspirin a marked increase was seen in platelet glycoprotein IIIa expression in the aspirin-resistant but not aspirin-sensitive subjects. An increase in platelet glycoprotein IIIa expression with aspirin resistance was confirmed in a separate cohort of 17 patients with stable coronary artery disease on long term aspirin treatment, four of whom exhibited aspirin resistance. Conclusions In a healthy population, true aspirin resistance is uncommon but exists. Resistance is associated with an increase in platelet glycoprotein IIIa expression in response to aspirin. These data shed new light on the mechanism of aspirin resistance, and provide the potential to identify aspirin-resistant subjects using a novel biomarker. PMID:25099258

UNC93B1 mediates host resistance to infection with Toxoplasma gondii.

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Mariane B Melo

2010-08-01

Full Text Available UNC93B1 associates with Toll-Like Receptor (TLR 3, TLR7 and TLR9, mediating their translocation from the endoplasmic reticulum to the endolysosome, hence allowing proper activation by nucleic acid ligands. We found that the triple deficient '3d' mice, which lack functional UNC93B1, are hyper-susceptible to infection with Toxoplasma gondii. We established that while mounting a normal systemic pro-inflammatory response, i.e. producing abundant MCP-1, IL-6, TNFα and IFNγ, the 3d mice were unable to control parasite replication. Nevertheless, infection of reciprocal bone marrow chimeras between wild-type and 3d mice with T. gondii demonstrated a primary role of hemopoietic cell lineages in the enhanced susceptibility of UNC93B1 mutant mice. The protective role mediated by UNC93B1 to T. gondii infection was associated with impaired IL-12 responses and delayed IFNγ by spleen cells. Notably, in macrophages infected with T. gondii, UNC93B1 accumulates on the parasitophorous vacuole. Furthermore, upon in vitro infection the rate of tachyzoite replication was enhanced in non-activated macrophages carrying mutant UNC93B1 as compared to wild type gene. Strikingly, the role of UNC93B1 on intracellular parasite growth appears to be independent of TLR function. Altogether, our results reveal a critical role for UNC93B1 on induction of IL-12/IFNγ production as well as autonomous control of Toxoplasma replication by macrophages.

Interaction of the regulatory subunit of the cAMP-dependent protein kinase with PATZ1 (ZNF278)

Energy Technology Data Exchange (ETDEWEB)

Yang, Weng-Lang [Long Island Jewish Medical Center, North Shore University Hospital, Manhasset, NY 11030 (United States); Ravatn, Roald [Department of Medicine, University of Toledo, College of Medicine, Toledo, OH 43614 (United States); Kudoh, Kazuya [Department of Medicine, University of Toledo, College of Medicine, Toledo, OH 43614 (United States); Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Saitama (Japan); Alabanza, Leah [Department of Medicine, University of Toledo, College of Medicine, Toledo, OH 43614 (United States); Chin, Khew-Voon, E-mail: khew-voon.chin@utoledo.edu [Department of Medicine, University of Toledo, College of Medicine, Toledo, OH 43614 (United States)

2010-01-15

The effects of cAMP in cell are predominantly mediated by the cAMP-dependent protein kinase (PKA), which is composed of two genetically distinct subunits, catalytic (C) and regulatory (R), forming a tetrameric holoenzyme R{sub 2}C{sub 2}. The only known function for the R subunit is that of inhibiting the activity of the C subunit kinase. It has been shown that overexpression of RI{alpha}, but not the C subunit kinase, is associated with neoplastic transformation. In addition, it has also been demonstrated that mutation in the RI{alpha}, but not the C subunit is associated with increased resistance to the DNA-damaging anticancer drug cisplatin, thus suggesting that the RI{alpha} subunit of PKA may have functions independent of the kinase. We show here that the RI{alpha} subunit interacts with a BTB/POZ domain zinc-finger transcription factor, PATZ1 (ZNF278), and co-expression with RI{alpha} results in its sequestration in the cytoplasm. The cytoplasmic/nuclear translocation is inducible by cAMP. C-terminus deletion abolishes PATZ1 interaction with RI{alpha} and results in its localization in the nucleus. PATZ1 transactivates the cMyc promoter and the presence of cAMP and co-expression with RI{alpha} modulates its transactivation. Moreover, PATZ1 is aberrantly expressed in cancer. Taken together, our results showed a potentially novel mechanism of cAMP signaling mediated through the interaction of RI{alpha} with PATZ1 that is independent of the kinase activity of PKA, and the aberrant expression of PATZ1 in cancer point to its role in cell growth regulation.

Further Evidence for the Impact of a Genome-Wide-Supported Psychosis Risk Variant in ZNF804A on the Theory of Mind Network

Science.gov (United States)

Mohnke, Sebastian; Erk, Susanne; Schnell, Knut; Schütz, Claudia; Romanczuk-Seiferth, Nina; Grimm, Oliver; Haddad, Leila; Pöhland, Lydia; Garbusow, Maria; Schmitgen, Mike M; Kirsch, Peter; Esslinger, Christine; Rietschel, Marcella; Witt, Stephanie H; Nöthen, Markus M; Cichon, Sven; Mattheisen, Manuel; Mühleisen, Thomas; Jensen, Jimmy; Schott, Björn H; Maier, Wolfgang; Heinz, Andreas; Meyer-Lindenberg, Andreas; Walter, Henrik

2014-01-01

The single-nucleotide polymorphism (SNP) rs1344706 in ZNF804A is one of the best-supported risk variants for psychosis. We hypothesized that this SNP contributes to the development of schizophrenia by affecting the ability to understand other people's mental states. This skill, commonly referred to as Theory of Mind (ToM), has consistently been found to be impaired in schizophrenia. Using functional magnetic resonance imaging, we previously showed that in healthy individuals rs1344706 impacted on activity and connectivity of key areas of the ToM network, including the dorsomedial prefrontal cortex, temporo-parietal junction, and the posterior cingulate cortex, which show aberrant activity in schizophrenia patients, too. We aimed to replicate these results in an independent sample of 188 healthy German volunteers. In order to assess the reliability of brain activity elicited by the ToM task, 25 participants performed the task twice with an interval of 14 days showing excellent accordance in recruitment of key ToM areas. Confirming our previous results, we observed decreasing activity of the left temporo-parietal junction, dorsomedial prefrontal cortex, and the posterior cingulate cortex with increasing number of risk alleles during ToM. Complementing our replication sample with the discovery sample, analyzed in a previous report (total N=297), further revealed negative genotype effects in the left dorsomedial prefrontal cortex as well as in the temporal and parietal regions. In addition, as shown previously, rs1344706 risk allele dose positively predicted increased frontal–temporo-parietal connectivity. These findings confirm the effects of the psychosis risk variant in ZNF804A on the dysfunction of the ToM network. PMID:24247043

Increased Resistance of Skin Flora to Antimicrobial Prophylaxis in Patients Undergoing Hip Revision Arthroplasty.

Science.gov (United States)

Mühlhofer, Heinrich M L; Deiss, Lukas; Mayer-Kuckuk, Philipp; Pohlig, Florian; Harrasser, Norbert; Lenze, Ulrich; Gollwitzer, Hans; Suren, Christian; Prodinger, Peter; VON Eisenhart-Rothe, Rüdiger; Schauwecker, Johannes

2017-01-01

Prosthetic joint infection (PJI) remains a major complication after total joint replacement and is the primary indication for revision arthroplasty. Specifically, coagulase-negative Staphylococci (CNS) can cause low-grade infections. Despite the use of cephalosporin-based antimicrobial prophylaxis (AMP) and antiseptic treatment at the surgical site, evidence suggests that a significant number of cases of dermal CNS results in low-grade PJI. Thus, this study examined the bacterial colonization and resistance patterns at the surgical site. We hypothesized that the bacteria developed resistance to antibiotics that are frequently used in primary and revision total hip arthroplasty (THA) procedures. Ninety patients, including 63 primary and 27 revision THA patients, were enrolled in this study. For each patient, a single swab of the skin at the surgical site was subjected to clinical microbiology to assess bacterial colonization. Furthermore, resistance to a sentinel panel of antibiotics (benzylpenicillin, erythromycin, tetracycline, oxacillin, fusidic acid, clindamycin, gentamicin, levofloxacin/moxifloxacin, rifampicin, linezolid and vancomycin) was tested. In 96.7% of the patients, at least one bacterial strain was identified at the surgical site, with CNS strains comprising 93.1% of the total. The sentinel panel showed that 30.7% of the CNS strains exhibited maximal resistance to oxacillin, a commonly used cephalosporin. Additionally, oxacillin resistance increased 1.9-fold (p=0.042) between primary and revision THA. Notably, 8.1% of the CNS stains found on patients undergoing primary THA were resistant to gentamicin, an aminoglycoside, and this rate increased 4.7-fold (p=0.001) for patients undergoing revision THA. CNS strains have significant resistance to standard AMP, particularly in individuals undergoing revision THA. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Cu2+ in layered compounds: origin of the compressed geometry in the model system K2ZnF4:Cu2+.

Science.gov (United States)

Aramburu, J A; García-Lastra, J M; García-Fernández, P; Barriuso, M T; Moreno, M

2013-06-17

Many relevant properties (including superconductivity and colossal magnetoresistance) of layered materials containing Cu(2+), Ag(2+), or Mn(3+) ions are commonly related to the Jahn-Teller instability. Along this line, the properties of the CuF6(4-) complex in the K2ZnF4 layered perovskite have recently been analyzed using a parametrized Jahn-Teller model with an imposed strain [Reinen, D. Inorg. Chem.2012, 51, 4458]. Here, we present results of ab initio periodic supercell and cluster calculations on K2ZnF4:Cu(2+), showing unequivocally that the actual origin of the unusual compressed geometry of the CuF6(4-) complex along the crystal c axis in that tetragonal lattice is due to the presence of an electric field due to the crystal surrounding the impurity. Our calculations closely reproduce the experimental optical spectrum. The calculated values of the equilibrium equatorial and axial Cu(2+)-F(-) distances are, respectively, R(ax) = 193 pm and R(eq) = 204 pm, and so the calculated distortion R(ax) - R(eq) = 11 pm is three times smaller than the estimated through the parametrized Jahn-Teller model. As a salient feature, we find that if the CuF6(4-) complex would assume a perfect octahedral geometry (R(ax) = R(eq) = 203 pm) the antibonding a(1g)*(∼3z(2) - r(2)) orbital is placed above b(1g)*(∼x(2) - y(2)) with a transition energy E((2)A(1g) → (2)B(1g)) = 0.34 eV. This surprising fact stresses that about half the experimental value E((2)A(1g) → (2)B(1g)) = 0.70 eV is not due to the small shortening of the axial Cu(2+)-F(-) distance, but it comes from the electric field, E(R)(r), created by the rest of the lattice ions on the CuF6(4-) complex. This internal field, displaying tetragonal symmetry, is thus responsible for the compressed geometry in K2ZnF4:Cu(2+) and the lack of symmetry breaking behind the ligand relaxation. Moreover, we show that the electronic energy gain in this process comes from bonding orbitals and not from antibonding ones. The present

Genetic investigation of 93 families with microphthalmia or posterior microphthalmos.

Science.gov (United States)

Patel, N; Khan, A O; Alsahli, S; Abdel-Salam, G; Nowilaty, S R; Mansour, A M; Nabil, A; Al-Owain, M; Sogati, S; Salih, M A; Kamal, A M; Alsharif, H; Alsaif, H S; Alzahrani, S S; Abdulwahab, F; Ibrahim, N; Hashem, M; Faquih, T; Shah, Z A; Abouelhoda, M; Monies, D; Dasouki, M; Shaheen, R; Wakil, S M; Aldahmesh, M A; Alkuraya, F S

2018-06-01

Microphthalmia is a developmental eye defect that is highly variable in severity and in its potential for systemic association. Despite the discovery of many disease genes in microphthalmia, at least 50% of patients remain undiagnosed genetically. Here, we describe a cohort of 147 patients (93 families) from our highly consanguineous population with various forms of microphthalmia (including the distinct entity of posterior microphthalmos) that were investigated using a next-generation sequencing multi-gene panel (i-panel) as well as whole exome sequencing and molecular karyotyping. A potentially causal mutation was identified in the majority of the cohort with microphthalmia (61%) and posterior microphthalmos (82%). The identified mutations (55 point mutations, 15 of which are novel) spanned 24 known disease genes, some of which have not or only very rarely been linked to microphthalmia (PAX6, SLC18A2, DSC3 and CNKSR1). Our study has also identified interesting candidate variants in 2 genes that have not been linked to human diseases (MYO10 and ZNF219), which we present here as novel candidates for microphthalmia. In addition to revealing novel phenotypic aspects of microphthalmia, this study expands its allelic and locus heterogeneity and highlights the need for expanded testing of patients with this condition. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Progressive increase in point mutations associates chloroquine resistance: Even after withdrawal of chloroquine use in India

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Sabyasachi Das

2017-12-01

Full Text Available Chloroquine (CQ is highly effective against P. vivax, due to the rapid spread of CQ resistance in P. falciparum parasites; it is no longer the drug of choice against P. falciparum. This study elucidates the scenario of chloroquine efficacy at times that coincided with a new drug policy and especially assessed the chloroquine resistant molecular markers after withdrawal of chloroquine in Kolkata and Purulia, two malaria endemic zones of West Bengal, India. In vitro CQ susceptibility was tested in 781 patients with P. falciparum mono infections between 2008 and 2013, of which 338 patients had received CQ in 2008–2009. Genotyping of the pfcrt and the pfmdr1 gene was carried out in all isolates. Early treatment failure was detected in 114 patients {43 (31·39% from Kolkata and 71 (35·32% from Purulia} while recrudescence was identified in 13 (9.49% and 17 (8.46% patients from Kolkata and Purulia respectively. In vivo chloroquine resistance was strongly associated with CVMNT-YYSNY (p < 0.01 and SVMNT-YYSNY (p < 0.05 allele in Kolkata. In Purulia chloroquine resistance was associated with CVMNK-YYSNY (P < 0.005, SVMNT-YYSNY (P < 0.01 allele. The proportion of in vitro chloroquine resistance increased in subsequent years to 87.23% and 93·10% in 2013, in Kolkata and Purulia, respectively. Isolates with SVMNT-YFSND, SVMNT-YFSNY, CVIET-YFSND and CVIET-YYSNY haplotypes increased gradually (p < 0.05 from 2010 to 2013, leading to a rise in IC50 (p < 0.05 of chloroquine. An increase in in vitro chloroquine resistance and candidate gene mutations even after five years of chloroquine withdrawal against P. falciparum calls for synchronized research surveillance and proper containment strategies. Keywords: Plasmodium falciparum, ChloroQuine resistance in India, pfcrt polymorphism, pfmdr1 mutation, In vitro chloroquine resistance

The dominant Australian community-acquired methicillin-resistant Staphylococcus aureus clone ST93-IV [2B] is highly virulent and genetically distinct.

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Kyra Y L Chua

Full Text Available Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA USA300 has spread rapidly across North America, and CA-MRSA is also increasing in Australia. However, the dominant Australian CA-MRSA strain, ST93-IV [2B] appears distantly related to USA300 despite strikingly similar clinical and epidemiological profiles. Here, we compared the virulence of a recent Australian ST93 isolate (JKD6159 to other MRSA, including USA300, and found that JKD6159 was the most virulent in a mouse skin infection model. We fully sequenced the genome of JKD6159 and confirmed that JKD6159 is a distinct clone with 7616 single nucleotide polymorphisms (SNPs distinguishing this strain from all other S. aureus genomes. Despite its high virulence there were surprisingly few virulence determinants. However, genes encoding α-hemolysin, Panton-Valentine leukocidin (PVL and α-type phenol soluble modulins were present. Genome comparisons revealed 32 additional CDS in JKD6159 but none appeared to encode new virulence factors, suggesting that this clone's enhanced pathogenicity could lie within subtler genome changes, such as SNPs within regulatory genes. To investigate the role of accessory genome elements in CA-MRSA epidemiology, we next sequenced three additional Australian non-ST93 CA-MRSA strains and compared them with JKD6159, 19 completed S. aureus genomes and 59 additional S. aureus genomes for which unassembled genome sequence data was publicly available (82 genomes in total. These comparisons showed that despite its distinctive genotype, JKD6159 and other CA-MRSA clones (including USA300 share a conserved repertoire of three notable accessory elements (SSCmecIV, PVL prophage, and pMW2. This study demonstrates that the genetically distinct ST93 CA-MRSA from Australia is highly virulent. Our comparisons of geographically and genetically diverse CA-MRSA genomes suggest that apparent convergent evolution in CA-MRSA may be better explained by the rapid

Search for KPNA7 cargo proteins in human cells reveals MVP and ZNF414 as novel regulators of cancer cell growth.

Science.gov (United States)

Vuorinen, Elisa M; Rajala, Nina K; Rauhala, Hanna E; Nurminen, Anssi T; Hytönen, Vesa P; Kallioniemi, Anne

2017-01-01

Karyopherin alpha 7 (KPNA7) belongs to a family of nuclear import proteins that recognize and bind nuclear localization signals (NLSs) in proteins to be transported to the nucleus. Previously we found that KPNA7 is overexpressed in a subset of pancreatic cancer cell lines and acts as a critical regulator of growth in these cells. This characteristic of KPNA7 is likely to be mediated by its cargo proteins that are still mainly unknown. Here, we used protein affinity chromatography in Hs700T and MIA PaCa-2 pancreatic cancer cell lines and identified 377 putative KPNA7 cargo proteins, most of which were known or predicted to localize to the nucleus. The interaction was confirmed for two of the candidates, MVP and ZNF414, using co-immunoprecipitation, and their transport to the nucleus was hindered by siRNA based KPNA7 silencing. Most importantly, silencing of MVP and ZNF414 resulted in marked reduction in Hs700T cell growth. In conclusion, these data uncover two previously unknown human KPNA7 cargo proteins with distinct roles as novel regulators of pancreatic cancer cell growth, thus deepening our understanding on the contribution of nuclear transport in cancer pathogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder.

LENUS (Irish Health Repository)

Williams, H J

2011-04-01

A recent genome-wide association study (GWAS) reported evidence for association between rs1344706 within ZNF804A (encoding zinc-finger protein 804A) and schizophrenia (P=1.61 × 10(-7)), and stronger evidence when the phenotype was broadened to include bipolar disorder (P=9.96 × 10(-9)). In this study we provide additional evidence for association through meta-analysis of a larger data set (schizophrenia\\/schizoaffective disorder N=18 945, schizophrenia plus bipolar disorder N=21 274 and controls N=38 675). We also sought to better localize the association signal using a combination of de novo polymorphism discovery in exons, pooled de novo polymorphism discovery spanning the genomic sequence of the locus and high-density linkage disequilibrium (LD) mapping. The meta-analysis provided evidence for association between rs1344706 that surpasses widely accepted benchmarks of significance by several orders of magnitude for both schizophrenia (P=2.5 × 10(-11), odds ratio (OR) 1.10, 95% confidence interval 1.07-1.14) and schizophrenia and bipolar disorder combined (P=4.1 × 10(-13), OR 1.11, 95% confidence interval 1.07-1.14). After de novo polymorphism discovery and detailed association analysis, rs1344706 remained the most strongly associated marker in the gene. The allelic association at the ZNF804A locus is now one of the most compelling in schizophrenia to date, and supports the accumulating data suggesting overlapping genetic risk between schizophrenia and bipolar disorder.

Emotions and stress increase respiratory resistance in asthma.

Science.gov (United States)

Ritz, T; Steptoe, A; DeWilde, S; Costa, M

2000-01-01

Clinical reports suggest that various emotions and types of stress can precipitate asthmatic symptoms, but there is little experimental evidence to substantiate this claim. We studied the impact of different emotional states and stress on respiratory resistance in asthmatic and nonasthmatic individuals. Participants (24 asthmatic and 24 nonasthmatic patients) viewed short film sequences selected to induce anxiety, anger, depression, elation, happiness, contentment, or a neutral affective state and completed two stressful tasks, mental arithmetic to induce active coping efforts and viewing of medical slides to induce passive coping efforts. Oscillatory resistance, heart rate, blood pressure, baroreflex sensitivity, skin conductance level, respiration rate and volume, and self-reported affective state were measured throughout the session. Uniform increases in oscillatory resistance were found in all emotional states compared with the neutral state and during mental arithmetic in both groups. Asthmatic patients showed stronger reactions to the medical slides than healthy control subjects, with significant increases in oscillatory resistance, blood pressure, skin conductance level, and minute volume, as well as higher levels of self-reported depression, arousal, and shortness of breath. Changes in oscillatory resistance were inconsistently correlated with other physiological indices. Various emotional states and stress increase oscillatory resistance largely independently of concurrent increases in autonomic or ventilatory activity. The particular sensitivity of asthmatics to passive coping demand requires additional research.

Development of Castration Resistant Prostate Cancer can be Predicted by a DNA Hypermethylation Profile.

Science.gov (United States)

Angulo, Javier C; Andrés, Guillermo; Ashour, Nadia; Sánchez-Chapado, Manuel; López, Jose I; Ropero, Santiago

2016-03-01

Detection of DNA hypermethylation has emerged as a novel molecular biomarker for prostate cancer diagnosis and evaluation of prognosis. We sought to define whether a hypermethylation profile of patients with prostate cancer on androgen deprivation would predict castrate resistant prostate cancer. Genome-wide methylation analysis was performed using a methylation cancer panel in 10 normal prostates and 45 tumor samples from patients placed on androgen deprivation who were followed until castrate resistant disease developed. Castrate resistant disease was defined according to EAU (European Association of Urology) guideline criteria. Two pathologists reviewed the Gleason score, Ki-67 index and neuroendocrine differentiation. Hierarchical clustering analysis was performed and relationships with outcome were investigated by Cox regression and log rank analysis. We found 61 genes that were significantly hypermethylated in greater than 20% of tumors analyzed. Three clusters of patients were characterized by a DNA methylation profile, including 1 at risk for earlier castrate resistant disease (log rank p = 0.019) and specific mortality (log rank p = 0.002). Hypermethylation of ETV1 (HR 3.75) and ZNF215 (HR 2.89) predicted disease progression despite androgen deprivation. Hypermethylation of IRAK3 (HR 13.72), ZNF215 (HR 4.81) and SEPT9 (HR 7.64) were independent markers of prognosis. Prostate specific antigen greater than 25 ng/ml, Gleason pattern 5, Ki-67 index greater than 12% and metastasis at diagnosis also predicted a negative response to androgen deprivation. Study limitations included the retrospective design and limited number of cases. Epigenetic silencing of the mentioned genes could be novel molecular markers for the prognosis of advanced prostate cancer. It might predict castrate resistance during hormone deprivation and, thus, disease specific mortality. Gene hypermethylation is associated with disease progression in patients who receive hormone therapy. It

Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness.

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Yi Lu

2010-05-01

Full Text Available Central corneal thickness (CCT, one of the most highly heritable human traits (h(2 typically>0.9, is important for the diagnosis of glaucoma and a potential risk factor for glaucoma susceptibility. We conducted genome-wide association studies in five cohorts from Australia and the United Kingdom (total N = 5058. Three cohorts were based on individually genotyped twin collections, with the remaining two cohorts genotyped on pooled samples from singletons with extreme trait values. The pooled sample findings were validated by individual genotyping the pooled samples together with additional samples also within extreme quantiles. We describe methods for efficient combined analysis of the results from these different study designs. We have identified and replicated quantitative trait loci on chromosomes 13 and 16 for association with CCT. The locus on chromosome 13 (nearest gene FOXO1 had an overall meta-analysis p-value for all the individually genotyped samples of 4.6x10(-10. The locus on chromosome 16 was associated with CCT with p = 8.95x10(-11. The nearest gene to the associated chromosome 16 SNPs was ZNF469, a locus recently implicated in Brittle Cornea Syndrome (BCS, a very rare disorder characterized by abnormal thin corneas. Our findings suggest that in addition to rare variants in ZNF469 underlying CCT variation in BCS patients, more common variants near this gene may contribute to CCT variation in the general population.

The Rat Homolog of the Schizophrenia Susceptibility Gene ZNF804A Is Highly Expressed during Brain Development, Particularly in Growth Cones

DEFF Research Database (Denmark)

Hinna, Katja Hvid; Rich, Karen; Fex Svenningsen, Åsa

2015-01-01

it decreases towards adult levels. This time point is developmentally the equivalent to the second trimester of fetal development in humans. An exception to this expression pattern is the hippocampus where the expression of Zfp804A appears to increase again in the adult brain. Using laser capture...... developmental mechanisms are suggested in the pathophysiology for schizophrenia, expression of Zfp804A, the rat homolog of ZNF804A, was investigated in the developing rat brain. We found that expression of Zfp804A in most brain regions is developmentally regulated and peaks around birth, where after...... expression was therefore investigated with immunochemistry in such cultures. Interestingly, before day 4, the protein is mostly found in the perinuclear region of the cell but at day 4, ZFP804A was instead found throughout the cell and particularly in the growth cones. In conclusion we demonstrate that Zfp...

93Tc and sup(93m)Tc gamma spectra

International Nuclear Information System (INIS)

Podkopaev, Yu.N.; Zarubin, P.P.; Kobelev, V.F.; Padalko, V.Yu.; Khrisanfov, Yu.V.

1977-01-01

The sup(93,93m)Tc decay was studied. The spectra of γ-rays accompanying the decay of this nuclide were studied. 93 Tc and sup(93m)Tc were obtained in the (dn)-reaction on 92 Mo. To ensure a more reliable identification of γ-rays, the isotopic composition of the targets, the bombardment time, the energy of the bombarding deuterons (5-12 MeV) and the spectrum processing program were varied. The energies and relative intensities of the γ-rays of the 93 Tc and sup(93m)Tc decay are listed in tables together with data of other investigatxons. The results obtained largely confirm the known data. Four new transitions were added in the sup(93m)Tc spectrum namely 1046.8, 2011.8, 2182.0, and 2861.5 keV. The 2739.0 keV transition was eliminated from the 93 Tc spectrum. The appropriate changes and additions were made in the 93 Tc decay scheme, and three new levels were introduced: 2479.0, 2821.7, and 3025.8 keV. The values of log ft of some levels of 93 Tc were estimated

A polymorphism in the splice donor site of ZNF419 results in the novel renal cell carcinoma-associated minor histocompatibility antigen ZAPHIR.

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Kelly Broen

Full Text Available Nonmyeloablative allogeneic stem cell transplantation (SCT can induce remission in patients with renal cell carcinoma (RCC, but this graft-versus-tumor (GVT effect is often accompanied by graft-versus-host disease (GVHD. Here, we evaluated minor histocompatibility antigen (MiHA-specific T cell responses in two patients with metastatic RCC who were treated with reduced-intensity conditioning SCT followed by donor lymphocyte infusion (DLI. One patient had stable disease and emergence of SMCY.A2-specific CD8+ T cells was observed after DLI with the potential of targeting SMCY-expressing RCC tumor cells. The second patient experienced partial regression of lung metastases from whom we isolated a MiHA-specific CTL clone with the capability of targeting RCC cell lines. Whole genome association scanning revealed that this CTL recognizes a novel HLA-B7-restricted MiHA, designated ZAPHIR, resulting from a polymorphism in the splice donor site of the ZNF419 gene. Tetramer analysis showed that emergence of ZAPHIR-specific CD8+ T cells in peripheral blood occurred in the absence of GVHD. Furthermore, the expression of ZAPHIR in solid tumor cell lines indicates the involvement of ZAPHIR-specific CD8+ T cell responses in selective GVT immunity. These findings illustrate that the ZNF419-encoded MiHA ZAPHIR is an attractive target for specific immunotherapy after allogeneic SCT.

Increasing quinolone resistance in Salmonella enterica serotype enteritidis

DEFF Research Database (Denmark)

Mølbak, K.; Gerner-Smidt, P.; Wegener, Henrik Caspar

2002-01-01

Until recently, Salmonella enterica serotype Enteritidis has remained sensitive to most antibiotics. However, national surveillance data from Denmark show that quinolone resistance in S. Enteritidis has increased from 0.8% in 1995 to 8.5% in 2000. These data support concerns that the current use...... of quinolone in food animals leads to increasing resistance in S. Enteritidis and that action should be taken to limit such use....

Mouse Homologue of the Schizophrenia Susceptibility Gene ZNF804A as a Target of Hoxc8

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Hyun Joo Chung

2010-01-01

Full Text Available Using a ChIP-cloning technique, we identified a Zinc finger protein 804a (Zfp804a as one of the putative Hoxc8 downstream target genes. We confirmed binding of Hoxc8 to an intronic region of Zfp804a by ChIP-PCR in F9 cells as well as in mouse embryos. Hoxc8 upregulated Zfp804a mRNA levels and augmented minimal promoter activity in vitro. In E11.5 mouse embryos, Zfp804a and Hoxc8 were coexpressed. Recent genome-wide studies identified Zfp804a (or ZNF804A in humans as a plausible marker for schizophrenia, leading us to hypothesize that this embryogenic regulatory control might also exert influence in development of complex traits such as psychosis.

Investigation of the ZNF804A gene polymorphism with genetic risk for bipolar disorder in attention deficit hyperactivity disorder

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Xu Xiaohui

2013-01-01

Full Text Available Abstract Background Genome-wide association studies (GWAS have been conducted on many psychiatric disorders. Evidence from large GWAS indicates that the single nucleotide polymorphism (SNP rs1344706 in the zinc-finger protein 804A gene (ZNF804A is associated with psychotic disorders including bipolar disorder and schizophrenia. One study also found significant association between rs1344706 and the executive control network of attention. In this study we examine the role of the rs1344706 polymorphism that previously showed association with BD and is known to alter expression of the gene in two clinical family-based ADHD samples from the UK and Taiwan. Findings To investigate the association between rs1344706 and ADHD, two family samples of ADHD probands from the United Kingdom (n = 180 and Taiwan (n = 212 were genotyped using TaqMan SNP genotyping assays and analysed using within-family transmission disequilibrium test. No significant associations were found between rs1344706 polymorphism and ADHD in either of the samples from Taiwan (P = 0.91 and UK (P = 0.41. Even combining the two datasets together the A allele of rs1344706 SNP was still not significantly over-transmitted to affected probands (P = 0.50. Furthermore, there was no evidence of association with the specific symptoms subgroups of inattention or hyperactivity-impulsivity. Conclusions In this study we used family-based ADHD data in the UK and Taiwanese population to test for an association between rs1344706 SNP in the ZNF804A gene and ADHD. Results showed no significant association of rs1344706 with ADHD in UK and Taiwanese samples.

The B-subdomain of the Xenopus laevis XFIN KRAB-AB domain is responsible for its weaker transcriptional repressor activity compared to human ZNF10/Kox1.

Science.gov (United States)

Born, Nadine; Thiesen, Hans-Jürgen; Lorenz, Peter

2014-01-01

The Krüppel-associated box (KRAB) domain interacts with the nuclear hub protein TRIM28 to initiate or mediate chromatin-dependent processes like transcriptional repression, imprinting or suppression of endogenous retroviruses. The prototype KRAB domain initially identified in ZNF10/KOX1 encompasses two subdomains A and B that are found in hundreds of zinc finger transcription factors studied in human and murine genomes. Here we demonstrate for the first time transcriptional repressor activity of an amphibian KRAB domain. After sequence correction, the updated KRAB-AB domain of zinc finger protein XFIN from the frog Xenopus laevis was found to confer transcriptional repression in reporter assays in Xenopus laevis A6 kidney cells as well as in human HeLa, but not in the minnow Pimephales promelas fish cell line EPC. Binding of the XFIN KRAB-AB domain to human TRIM28 was demonstrated in a classical co-immunoprecipitation approach and visualized in a single-cell compartmentalization assay. XFIN-AB displayed reduced potency in repression as well as lower strength of interaction with TRIM28 compared to ZNF10 KRAB-AB. KRAB-B subdomain swapping between the two KRAB domains indicated that it was mainly the KRAB-B subdomain of XFIN that was responsible for its lower capacity in repression and binding to human TRIM28. In EPC fish cells, ZNF10 and XFIN KRAB repressor activity could be partially restored to low levels by adding exogenous human TRIM28. In contrast to XFIN, we did not find any transcriptional repression activity for the KRAB-like domain of human PRDM9 in HeLa cells. PRDM9 is thought to harbor an evolutionary older domain related to KRAB whose homologs even occur in invertebrates. Our results support the notion that functional bona fide KRAB domains which confer transcriptional repression and interact with TRIM28 most likely co-evolved together with TRIM28 at the beginning of tetrapode evolution.

Increased minimal vascular resistance and arteriolar hyalinosis in skin on the leg in insulin-dependent diabetic patients

DEFF Research Database (Denmark)

Kastrup, J; Nørgaard, T; Parving, H H

1987-01-01

Minimal vascular resistance (MVR) was determined in a paralysed cutaneous vascular bed at the dorsum of the foot in diabetic patients. Twelve long-term insulin-dependent diabetic (IDDM) patients with and nine short-term IDDM patients without nephropathy and retinopathy and eight control subjects......-wise increases of external counter pressure. The MVR was calculated from the reciprocal of the slope of the relationship between blood flow and applied pressure. The MVR was significantly increased in diabetic patients with (mean: 9.3 mmHg ml-1.100 g.min) and without nephropathy and retinopathy (8.5 mmHg ml-1.......100 g.min) compared with non-diabetic subjects (5.2 mmHg ml-1.100 g.min) (p less than 0.001 and p less than 0.005, respectively). Diabetic microangiopathy (increased hyalinosis of the basement membranes in the terminal arterioles) was found in skin biopsies in nine of the 12 long-term IDDM patients...

Increasing incidence of fluoroquinolone-resistant Mycobacterium tuberculosis in Mumbai, India.

Science.gov (United States)

Agrawal, D; Udwadia, Z F; Rodriguez, C; Mehta, A

2009-01-01

Tertiary referral centre, private hospital, Mumbai, India. To analyse the incidence of fluoroquinolone (FQ) resistant Mycobacterium tuberculosis (TB) in our laboratory from 1995 to 2004. Retrospective review and analysis of the drug susceptibility test records of all M. tuberculosis culture-positive samples from our Microbiology Department from 1995 to 2004. FQ resistance has increased exponentially in our laboratory, from 3% in 1996 to 35% in 2004. The incidence of multidrug-resistant tuberculosis has also increased during the same period, from 33% in 1995 to 56% in 2004. The incidence of FQ-resistant M. tuberculosis is gradually increasing to alarming levels. This may be due to widespread use of this vital group of drugs in the treatment of community-acquired infections. We urge that these broad spectrum antibiotics be used judiciously, and ideally be reserved for treatment of resistant TB in TB-endemic areas.

Sucralose Increases Antimicrobial Resistance and Stimulates Recovery of Escherichia coli Mutants.

Science.gov (United States)

Qu, Yilin; Li, Rongyan; Jiang, Mingshan; Wang, Xiuhong

2017-07-01

Because of heavy use of antimicrobials, antimicrobial resistance in bacteria has become of great concern. The effect of some widely used food additives such as sucralose on bacteria in the gut and the environment has also drawn increasing attention. In this study, we investigated the interaction between antimicrobials and sucralose impacting antimicrobial resistance and mutation of Escherichia coli (E. coli). To examine antimicrobial resistance and mutation frequency, different subinhibitory concentrations of sucralose were added to cultures of E.coli BW25113 that were then treated with antimicrobials, oxolinic acid, or moxifloxacin. Then the E.coli were assayed for bacterial survival and recovery of mutants resistant to an unrelated antimicrobial, rifampicin. Pre-treatment of E.coli BW25113 with 1/2 minimal inhibitory concentration (MIC) of sucralose increased the survival rate in oxolinic acid or moxifloxacin. A 1/3 MIC of sucralose increased rifampicin-resistant mutation rate of E.coli BW25113 after 72 h, while rifampicin-resistant mutation rate was increased when co-treated with 1/8 MIC, 1/4 MIC, 1/3 MIC sucralose, and oxolinic acid after 24 h. Sucralose can increase the antimicrobial resistance and mutation frequency of E.coli to some antimicrobials.

Increased radiation resistance in lithium-counterdoped silicon solar cells

Science.gov (United States)

Weinberg, I.; Swartz, C. K.; Mehta, S.

1984-01-01

Lithium-counterdoped n(+)p silicon solar cells are found to exhibit significantly increased radiation resistance to 1-MeV electron irradiation when compared to boron-doped n(+)p silicon solar cells. In addition to improved radiation resistance, considerable damage recovery by annealing is observed in the counterdoped cells at T less than or equal to 100 C. Deep level transient spectroscopy measurements are used to identify the defect whose removal results in the low-temperature aneal. It is suggested that the increased radiation resistance of the counterdoped cells is primarily due to interaction of the lithium with interstitial oxygen.

Ethanologenic bacteria with increased resistance to furfural

Science.gov (United States)

Miller, Elliot Norman; Jarboe, Laura R.; Yomano, Lorraine P.; York, Sean W.; Shanmugam, Keelnatham; Ingram, Lonnie O'Neal

2015-10-06

The invention relates to bacterium that have increased resistance to furfural and methods of preparation. The invention also relates to methods of producing ethanol using the bacterium and corresponding kits.

Glyphosate-Resistant Goosegrass from Mississippi

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Vijay K. Nandula

2013-05-01

Full Text Available A suspected glyphosate-resistant goosegrass [Eleusine indica (L. Gaertn.] population, found in Washington County, Mississippi, was studied to determine the level of resistance and whether the resistance was due to a point mutation, as was previously identified in a Malaysian population. Whole plant dose response assays indicated a two- to four-fold increase in resistance to glyphosate. Leaf disc bioassays based on a glyphosate-dependent increase in shikimate levels indicated a five- to eight-fold increase in resistance. Sequence comparisons of messenger RNA for epsps, the gene encoding the enzyme 5-enolpyruvylshikimate-3-phosphate synthase, from resistant and sensitive goosegrass, revealed a cytosine to thymine nucleotide change at position 319 in the resistant accessions. This single nucleotide polymorphism causes a proline to serine amino acid substitution at position 106 in 5-enolpyruvylshikimate-3-phosphate synthase. A real-time polymerase chain reaction assay using DNA probes specific for the nucleotide change at position 319 was developed to detect this polymorphism. Goosegrass from 42 locations were screened, and the results indicated that glyphosate-resistant goosegrass remained localized to where it was discovered. Pendimethalin, s-metolachlor, clethodim, paraquat and fluazifop controlled resistant goosegrass 93% to 100%, indicating that several control options for glyphosate-resistant goosegrass are available.

Jahn-Teller and Non-Jahn-Teller Systems Involving CuF64- Units: Role of the Internal Electric Field in Ba2ZnF6:Cu2+ and Other Insulating Systems

DEFF Research Database (Denmark)

Aramburu, J. A.; Garcia-Fernandez, P.; García Lastra, Juan Maria

2017-01-01

The applicability of the Jahn-Teller (JT) framework to 6-fold coordinated d9 ions whose local symmetry is not strictly octahedral is explored by means of first principle calculations. Our results contradict much of the existing literature where these systems are analyzed within the quasi-JT regime...... transitions for CuF64- units formed in Cu2+-doped the tetragonal Ba2ZnF6 host lattice. While the experimental d-d transitions cannot be reproduced through the isolated CuF64- unit at the equilibrium geometry, a reasonable agreement is reached adding in the calculation the internal electric field, ER...... state with the hole in the a1g(∼ 3z2-r2) level while it is always placed in the b1g(∼ x2-y2) level for MX6 complexes (M = Cu2+, Ag2+, NiΤ; X = F--, Cl-) in cubic lattices displaying a static JT effect. While the experimental results of CuF64- in Ba2ZnF6 cannot be understood within the JT framework...

Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

NARCIS (Netherlands)

F.J. Couch (Fergus); M.M. Gaudet (Mia); A.C. Antoniou (Antonis); S.J. Ramus (Susan); K.B. Kuchenbaecker (Karoline); P. Soucy (Penny); J. Beesley (Jonathan); X. Chen (Xiaoqing); X. Wang (Xing); T. Kircchoff (Tomas); L. McGuffog (Lesley); D. Barrowdale (Daniel); A. Lee (Andrew); S. Healey (Sue); O. Sinilnikova (Olga); I.L. Andrulis (Irene); H. Ozcelik (Hilmi); A.M. Mulligan (Anna Marie); M. Thomassen (Mads); A-M. Gerdes (Anne-Marie); U.B. Jensen; A.-B. Skytte (Anne-Bine); T.A. Kruse (Torben); M.A. Caligo (Maria); A. von Wachenfeldt (Anna); G. Barbany-Bustinza (Gisela); N. Loman (Niklas); M. Soller (Maria); H. Ehrencrona (Hans); P. Karlsson (Per); K.L. Nathanson (Katherine); R. Rebbeck (Timothy); S.M. Domchek (Susan); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); K. Durda (Katarzyna); E. Zołwocka (Elzbieta); T. Huzarski (Tomasz); T. Byrski (Tomasz); J. Gronwald (Jacek); C. Cybulski (Cezary); B. Górski (Bohdan); A. Osorio (Ana); M. Durán (Mercedes); M.I. Tejada; J. Benítez (Javier); U. Hamann (Ute); F.B.L. Hogervorst (Frans); T.A.M. van Os (Theo); F.E. van Leeuwen (Flora); E.J. Meijers-Heijboer (Hanne); J.T. Wijnen (Juul); M.J. Blok (Marinus); C.M. Kets; M.J. Hooning (Maartje); R.A. Oldenburg (Rogier); M.G.E.M. Ausems (Margreet); S. Peock (Susan); D. Frost (Debra); S.D. Ellis (Steve); R. Platte (Radka); E. Fineberg (Elena); D.G. Evans (Gareth); C. Jacobs (Chris); R. Eeles (Rosalind); J.W. Adlard (Julian); R. Davidson (Rosemarie); D. Eccles (Diana); T.J. Cole (Trevor); J. Cook (Jackie); J. Paterson (Joan); C. Brewer (Carole); F. Douglas (Fiona); S.V. Hodgson (Shirley); P.J. Morrison (Patrick); L.J. Walker (Lisa); M.E. Porteous (Mary); M.J. Kennedy (John); L. Side (Lucy); B. Bove (B.); A.K. Godwin (Andrew); D. Stoppa-Lyonnet (Dominique); M. Fassy-Colcombet (Marion); L. Castera (Laurent); F. Cornelis (Franco̧is); S. Mazoyer (Sylvie); M. Léone (Mélanie); N. Boutry-Kryza (N.); B. Bressac-de Paillerets (Brigitte); O. Caron (Olivier); P. Pujol (Pascal); I. Coupier (Isabelle); C.D. Delnatte (Capucine); L. Akloul (Linda); H. Lynch (Henry); C.L. Snyder (Carrie); S.S. Buys (Saundra); M.B. Daly (Mary); M.-B. Terry (Mary-Beth); W. Chung (Wendy); E.M. John (Esther); A. Miron (Alexander); M.C. Southey (Melissa); J.L. Hopper (John); D. Goldgar (David); C.F. Singer (Christian); C. Rappaport (Christine); M.-K. Tea; A. Fink-Retter (Anneliese); T.V.O. Hansen (Thomas); F.C. Nielsen (Finn); A. Arason (Adalgeir); J. Vijai (Joseph); S. Shah (Sonia); K. Sarrel (Kara); M. Robson (Mark); M. Piedmonte (Marion); K. Phillips (Kelly); J. Basil (Jack); W.S. Rubinstein (Wendy); J.F. Boggess (John); K. Wakeley (Katie); A. Ewart-Toland (Amanda); M. Montagna (Marco); S. Agata (Simona); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); R. Janavicius (Ramunas); C. Lazaro (Conxi); I. Blanco (Ignacio); L. Feliubadaló (L.); J. Brunet (Joan); S.A. Gayther (Simon); P.D.P. Pharoah (Paul); K. Odunsi (Kunle); B.Y. Karlan (Beth); C.S. Walsh (Christine); E. Olah; S.-H. Teo (Soo-Hwang); P.A. Ganz (Patricia); M.S. Beattie (Mary); E.J. van Rensburg (Elizabeth); C.M. Dorfling (Cecelia); O. Diez (Orland); A. Kwong (Ava); R.K. Schmutzler (Rita); B. Wapenschmidt (Barbara); C.W. Engel (Christoph); A. Meindl (Alfons); N. Ditsch (Nina); N. Arnold (Norbert); S. Heidemann (Simone); D. Niederacher (Dieter); S. Preisler-Adams (Sabine); D. Gadzicki (Dorothea); R. Varon-Mateeva (Raymonda); H. Deissler (Helmut); P.A. Gehrig (Paola A.); C. Sutter (Christian); K. Kast (Karin); B. Fiebig (Britta); W. Heinritz (Wolfram); T. Caldes (Trinidad); M. de La Hoya (Miguel); T.A. Muranen (Taru); H. Nevanlinna (Heli); M. Tischkowitz (Marc); A.B. Spurdle (Amanda); S.L. Neuhausen (Susan); Y.C. Ding (Yuan); N.M. Lindor (Noralane); Z. Fredericksen (Zachary); V.S. Pankratz (Shane); P. Peterlongo (Paolo); S. Manoukian (Siranoush); B. Peissel (Bernard); D. Zaffaroni (D.); M. Barile (Monica); L. Bernard (Loris); A. Viel (Alessandra); G. Giannini (Giuseppe); L. Varesco (Liliana); P. Radice (Paolo); M.H. Greene (Mark); P.L. Mai (Phuong); D.F. Easton (Douglas); G. Chenevix-Trench (Georgia); K. Offit (Kenneth); J. Simard (Jacques)

2012-01-01

textabstractBackground: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for

Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

NARCIS (Netherlands)

Couch, Fergus J.; Gaudet, Mia M.; Antoniou, Antonis C.; Ramus, Susan J.; Kuchenbaecker, Karoline B.; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; Wang, Xianshu; Kirchhoff, Tomas; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Sinilnikova, Olga M.; Andrulis, Irene L.; Ozcelik, Hilmi; Mulligan, Anna Marie; Thomassen, Mads; Gerdes, Anne-Marie; Jensen, Uffe Birk; Skytte, Anne-Bine; Kruse, Torben A.; Caligo, Maria A.; von Wachenfeldt, Anna; Barbany-Bustinza, Gisela; Loman, Niklas; Soller, Maria; Ehrencrona, Hans; Karlsson, Per; Nathanson, Katherine L.; Rebbeck, Timothy R.; Domchek, Susan M.; Jakubowska, Ania; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Zlowocka, Elzbieta; Huzarski, Tomasz; Byrski, Tomasz; Gronwald, Jacek; Cybulski, Cezary; Górski, Bohdan; Osorio, Ana; Durán, Mercedes; Tejada, María Isabel; Benitez, Javier; Hamann, Ute; Hogervorst, Frans B. L.; van Os, Theo A.; van Leeuwen, Flora E.; Meijers-Heijboer, Hanne E. J.; Wijnen, Juul; Blok, Marinus J.; Kets, Marleen; Hooning, Maartje J.; Oldenburg, Rogier A.; Ausems, Margreet G. E. M.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Jacobs, Chris; Eeles, Rosalind A.; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana M.; Cole, Trevor; Cook, Jackie; Paterson, Joan; Brewer, Carole; Douglas, Fiona; Hodgson, Shirley V.; Morrison, Patrick J.; Walker, Lisa; Porteous, Mary E.; Kennedy, M. John; Side, Lucy E.; Bove, Betsy; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Fassy-Colcombet, Marion; Castera, Laurent; Cornelis, François; Mazoyer, Sylvie; Léoné, Mélanie; Boutry-Kryza, Nadia; Bressac-de Paillerets, Brigitte; Caron, Olivier; Pujol, Pascal; Coupier, Isabelle; Delnatte, Capucine; Akloul, Linda; Lynch, Henry T.; Snyder, Carrie L.; Buys, Saundra S.; Daly, Mary B.; Terry, Marybeth; Chung, Wendy K.; John, Esther M.; Miron, Alexander; Southey, Melissa C.; Hopper, John L.; Goldgar, David E.; Singer, Christian F.; Rappaport, Christine; tea, Muy-Kheng M.; Fink-Retter, Anneliese; Hansen, Thomas V. O.; Nielsen, Finn C.; Arason, Aðalgeir; Vijai, Joseph; Shah, Sohela; Sarrel, Kara; Robson, Mark E.; Piedmonte, Marion; Phillips, Kelly; Basil, Jack; Rubinstein, Wendy S.; Boggess, John; Wakeley, Katie; Ewart-Toland, Amanda; Montagna, Marco; Agata, Simona; Imyanitov, Evgeny N.; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Feliubadalo, Lidia; Brunet, Joan; Gayther, Simon A.; Pharoah, Paul P. D.; Odunsi, Kunle O.; Karlan, Beth Y.; Walsh, Christine S.; Olah, Edith; teo, Soo Hwang; Ganz, Patricia A.; Beattie, Mary S.; van Rensburg, Elizabeth J.; Dorfling, Cecelia M.; Diez, Orland; Kwong, Ava; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorothea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Heinritz, Wolfram; Caldes, Trinidad; de la Hoya, Miguel; Muranen, Taru A.; Nevanlinna, Heli; Tischkowitz, Marc D.; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan Chun; Lindor, Noralane M.; Fredericksen, Zachary; Pankratz, V. Shane; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Barile, Monica; Bernard, Loris; Viel, Alessandra; Giannini, Giuseppe; Varesco, Liliana; Radice, Paolo; Greene, Mark H.; Mai, Phuong L.; Easton, Douglas F.; Chenevix-Trench, Georgia; Offit, Kenneth; Simard, Jacques

2012-01-01

Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these

Biodiversity increases the resistance of ecosystem productivity to climate extremes.

Science.gov (United States)

Isbell, Forest; Craven, Dylan; Connolly, John; Loreau, Michel; Schmid, Bernhard; Beierkuhnlein, Carl; Bezemer, T Martijn; Bonin, Catherine; Bruelheide, Helge; de Luca, Enrica; Ebeling, Anne; Griffin, John N; Guo, Qinfeng; Hautier, Yann; Hector, Andy; Jentsch, Anke; Kreyling, Jürgen; Lanta, Vojtěch; Manning, Pete; Meyer, Sebastian T; Mori, Akira S; Naeem, Shahid; Niklaus, Pascal A; Polley, H Wayne; Reich, Peter B; Roscher, Christiane; Seabloom, Eric W; Smith, Melinda D; Thakur, Madhav P; Tilman, David; Tracy, Benjamin F; van der Putten, Wim H; van Ruijven, Jasper; Weigelt, Alexandra; Weisser, Wolfgang W; Wilsey, Brian; Eisenhauer, Nico

2015-10-22

It remains unclear whether biodiversity buffers ecosystems against climate extremes, which are becoming increasingly frequent worldwide. Early results suggested that the ecosystem productivity of diverse grassland plant communities was more resistant, changing less during drought, and more resilient, recovering more quickly after drought, than that of depauperate communities. However, subsequent experimental tests produced mixed results. Here we use data from 46 experiments that manipulated grassland plant diversity to test whether biodiversity provides resistance during and resilience after climate events. We show that biodiversity increased ecosystem resistance for a broad range of climate events, including wet or dry, moderate or extreme, and brief or prolonged events. Across all studies and climate events, the productivity of low-diversity communities with one or two species changed by approximately 50% during climate events, whereas that of high-diversity communities with 16-32 species was more resistant, changing by only approximately 25%. By a year after each climate event, ecosystem productivity had often fully recovered, or overshot, normal levels of productivity in both high- and low-diversity communities, leading to no detectable dependence of ecosystem resilience on biodiversity. Our results suggest that biodiversity mainly stabilizes ecosystem productivity, and productivity-dependent ecosystem services, by increasing resistance to climate events. Anthropogenic environmental changes that drive biodiversity loss thus seem likely to decrease ecosystem stability, and restoration of biodiversity to increase it, mainly by changing the resistance of ecosystem productivity to climate events.

Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

DEFF Research Database (Denmark)

Couch, Fergus J; Gaudet, Mia M; Antoniou, Antonis C

2012-01-01

Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mut...

Pre-cold stress increases acid stress resistance and induces amino ...

African Journals Online (AJOL)

Pre-cold stress increases acid stress resistance and induces amino acid homeostasis in Lactococcus lactis NZ9000. ... Purpose: To investigate the effects of pre-cold stress treatments on subsequent acid stress resistance ... from 32 Countries:.

Specificity protein 1-zinc finger protein 179 pathway is involved in the attenuation of oxidative stress following brain injury

Directory of Open Access Journals (Sweden)

Jian-Ying Chuang

2017-04-01

Full Text Available After sudden traumatic brain injuries, secondary injuries may occur during the following days or weeks, which leads to the accumulation of reactive oxygen species (ROS. Since ROS exacerbate brain damage, it is important to protect neurons against their activity. Zinc finger protein 179 (Znf179 was shown to act as a neuroprotective factor, but the regulation of gene expression under oxidative stress remains unknown. In this study, we demonstrated an increase in Znf179 protein levels in both in vitro model of hydrogen peroxide (H2O2-induced ROS accumulation and animal models of traumatic brain injury. Additionally, we examined the sub-cellular localization of Znf179, and demonstrated that oxidative stress increases Znf179 nuclear shuttling and its interaction with specificity protein 1 (Sp1. Subsequently, the positive autoregulation of Znf179 expression, which is Sp1-dependent, was further demonstrated using luciferase reporter assay and green fluorescent protein (GFP-Znf179-expressing cells and transgenic mice. The upregulation of Sp1 transcriptional activity induced by the treatment with nerve growth factor (NGF led to an increase in Znf179 levels, which further protected cells against H2O2-induced damage. However, Sp1 inhibitor, mithramycin A, was shown to inhibit NGF effects, leading to a decrease in Znf179 expression and lower cellular protection. In conclusion, the results obtained in this study show that Znf179 autoregulation through Sp1-dependent mechanism plays an important role in neuroprotection, and NGF-induced Sp1 signaling may help attenuate more extensive (ROS-induced damage following brain injury.

A 2-megabase physical contig incorporating 43 DNA markers on the human X chromosome at p11.23-p11.22 from ZNF21 to DXS255

Energy Technology Data Exchange (ETDEWEB)

Boycott, K.M.; Bech-Hansen, N.T. [Univ. of Calgary, Alberta (Canada); Halley, G.R.; Schlessinger, D. [Washington Univ. School of Medicine, St. Louis, MO (United States)

1996-05-01

A comprehensive physical contig of yeast artificial chromosomes (YACs) and cosmid clones between ZNF21 and DXS255 has been constructed, spanning 2 Mb within the region Xp11.23-p11.22. As a portion of the region was found to be particularly unstable in yeast, the integrity of the contig is dependent on additional information provided by the sequence-tagged site (STS) content of cosmid clones and DNA marker retention in conventional and radiation hybrids. The contig was formatted with 43 DNA markers, including 19 new STSs from YAC insert ends and an internal Alu-PCR product. The density of STSs across the contig ranges from one marker every 20 kb to one every 60 kb, with an average density of one marker every 50 kb. The relative order of previously known gene and expressed sequence tags in this region is predicted to be Xpter-ZNF21-DXS7465E (MG66)-DXS7927E (MG81)-WASP, DXS1011E, DXS7467E (MG21)-DXS-7466E (MG44)-GATA1-DXS7469E (Xp664)-TFE3-SYP (DXS1007E)-Xcen. This contig extends the coverage in Xp11 and provides a framework for the future identification and mapping of new genes, as well as the resources for developing DNA sequencing templates. 47 refs., 1 fig., 4 tabs.

Helicobacter pylori resistance to metronidazole and clarithromycin in Ireland.

LENUS (Irish Health Repository)

O'connor, Anthony

2012-02-01

INTRODUCTION: Helicobacter pylori eradication rates have fallen considerably in recent years. Antibiotic resistance is thought to be rising. OBJECTIVES: To examine the levels of resistance to metronidazole (MTZ) and clarithromycin (CLA) in H. pylori, isolates were taken in a reference centre in Ireland from 2007 to 2008 and were compared to a similar cohort from a study in 1997. METHOD: Antimicrobial susceptibilities were tested by E-test. Frequencies of spontaneous metronidazole and clarithromycin resistance were measured on an agar plate containing the antibiotics at concentrations of 2x and 4x minimum inhibition concentration values. Clinical data were obtained from charts, laboratory and endoscopy reports. RESULTS: Two hundred and twenty-two patients were analyzed, 98 were females. Colonies amenable to culture were grown in 219 patients. Thirty-seven had prior attempts at eradication therapy (all with amoxicillin-CLA-proton pump inhibitor. A total of 31.5% of the patients had strains resistant to MTZ and 13.2% of the patients were noted to have strains resistant to CLA. About 8.6% of the patients had strains resistant to both the agents. CLA resistance was 9.3% in those who had no prior eradication therapy compared with 32.4% of those who had. CLA resistance increased from 3.9%, among treatment-naive patients in 1997, to 9.3% in our study. MTZ resistance was 29.1% in the treatment-naive population. In 1997, MTZ resistance in the treatment-naive cohort was 27.1%. MTZ resistance was more likely to occur in females (35.4 vs. 28.5%) than in males. CONCLUSION: This study shows that resistance to CLA among Irish patients infected with H. pylori has increased since 1997. The future of treatment may well lie in the widespread use of sensitivity testing before the treatment. This would promote an accurate treatment.

Elastic Resistance Effectiveness on Increasing Strength of Shoulders and Hips.

Science.gov (United States)

Picha, Kelsey J; Almaddah, Muataz R; Barker, Jordan; Ciochetty, Tavis; Black, W Scott; Uhl, Tim L

2017-09-12

Elastic resistance is a common training method used to gain strength. Currently, progression with elastic resistance is based on the perceived exertion of the exercise or completion of targeted repetitions; exact resistance is typically unknown. This study's objective is to determine if knowledge of load during elastic resistance exercise will increase strength gains during exercises. Participants were randomized into two strength training groups, elastic resistance only and elastic resistance using a load cell (LC) that displays force during exercise. The LC group used a Smart Handle (Patterson Medical Supply, Chicago, IL) to complete all exercises. Each participant completed the same exercises three times weekly for 8 weeks. The LC group was provided with a set load for exercises whereas the elastic resistance only group was not. Participant's strength was tested at baseline and program completion, measuring isometric strength for shoulder abduction (SAb), shoulder external rotation (SER), hip abduction (HAb), and hip extension (HEx). Independent t-tests were used to compare the normalized torques between groups. No significant differences were found between groups. Shoulder strength gains did not differ between groups (SAb p>0.05; SER p>0.05). Hip strength gains did not differ between groups (HAb p>0.05; HEx p>0.05). Both groups increased strength due to individual supervision, constantly evaluating degree of difficulty associated with exercise and providing feedback while using elastic resistance. Using a LC is as effective as supervised training and could provide value in a clinic setting when patients are working unsupervised.

Does employee resistance during a robbery increase the risk of customer injury?

Science.gov (United States)

Yau, Rebecca K; Casteel, Carri; Nocera, Maryalice; Bishop, Stephanie F; Peek-Asa, Corinne

2015-04-01

Retail business robberies can lead to employee and customer injury. Previous work demonstrates that employee resistance increases employee injury risk; limited research has investigated customer injuries. This study examines associations between employee resistance against perpetrators and the risk of customer injury. Retail and service robbery reports were obtained from a metropolitan police department. Generalized estimating equations estimated risk ratios and 95% confidence intervals (CIs). Customers were injured in 75 out of 697 robberies. Employees resisted the perpetrator in 32 out of 697 robberies. Customers had higher injury risk when employees resisted the perpetrator, compared with robberies where employees did not resist (adjusted risk ratio [95% CI], 2.6 [1.5 to 4.5]). Employee resistance against a perpetrator during a robbery increased customer injury risk. Businesses can train employees to not resist during a robbery, providing benefits for both customers and the business itself.

Antimicrobial drug resistance evaluations and monitoring in Escherichia coli isolated from poultry environment at different time intervals

International Nuclear Information System (INIS)

Anwar, R.; Khan, M.A.

2004-01-01

A high prevalence of multiple drug resistance was observed in population of E. coli isolated in 1992-93 from poultry carcasses, fluff, hatchery environment and water at different broiler farms in Karachi, Pakistan. Five hundred isolate of E. coli were made of which 375 were tested for their sensitivity of five antimicrobials using the tube dilution method. Similarly, during 1995-1996, 430 E. coli isolates were made (from the same farms) of which 315 were tested for their sensitivity to the same antimicrobials studied in 1992-93. E. coli isolates during 1992-93 and 1995-96 showed increase in resistance from 50 to 56% against amoxicillin, from 62 to 71% against neomycin, from 97 to 100% against oxytetracycline, from 95 to 100% against tetracycline and from 95 to 98% against trimethoprim. It appears that exposure of E. coli of poultry origin in Pakistan to the five studies antimicrobials could well be the cause of increasing antimicrobials resistance. This data supports the growing contention that subtherapeutic doses of antimicrobials should be eliminated as a means of promoting rapid growth. (author)

Antimicrobial drug resistance evaluations and monitoring in Escherichia coli isolated from poultry environment at different time intervals

Energy Technology Data Exchange (ETDEWEB)

Anwar, R; Khan, M A [University of Karachi (Pakistan). Inst. of Environmental Studies

2004-06-01

A high prevalence of multiple drug resistance was observed in population of E. coli isolated in 1992-93 from poultry carcasses, fluff, hatchery environment and water at different broiler farms in Karachi, Pakistan. Five hundred isolate of E. coli were made of which 375 were tested for their sensitivity of five antimicrobials using the tube dilution method. Similarly, during 1995-1996, 430 E. coli isolates were made (from the same farms) of which 315 were tested for their sensitivity to the same antimicrobials studied in 1992-93. E. coli isolates during 1992-93 and 1995-96 showed increase in resistance from 50 to 56% against amoxicillin, from 62 to 71% against neomycin, from 97 to 100% against oxytetracycline, from 95 to 100% against tetracycline and from 95 to 98% against trimethoprim. It appears that exposure of E. coli of poultry origin in Pakistan to the five studies antimicrobials could well be the cause of increasing antimicrobials resistance. This data supports the growing contention that subtherapeutic doses of antimicrobials should be eliminated as a means of promoting rapid growth. (author)

Increase in cellular concrete resistance to brittle fracture

International Nuclear Information System (INIS)

Chernyshov, E.M.; Krokhin, A.M.

1979-01-01

Considered are theoretical premises of decrease in cellular concrete resistance to brittle fracture at the expense of dispersed reinforcement. It is stated experimentally that the introduction of 3% asbestos fibers permits to increase the ultimate extensibility and strength during cellular concrete tension by 15-30% and to increase in unit rupture work 1.4-1.6 time more and therefore to decrease its brittleness

Determination of zirconium 93 and molybdenum 93 in reprocessing nuclear waste

International Nuclear Information System (INIS)

Puech, P.

1998-01-01

The aim of this work is to find new determination methods of zirconium 93 and molybdenum 93 (two long-lived radioelements) contained in reprocessing nuclear waste. 93 Zr has a very long period: 1.5 * 10 6 years. The measurement of this isotope is more performing by the ICP-MS method than by the classical radiochemical measurement methods. 93 Mo disintegrates with a radioactive period of 4000 years and can be detected by radiochemical measurement in particular by X spectrometry. But these radioelements cannot be directly measured on the reprocessing nuclear waste; they require a preliminary chemical separation (removing the radioelements able to interfere and those responsible of the radioactivity of the nuclear waste). The separation is implemented with very potentially selective techniques, using Mo and Zr specific extracting molecules: solvent extraction, emulsified liquid membrane extraction and liquid chromatography extraction (on a resin impregnated by solvent). Studies carried out in CEA/Cadarache, on a synthetic solution simulating a reprocessing nuclear waste, have allowed to show the selective properties of the L'-benzoinoxime for extracting Mo and of TBP for extracting Zr for the three studied techniques. The optimal extraction and separation conditions have been reached with a methodology including experiment plans. At last, the methods have been tested on real reprocessing nuclear waste at Cogema/La Hague. 93 Zr and 93 Mo have been measured in a dissolution solution and in a fission product solution. The obtained values are 2 * 10 6 Bq/l and 10 7 Bq/l for 93 Zr and 500 Bq/l for 93 Mo in a dissolution solution. These methods have allowed to determine too the isotopic compositions for Mo and Zr elements contained in reprocessing nuclear waste. The results are in accordance with those obtained with the Cesar code. (O.M.)

Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number.

Science.gov (United States)

Price, Ric N; Uhlemann, Anne-Catrin; Brockman, Alan; McGready, Rose; Ashley, Elizabeth; Phaipun, Lucy; Patel, Rina; Laing, Kenneth; Looareesuwan, Sornchai; White, Nicholas J; Nosten, François; Krishna, Sanjeev

The borders of Thailand harbour the world's most multidrug resistant Plasmodium falciparum parasites. In 1984 mefloquine was introduced as treatment for uncomplicated falciparum malaria, but substantial resistance developed within 6 years. A combination of artesunate with mefloquine now cures more than 95% of acute infections. For both treatment regimens, the underlying mechanisms of resistance are not known. The relation between polymorphisms in the P falciparum multidrug resistant gene 1 (pfmdr1) and the in-vitro and in-vivo responses to mefloquine were assessed in 618 samples from patients with falciparum malaria studied prospectively over 12 years. pfmdr1 copy number was assessed by a robust real-time PCR assay. Single nucleotide polymorphisms of pfmdr1, P falciparum chloroquine resistance transporter gene (pfcrt) and P falciparum Ca2+ ATPase gene (pfATP6) were assessed by PCR-restriction fragment length polymorphism. Increased copy number of pfmdr1 was the most important determinant of in-vitro and in-vivo resistance to mefloquine, and also to reduced artesunate sensitivity in vitro. In a Cox regression model with control for known confounders, increased pfmdr1 copy number was associated with an attributable hazard ratio (AHR) for treatment failure of 6.3 (95% CI 2.9-13.8, p<0.001) after mefloquine monotherapy and 5.4 (2.0-14.6, p=0.001) after artesunate-mefloquine therapy. Single nucleotide polymorphisms in pfmdr1 were associated with increased mefloquine susceptibility in vitro, but not in vivo. Amplification in pfmdr1 is the main cause of resistance to mefloquine in falciparum malaria. Multidrug resistant P falciparum malaria is common in southeast Asia, but difficult to identify and treat. Genes that encode parasite transport proteins maybe involved in export of drugs and so cause resistance. In this study we show that increase in copy number of pfmdr1, a gene encoding a parasite transport protein, is the best overall predictor of treatment failure with

INCREASED PROLIFERATION RESISTANCE FOR 21ST CENTURY NUCLEAR POWER

International Nuclear Information System (INIS)

Demuth, Scott F.; Thomas, Ken E.; Wallace, Richard K.

2007-01-01

World energy demand and greenhouse gases are expected to significantly increase in the near future. Key developing countries have identified nuclear power as a major contributor to their future energy sources. Consequently, the US and others are currently exploring the concept of a Global Nuclear Energy Partnership (GNEP) to address the concerns of nuclear proliferation. This effort is also being encouraged by the International Atomic Energy Agency (IAEA). While the IAEA currently provides the framework for monitoring of state sponsored nuclear proliferation by way of international treaties, a complimentary action is to promote more proliferation resistant fuel cycles and advanced safeguards technology. As such, it is the responsibility of current technology owners to increase their nuclear fuel cycle proliferation resistance. For those countries that have an active and well-developed fuel cycle, it will require future enhancements. For those countries with extensive nuclear energy experience, yet less active programs, it requires re-engagement for technology development and deployment. The following paper discusses potential fuel cycle and technology changes that affect proliferation resistance; and consequently, may form the basis of future technology development efforts.

Dragon (RGMb) induces oxaliplatin resistance in colon cancer cells.

Science.gov (United States)

Shi, Ying; Huang, Xiao-Xiao; Chen, Guo-Bin; Wang, Ying; Zhi, Qiang; Liu, Yuan-Sheng; Wu, Xiao-Ling; Wang, Li-Fen; Yang, Bing; Xiao, Chuan-Xing; Xing, Hui-Qin; Ren, Jian-Lin; Xia, Yin; Guleng, Bayasi

2016-07-26

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer mortality. Chemotherapy resistance remains a major challenge for treating advanced CRC. Therefore, the identification of targets that induce drug resistance is a priority for the development of novel agents to overcome resistance. Dragon (also known as RGMb) is a member of the repulsive guidance molecule (RGM) family. We previously showed that Dragon expression increases with CRC progression in human patients. In the present study, we found that Dragon inhibited apoptosis and increased viability of CMT93 and HCT116 cells in the presence of oxaliplatin. Dragon induced resistance of xenograft tumor to oxaliplatinin treatment in mice. Mechanistically, Dragon inhibited oxaliplatin-induced JNK and p38 MAPK activation, and caspase-3 and PARP cleavages. Our results indicate that Dragon may be a novel target that induces drug resistance in CRC.

Deletion of Lytic Transglycosylases Increases Beta-Lactam Resistance in Shewanella oneidensis

Science.gov (United States)

Yin, Jianhua; Sun, Yiyang; Sun, Yijuan; Yu, Zhiliang; Qiu, Juanping; Gao, Haichun

2018-01-01

Production of chromosome-encoded β-lactamases confers resistance to β-lactams in many Gram-negative bacteria. Some inducible β-lactamases, especially the class C β-lactamase AmpC in Enterobacteriaceae, share a common regulatory mechanism, the ampR-ampC paradigm. Induction of ampC is intimately linked to peptidoglycan recycling, and the LysR-type transcriptional regulator AmpR plays a central role in the process. However, our previous studies have demonstrated that the expression of class D β-lactamase gene blaA in Shewanella oneidensis is distinct from the established paradigm since an AmpR homolog is absent and major peptidoglycan recycling enzymes play opposite roles in β-lactamase expression. Given that lytic transglycosylases (LTs), a class of peptidoglycan hydrolases cleaving the β-1,4 glycosidic linkage in glycan strands of peptidoglycan, can disturb peptidoglycan recycling, and thus may affect induction of blaA. In this study, we investigated impacts of such enzymes on susceptibility to β-lactams. Deletion of three LTs (SltY, MltB and MltB2) increased β-lactam resistance, while four other LTs (MltD, MltD2, MltF, and Slt2) seemed dispensable to β-lactam resistance. The double LT mutants ΔmltBΔmltB2 and ΔsltYΔmltB2 had β-lactam resistance stronger than any of the single mutants. Deletion of ampG (encoding permease AmpG) and mrcA (encoding penicillin binding protein 1a, PBP1a) from both double LT mutants further increased the resistance to β-lactams. Notably, all increased β-lactam resistance phenotypes were in accordance with enhanced blaA expression. Although significant, the increase in β-lactamase activity after inactivating LTs is much lower than that produced by PBP1a inactivation. Our data implicate that LTs play important roles in blaA expression in S. oneidensis. PMID:29403465

Increase of resistance to cracking on stress relieving of hardened steel

International Nuclear Information System (INIS)

Velichko, V.V.; Zabil'skij, V.V.; Mikheev, G.M.

1995-01-01

Regularities of increase of resistance to cracking during stress relieving of hardened low-alloyed steels were studied, using complex of methods. Effect of carbon, stress concentrator radius, duration and temperature of stress relieving was studies in particular. Results of investigating kinetics of change of physicomechanical properties, hydrogen desorption from hardened specimens showed, that increase of resistance to cracking was caused by desorption from grain boundaries of diffusion-mobile hydrogen, formed during hardening. 18 refs., 8 figs

Interference-free determination of sub ng kg-1 levels of long-lived 93Zr in the presence of high concentrations (μg kg-1) of 93Mo and 93Nb using ICP-MS/MS.

Science.gov (United States)

Petrov, Panayot; Russell, Ben; Douglas, David N; Goenaga-Infante, Heidi

2018-01-01

Long-lived high abundance radionuclides are of increasing interest with regard to decommissioning of nuclear sites and longer term nuclear waste storage and disposal. In many cases, no routine technique is available for their measurement in nuclear waste and low-level (ng kg -1 ) environmental samples. Recent advances in ICP-MS technology offer attractive features for the selective and sensitive determination of a wide range of long-lived radionuclides. In this work, inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS)-based methodology, suitable for accurate routine determinations of 93 Zr at very low (ng kg -1 ) levels in the presence of high levels (μg kg -1 ) of the isobaric interferents 93 Nb and 93 Mo (often present in nuclear waste samples), is reported for the first time. Additionally, a novel and systematic strategy for method development based on the use of non-radioactive isotopes is proposed. It relies on gas-phase chemical reactions for different molecular ion formation to achieve isobaric interference removal. Using cell gas mixtures of NH 3 /He/H 2 or H 2 /O 2 , and suitable mass shifts, the signal from the 93 Nb and 93 Mo isobaric interferences on 93 Zr were suppressed by up to 5 orders of magnitude. The achieved limit of detection for 93 Zr was 1.3 × 10 -5  Bq g -1 (equivalent to 0.14 ng kg -1 ). The sample analysis time is 2 min, which represents a significant improvement in terms of sample throughput, compared to liquid scintillation counting methods. The method described here can be used for routine measurements of 93 Zr at environmentally relevant levels. It can also be combined with radiometric techniques for use towards the standardisation of 93 Zr measurements. Graphical abstract Interference-free determination of 93 Zr in the presence of high concentrations of isobaric 93 Mo and 93 Nb by ICP-MS/MS.

Zinc-finger protein 418 overexpression protects against cardiac hypertrophy and fibrosis.

Directory of Open Access Journals (Sweden)

Liming Pan

Full Text Available This study aimed to investigated the effect and mechanism of zinc-finger protein 418 (ZNF418 on cardiac hypertrophy caused by aortic banding (AB, phenylephrine (PE or angiotensin II (Ang II in vivo and in vitro.The expression of ZNF418 in hearts of patients with dilated cardiomyopathy (DCM or hypertrophic cardiomyopathy (HCM and AB-induced cardiac hypertrophy mice, as well as in Ang II- or PE-induced hypertrophic primary cardiomyocytes was detected by western blotting. Then, the expression of ZNF418 was up-regulated or down-regulated in AB-induced cardiac hypertrophy mice and Ang II -induced hypertrophic primary cardiomyocytes. The hypertrophic responses and fibrosis were evaluated by echocardiography and histological analysis. The mRNA levels of hypertrophy markers and fibrotic markers were detected by RT-qPCR. Furthermore, the phosphorylation and total levels of c-Jun were measured by western blotting.ZNF418 was markedly down-regulated in hearts of cardiac hypertrophy and hypertrophic primary cardiomyocytes. Down-regulated ZNF418 exacerbated the myocyte size and fibrosis, moreover increased the mRNA levels of ANP, BNP, β-MHC, MCIP1.4, collagen 1a, collagen III, MMP-2 and fibronection in hearts of AB-treated ZNF418 knockout mice or Ang II-treated cardiomyocytes with AdshZNF418. Conversely, these hypertrophic responses were reduced in the ZNF418 transgenic (TG mice treated by AB and the AdZNF418-transfected primary cardiomyocytes treated by Ang II. Additionally, the deficiency of ZNF418 enhanced the phosphorylation level of c-jun, and overexpression of ZNF418 suppressed the phosphorylation level of c-jun in vivo and in vitro.ZNF418 maybe attenuate hypertrophic responses by inhibiting the activity of c-jun/AP-1.

Prolonged exposure of methicillin-resistant Staphylococcus aureus (MRSA) COL strain to increasing concentrations of oxacillin results in a multidrug-resistant phenotype

DEFF Research Database (Denmark)

Martins, Ana; Couto, Isabel; Aagaard, Lone

2007-01-01

Our previous studies demonstrated that exposure of a bacterium to increasing concentrations of an antibiotic would increase resistance to that antibiotic as a consequence of activating efflux pumps. This study utilises the same approach; however, it employs the methicillin-resistant Staphylococcus...... aureus (MRSA) COL strain, which is highly resistant to oxacillin (OXA). MRSA COL was adapted to 3200 mg/L of OXA. Changes in resistance to other antibiotics were evaluated and efflux pump activity during the adaptation process was determined. MRSA COL was exposed to stepwise two-fold increases of OXA....... At the end of each step, minimum inhibitory concentration determination for erythromycin (ERY) and other antibiotics was conducted. Reserpine (RES) was employed to evaluate whether resistance to ERY was dependent on efflux pump activity. Efflux pump activity was also evaluated using the ethidium bromide (EB...

Increased corrosion resistance of basalt reinforced cement compositions with nanosilica

OpenAIRE

URKHANOVA Larisa Alekseevna; LKHASARANOV Solbon Aleksandrovich; ROZINA Victoria Yevgenievna; BUYANTUEV Sergey Lubsanovich; BARDAKHANOV Sergey Prokopievich

2014-01-01

Disperse fiber reinforcement is used to improve deformation and shrinkage characteristics, flexural strength of concrete. Basalt roving and thin staple fiber are often used as mineral fibers. The paper considers the problems of using thin basalt fiber produced by centrifugal-blow method. Evaluation of the corrosion resistance of basalt fiber as part of the cement matrix was performed. Nanodispersed silica produced by electron beam accelerator was used to increase corrosion resistance of ba...

Increased Cardiometabolic Risk and Worsening Hypoxemia at High Altitude

OpenAIRE

Miele, Catherine H.; Schwartz, Alan R.; Gilman, Robert H.; Pham, Luu; Wise, Robert A.; Davila-Roman, Victor G.; Jun, Jonathan C.; Polotsky, Vsevolod Y.; Miranda, J. Jaime; Leon-Velarde, Fabiola; Checkley, William

2016-01-01

Miele, Catherine H., Alan R. Schwartz, Robert H. Gilman, Luu Pham, Robert A. Wise, Victor G. Davila-Roman, Jonathan C. Jun, Vsevolod Y. Polotsky, J. Jaime Miranda, Fabiola Leon-Velarde, and William Checkley. Increased cardiometabolic risk and worsening hypoxemia at high altitude. High Alt Med Biol. 17:93���100, 2016.���Metabolic syndrome, insulin resistance, diabetes, and dyslipidemia are associated with an increased risk of cardiovascular disease. While excessive erythrocytosis is associated...

Increased corrosion resistance of basalt reinforced cement compositions with nanosilica

Directory of Open Access Journals (Sweden)

URKHANOVA Larisa Alekseevna

2014-08-01

Full Text Available Disperse fiber reinforcement is used to improve deformation and shrinkage characteristics, flexural strength of concrete. Basalt roving and thin staple fiber are often used as mineral fibers. The paper considers the problems of using thin basalt fiber produced by centrifugal-blow method. Evaluation of the corrosion resistance of basalt fiber as part of the cement matrix was performed. Nanodispersed silica produced by electron beam accelerator was used to increase corrosion resistance of basalt fiber.

Clarithromycin increases linezolid exposure in multidrug-resistant tuberculosis patients

NARCIS (Netherlands)

Bolhuis, Mathieu S.; van Altena, Richard; van Soolingen, Dick; de Lange, Wiel C. M.; Uges, Donald R. A.; van der Werf, Tjip S.; Kosterink, Jos G. W.; Alffenaar, Jan-Willem C.

2013-01-01

The use of linezolid for the treatment of multidrug-resistant tuberculosis is limited by dose-and time-dependent toxicity. Recently, we reported a case of pharmacokinetic drug drug interaction between linezolid and clarithromycin that resulted in increased linezolid exposure. The aim of this

Neratinib resistance and cross-resistance to other HER2-targeted drugs due to increased activity of metabolism enzyme cytochrome P4503A4.

Science.gov (United States)

Breslin, Susan; Lowry, Michelle C; O'Driscoll, Lorraine

2017-02-28

Neratinib is in Phase 3 clinical trials but, unfortunately, the development of resistance is inevitable. Here, we investigated the effects of acquired neratinib resistance on cellular phenotype and the potential mechanism of this resistance. Neratinib-resistant variants of HER2-positive breast cancer cells were developed and their cross-resistance investigated using cytotoxicity assays. Similarly, sensitivity of trastuzumab-resistant and lapatinib-resistant cells to neratinib was assessed. Cellular phenotype changes were evaluated using migration, invasion and anoikis assays. Immunoblotting for HER family members and drug efflux pumps, as well as enzyme activity assays were performed. Neratinib resistance conferred cross-resistance to trastuzumab, lapatinib and afatinib. Furthermore, the efficacy of neratinib was reduced in trastuzumab- and lapatinib-resistant cells. Neratinib-resistant cells were more aggressive than their drug-sensitive counterparts, with increased CYP3A4 activity identified as a novel mechanism of neratinib resistance. The potential of increased CYP3A4 activity as a biomarker and/or target to add value to neratinib warrants investigation.

HIV drug resistance in infants increases with changing prevention of mother-to-child transmission regimens.

Science.gov (United States)

Poppe, Lisa K; Chunda-Liyoka, Catherine; Kwon, Eun H; Gondwe, Clement; West, John T; Kankasa, Chipepo; Ndongmo, Clement B; Wood, Charles

2017-08-24

The objectives of this study were to determine HIV drug resistance (HIVDR) prevalence in Zambian infants upon diagnosis, and to determine how changing prevention of mother-to-child transmission (PMTCT) drug regimens affect drug resistance. Dried blood spot (DBS) samples from infants in the Lusaka District of Zambia, obtained during routine diagnostic screening, were collected during four different years representing three different PMTCT drug treatment regimens. DNA extracted from dried blood spot samples was used to sequence a 1493 bp region of the reverse transcriptase gene. Sequences were analyzed via the Stanford HIVDRdatabase (http://hivdb.standford.edu) to screen for resistance mutations. HIVDR in infants increased from 21.5 in 2007/2009 to 40.2% in 2014. Nonnucleoside reverse transcriptase inhibitor resistance increased steadily over the sampling period, whereas nucleoside reverse transcriptase inhibitor resistance and dual class resistance both increased more than threefold in 2014. Analysis of drug resistance scores in each group revealed increasing strength of resistance over time. In 2014, children with reported PMTCT exposure, defined as infant prophylaxis and/or maternal treatment, showed a higher prevalence and strength of resistance compared to those with no reported exposure. HIVDR is on the rise in Zambia and presents a serious problem for the successful lifelong treatment of HIV-infected children. PMTCT affects both the prevalence and strength of resistance and further research is needed to determine how to mitigate its role leading to resistance.

Carboxylesterase-mediated insecticide resistance: Quantitative increase induces broader metabolic resistance than qualitative change.

Science.gov (United States)

Cui, Feng; Li, Mei-Xia; Chang, Hai-Jing; Mao, Yun; Zhang, Han-Ying; Lu, Li-Xia; Yan, Shuai-Guo; Lang, Ming-Lin; Liu, Li; Qiao, Chuan-Ling

2015-06-01

Carboxylesterases are mainly involved in the mediation of metabolic resistance of many insects to organophosphate (OP) insecticides. Carboxylesterases underwent two divergent evolutionary events: (1) quantitative mechanism characterized by the overproduction of carboxylesterase protein; and (2) qualitative mechanism caused by changes in enzymatic properties because of mutation from glycine/alanine to aspartate at the 151 site (G/A151D) or from tryptophan to leucine at the 271 site (W271L), following the numbering of Drosophila melanogaster AChE. Qualitative mechanism has been observed in few species. However, whether this carboxylesterase mutation mechanism is prevalent in insects remains unclear. In this study, wild-type, G/A151D and W271L mutant carboxylesterases from Culex pipiens and Aphis gossypii were subjected to germline transformation and then transferred to D. melanogaster. These germlines were ubiquitously expressed as induced by tub-Gal4. In carboxylesterase activity assay, the introduced mutant carboxylesterase did not enhance the overall carboxylesterase activity of flies. This result indicated that G/A151D or W271L mutation disrupted the original activities of the enzyme. Less than 1.5-fold OP resistance was only observed in flies expressing A. gossypii mutant carboxylesterases compared with those expressing A. gossypii wild-type carboxylesterase. However, transgenic flies universally showed low resistance to OP insecticides compared with non-transgenic flies. The flies expressing A. gossypii W271L mutant esterase exhibited 1.5-fold resistance to deltamethrin, a pyrethroid insecticide compared with non-transgenic flies. The present transgenic Drosophila system potentially showed that a quantitative increase in carboxylesterases induced broader resistance of insects to insecticides than a qualitative change. Copyright © 2014 Elsevier Inc. All rights reserved.

Increasing trend of metronidazole resistance in the treatment of ...

African Journals Online (AJOL)

Helicobacter pylori are gram negative spiral bacteria that colonize the human stomach. Infection with H. pylori is associated with chronic gastritis, peptic ulcer, gastric adenocarcinoma and gastric mucosaassociated lymphoid tissue (MALT) lymphoma. Antibiotic resistance is an ever increasing problem with the treatment of ...

Evolution of methicillin-resistant Staphylococcus aureus towards increasing resistance

DEFF Research Database (Denmark)

Strommenger, Birgit; Bartels, Mette Damkjær; Kurt, Kevin

2014-01-01

To elucidate the evolutionary history of Staphylococcus aureus clonal complex (CC) 8, which encompasses several globally distributed epidemic lineages, including hospital-associated methicillin-resistant S. aureus (MRSA) and the highly prevalent community-associated MRSA clone USA300.......To elucidate the evolutionary history of Staphylococcus aureus clonal complex (CC) 8, which encompasses several globally distributed epidemic lineages, including hospital-associated methicillin-resistant S. aureus (MRSA) and the highly prevalent community-associated MRSA clone USA300....

Fitness cost of resistance to Bt cotton linked with increased gossypol content in pink bollworm larvae.

Directory of Open Access Journals (Sweden)

Jennifer L Williams

Full Text Available Fitness costs of resistance to Bacillus thuringiensis (Bt crops occur in the absence of Bt toxins, when individuals with resistance alleles are less fit than individuals without resistance alleles. As costs of Bt resistance are common, refuges of non-Bt host plants can delay resistance not only by providing susceptible individuals to mate with resistant individuals, but also by selecting against resistance. Because costs typically vary across host plants, refuges with host plants that magnify costs or make them less recessive could enhance resistance management. Limited understanding of the physiological mechanisms causing fitness costs, however, hampers attempts to increase costs. In several major cotton pests including pink bollworm (Pectinophora gossypiella, resistance to Cry1Ac cotton is associated with mutations altering cadherin proteins that bind this toxin in susceptible larvae. Here we report that the concentration of gossypol, a cotton defensive chemical, was higher in pink bollworm larvae with cadherin resistance alleles than in larvae lacking such alleles. Adding gossypol to the larval diet decreased larval weight and survival, and increased the fitness cost affecting larval growth, but not survival. Across cadherin genotypes, the cost affecting larval growth increased as the gossypol concentration of larvae increased. These results suggest that increased accumulation of plant defensive chemicals may contribute to fitness costs associated with resistance to Bt toxins.

Changing prevalence and resistance patterns in children with drug-resistant tuberculosis in Mumbai.

Science.gov (United States)

Shah, Ira; Shah, Forum

2017-05-01

The prevalence of drug-resistant (DR) tuberculosis (TB) in children is increasing. Although, in India, multi-drug-resistant (MDR) TB rates have been relatively stable, the number of children with pre-extensively drug-resistant and extensively drug-resistant (XDR) TB is increasing. To determine whether the prevalence of DR TB in children in Mumbai is changing and to study the evolving patterns of resistance. A retrospective study was undertaken in 1311 paediatric patients referred between April 2007 and March 2013 to the Paediatric TB clinic at B. J. Wadia Hospital for Children, Mumbai. Children were defined as having DR TB on the basis of drug susceptibility testing (DST) of Mycobacterium tuberculosis grown on culture of body fluids (in the case of extra pulmonary TB) or from gastric lavage/bronchi-alveolar lavage/sputum in patients with pulmonary TB or from DST of the contacts. The prevalence of DR TB was calculated and the type of DR was evaluated yearly and in the pre-2010 and post-2010 eras. The overall prevalence of DR TB was 86 (6.6%) with an increase from 23 (5.6%) patients pre-2010 to 63 (7%) post-2010 (P = 0.40). Nine (10.4%) patients were diagnosed on the basis of contact with a parent with DR TB. Overall fluoroquinolone resistance increased from 9 (39.1%) pre-2010 to 59 (93.7%) post-2010 (P = 0.0001): moxifloxacin resistance increased from 2 (8.7%) to 29 (46%) (P = 0.0018) and ofloxacin resistance increased from 7 (30.4%) to 30 (47.6%) (P = 0.14). Ethionamide resistance also increased from 6 (26.1%) to 31 (49.2%) (P = 0.04), aminoglycoside resistance was one (4.3%) pre-2010 and 12 (19%) post-2010 (P = 0.17) and resistance remained virtually the same for both amikacin [0 pre-2010 and 6 (9.5%) after 2010] and kanamycin [one (4.3%) pre- and 6 (9.5%) post-2010]. Of the first-line drugs, resistance remained the same for isoniazid [23 (100%) to 61 (96.8%)], rifampicin [22 (95.7%) to 51 (80.9%),P = 0.17], pyrazinamide [15 (65.2%) to

Immobilisation increases yeast cells' resistance to dehydration-rehydration treatment.

Science.gov (United States)

Borovikova, Diana; Rozenfelde, Linda; Pavlovska, Ilona; Rapoport, Alexander

2014-08-20

This study was performed with the goal of revealing if the dehydration procedure used in our new immobilisation method noticeably decreases the viability of yeast cells in immobilised preparations. Various yeasts were used in this research: Saccharomyces cerevisiae cells that were rather sensitive to dehydration and had been aerobically grown in an ethanol-containing medium, a recombinant strain of S. cerevisiae grown in aerobic conditions which were completely non-resistant to dehydration and an anaerobically grown bakers' yeast strain S. cerevisiae, as well as a fairly resistant Pichia pastoris strain. Experiments performed showed that immobilisation of all these strains essentially increased their resistance to a dehydration-rehydration treatment. The increase of cells' viability (compared with control cells dehydrated in similar conditions) was from 30 to 60%. It is concluded that a new immobilisation method, which includes a dehydration stage, does not lead to an essential loss of yeast cell viability. Correspondingly, there is no risk of losing the biotechnological activities of immobilised preparations. The possibility of producing dry, active yeast preparations is shown, for those strains that are very sensitive to dehydration and which can be used in biotechnology in an immobilised form. Finally, the immobilisation approach can be used for the development of efficient methods for the storage of recombinant yeast strains. Copyright © 2014 Elsevier B.V. All rights reserved.

42 CFR 93.222 - Research.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Research. 93.222 Section 93.222 Public Health... STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH MISCONDUCT Definitions § 93.222 Research. Research means a systematic experiment, study, evaluation...

9 CFR 93.801 - Prohibitions.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Prohibitions. 93.801 Section 93.801 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... CONVEYANCE AND SHIPPING CONTAINERS Elephants, Hippopotami, Rhinoceroses, and Tapirs § 93.801 Prohibitions...

14 CFR 93.51 - Applicability.

Science.gov (United States)

2010-01-01

... AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES Anchorage, Alaska, Terminal Area § 93.51... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Applicability. 93.51 Section 93.51..., Terminal Area. [Doc. No. FAA-2002-13235, 68 FR 9795, Feb. 28, 2003] ...

42 CFR 93.204 - Contract.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Contract. 93.204 Section 93.204 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS... MISCONDUCT Definitions § 93.204 Contract. Contract means an acquisition instrument awarded under the HHS...

Genetic variation associated with increased insecticide resistance in the malaria mosquito, Anopheles coluzzii.

Science.gov (United States)

Main, Bradley J; Everitt, Amanda; Cornel, Anthony J; Hormozdiari, Fereydoun; Lanzaro, Gregory C

2018-04-04

Malaria mortality rates in sub-Saharan Africa have declined significantly in recent years as a result of increased insecticide-treated bed net (ITN) usage. A major challenge to further progress is the emergence and spread of insecticide resistance alleles in the Anopheles mosquito vectors, like An. coluzzii. A non-synonymous mutation in the para voltage-gated sodium channel gene reduces pyrethroid-binding affinity, resulting in knockdown resistance (kdr). Metabolic mechanisms of insecticide resistance involving detoxification genes like cytochrome P450 genes, carboxylesterases, and glutathione S-transferases are also important. As some gene activity is tissue-specific and/or environmentally induced, gene regulatory variation may be overlooked when comparing expression from whole mosquito bodies under standard rearing conditions. We detected complex insecticide resistance in a 2014 An. coluzzii colony from southern Mali using bottle bioassays. Additional bioassays involving recombinant genotypes from a cross with a relatively susceptible 1995 An. coluzzii colony from Mali confirmed the importance of kdr and associated increased permethrin resistance to the CYP9K1 locus on the X chromosome. Significant differential expression of CYP9K1 was not observed among these colonies in Malpighian tubules. However, the P450 gene CYP6Z1 was overexpressed in resistant individuals following sublethal permethrin exposure and the carboxylesterase gene COEAE5G was constitutively overexpressed. The significant P450-related insecticide resistance observed in the 2014 An. coluzzii colony indicates that ITNs treated with the P450 inhibitor piperonyl butoxide (PBO) would be more effective in this region. The known insecticide resistance gene CYP6Z1 was differentially expressed exclusively in the context of sublethal permethrin exposure, highlighting the importance of tissue-specificity and environmental conditions in gene expression studies. The increased activity of the carboxylesterase

EPR study of Gd sup 3 sup + centres in Tl sub 2 ZnF sub 4 crystals

CERN Document Server

Arakawa, M; Ebisu, H; Takeuchi, H

2003-01-01

EPR measurements have been made at room temperature on Tl sub 2 ZnF sub 4 crystals doped with Gd sup 3 sup + and co-doped with Gd sup 3 sup + and Li sup +. For crystals doped only with Gd sup 3 sup + , a spectrum with tetragonal symmetry (A centre) is observed. For co-doped crystals new spectra with tetragonal (B centre) and monoclinic (C centre) symmetries are observed in place of the spectrum of the A centre. The A centre is identified as the substitutional Gd sup 3 sup + ion at a Zn sup 2 sup + site in six-fold coordination without any local charge compensation in its immediate neighbourhood. On the basis of spin Hamiltonian separation analysis, the separated parameter b sub 2 sub a sub ( sub 1 sub ) for the C centre has a value close to the b sub 2 sup 0 parameter for the B centre. The B and C centres in co-doped crystals are ascribed to a Gd sup 3 sup + ion substituted for a Tl sup + site in nine-fold coordination, where the divalent excess positive charge on Gd sup 3 sup + is compensated by a Li sup + i...

9 CFR 93.500 - Definitions.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Definitions. 93.500 Section 93.500... CONVEYANCE AND SHIPPING CONTAINERS Swine § 93.500 Definitions. Wherever in this subpart the following terms..., Spain, Sweden, and the United Kingdom (England, Scotland, Wales, the Isle of Man, and Northern Ireland...

28 CFR 93.1 - Purpose.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Purpose. 93.1 Section 93.1 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROVISIONS IMPLEMENTING THE VIOLENT CRIME CONTROL AND LAW ENFORCEMENT ACT OF 1994 Drug Courts § 93.1 Purpose. This part sets forth requirements and procedures to ensure...

Coaxial Tubing Systems Increase Artificial Airway Resistance and Work of Breathing.

Science.gov (United States)

Wenzel, Christin; Schumann, Stefan; Spaeth, Johannes

2017-09-01

Tubing systems are an essential component of the ventilation circuit, connecting the ventilator to the patient's airways. Coaxial tubing systems incorporate the inspiratory tube within the lumen of the expiratory one. We hypothesized that by design, these tubing systems increase resistance to air flow compared with conventional ones. We investigated the flow-dependent pressure gradient across coaxial, conventional disposable, and conventional reusable tubing systems from 3 different manufacturers. Additionally, the additional work of breathing and perception of resistance during breathing through the different devices were determined in 18 healthy volunteers. The pressure gradient across coaxial tubing systems was up to 6 times higher compared with conventional ones (1.90 ± 0.03 cm H 2 O vs 0.34 ± 0.01 cm H 2 O, P tubing systems, accordingly. Our findings suggest that the use of coaxial tubing systems should be carefully considered with respect to their increased resistance. Copyright © 2017 by Daedalus Enterprises.

29 CFR 93.105 - Definitions.

Science.gov (United States)

2010-07-01

... services in the private sector. (o) Recipient includes all contractors, subcontractors at any tier, and... 29 Labor 1 2010-07-01 2010-07-01 true Definitions. 93.105 Section 93.105 Labor Office of the Secretary of Labor NEW RESTRICTIONS ON LOBBYING General § 93.105 Definitions. For purposes of this part: (a...

Effect of rs1344706 in the ZNF804A gene on the brain network

Directory of Open Access Journals (Sweden)

Xiongying Chen

2018-01-01

Full Text Available ZNF804A rs1344706 (A/C was the first SNP that reached genome-wide significance for schizophrenia. Recent studies have linked rs1344706 to functional connectivity among specific brain regions. However, no study thus far has examined the role of this SNP in the entire functional connectome. In this study, we used degree centrality to test the role of rs1344706 in the whole-brain voxel-wise functional connectome during the resting state. 52 schizophrenia patients and 128 healthy controls were included in the final analysis. In our whole-brain analysis, we found a significant interaction effect of genotype × diagnosis at the precuneus (PCU (cluster size = 52 voxels, peak voxel MNI coordinates: x = 9, y = −69, z = 63, F = 32.57, FWE corrected P < 0.001. When we subdivided the degree centrality network according to anatomical distance, the whole-brain analysis also found a significant interaction effect of genotype × diagnosis at the PCU with the same peak in the short-range degree centrality network (cluster size = 72 voxels, F = 37.29, FWE corrected P < 0.001. No significant result was found in the long-range degree centrality network. Our results elucidated the contribution of rs1344706 to functional connectivity within the brain network, and may have important implications for our understanding of this risk gene's role in functional dysconnectivity in schizophrenia.

42 CFR 93.512 - Discovery.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Discovery. 93.512 Section 93.512 Public Health... Process § 93.512 Discovery. (a) Request to provide documents. A party may only request another party to...) Responses to a discovery request. Within 30 days of receiving a request for the production of documents, a...

21 CFR 808.93 - Texas.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Texas. 808.93 Section 808.93 Food and Drugs FOOD... and Local Exemptions § 808.93 Texas. (a) The following Texas medical device requirement is enforceable... that, in enforcing this requirement, Texas apply the definition of “used hearing aid” in § 801.420(a)(6...

Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression

DEFF Research Database (Denmark)

Darabi, Hatef; McCue, Karen; Beesley, Jonathan

2015-01-01

of association with both estrogen receptor (ER)-positive (OR = 0.85 [0.82-0.88]) and ER-negative (OR = 0.87 [0.82-0.91]) disease, and was also the SNP most strongly associated with percent mammographic density. iCHAV2 (lead SNP, chr10: 64,258,684:D) and iCHAV3 (lead SNP, rs7922449) were also associated with ER......-positive (OR = 0.93 [0.91-0.95] and OR = 1.06 [1.03-1.09]) and ER-negative (OR = 0.95 [0.91-0.98] and OR = 1.08 [1.04-1.13]) disease. There was weaker evidence for iCHAV4, located 5' of ADO, associated only with ER-positive breast cancer (OR = 0.93 [0.90-0.96]). We found 12, 17, 18, and 2 candidate causal SNPs...... for breast cancer in iCHAVs 1-4, respectively. Chromosome conformation capture analysis showed that iCHAV2 interacts with the ZNF365 and NRBF2 (more than 600 kb away) promoters in normal and cancerous breast epithelial cells. Luciferase assays did not identify SNPs that affect transactivation of ZNF365...

Advanced Wear-resistant Nanocomposites for Increased Energy Efficiency

Energy Technology Data Exchange (ETDEWEB)

Cook, B. A.; Harringa, J. L.; Russel, A. M.

2012-12-01

This report summarizes the work performed by an Ames-led project team under a 4-year DOE-ITP sponsored project titled, 'Advanced Wear-resistant Nanocomposites for Increased Energy Efficiency.' The Report serves as the project deliverable for the CPS agreement number 15015. The purpose of this project was to develop and commercialize a family of lightweight, bulk composite materials that are highly resistant to degradation by erosive and abrasive wear. These materials, based on AlMgB{sub 14}, are projected to save over 30 TBtu of energy per year when fully implemented in industrial applications, with the associated environmental benefits of eliminating the burning of 1.5 M tons/yr of coal and averting the release of 4.2 M tons/yr of CO{sub 2} into the air. This program targeted applications in the mining, drilling, machining, and dry erosion applications as key platforms for initial commercialization, which includes some of the most severe wear conditions in industry. Production-scale manufacturing of this technology has begun through a start-up company, NewTech Ceramics (NTC). This project included providing technical support to NTC in order to facilitate cost-effective mass production of the wear-resistant boride components. Resolution of issues related to processing scale-up, reduction in energy intensity during processing, and improving the quality and performance of the composites, without adding to the cost of processing were among the primary technical focus areas of this program. Compositional refinements were also investigated in order to achieve the maximum wear resistance. In addition, synthesis of large-scale, single-phase AlMgB{sub 14} powder was conducted for use as PVD sputtering targets for nanocoating applications.

GCKR variants increase triglycerides while protecting from insulin resistance in Chinese children.

Science.gov (United States)

Shen, Yue; Wu, Lijun; Xi, Bo; Liu, Xin; Zhao, Xiaoyuan; Cheng, Hong; Hou, Dongqing; Wang, Xingyu; Mi, Jie

2013-01-01

Variants in gene encoding glucokinase regulator protein (GCKR) were found to have converse effects on triglycerides and glucose metabolic traits. We aimed to investigate the influence of GCKR variants for triglycerides and glucose metabolic traits in Chinese children and adults. We genotyped two GCKR variants rs1260326 and rs1260333 in children and adults, and analyzed the association between two variants and triglycerides, glucose, insulin and HOMA-IR using linear regression model, and estimated the effect on insulin resistance using logistic regression model. Rs1260326 and rs1260333 associated with increased triglycerides in children and adults (ptriglycerides in Chinese children and adults. Triglycerides-increasing alleles of GCKR variants reduce insulin and HOMA-IR index, and protect from insulin resistance in children. Our results suggested GCKR has an effect on development of insulin resistance in Chinese children.

Critical role of zinc finger protein 521 in the control of growth, clonogenicity and tumorigenic potential of medulloblastoma cells.

Science.gov (United States)

Spina, Raffaella; Filocamo, Gessica; Iaccino, Enrico; Scicchitano, Stefania; Lupia, Michela; Chiarella, Emanuela; Mega, Tiziana; Bernaudo, Francesca; Pelaggi, Daniela; Mesuraca, Maria; Pazzaglia, Simonetta; Semenkow, Samantha; Bar, Eli E; Kool, Marcel; Pfister, Stefan; Bond, Heather M; Eberhart, Charles G; Steinkühler, Christian; Morrone, Giovanni

2013-08-01

The stem cell-associated transcription co-factor ZNF521 has been implicated in the control of hematopoietic, osteo-adipogenic and neural progenitor cells. ZNF521 is highly expressed in cerebellum and in particular in the neonatal external granule layer that contains candidate medulloblastoma cells-of-origin, and in the majority of human medulloblastomas. Here we have explored its involvement in the control of human and murine medulloblastoma cells. The effect of ZNF521 on growth and tumorigenic potential of human medulloblastoma cell lines as well as primary Ptc1-/+ mouse medulloblastoma cells was investigated in a variety of in vitro and in vivo assays, by modulating its expression using lentiviral vectors carrying the ZNF521 cDNA, or shRNAs that silence its expression. Enforced overexpression of ZNF521 in DAOY medulloblastoma cells significantly increased their proliferation, growth as spheroids and ability to generate clones in single-cell cultures and semisolid media, and enhanced their migratory ability in wound-healing assays. Importantly, ZNF521-expressing cells displayed a greatly enhanced tumorigenic potential in nude mice. All these activities required the ZNF521 N-terminal motif that recruits the nucleosome remodeling and histone deacetylase complex, which might therefore represent an appealing therapeutic target. Conversely, silencing of ZNF521 in human UW228 medulloblastoma cells that display high baseline expression decreased their proliferation, clonogenicity, sphere formation and wound-healing ability. Similarly, Zfp521 silencing in mouse Ptc1-/+ medulloblastoma cells drastically reduced their growth and tumorigenic potential. Our data strongly support the notion that ZNF521, through the recruitment of the NuRD complex, contributes to the clonogenic growth, migration and tumorigenicity of medulloblastoma cells.

Structural and functional organization of the HF.10 human zinc finger gene (ZNF35) located on chromosome 3p21-p22

DEFF Research Database (Denmark)

Lanfrancone, L; Pengue, G; Pandolfi, P P

1992-01-01

We report the structural and functional characterization of the HF.10 zinc finger gene (ZNF35) in normal human cells, as well as a processed pseudogene. The HF.10 gene spans about 13 kb and it is interrupted by three introns. All 11 zinc finger DNA-binding domains are contiguously encoded within...... and partial nucleotide sequencing of the HF.10 pseudogene indicated that it has arisen by retroposition of spliced HF.10 mRNA. In situ hybridization experiments revealed that both the functional locus and the pseudogene map to chromosome 3p21p22, a region that is frequently deleted in small cell lung...... and renal carcinomas. Hybridization of the HF.10 gene and the HF.10 pseudogene DNA probes to metaphases from a small cell lung carcinoma cell line with the 3p deletion revealed that both loci are part of the deleted chromosome region....

Epidemic Increase in Methicillin-resistant Staphylococcus aureus in Copenhagen

DEFF Research Database (Denmark)

Westh, Henrik; Boye, Kit; Bartels, Mette Damkjær

2006-01-01

INTRODUCTION: We have found an epidemic increase in methicillin-resistant Staphylococcus aureus (MRSA) in Copenhagen. The increase has a complex background and involves hospitals, nursing homes and persons nursed in their own home. MATERIAL AND METHODS: We found 33 MRSA patients in 2003 and 121...... in 2004. All isolates have been spa-typed and epidemiologic information collected. RESULTS: The number of MRSA cases has a doubling time of about six months. The epidemic has been caused by many different MRSA types and 31 staphylococcus protein A genotypes (spa types). MRSA has caused several hospital...

9 CFR 93.325 - Horses from Mexico.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Horses from Mexico. 93.325 Section 93... CONVEYANCE AND SHIPPING CONTAINERS Horses Mexico 18 § 93.325 Horses from Mexico. Horses offered for entry from Mexico shall be inspected as provided in §§ 93.306 and 93.323; shall be accompanied by a...

Increased p38-MAPK is responsible for chemotherapy resistance in human gastric cancer cells

International Nuclear Information System (INIS)

Guo, Xianling; Zhang, Baihe; Wu, Mengchao; Wei, Lixin; Ma, Nannan; Wang, Jin; Song, Jianrui; Bu, Xinxin; Cheng, Yue; Sun, Kai; Xiong, Haiyan; Jiang, Guocheng

2008-01-01

Chemoresistance is one of the main obstacles to successful cancer therapy and is frequently associated with Multidrug resistance (MDR). Many different mechanisms have been suggested to explain the development of an MDR phenotype in cancer cells. One of the most studied mechanisms is the overexpression of P-glycoprotein (P-gp), which is a product of the MDR1 gene. Tumor cells often acquire the drug-resistance phenotype due to upregulation of the MDR1 gene. Overexpression of MDR1 gene has often been reported in primary gastric adenocarcinoma. This study investigated the role of p38-MAPK signal pathway in vincristine-resistant SGC7901/VCR cells. P-gp and MDR1 RNA were detected by Western blot analysis and RT-PCR amplification. Mitgen-activated protein kinases and function of P-gp were demonstrated by Western blot and FACS Aria cytometer analysis. Ap-1 activity and cell apoptosis were detected by Dual-Luciferase Reporter Assay and annexin V-PI dual staining. The vincristine-resistant SGC7901/VCR cells with increased expression of the multidrug-resistance 1 (MDR1) gene were resistant to P-gp-related drug and P-gp-unrelated drugs. Constitutive increases of phosphorylated p38-MAPK and AP-1 activities were also found in the drug-resistant cells. Inhibition of p38-MAPK by SB202190 reduced activator protein-1 (AP-1) activity and MDR1 expression levels and increased the sensitivity of SGC7901/VCR cells to chemotherapy. Activation of the p38-MAPK pathway might be responsible for the modulation of P-glycoprotein-mediated and P-glycoprotein-unmediated multidrug resistance in the SGC7901/VCR cell line

A new β chain hemoglobin variant with increased oxygen affinity: Hb Santa Giusta Sardegna [β93(F9)Cys→Trp; HBB c.282T>G].

Science.gov (United States)

Fais, Antonella; Sollaino, Maria Carla; Barella, Susanna; Perseu, Lucia; Era, Benedetta; Corda, Marcella

2012-01-01

During a screening program for the identification of β-thalassemia (β-thal) carriers in Sardinia, Italy, we identified two subjects with increased hemoglobin (Hb) levels and an abnormal Hb variant. The same variant was detected in a family member. DNA sequencing revealed a TGT > TGG mutation at codon 93 of the β-globin gene. Structural analysis demonstrated that the cystine residue at position 93 of the β chain was substituted by tryptophan. Since this amino acid substitution had not yet been reported, we designated this variant Hb Santa Giusta Sardegna for the place of birth of the subjects. This amino acid substitution occurs at the tyrosine pocket of the β chain as well as at the α1β2/α2β1 contact of the quaternary structure of the molecule. The presence of this Hb in the hemolysate causes an increased oxygen affinity, a slightly reduced Bohr effect and a reduced heme-heme interaction (n(50), Hill's constant) in comparison with those of Hb A.

Caloric restriction shortens lifespan through an increase in lipid peroxidation, inflammation and apoptosis in the G93A mouse, an animal model of ALS.

Directory of Open Access Journals (Sweden)

Barkha P Patel

2010-02-01

Full Text Available Caloric restriction (CR extends lifespan through a reduction in oxidative stress, delays the onset of morbidity and prolongs lifespan. We previously reported that long-term CR hastened clinical onset, disease progression and shortened lifespan, while transiently improving motor performance in G93A mice, a model of amyotrophic lateral sclerosis (ALS that shows increased free radical production. To investigate the long-term CR-induced pathology in G93A mice, we assessed the mitochondrial bioenergetic efficiency and oxidative capacity (CS--citrate synthase content and activity, cytochrome c oxidase--COX activity and protein content of COX subunit-I and IV and UCP3-uncoupling protein 3, oxidative damage (MDA--malondialdehyde and PC--protein carbonyls, antioxidant enzyme capacity (Mn-SOD, Cu/Zn-SOD and catalase, inflammation (TNF-alpha, stress response (Hsp70 and markers of apoptosis (Bax, Bcl-2, caspase 9, cleaved caspase 9 in their skeletal muscle. At age 40 days, G93A mice were divided into two groups: Ad libitum (AL; n = 14; 7 females or CR (n = 13; 6 females, with a diet equal to 60% of AL. COX/CS enzyme activity was lower in CR vs. AL male quadriceps (35%, despite a 2.3-fold higher COX-IV/CS protein content. UCP3 was higher in CR vs. AL females only. MnSOD and Cu/Zn-SOD were higher in CR vs. AL mice and CR vs. AL females. MDA was higher (83% in CR vs. AL red gastrocnemius. Conversely, PC was lower in CR vs. AL red (62% and white (30% gastrocnemius. TNF-alpha was higher (52% in CR vs. AL mice and Hsp70 was lower (62% in CR vs. AL quadriceps. Bax was higher in CR vs. AL mice (41% and CR vs. AL females (52%. Catalase, Bcl-2 and caspases did not differ. We conclude that CR increases lipid peroxidation, inflammation and apoptosis, while decreasing mitochondrial bioenergetic efficiency, protein oxidation and stress response in G93A mice.

Cisplatin-resistant cells express increased levels of a factor that recognizes damaged DNA

International Nuclear Information System (INIS)

Chu, G.; Chang, E.

1990-01-01

Cancer treatment with the drug cisplatin is often thwarted by the emergence of drug-resistant cells. To study this phenomenon, the authors identified two independent cellular factors that recognize cisplatin-damaged DNA. One of the two factors, designated XPE binding factor, is deficient in complementation group E of xeroderma pigmentosum, an inherited disease characterized by defective repair of DNA damaged by ultraviolet radiation, cisplatin, and other agents. Human tumor cell lines selected for resistance to cisplatin showed more efficient DNA repair and increased expression of XPE binding factor. These results suggest that XPE binding factor may be responsible, at least in part, for the development of cisplatin resistance in human tumors and that the mechanism may be increased DNA repair

Subinhibitory concentrations of imipenem induce increased resistance to methicillin and imipenem in vitro in methicillin-resistant Staphylococcus aureus.

OpenAIRE

Forbes, B A; McClatchey, K D; Schaberg, D R

1984-01-01

Methicillin-resistant (MR) Staphylococcus aureus that was susceptible to less than 0.75 micrograms of imipenem per ml demonstrated inducible resistance. MR S. aureus preincubated with 0.05 microgram of imipenem per ml grew in medium with an imipenem concentration of 32 micrograms/ml, and methicillin MICs increased 20-fold. Non-MR S. aureus exhibited no induction. Preincubation with methicillin produced no effect. Induction appeared to be a unique interaction of imipenem with MR S. aureus.

14 CFR 437.93 - Compliance monitoring.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Compliance monitoring. 437.93 Section 437.93 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT....93 Compliance monitoring. A permittee must allow access by, and cooperate with, federal officers or...

Deletion variant near ZNF389 is associated with control of ovine lentivirus in multiple sheep flocks

Science.gov (United States)

White, S N; Mousel, M R; Reynolds, J O; Herrmann-Hoesing, L M; Knowles, D P

2014-01-01

Ovine lentivirus (OvLV) is a macrophage-tropic lentivirus found in many countries that causes interstitial pneumonia, mastitis, arthritis and cachexia in sheep. There is no preventive vaccine and no cure, but breed differences suggest marker-assisted selective breeding might improve odds of infection and control of OvLV post-infection. Although variants in TMEM154 have consistent association with odds of infection, no variant in any gene has been associated with host control of OvLV post-infection in multiple animal sets. Proviral concentration is a live-animal diagnostic measure of OvLV control post-infection related to severity of OvLV-induced lesions. A recent genome-wide association study identified a region including four zinc finger genes associated with proviral concentration in one Rambouillet flock. To refine this region, we tested additional variants and identified a small insertion/deletion variant near ZNF389 that showed consistent association with proviral concentration in three animal sets (P sheep from multiple locations and management conditions. Strikingly, one flock had exceptionally high prevalence (>87%, including yearlings) and mean proviral concentration (>950 copies/μg), possibly due to needle sharing. The best estimate of proviral concentration by genotype, obtained from all 1310 OvLV-positive animals tested, showed insertion homozygotes had less than half the proviral concentration of other genotypes (P sheep flocks. PMID:24303974

Concentric resistance training increases muscle strength without affecting microcirculation

Energy Technology Data Exchange (ETDEWEB)

Weber, Marc-Andre [Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg (Germany)], E-mail: MarcAndre.Weber@med.uni-heidelberg.de; Hildebrandt, Wulf [Immunochemistry, German Cancer Research Center (dkfz), Heidelberg (Germany); Schroeder, Leif [Medical Physics in Radiology, German Cancer Research Center (dkfz), Heidelberg (Germany); Kinscherf, Ralf [Department of Anatomy and Developmental Biology, University of Heidelberg, Heidelberg (Germany); Krix, Martin [Radiology, German Cancer Research Center (dkfz), Heidelberg (Germany); Bachert, Peter [Medical Physics in Radiology, German Cancer Research Center (dkfz), Heidelberg (Germany); Delorme, Stefan; Essig, Marco [Radiology, German Cancer Research Center (dkfz), Heidelberg (Germany); Kauczor, Hans-Ulrich [Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg (Germany); Krakowski-Roosen, Holger [National Center for Tumor Diseases (NCT), Heidelberg (Germany)

2010-03-15

Purpose: While the evidence is conclusive regarding the positive effects of endurance training, there is still some controversy regarding the effects of resistance training on muscular capillarity. Thus, the purpose was to assess whether resistance strength training influences resting skeletal muscle microcirculation in vivo. Materials and methods: Thirty-nine middle-aged subjects (15 female, 24 male; mean age, 54 {+-} 9 years) were trained twice a week on an isokinetic system (altogether 16 sessions lasting 50 min, intensity 75% of maximum isokinetic and isometric force of knee flexors and extensors). To evaluate success of training, cross-sectional area (CSA) of the quadriceps femoris muscle and its isokinetic and isometric force were quantified. Muscular capillarization was measured in biopsies of the vastus lateralis muscle. In vivo, muscular energy and lipid metabolites were quantified by magnetic resonance spectroscopy and parameters of muscular microcirculation, such as local blood volume, blood flow and velocity, by contrast-enhanced ultrasound analyzing replenishment kinetics. Results: The significant (P < 0.001) increase in CSA (60 {+-} 16 before vs. 64 {+-} 15 cm{sup 2} after training) and in absolute muscle strength (isometric, 146 {+-} 44 vs. 174 {+-} 50 Nm; isokinetic, 151 {+-} 53 vs. 174 {+-} 62 Nm) demonstrated successful training. Neither capillary density ex vivo (351 {+-} 75 vs. 326 {+-} 62) nor ultrasonographic parameters of resting muscle perfusion were significantly different (blood flow, 1.2 {+-} 1.2 vs. 1.1 {+-} 1.1 ml/min/100 g; blood flow velocity, 0.49 {+-} 0.44 vs. 0.52 {+-} 0.74 mm s{sup -1}). Also, the intensities of high-energy phosphates phosphocreatine and {beta}-adenosintriphosphate were not different after training within the skeletal muscle at rest ({beta}-ATP/phosphocreatine, 0.29 {+-} 0.06 vs. 0.28 {+-} 0.04). Conclusion: The significant increase in muscle size and strength in response to concentric isokinetic and isometric

10 CFR 76.93 - Quality assurance.

Science.gov (United States)

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Quality assurance. 76.93 Section 76.93 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Safety § 76.93 Quality assurance. The Corporation shall establish, maintain, and execute a quality assurance program satisfying each of...

25 CFR 700.93 - Relocation plan.

Science.gov (United States)

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Relocation plan. 700.93 Section 700.93 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.93 Relocation plan. The relocation plan shall be the plan prepared...

40 CFR 93.154 - Conformity analysis.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Conformity analysis. 93.154 Section 93...) DETERMINING CONFORMITY OF FEDERAL ACTIONS TO STATE OR FEDERAL IMPLEMENTATION PLANS Determining Conformity of General Federal Actions to State or Federal Implementation Plans § 93.154 Conformity analysis. Any Federal...

Mixed-Methods Resistance Training Increases Power and Strength of Young and Older Men.

Science.gov (United States)

Newton, Robert U.; Hakkinen, Keijo; Hakkinen, Arja; McCormick, Matt; Volek, Jeff; Kraemer, William J.

2002-01-01

Examined the effects of a 10-week, mixed-methods resistance training program on young and older men. Although results confirmed some age-related reductions in muscle strength and power, the older men demonstrated similar capacity to the younger men for increases in muscle strength and power via an appropriate, periodized resistance training…

Insulin-mediated increases in renal plasma flow are impaired in insulin-resistant normal subjects

NARCIS (Netherlands)

ter Maaten, JC; Bakker, SJL; Serne, EH; Moshage, HJ; Gans, ROB

2000-01-01

Background Impaired vasodilatation in skeletal muscle is a possible mechanism linking insulin resistance to blood pressure regulation. Increased renal vascular resistance has been demonstrated in the offspring of essential hypertensives. We assessed whether insulin-mediated renal vasodilatation is

9 CFR 93.916 - Special provisions.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Special provisions. 93.916 Section 93... § 93.916 Special provisions. (a) Slaughter. Live VHS-regulated fish from VHS-regulated regions may be... establishment discharges its waste water to a municipal sewage system that includes waste water disinfection...

The contribution of agricultural insecticide use to increasing insecticide resistance in African malaria vectors

OpenAIRE

Reid, Molly C.; McKenzie, F. Ellis

2016-01-01

The fight against malaria is increasingly threatened by failures in vector control due to growing insecticide resistance. This review examines the recent primary research that addresses the putative relationship between agricultural insecticide use and trends in insecticide resistance. To do so, descriptive evidence offered by the new research was categorized, and additional factors that impact the relationship between agricultural insecticide use and observed insecticide resistance in malari...

7 CFR 93.4 - Analytical methods.

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2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Analytical methods. 93.4 Section 93.4 Agriculture... PROCESSED FRUITS AND VEGETABLES Citrus Juices and Certain Citrus Products § 93.4 Analytical methods. (a) The majority of analytical methods for citrus products are found in the Official Methods of Analysis of AOAC...

14 CFR 125.93 - Airplane limitations.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Airplane limitations. 125.93 Section 125.93...: AIRPLANES HAVING A SEATING CAPACITY OF 20 OR MORE PASSENGERS OR A MAXIMUM PAYLOAD CAPACITY OF 6,000 POUNDS OR MORE; AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Airplane Requirements § 125.93 Airplane...

Decision and cost analysis of empirical antibiotic therapy of acute sinusitis in the era of increasing antimicrobial resistance: do we have an additional tool for antibiotic policy decisions?

Science.gov (United States)

Babela, Robert; Jarcuska, Pavol; Uraz, Vladimir; Krčméry, Vladimír; Jadud, Branislav; Stevlik, Jan; Gould, Ian M

2017-11-01

No previous analyses have attempted to determine optimal therapy for upper respiratory tract infections on the basis of cost-minimization models and the prevalence of antimicrobial resistance among respiratory pathogens in Slovakia. This investigation compares macrolides and cephalosporines for empirical therapy and look at this new tool from the aspect of potential antibiotic policy decision-making process. We employed a decision tree model to determine the threshold level of macrolides and cephalosporines resistance among community respiratory pathogens that would make cephalosporines or macrolides cost-minimising. To obtain information on clinical outcomes and cost of URTIs, a systematic review of the literature was performed. The cost-minimization model of upper respiratory tract infections (URTIs) treatment was derived from the review of literature and published models. We found that the mean cost of empirical treatment with macrolides for an URTIs was €93.27 when the percentage of resistant Streptococcus pneumoniae in the community was 0%; at 5%, the mean cost was €96.45; at 10%, €99.63; at 20%, €105.99, and at 30%, €112.36. Our model demonstrated that when the percentage of macrolide resistant Streptococcus pneumoniae exceeds 13.8%, use of empirical cephalosporines rather than macrolides minimizes the treatment cost of URTIs. Empirical macrolide therapy is less expensive than cephalosporines therapy for URTIs unless macrolide resistance exceeds 13.8% in the community. Results have important antibiotic policy implications, since presented model can be use as an additional decision-making tool for new guidelines and reimbursement processes by local authorities in the era of continual increase in antibiotic resistance.

Wear resistance of AISI 304 stainless steel submitted to low temperature plasma carburizing

Directory of Open Access Journals (Sweden)

Marcos Antônio Barcelos

Full Text Available Abstract Despite the AISI 304 stainless steel has high corrosion/oxidation resistance, its tribological properties are poor, being one of the barriers for use in severe wear applications. Thus, there is a wide field for studying technologies that aim to increase the surface hardness and wear resistance of this material. In this work, hardness and wear resistance for AISI 304 stainless steel submitted to the thermochemical treatment by low temperature plasma carburizing (LTPC in a fixed gas mixture composition of 93% H2 and 7% CH4 are presented. Through the evaluation of the carburizing layers, it was possible to observe a substantial improvement in tribological properties after all temperature and time of treatment. This improvement is directly related to the increase of the process variables; among them temperature has a stronger influence on the wear resistance obtained using LTPC process.

Increased corrosion resistance of the AZ80 magnesium alloy by rapid solidification.

Science.gov (United States)

Aghion, E; Jan, L; Meshi, L; Goldman, J

2015-11-01

Magnesium (Mg) and Mg-alloys are being considered as implantable biometals. Despite their excellent biocompatibility and good mechanical properties, their rapid corrosion is a major impediment precluding their widespread acceptance as implantable biomaterials. Here, we investigate the potential for rapid solidification to increase the corrosion resistance of Mg alloys. To this end, the effect of rapid solidification on the environmental and stress corrosion behavior of the AZ80 Mg alloy vs. its conventionally cast counterpart was evaluated in simulated physiological electrolytes. The microstructural characteristics were examined by optical microscopy, SEM, TEM, and X-ray diffraction analysis. The corrosion behavior was evaluated by immersion, salt spraying, and potentiodynamic polarization. Stress corrosion resistance was assessed by Slow Strain Rate Testing. The results indicate that the corrosion resistance of rapidly solidified ribbons is significantly improved relative to the conventional cast alloy due to the increased Al content dissolved in the α-Mg matrix and the correspondingly reduced presence of the β-phase (Mg17 Al12 ). Unfortunately, extrusion consolidated solidified ribbons exhibited a substantial reduction in the environmental performance and stress corrosion resistance. This was mainly attributed to the detrimental effect of the extrusion process, which enriched the iron impurities and increased the internal stresses by imposing a higher dislocation density. In terms of immersion tests, the average corrosion rate of the rapidly solidified ribbons was <0.4 mm/year compared with ∼2 mm/year for the conventionally cast alloy and 26 mm/year for the rapidly solidified extruded ribbons. © 2014 Wiley Periodicals, Inc.

Association Between rs1344706 of ZNF804A and Schizophrenia: A Meta-analysis

Directory of Open Access Journals (Sweden)

Meiyan Zhu

2014-12-01

Full Text Available Schizophrenia is one of the most serious mental diseases found in humans. Previous studies indicated that the single nucleotide polymorphism (SNP rs1344706 in the gene ZNF804A encoding zinc finger protein 804A was associated with schizophrenia in Caucasian population but not in Chinese Han population. However, current results are conflicting in Asian population. In the present study, a meta-analysis was performed to revisit the association between rs1344706 and the risk of schizophrenia in Asian, Caucasian and other populations. Electronic search of PubMed database identified 25 case–control studies with available genotype frequencies of rs1344706 for the meta-analysis, involving a total of 15,788 cases and 22,654 controls. A pooled odds ratio (OR with 95% confidence interval (CI was used to assess the association. The current meta-analysis showed an association between rs1344706 and schizophrenia in Caucasian populations (P = 0.028, OR = 1.138, 95% CI: 1.014–1.278; P = 0.004 for heterogeneity and Asian populations (P = 0.008, OR = 1.092, 95% CI: 1.023–1.165; P = 0.001 for heterogeneity, but not in other populations (P = 0.286, OR = 1.209, 95% CI: 0.853–1.714, P = 0.120 for heterogeneity. Egger’s test (P > 0.05 and Begg’s test (P > 0.05 are both suggestive of the lack of publication bias for the included studies. Thus, the absence of association in other populations suggests a genetic heterogeneity in the susceptibility of schizophrenia and demonstrates the difficulties in replicating genome-wide association study findings regarding schizophrenia across different ethnic populations. To validate the association between rs1344706 and schizophrenia, further studies with larger participant populations worldwide are needed.

Increase of the electrical resistance of thin copper film due to 14 MeV neutron irradiation

International Nuclear Information System (INIS)

Agrawal, S.K.; Kumar, U.; Nigam, A.K.; Singh, S.P.

1981-01-01

The variation in the electrical resistance of thin copper film (500 A 0 thick), grown on the glass slide has been measured with increasing 14 MeV neutron irradiation time. The electrical resistance vs irradiation time curve shows an interesting behaviour after an irradiation of 40 minutes. However, there is a net increase in the electrical resistance with increasing neutron dose. The maximum increase in the observed electrical resistance after an irradiation of 115 mins, is 4.45%. The microstructural studies of irradiated film were made using TEM and TED techniques. The TEM patterns up to an irradiation time of 1.00 hr do not show any appreciable change in the microstructure. The TED patterns also do not show any appreciable change in the diffraction pattern up to an irradiation time of 1.0 hr. But after an irradiation time of 1.5 hrs, two extra rings appear in the TED pattern which disappear with increasing neutron irradiation time

42 CFR 93.210 - Good faith.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Good faith. 93.210 Section 93.210 Public Health... MISCONDUCT Definitions § 93.210 Good faith. Good faith as applied to a complainant or witness, means having a... allegation or cooperation with a research misconduct proceeding is not in good faith if made with knowing or...

Jahn-Teller and Non-Jahn-Teller Systems Involving CuF64- Units: Role of the Internal Electric Field in Ba2ZnF6:Cu2+ and Other Insulating Systems

DEFF Research Database (Denmark)

Aramburu, J. A.; Garcia-Fernandez, P.; García Lastra, Juan Maria

2017-01-01

transitions for CuF64- units formed in Cu2+-doped the tetragonal Ba2ZnF6 host lattice. While the experimental d-d transitions cannot be reproduced through the isolated CuF64- unit at the equilibrium geometry, a reasonable agreement is reached adding in the calculation the internal electric field, ER...... it is pointed out that a quasi-JT situation can however happen for a d9 ion in a cubic lattice under a strain of ∼10-3 in agreement with experimental data. The present results stress the key role played by the internal electric fields for a quantitative understanding of compounds with transition metal cations...

9 CFR 93.317 - Horses from Canada.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Horses from Canada. 93.317 Section 93... CONVEYANCE AND SHIPPING CONTAINERS Horses Canada 16 § 93.317 Horses from Canada. (a) Except as provided in paragraph (c) of this section, horses from Canada shall be inspected as provided in § 93.306; shall be...

Impetigo: A need for new therapies in a world of increasing antimicrobial resistance.

Science.gov (United States)

D'Cunha, N M; Peterson, G M; Baby, K E; Thomas, J

2018-02-01

Impetigo is a highly contagious bacterial skin infection and is one of the most common skin infections in children. Antibiotics are the first-line treatment when multiple lesions exist, but with an increasing prevalence of antibiotic-resistant bacteria the successful management of impetigo in the future is an area of concern. Current treatment options that favour the use of oral antibiotic therapy are increasingly problematic. Widespread use of these agents contributes to antimicrobial resistance and has adverse consequences for individuals and communities. There is a need for new topical antimicrobials and antiseptics as an alternative treatment strategy. To successfully treat impetigo into the future and ensure that therapy does not contribute to bacterial resistance, additional research is required to ascertain the usefulness of alternative agents, including new topical antimicrobials and antiseptics. © 2017 John Wiley & Sons Ltd.

14 CFR 141.93 - Enrollment.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Enrollment. 141.93 Section 141.93 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SCHOOLS AND... limitations and simulated emergency landing instructions; and (x) A description of and instructions regarding...

Field and polarity dependence of time-to-resistance increase in Fe-O films studied by constant voltage stress method

International Nuclear Information System (INIS)

Eriguchi, Koji; Ohta, Hiroaki; Ono, Kouichi; Wei Zhiqiang; Takagi, Takeshi

2009-01-01

Constant voltage stress (CVS) was applied to Fe-O films prepared by a sputtering process to investigate a stress-induced resistance increase leading to a fundamental mechanism for switching behaviors. Under the CVS, an abrupt resistance increase was found for both stress polarities. A conduction mechanism after the resistance increase exhibited non-Ohmic transport. The time-to-resistance increase (t r ) under the CVS was revealed to strongly depend on stress voltage as well as the polarity. From a polarity-dependent resistance increase determined by a time-zero measurement, the voltage and polarity-dependent t r were discussed on the basis of field- and structure-enhanced thermochemical reaction mechanisms

Irradiated aromatic polysulphones of increased flow resistance and molecular weight

International Nuclear Information System (INIS)

Staniland, P.A.; Jarrett, W.G.

1976-01-01

Aromatic polymers of increased resistance to flow and molecular weight are obtained by irradiation using β-rays or γ-rays at temperatures up to 400 0 C of an aromatic polymer whose molecular chains comprise benzenoid groups and bivalent linking groups, and where irradiation is γ-rays by heating subsequent to irradiation at 200 to 400 0 C

42 CFR 93.108 - Confidentiality.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Confidentiality. 93.108 Section 93.108 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.208 - Evidence.

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2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Evidence. 93.208 Section 93.208 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.226 - Retaliation.

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2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Retaliation. 93.226 Section 93.226 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.211 - Hearing.

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2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Hearing. 93.211 Section 93.211 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH MISCONDUCT...

42 CFR 93.225 - Respondent.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Respondent. 93.225 Section 93.225 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.213 - Institution.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Institution. 93.213 Section 93.213 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.212 - Inquiry.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Inquiry. 93.212 Section 93.212 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH MISCONDUCT...

42 CFR 93.201 - Allegation.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Allegation. 93.201 Section 93.201 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.215 - Investigation.

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2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Investigation. 93.215 Section 93.215 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.102 - Applicability.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Applicability. 93.102 Section 93.102 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.203 - Complainant.

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2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Complainant. 93.203 Section 93.203 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.218 - Person.

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2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Person. 93.218 Section 93.218 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH MISCONDUCT...

42 CFR 93.216 - Notice.

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2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Notice. 93.216 Section 93.216 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH MISCONDUCT...

Enhanced resistance to fluoroquinolones in laboratory-grown mutants & clinical isolates of Shigella due to synergism between efflux pump expression & mutations in quinolone resistance determining region

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Neelam Taneja

2015-01-01

Full Text Available Background & objectives: There is a worldwide emergence of fluoroquinolone resistance in Shigella species. To understand the molecular mechanisms associated with fluoroquinolone resistance, naturally occurring fluoroquinolone-resistant strains and laboratory-induced spontaneous mutants of Shigella spp. were used and the relative contributions of acrAB-tolC efflux pumps, gyrase and topoisomerase target gene mutations towards fluoroquinolone resistance were determined. Methods: Eight Shigella flexneri and six S. dysenteriae clinical isolates were studied. Three consecutive mutants resistant to ciprofloxacin for S. flexneri SFM1 (≥0.25 µg/ml, SFM2 (≥4 µg/ml and SFM3 (≥32 µg/ml were selected in 15 steps from susceptible isolates by serial exposure to increasing concentrations of nalidixic acid and ciprofloxacin. Similarly, two mutants for S. dysenteriae SDM1 (≥0.25 µg/ml and SDM2 (≥4 µg/ml were selected in eight steps. After PCR amplification sequence analyses of gyrase and topoisomerase target genes were performed. Expression of efflux genes acrA, acrB, acrR and tolC was measured using real-time PCR. Results: Mutations were observed in gyrA Ser [83]→Leu, Asp [87]→Asn/Gly, Val [196]→Ala and in parC Phe [93]→Val, Ser [80]→Ile, Asp [101]→Glu and Asp [110]→Glu. Overall, acrA and acrB overexpression was associated with fluoroquinolone resistance ( p0 <0.05; while tolC and acrR expression levels did not. Interpretation & conclusions: Fluoroquinolone resistance in Shigella spp. is the end product of either a single or a combination of mutations in QRDRs and/ or efflux activity. Novel polymorphisms were observed at Val [196]→Ala in gyrA in clinical isolates and Phe [93]→Val, Asp [101]→Glu, Asp [110]→Glu and in parC in majority of laboratory-grown mutants.

A treatment plant receiving waste water from multiple bulk drug manufacturers is a reservoir for highly multi-drug resistant integron-bearing bacteria.

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Nachiket P Marathe

Full Text Available The arenas and detailed mechanisms for transfer of antibiotic resistance genes between environmental bacteria and pathogens are largely unclear. Selection pressures from antibiotics in situations where environmental bacteria and human pathogens meet are expected to increase the risks for such gene transfer events. We hypothesize that waste-water treatment plants (WWTPs serving antibiotic manufacturing industries may provide such spawning grounds, given the high bacterial densities present there together with exceptionally strong and persistent selection pressures from the antibiotic-contaminated waste. Previous analyses of effluent from an Indian industrial WWTP that processes waste from bulk drug production revealed the presence of a range of drugs, including broad spectrum antibiotics at extremely high concentrations (mg/L range. In this study, we have characterized the antibiotic resistance profiles of 93 bacterial strains sampled at different stages of the treatment process from the WWTP against 39 antibiotics belonging to 12 different classes. A large majority (86% of the strains were resistant to 20 or more antibiotics. Although there were no classically-recognized human pathogens among the 93 isolated strains, opportunistic pathogens such as Ochrobactrum intermedium, Providencia rettgeri, vancomycin resistant Enterococci (VRE, Aerococcus sp. and Citrobacter freundii were found to be highly resistant. One of the O. intermedium strains (ER1 was resistant to 36 antibiotics, while P. rettgeri (OSR3 was resistant to 35 antibiotics. Class 1 and 2 integrons were detected in 74/93 (80% strains each, and 88/93 (95% strains harbored at least one type of integron. The qPCR analysis of community DNA also showed an unprecedented high prevalence of integrons, suggesting that the bacteria living under such high selective pressure have an appreciable potential for genetic exchange of resistance genes via mobile gene cassettes. The present study provides

Field and polarity dependence of time-to-resistance increase in Fe–O films studied by constant voltage stress method

OpenAIRE

Eriguchi, Koji; Wei, Zhiqiang; Takagi, Takeshi; Ohta, Hiroaki; Ono, Kouichi

2009-01-01

Constant voltage stress (CVS) was applied to Fe–O films prepared by a sputtering process to investigate a stress-induced resistance increase leading to a fundamental mechanism for switching behaviors. Under the CVS, an abrupt resistance increase was found for both stress polarities. A conduction mechanism after the resistance increase exhibited non-Ohmic transport. The time-to-resistance increase (tr) under the CVS was revealed to strongly depend on stress voltage as well as the polarity. Fro...

Radiation resistance in mice increased following chronic application of Li/sub 2/CO/sub 3/

Energy Technology Data Exchange (ETDEWEB)

Vacek, A.; Sikulova, J.; Bartonickova, A. (Ceskoslovenska Akademie Ved, Brno. Biofysikalni Ustav)

1982-01-01

In experiments on strain H mice the increased radiation resistance of mice was analysed after three weeks' feeding with a diet including Li given as lithium carbonicum. The concentration of Li in the serum during the first three days of feeding was increased to 0.5 mmol/l and remained at that level to the end of feeding. The application of Li increased the overall number of stem cells in the spleen by 80 per cent compared with the control group. D/sub 0/ of the line of dependence of the number of endogenous colonies on radiation dose increased following Li application by 1.2 Gy compared with controls. The proliferation activity of haemopoietic stem cells observed 90 min after injection of hydroxyurea was, after 21 days feeding with a mixture containing Li, increased by 200 per cent. The results support the idea that the increased radiation resistance of mice following feeding with Li salts before irradiation may be due to the increased content and resistance of the haemopoietic stem cells, as well as activation of granulopoiesis.

Growth on Alpha-Ketoglutarate Increases Oxidative Stress Resistance in the Yeast Saccharomyces cerevisiae

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Maria Bayliak

2017-01-01

Full Text Available Alpha-ketoglutarate (AKG is an important intermediate in cell metabolism, linking anabolic and catabolic processes. The effect of exogenous AKG on stress resistance in S. cerevisiae cells was studied. The growth on AKG increased resistance of yeast cells to stresses, but the effects depended on AKG concentration and type of stressor. Wild-type yeast cells grown on AKG were more resistant to hydrogen peroxide, menadione, and transition metal ions (Fe2+ and Cu2+ but not to ethanol and heat stress as compared with control ones. Deficiency in SODs or catalases abolished stress-protective effects of AKG. AKG-supplemented growth led to higher values of total metabolic activity, level of low-molecular mass thiols, and activities of catalase and glutathione reductase in wild-type cells compared with the control. The results suggest that exogenous AKG may enhance cell metabolism leading to induction of mild oxidative stress. It turn, it results in activation of antioxidant system that increases resistance of S. cerevisiae cells to H2O2 and other stresses. The presence of genes encoding SODs or catalases is required for the expression of protective effects of AKG.

42 CFR 93.101 - Purpose.

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2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Purpose. 93.101 Section 93.101 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH MISCONDUCT General...

Unlike physical exercise, modified environment increases the lifespan of SOD1G93A mice however both conditions induce cellular changes.

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Yannick N Gerber

Full Text Available Amyotrophic lateral sclerosis (ALS is characterized by a gradual muscular paralysis resulting from progressive motoneurons death. ALS etiology remains unknown although it has been demonstrated to be a multifactorial disease involving several cellular partners. There is currently no effective treatment. Even if the effect of exercise is under investigation for many years, whether physical exercise is beneficial or harmful is still under debate.We investigated the effect of three different intensities of running exercises on the survival of SOD1(G93A mice. At the early-symptomatic stage (P60, males were isolated and randomly assigned to 5 conditions: 2 sedentary groups ("sedentary" and "sedentary treadmill" placed on the inert treadmill, and 3 different training intensity groups (5 cm/s, 10 cm/s and 21 cm/s; 15 min/day, 5days/week. We first demonstrated that an appropriate "control" of the environment is of the utmost importance since comparison of the two sedentary groups evidenced an 11.6% increase in survival in the "sedentary treadmill" group. Moreover, we showed by immunohistochemistry that this increased lifespan is accompanied with motoneurons survival and increased glial reactivity in the spinal cord. In a second step, we showed that when compared with the proper control, all three running-based training did not modify lifespan of the animals, but result in motoneurons preservation and changes in glial cells activation.We demonstrate that increase in survival induced by a slight daily modification of the environment is associated with motoneurons preservation and strong glial modifications in the lumbar spinal cord of SOD1(G93A. Using the appropriate control, we then demonstrate that all running intensities have no effect on the survival of ALS mice but induce cellular modifications. Our results highlight the critical importance of the control of the environment in ALS studies and may explain discrepancy in the literature regarding the

Crack resistance increasing in epoxide-rubber coatings of NPP room floors

International Nuclear Information System (INIS)

Khorenzhenko, V.I.

1986-01-01

Problems of crack resistance increasing in epoxide-rubber coatings for the floors are considered. Exploitation experience of the floors in the special rooms of NPP is given. Perspectivity of application of the compositions described as the building materials for nuclear power stations is pointed out

Detection of Macrolide, Lincosamide and Streptogramin Resistance among Methicillin Resistant Staphylococcus aureus (MRSA in Mumbai

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Arunagiri Subramanian

2015-01-01

Full Text Available Background: The increase in incidence of Methicillin Resistant Staphyloccocus aureus (MRSA and its extraordinary potential to develop antimicrobial resistance has highlighted the need for better agents to treat such infections. This has led to a renewed interest in use of new drugs for treatment with clindamycin and quinuprsitin-dalfopristin being the preferred choice for treatment. Aim & Objectives: This study was undertaken to detect the prevalence of MacrolideLincosamide-Streptogramin (MLS resistance among clinical isolates of MRSA.Material and Methods:Two hundred and thirty clinical isolates of S. aureus were subjected to routine antibiotic susceptibility testing including cefoxitin, erythromycin and quinupristindalfopristin. Inducible resistance to clindamycin was tested by 'D' test as per Clinical and Laboratory Standards Institute (CLSI guidelines. Results: Out of all S. aureus isolates, 93.91% were identified as MRSA. In the disc diffusion testing, 81.5% of isolates showed erythromycin resistance. Among these, the prevalence of constitutive (cMLS , inducible (iMLS b b and MS-phenotype were 35.80%, 31.82% and 32.39% respectively by the D-test method. 77.8% of isolates were resistant to quinupristin-dalfopristin and the Minimum Inhibitory Concentration (MIC ranged from 4–32 µg/ml. 89.20% of isolates were resistant to both quinupristin-dalfopristin and erythromycin of which 35.03%, 35.67% and 29.30% belonged to iMLS , cMLS and MS phenotype respectively. Conclusion: The emergence of quinupristindalfopristin resistance and MLS phenotypes brings b about the need for the simple and reliable D-test in routine diagnosis and further susceptibility testing for proper antimicrobial therapy.

28 CFR 93.3 - Definitions.

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2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Definitions. 93.3 Section 93.3 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROVISIONS IMPLEMENTING THE VIOLENT CRIME CONTROL AND LAW... 901(a)(2) of the Omnibus Crime Control and Safe Streets Act of 1968, as amended. (b) Unit of Local...

32 CFR 93.7 - Responsibilities.

Science.gov (United States)

2010-07-01

... ACCEPTANCE OF SERVICE OF PROCESS; RELEASE OF OFFICIAL INFORMATION IN LITIGATION; AND TESTIMONY BY NSA... overseeing NSA compliance with § 93.1(a) and this part 93, and for consulting with DoJ when appropriate. In response to a litigation demand requesting official information or the testimony of NSA personnel as...

Exposure to dairy manure leads to greater antibiotic resistance and increased mass-specific respiration in soil microbial communities

Science.gov (United States)

Avera, Bethany; Badgley, Brian; Barrett, John E.; Franklin, Josh; Knowlton, Katharine F.; Ray, Partha P.; Smitherman, Crystal

2017-01-01

Intensifying livestock production to meet the demands of a growing global population coincides with increases in both the administration of veterinary antibiotics and manure inputs to soils. These trends have the potential to increase antibiotic resistance in soil microbial communities. The effect of maintaining increased antibiotic resistance on soil microbial communities and the ecosystem processes they regulate is unknown. We compare soil microbial communities from paired reference and dairy manure-exposed sites across the USA. Given that manure exposure has been shown to elicit increased antibiotic resistance in soil microbial communities, we expect that manure-exposed sites will exhibit (i) compositionally different soil microbial communities, with shifts toward taxa known to exhibit resistance; (ii) greater abundance of antibiotic resistance genes; and (iii) corresponding maintenance of antibiotic resistance would lead to decreased microbial efficiency. We found that bacterial and fungal communities differed between reference and manure-exposed sites. Additionally, the β-lactam resistance gene ampC was 5.2-fold greater under manure exposure, potentially due to the use of cephalosporin antibiotics in dairy herds. Finally, ampC abundance was positively correlated with indicators of microbial stress, and microbial mass-specific respiration, which increased 2.1-fold under manure exposure. These findings demonstrate that the maintenance of antibiotic resistance associated with manure inputs alters soil microbial communities and ecosystem function. PMID:28356447

Exposure to dairy manure leads to greater antibiotic resistance and increased mass-specific respiration in soil microbial communities.

Science.gov (United States)

Wepking, Carl; Avera, Bethany; Badgley, Brian; Barrett, John E; Franklin, Josh; Knowlton, Katharine F; Ray, Partha P; Smitherman, Crystal; Strickland, Michael S

2017-03-29

Intensifying livestock production to meet the demands of a growing global population coincides with increases in both the administration of veterinary antibiotics and manure inputs to soils. These trends have the potential to increase antibiotic resistance in soil microbial communities. The effect of maintaining increased antibiotic resistance on soil microbial communities and the ecosystem processes they regulate is unknown. We compare soil microbial communities from paired reference and dairy manure-exposed sites across the USA. Given that manure exposure has been shown to elicit increased antibiotic resistance in soil microbial communities, we expect that manure-exposed sites will exhibit (i) compositionally different soil microbial communities, with shifts toward taxa known to exhibit resistance; (ii) greater abundance of antibiotic resistance genes; and (iii) corresponding maintenance of antibiotic resistance would lead to decreased microbial efficiency. We found that bacterial and fungal communities differed between reference and manure-exposed sites. Additionally, the β-lactam resistance gene ampC was 5.2-fold greater under manure exposure, potentially due to the use of cephalosporin antibiotics in dairy herds. Finally, ampC abundance was positively correlated with indicators of microbial stress, and microbial mass-specific respiration, which increased 2.1-fold under manure exposure. These findings demonstrate that the maintenance of antibiotic resistance associated with manure inputs alters soil microbial communities and ecosystem function. © 2017 The Author(s).

Measurement of cross-sections for the 93Nb(p,n)93mMo and 93Nb(p,pn)92mNb reactions up to ∼20 MeV energy

Science.gov (United States)

Lawriniang, B.; Ghosh, R.; Badwar, S.; Vansola, V.; Santhi Sheela, Y.; Suryanarayana, S. V.; Naik, H.; Naik, Y. P.; Jyrwa, B.

2018-05-01

Excitation functions of the 93Nb(p,n)93mMo and 93Nb(p,pn)92mNb reactions were measured from threshold energies to ∼ 20MeV by employing stacked foil activation technique in combination with the off-line γ-ray spectroscopy at the BARC-TIFR Pelletron facility, Mumbai. For the 20 MeV proton beam, the energy degradation along the stack was calculated using the computer code SRIM 2013. The proton beam intensity was determined via the natCu(p,x)62Zn monitor reaction. The experimental data obtained were compared with the theoretical results from TALYS-1.8 as well as with the literature data available in EXFOR. It was found that for the 93Nb(p,n)92mMo reaction, the present data are in close agreement with some of the recent literature data and the theoretical values based on TALYS-1.8 but are lower than the other literature data. In the case of 93Nb(p,pn)93mNb reaction, present data agree very well with the literature data and the theoretical values.

32 CFR 93.6 - Fees.

Science.gov (United States)

2010-07-01

... SERVICE OF PROCESS; RELEASE OF OFFICIAL INFORMATION IN LITIGATION; AND TESTIMONY BY NSA PERSONNEL AS WITNESSES § 93.6 Fees. Consistent with the guidelines in § 93.1(e), NSA may charge reasonable fees to... providing such information, and may include: (a) The costs of time expended by NSA employees to process and...

The contribution of agricultural insecticide use to increasing insecticide resistance in African malaria vectors.

Science.gov (United States)

Reid, Molly C; McKenzie, F Ellis

2016-02-19

The fight against malaria is increasingly threatened by failures in vector control due to growing insecticide resistance. This review examines the recent primary research that addresses the putative relationship between agricultural insecticide use and trends in insecticide resistance. To do so, descriptive evidence offered by the new research was categorized, and additional factors that impact the relationship between agricultural insecticide use and observed insecticide resistance in malaria vectors were identified. In 23 of the 25 relevant recent publications from across Africa, higher resistance in mosquito populations was associated with agricultural insecticide use. This association appears to be affected by crop type, farm pest management strategy and urban development.

Increasing the radiation resistance of single-crystal silicon epitaxial layers

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Kurmashev Sh. D.

2014-12-01

Full Text Available The authors investigate the possibility of increasing the radiation resistance of silicon epitaxial layers by creating radiation defects sinks in the form of dislocation networks of the density of 109—1012 m–2. Such networks are created before the epitaxial layer is applied on the front surface of the silicon substrate by its preliminary oxidation and subsequent etching of the oxide layer. The substrates were silicon wafers KEF-4.5 and KDB-10 with a diameter of about 40 mm, grown by the Czochralski method. Irradiation of the samples was carried out using electron linear accelerator "Electronics" (ЭЛУ-4. Energy of the particles was 2,3—3,0 MeV, radiation dose 1015—1020 m–2, electron beam current 2 mA/m2. It is shown that in structures containing dislocation networks, irradiation results in reduction of the reverse currents by 5—8 times and of the density of defects by 5—10 times, while the mobility of the charge carriers is increased by 1,2 times. Wafer yield for operation under radiation exposure, when the semiconductor structures are formed in the optimal mode, is increased by 7—10% compared to the structures without dislocation networks. The results obtained can be used in manufacturing technology for radiation-resistant integrated circuits (bipolar, CMOS, BiCMOS, etc..

Sequence-Specific Targeting of Bacterial Resistance Genes Increases Antibiotic Efficacy

Science.gov (United States)

Wong, Michael; Daly, Seth M.; Greenberg, David E.; Toprak, Erdal

2016-01-01

The lack of effective and well-tolerated therapies against antibiotic-resistant bacteria is a global public health problem leading to prolonged treatment and increased mortality. To improve the efficacy of existing antibiotic compounds, we introduce a new method for strategically inducing antibiotic hypersensitivity in pathogenic bacteria. Following the systematic verification that the AcrAB-TolC efflux system is one of the major determinants of the intrinsic antibiotic resistance levels in Escherichia coli, we have developed a short antisense oligomer designed to inhibit the expression of acrA and increase antibiotic susceptibility in E. coli. By employing this strategy, we can inhibit E. coli growth using 2- to 40-fold lower antibiotic doses, depending on the antibiotic compound utilized. The sensitizing effect of the antisense oligomer is highly specific to the targeted gene’s sequence, which is conserved in several bacterial genera, and the oligomer does not have any detectable toxicity against human cells. Finally, we demonstrate that antisense oligomers improve the efficacy of antibiotic combinations, allowing the combined use of even antagonistic antibiotic pairs that are typically not favored due to their reduced activities. PMID:27631336

Trophic compensation reinforces resistance: herbivory absorbs the increasing effects of multiple disturbances.

Science.gov (United States)

Ghedini, Giulia; Russell, Bayden D; Connell, Sean D

2015-02-01

Disturbance often results in small changes in community structure, but the probability of transitioning to contrasting states increases when multiple disturbances combine. Nevertheless, we have limited insights into the mechanisms that stabilise communities, particularly how perturbations can be absorbed without restructuring (i.e. resistance). Here, we expand the concept of compensatory dynamics to include countervailing mechanisms that absorb disturbances through trophic interactions. By definition, 'compensation' occurs if a specific disturbance stimulates a proportional countervailing response that eliminates its otherwise unchecked effect. We show that the compounding effects of disturbances from local to global scales (i.e. local canopy-loss, eutrophication, ocean acidification) increasingly promote the expansion of weedy species, but that this response is countered by a proportional increase in grazing. Finally, we explore the relatively unrecognised role of compensatory effects, which are likely to maintain the resistance of communities to disturbance more deeply than current thinking allows. © 2015 John Wiley & Sons Ltd/CNRS.

Mutants of Aspergillus nidulans with increased resistance to the alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine.

Science.gov (United States)

Hooley, P; Shawcross, S G; Strike, P

1988-05-01

The isolation and characterisation of mutants of Aspergillus nidulans showing resistance to MNNG is described. Such isolates were stable through prolonged subculture in the absence of the selective agent, and resistance segregated as an allele of a single gene in meiotic and mitotic analysis. MNNG-resistant strains showed an increase in resistance to EMS and UV irradiation but no cross-resistance to MMS was detected. Possible mechanisms of resistance to alkylating agents are discussed.

Production of mutants of Candida utilis with increased resistence against furfural

International Nuclear Information System (INIS)

Stehlik, G.; Baron, M.; Turanitz, K.; Schneider, F.

1978-01-01

By repeated γ-irradiation treatments and following selections a mutant of Candida utilis weissenbachii was isolated showing increased resistance against furfural as compared to its wild type. Growing and radiation survival behavior of these yeasts are compared. Analysis of furfural was done by gaschromatography on Porapak Q. (author)

9 CFR 93.409 - Articles accompanying ruminants.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Articles accompanying ruminants. 93.409 Section 93.409 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT...; REQUIREMENTS FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Ruminants § 93.409 Articles accompanying ruminants...

38 CFR 18b.93 - Expeditious treatment.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Expeditious treatment. 18b.93 Section 18b.93 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Judicial Standards of Practice § 18b.93 Expeditious treatment. Requests for expeditious treatment of...

Concentric resistance training increases muscle strength without affecting microcirculation

International Nuclear Information System (INIS)

Weber, Marc-Andre; Hildebrandt, Wulf; Schroeder, Leif; Kinscherf, Ralf; Krix, Martin; Bachert, Peter; Delorme, Stefan; Essig, Marco; Kauczor, Hans-Ulrich; Krakowski-Roosen, Holger

2010-01-01

Purpose: While the evidence is conclusive regarding the positive effects of endurance training, there is still some controversy regarding the effects of resistance training on muscular capillarity. Thus, the purpose was to assess whether resistance strength training influences resting skeletal muscle microcirculation in vivo. Materials and methods: Thirty-nine middle-aged subjects (15 female, 24 male; mean age, 54 ± 9 years) were trained twice a week on an isokinetic system (altogether 16 sessions lasting 50 min, intensity 75% of maximum isokinetic and isometric force of knee flexors and extensors). To evaluate success of training, cross-sectional area (CSA) of the quadriceps femoris muscle and its isokinetic and isometric force were quantified. Muscular capillarization was measured in biopsies of the vastus lateralis muscle. In vivo, muscular energy and lipid metabolites were quantified by magnetic resonance spectroscopy and parameters of muscular microcirculation, such as local blood volume, blood flow and velocity, by contrast-enhanced ultrasound analyzing replenishment kinetics. Results: The significant (P 2 after training) and in absolute muscle strength (isometric, 146 ± 44 vs. 174 ± 50 Nm; isokinetic, 151 ± 53 vs. 174 ± 62 Nm) demonstrated successful training. Neither capillary density ex vivo (351 ± 75 vs. 326 ± 62) nor ultrasonographic parameters of resting muscle perfusion were significantly different (blood flow, 1.2 ± 1.2 vs. 1.1 ± 1.1 ml/min/100 g; blood flow velocity, 0.49 ± 0.44 vs. 0.52 ± 0.74 mm s -1 ). Also, the intensities of high-energy phosphates phosphocreatine and β-adenosintriphosphate were not different after training within the skeletal muscle at rest (β-ATP/phosphocreatine, 0.29 ± 0.06 vs. 0.28 ± 0.04). Conclusion: The significant increase in muscle size and strength in response to concentric isokinetic and isometric resistance training occurs without an increase in the in vivo microcirculation of the skeletal muscles at

Characterization of carbapenem-resistant Gram-negative bacteria from Tamil Nadu.

Science.gov (United States)

Nachimuthu, Ramesh; Subramani, Ramkumar; Maray, Suresh; Gothandam, K M; Sivamangala, Karthikeyan; Manohar, Prasanth; Bozdogan, Bülent

2016-10-01

Carbapenem resistance is disseminating worldwide among Gram-negative bacteria. The aim of this study was to identify carbapenem-resistance level and to determine the mechanism of carbapenem resistance among clinical isolates from two centres in Tamil Nadu. In the present study, a total of 93 Gram-negative isolates, which is found to be resistant to carbapenem by disk diffusion test in two centres, were included. All isolates are identified at species level by 16S rRNA sequencing. Minimal inhibitory concentrations (MICs) of isolates for Meropenem were tested by agar dilution method. Presence of blaOXA, blaNDM, blaVIM, blaIMP and blaKPC genes was tested by PCR in all isolates. Amplicons were sequenced for confirmation of the genes. Among 93 isolates, 48 (%52) were Escherichia coli, 10 (%11) Klebsiella pneumoniae, nine (%10) Pseudomonas aeruginosa. Minimal inhibitory concentration results showed that of 93 suspected carbapenem-resistant isolates, 27 had meropenem MICs ≥ 2 μg/ml. The MIC range, MIC50 and MIC90 were 128 μg/ml, 0.12 and 16 μg/ml, respectively. Fig. 1 . Among meropenem-resistant isolates, E. coli were the most common (9/48, 22%), followed by K. pneumoniae (7/9, 77%), P. aeruginosa (6/10, 60%), Acinetobacter baumannii (2/2, 100%), Enterobacter hormaechei (2/3, 67%) and one Providencia rettgeri (1/1, 100%). PCR results showed that 16 of 93 carried blaNDM, three oxa181, and one imp4. Among blaNDM carriers, nine were E. coli, four Klebsiella pneumoniae, two E. hormaechei and one P. rettgeri. Three K. pneumoniae were OXA-181 carriers. The only imp4 carrier was P. aeruginosa. A total of seven carbapenem-resistant isolates were negatives by PCR for the genes studied. All carbapenem-resistance gene-positive isolates had meropenem MICs >2 μg/ml. Our results confirm the dissemination of NDM and emergence of OXA-181 beta-lactamase among Gram-negative bacteria in South India. This study showed the emergence of NDM producer in clinical isolates of E

Pediatric neck abscesses: No increase in methicillin-resistant Staphylococcus aureus.

Science.gov (United States)

Fellner, Avital; Marom, Tal; Muallem-Kalmovich, Limor; Shlamkovitch, Nathan; Eviatar, Ephraim; Lazarovitch, Tzilia; Pitaro, Jacob

2017-10-01

Recent studies from Western countries showed an increased incidence rate of methicillin-resistant Staphylococcus aureus (MRSA) isolated from pediatric neck abscesses cultures. We sought to examine the microbiology and antibiotic susceptibility of such samples over a 10-year period, and particularly of Staphylococcus aureus (SA), in order to determine whether a similar trend exists in our institution. A retrospective chart review of children ≤18 years that underwent needle aspiration or surgical drainage of neck abscesses, including suppurative lymphadenitis, retropharyngeal abscesses, and parapharyngeal abscesses was conducted between 1/1/06-31/12/15. Sixty-two children were identified with a male predominance (34, 55%). The median age was 2 years. There were 37 (60%) suppurative lymphadenitis, 15 (24%) parapharyngeal abscess, and 10 (16%) retropharyngeal abscess cases. Twenty-nine (47%) children received antibiotic treatment prior to admission, most commonly β-lactam agents. Of them, 15 (52%) had positive cultures, including 7 (47%) with SA. On admission, 45 (73%) children had already received amoxicillin-clavulanate. Of those who did not improve, 16 (26%) received ceftriaxone and clindamycin. Twenty-one (38%) cultures were negative. The most common isolated bacteria were SA in 13 (24%), Streptococcus pyogenes in 7 (13%), and Streptococcus viridians group in 9 (16%). Of the SA isolates, there was only 1 (8%) case of MRSA; however, there were 4 (31%) clindamycin-resistant SA isolates. Unlike previously published data, there was no increase in MRSA incidence at our institution. However, the high prevalence of clindamycin-resistant SA was in line with previous reports. These findings should be considered when starting empirical therapy in pediatric neck abscesses. Copyright © 2017 Elsevier B.V. All rights reserved.

Treatment Resistant Epilepsy in Autism Spectrum Disorder: Increased Risk for Females.

Science.gov (United States)

Blackmon, Karen; Bluvstein, Judith; MacAllister, William S; Avallone, Jennifer; Misajon, Jade; Hedlund, Julie; Goldberg, Rina; Bojko, Aviva; Mitra, Nirmala; Giridharan, Radha; Sultan, Richard; Keller, Seth; Devinsky, Orrin

2016-02-01

The male:female ratio in autism spectrum disorder (ASD) averages greater than 4:1 while the male:female ratio of ASD with epilepsy averages less than 3:1. This indicates an elevated risk of epilepsy in females with ASD; yet, it is unknown whether phenotypic features of epilepsy and ASD differ between males and females with this comorbidity. The goal of this study is to investigate sex differences in phenotypic features of epilepsy and ASD in a prospective sample of 130 children and young adults with an initial ASD diagnosis and subsequent epilepsy diagnosis. All participants were characterized by standardized diagnostic inventories, parent/caregiver completed questionnaires, and medical/academic record review. Diagnostic classifications of epilepsy, ASD, and intellectual disability were performed by board certified neurologists and a pediatric neuropsychologist. Results demonstrated a lower male:female ratio (1.8:1) in individuals with ASD and treatment-resistant epilepsy relative to those with ASD and treatment-responsive epilepsy (4.9:1), indicating a higher risk of treatment-resistant epilepsy in females. Mild neuroimaging abnormalities were more common in females than males and this was associated with increased risk of treatment-resistance. In contrast, ASD symptom severity was lower in females compared with males. Findings distinguish females with ASD and epilepsy as a distinct subgroup at higher risk for a more severe epilepsy phenotype in the context of a less severe ASD phenotype. Increased risk of anti-epileptic treatment resistance in females with ASD and epilepsy suggests that comprehensive genetic, imaging, and neurologic screening and enhanced treatment monitoring may be indicated for this subgroup. Autism Res 2016, 9: 311-320. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

9 CFR 93.508 - Articles accompanying swine.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Articles accompanying swine. 93.508 Section 93.508 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Swine § 93.508 Articles accompanying swine. No litter...

Development of High Resolution Resonance Ionization Mass Spectrometry for Neutron Dosimetry Technique with93Nb(n,n'93mNb Reaction

Directory of Open Access Journals (Sweden)

Tomita Hideki

2016-01-01

Full Text Available We have proposed an advanced technique to measure the 93mNb yield precisely by Resonance Ionization Mass Spectrometry, instead of conventional characteristic X-ray spectroscopy. 93mNb-selective resonance ionization is achievable by distinguishing the hyperfine splitting of the atomic energy levels between 93Nb and 93mNb at high resolution. In advance of 93mNb detection, we could successfully demonstrate high resolution resonant ionization spectroscopy of stable 93Nb using an all solid-state, narrow-band and tunable Ti:Sapphire laser system operated at 1 kHz repetition rate.

Increasing antibiotic resistance in preservative-tolerant bacterial strains isolated from cosmetic products.

Science.gov (United States)

Orús, Pilar; Gomez-Perez, Laura; Leranoz, Sonia; Berlanga, Mercedes

2015-03-01

To ensure the microbiological quality, consumer safety and organoleptic properties of cosmetic products, manufacturers need to comply with defined standards using several preservatives and disinfectants. A drawback regarding the use of these preservatives is the possibility of generating cross-insusceptibility to other disinfectants or preservatives, as well as cross resistance to antibiotics. Therefore, the objective of this study was to understand the adaptive mechanisms of Enterobacter gergoviae, Pseudomonas putida and Burkholderia cepacia that are involved in recurrent contamination in cosmetic products containing preservatives. Diminished susceptibility to formaldehyde-donors was detected in isolates but not to other preservatives commonly used in the cosmetics industry, although increasing resistance to different antibiotics (β-lactams, quinolones, rifampicin, and tetracycline) was demonstrated in these strains when compared with the wild-type strain. The outer membrane protein modifications and efflux mechanism activities responsible for the resistance trait were evaluated. The development of antibiotic-resistant microorganisms due to the selective pressure from preservatives included in cosmetic products could be a risk for the emergence and spread of bacterial resistance in the environment. Nevertheless, the large contribution of disinfection and preservation cannot be denied in cosmetic products. Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.

Intermittent hypoxia increases insulin resistance in genetically obese mice.

Science.gov (United States)

Polotsky, Vsevolod Y; Li, Jianguo; Punjabi, Naresh M; Rubin, Arnon E; Smith, Philip L; Schwartz, Alan R; O'Donnell, Christopher P

2003-10-01

Obstructive sleep apnoea, a syndrome that leads to recurrent intermittent hypoxia, is associated with insulin resistance in obese individuals, but the mechanisms underlying this association remain unknown. We utilized a mouse model to examine the effects of intermittent hypoxia on insulin resistance in lean C57BL/6J mice and leptin-deficient obese (C57BL/6J-Lepob) mice. In lean mice, exposure to intermittent hypoxia for 5 days (short term) resulted in a decrease in fasting blood glucose levels (from 173 +/- 11 mg dl-1 on day 0 to 138 +/- 10 mg dl-1 on day 5, P obese mice, short-term intermittent hypoxia led to a decrease in blood glucose levels accompanied by a 607 +/- 136 % (P intermittent hypoxia was completely abolished by prior leptin infusion. Obese mice exposed to intermittent hypoxia for 12 weeks (long term) developed a time-dependent increase in fasting serum insulin levels (from 3.6 +/- 1.1 ng ml-1 at baseline to 9.8 +/- 1.8 ng ml-1 at week 12, P intermittent hypoxia is dependent on the disruption of leptin pathways.

32 CFR 728.93 - Chart of adjuncts.

Science.gov (United States)

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Chart of adjuncts. 728.93 Section 728.93 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL MEDICAL AND DENTAL CARE FOR ELIGIBLE PERSONS AT NAVY MEDICAL DEPARTMENT FACILITIES Adjuncts to Medical Care § 728.93 Chart of...

40 CFR 406.93-406.94 - [Reserved

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true [Reserved] 406.93-406.94 Section 406.93-406.94 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GRAIN MILLS POINT SOURCE CATEGORY Ready-to-Eat Cereal Subcategory §§ 406.93-406.94 [Reserved] ...

9 CFR 93.418 - Cattle from Canada.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Cattle from Canada. 93.418 Section 93... CONVEYANCE AND SHIPPING CONTAINERS Ruminants Canada 8 § 93.418 Cattle from Canada. (a) Health certificates. Cattle intended for importation from Canada must be accompanied by a certificate issued in accordance...

Increased fitness and realized heritability in emamectin benzoate-resistant Chrysoperla carnea (Neuroptera: Chrysopidae).

Science.gov (United States)

Mansoor, Muhammad Mudassir; Abbas, Naeem; Shad, Sarfraz Ali; Pathan, Attaullah Khan; Razaq, Muhammad

2013-10-01

The common green lacewing Chrysoperla carnea is a key biological control agent employed in integrated pest management (IPM) programs for managing various insect pests. A field collected population of C. carnea was selected for emamectin benzoate resistance in the laboratory and fitness costs and realized heritability were investigated. After five generations of selection with emamectin benzoate, C. carnea developed a 318-fold resistance to the insecticide. The resistant population had a relative fitness of 1.49, with substantially higher emergence rate of healthy adults, fecundity and hatchability and shorter larval duration, pupal duration, and development time compared to the susceptible population. Mean population growth rates; such as the intrinsic rate of natural population increase and biotic potential were higher for the emamectin benzoate selected population compared to the susceptible population. The realized heritability (h(2)) value of emamectin benzoate resistance was 0.34 in emamectin benzoate selected population of C. carnea. Chrysoperla species which show resistance to insecticides makes them compatible with those IPM systems where emamectin benzoate is employed.

9 CFR 93.517 - Swine from Canada.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Swine from Canada. 93.517 Section 93... CONVEYANCE AND SHIPPING CONTAINERS Swine Canada 7 § 93.517 Swine from Canada. (a) For purposes other than immediate slaughter. Swine offered for importation from Canada for purposes other than immediate slaughter...

9 CFR 93.427 - Cattle from Mexico.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Cattle from Mexico. 93.427 Section 93... CONVEYANCE AND SHIPPING CONTAINERS Ruminants Mexico 10 § 93.427 Cattle from Mexico. (a) Cattle and other ruminants imported from Mexico, except animals being transported in bond for immediate return to Mexico or...

Selection for increased desiccation resistance in Drosophila melanogaster: Additive genetic control and correlated responses for other stresses

International Nuclear Information System (INIS)

Hoffmann, A.A.; Parsons, P.A.

1989-01-01

Previously we found that Drosophila melanogaster lines selected for increased desiccation resistance have lowered metabolic rate and behavioral activity levels, and show correlated responses for resistance to starvation and a toxic ethanol level. These results were consistent with a prediction that increased resistance to many environmental stresses may be genetically correlated because of a reduction in metabolic energy expenditure. Here we present experiments on the genetic basis of the selection response and extend the study of correlated responses to other stresses. The response to selection was not sex-specific and involved X-linked and autosomal genes acting additively. Activity differences contributed little to differences in desiccation resistance between selected and control lines. Selected lines had lower metabolic rates than controls in darkness when activity was inhibited. Adults from selected lines showed increased resistance to a heat shock, 60 Co-gamma-radiation, and acute ethanol and acetic acid stress. The desiccation, ethanol and starvation resistance of isofemale lines set up from the F2s of a cross between one of the selected and one of the control lines were correlated. Selected and control lines did not differ in ether-extractable lipid content or in resistance to acetone, ether or a cold shock

Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia

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Yuan-Fang Liu

2016-06-01

Full Text Available Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice. Eight gene expression subgroups associated with characteristic genetic abnormalities were identified, including leukemia with MEF2D and ZNF384 fusions in two distinct clusters. In subgroup G4 which was characterized by ERG deletion, DUX4-IGH fusion was detected in most cases. This comprehensive dataset allowed us to compare the features of molecular pathogenesis between adult and pediatric B-ALL and to identify signatures possibly related to the inferior outcome of adults to that of children. We found that, besides the known discrepancies in frequencies of prognostic markers, adult patients had more cooperative mutations and greater enrichment for alterations of epigenetic modifiers and genes linked to B-cell development, suggesting difference in the target cells of transformation between adult and pediatric patients and may explain in part the disparity in their responses to treatment.

9 CFR 93.435 - Sheep and goats.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Sheep and goats. 93.435 Section 93.435... CONVEYANCE AND SHIPPING CONTAINERS Ruminants Additional General Provisions § 93.435 Sheep and goats. (a) Except as provided in paragraph (b) of this section, all sheep and goats imported into the United States...

7 CFR 1948.93 - Appeal procedure.

Science.gov (United States)

2010-01-01

... 7 Agriculture 13 2010-01-01 2009-01-01 true Appeal procedure. 1948.93 Section 1948.93 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... accordance with FmHA Instruction 1900-B. ...

Studying titanium-molybdenum-zirconium alloys of increased corrosion resistance in acid solutions

International Nuclear Information System (INIS)

Tomashov, N.D.; Kazarin, V.I.; Mikheev, V.S.; Goncharenko, B.A.; Sigalovskaya, T.M.; Kalyanova, M.P.

1977-01-01

New promising Ti-Mo-Nb-Zr system alloys, possessing good workability and a high corrosion resistance in non-oxidizing solutions of acids, have been developed. The alloys may be recommended as structural materials for equipment operating in severely agressive acid media, such as hydrochloric, sulphuric and phosphoric acids. The corrosion resistance of alloys of the above system in solutions of H 2 SO 4 , HCl and H 3 PO 4 acids may be maximized by increasing the overall alloying to 42% (keeping the ratio of the alloying components Mo/Nb/Zr=4/1/1 unchanged), while retaining sufficiently good plasticity and workability

Microbial radio-resistance of Salmonella Typhimurium in egg increases due to repetitive irradiation with electron beam

International Nuclear Information System (INIS)

Tesfai, Adiam T.; Beamer, Sarah K.; Matak, Kristen E.; Jaczynski, Jacek

2011-01-01

Ionizing radiation improves food safety. However, foodborne pathogens develop increased resistance in response to sub-lethal stresses such as heat, pH, antibiotics, etc. Therefore, it is hypothesized that foodborne pathogens may develop increased radio-resistance to electron beam (e-beam) radiation. The objective was to determine if D 10 -value for Salmonella Typhimurium in de-shelled raw egg (egg white and yolk mixed together) increases due to repetitive processing with e-beam at sub-lethal doses. Survivors were enumerated on non-selective (TSA) and selective (XLD) media. Survivors from the highest dose were isolated and used in subsequent e-beam cycle. This process was repeated four times for a total of five e-beam cycles. D 10 -values for S. Typhimurium enumerated on TSA and XLD following each e-beam cycle were calculated as inverse reciprocal of the slope of survivor curves. D 10 -values for the ATCC strain were 0.59±0.031 and 0.46±0.022 kGy on TSA and XLD, respectively. However, following the fifth e-beam cycle, the respective D 10 -values increased (P 0.05) to develop radio-resistance faster on selective media, likely due to facilitated selection of radio-resistant cells within microbial population following each e-beam cycle. For all five e-beam cycles, S. Typhimurium had higher (P 10 -values on non-selective media, indicating that sub-lethal injury followed by cellular repair and recovery are important for radio-resistance and inactivation of this microorganism. This study demonstrated that e-beam efficiently inactivates S. Typhimurium in raw egg; however, similar to other inactivation techniques and factors affecting microbial growth, S. Typhimurium develops increased radio-resistance if repetitively processed with e-beam at sub-lethal doses.

Antimicrobial resistance in Neisseria gonorrhoeae in China: a meta-analysis.

Science.gov (United States)

Chen, Yawen; Gong, Yanhong; Yang, Tingting; Song, Xingyue; Li, Jing; Gan, Yong; Yin, Xiaoxv; Lu, Zuxun

2016-03-03

Neisseria gonorrhoeae (N. gonorrhoeae) resistance to antimicrobial has been a major concern in China, and epidemiological data on N. gonorrhoeae resistance are not well understood. This meta-analysis was aimed at summarizing the evidence on N. gonorrhoeae resistance to penicillin, tetracycline, ciprofloxacin, ceftriaxone and spectinomycin in China. Two researchers independently searched five databases to identify studies on N. gonorrhoeae resistance to antimicrobials from the databases' inception to November 7, 2014. A random-effects model was used to estimate the antimicrobial resistance rates and their corresponding 95% confidence intervals (CIs). Publication bias was assessed with the Begg rank correlation test and the Egger test. We included 127 studies in our synthesis reporting antimicrobial resistance. Our analyses demonstrated that N. gonorrhoeae resistance to penicillin and tetracycline respectively increased from 74.41% (95% CI: 64.1-84.7%) and 68.3% (95% CI: 58.7-78.0%) in 2000 to 84.2% (95% CI: 79.7-88.8%) and 82.4% (95% CI: 79.9-84.7%) in 2012. N. gonorrhoeae resistance to ciprofloxacin experienced a steady increase from 12.7% (95% CI, 8.6-16.7%) in 1995 and reached 93.8% (95% CI: 91.9-95.7%) in 2003. N. gonorrhoeae resistance to ceftriaxone was 1.7% (95% CI: 0.5-5.7%) before 1995 and 0.5% (95% CI: 0.2-1.4%) in 2012, and N. gonorrhoeae resistance to spectinomycin was less than 2% from 1995 to 2012. N. gonorrhoeae resistance rates to penicillin, tetracycline and ciprofloxacin were high in China. Ceftriaxone and spectinomycin remained effective therapy for the treatment of gonorrhea. It is essential to strengthen N. gonorrhoeae resistance surveillance and update treatment guidelines timely.

Increasing trend of community-acquired methicillin-resistant: Staphylococcal carriers: An alarming bell for urgent measures

Directory of Open Access Journals (Sweden)

Poongodi Lakshmi Santhana Kumarasamy

2015-01-01

Full Text Available Background: An increase in the incidence of infections caused by community-associated-methicillin resistant Staphylococcus aureus (MRSA has been reported. Hence, the knowledge of resistance pattern of these isolates is a precondition for alleviating emerging antibiotic resistance and devising better treatment strategies Aim: To find out the prevalence of community-acquired methicillin-resistant staphylococcal strains from nasal carriers. Materials and Methods: A total of 352 nasal swabs collected during routine health checkup were analyzed. Results: Of the 58 (16% staphylococci isolated, 32 (55% were S. aureus and 26 (45% were coagulase-negative staphylococci (CoNS. Methicillin resistance was observed in 7 (22% of staphylococci aureus and 11 (42% of CoNS. "D test" was positive in 1 (14% MRSA, 2 (8% methicillin-susceptible S. aureus and 2 (8% methicillin resistant-CoNS. Conclusion: Effective implementation of the antibiotic policy along with measures like hand wash, isolation of patients will reduce the incidence of resistance.

7 CFR 93.13 - Analytical methods.

Science.gov (United States)

2010-01-01

... No. 1, USDA, Agricultural Marketing Service, Science and Technology, 3521 South Agriculture Building... 7 Agriculture 3 2010-01-01 2010-01-01 false Analytical methods. 93.13 Section 93.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards...

Profiling of barrier capacitance and spreading resistance using a transient linearly increasing voltage technique.

Science.gov (United States)

Gaubas, E; Ceponis, T; Kusakovskij, J

2011-08-01

A technique for the combined measurement of barrier capacitance and spreading resistance profiles using a linearly increasing voltage pulse is presented. The technique is based on the measurement and analysis of current transients, due to the barrier and diffusion capacitance, and the spreading resistance, between a needle probe and sample. To control the impact of deep traps in the barrier capacitance, a steady state bias illumination with infrared light was employed. Measurements of the spreading resistance and barrier capacitance profiles using a stepwise positioned probe on cross sectioned silicon pin diodes and pnp structures are presented.

In Utero Estrogen Exposure Increases Antiestrogen Resistance by Inducing EMT

Science.gov (United States)

2015-02-01

currently unclear. Our recent preclinical study found that maternal exposure to excess estrogens during pregnancy increases the risk that AE resistance in...References: 1. Hilakivi-Clarke L, Clarke R, Onojafe I, Raygada M, Cho E, Lippman M. A maternal diet high in n-6-polyunsaturated fats alters mammary...the rate of obesity in this country (high fat diets resulting in elevated circulating estrogen levels), the prevelance of bisphenol A in our drinking

Bioenergy 93 conference

International Nuclear Information System (INIS)

1993-01-01

In this report the presentations given in the Bioenergy 93 Conference are published. The papers are grouped as follows: Opening addresses, biomass implementation strategies, nordic bioenergy research programs, production, handling and conversion of biofuels, combustion technology of biofuels and bioenergy visions

28 CFR 93.4 - Grant authority.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Grant authority. 93.4 Section 93.4 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROVISIONS IMPLEMENTING THE VIOLENT CRIME CONTROL... violent offenders, and (2) The integrated administration of other sanctions and services, which shall...

Recommendation 93-5 Implementation Plan

International Nuclear Information System (INIS)

1994-01-01

On July 19, 1993, the Defense Nuclear Facilities Safety Board (DNFSB) provided to the Secretary of Energy its Recommendation 93-5, which commented on the Hanford Tank Waste Characterization effort. Recommendation 93-5 highlighted the need to accelerate the characterization of the Hanford Site tank wastes to expedite the resolution of identified tank safety issues, and to provide timely design data in support of activities addressing the disposal of the tank wastes. The Department of Energy (DOE) and its prime contractor, Westinghouse Hanford Company (WHC), are in full agreement with the content of Recommendation 93-5 and have prepared this Implementation Plan to document those actions that have been or will be taken to meet Recommendation 93-5. The new Characterization Strategy embodied by this Plan acknowledges that waste distribution within a tank is the critical unknown with respect to successfully characterizing the tank for any Tank Waste Remediation Systems (TWRS) programmatic need. The new strategy has been incorporated into the following seven task: (1) strengthen technical management; (2) accelerate safety related characterization; (3) improve the quality and quantity of sampling (4) streamline tank access; (5) improve the quality and quantity of analyses; (6) improve data management; and (7) change control

Increasing resistance to quinolones: A four-year prospective study of urinary tract infection pathogens

Directory of Open Access Journals (Sweden)

Orhiosefe Omigie

2009-08-01

Full Text Available Orhiosefe Omigie, Lawrence Okoror, Patience Umolu, Gladys IkuuhDepartment of Microbiology, Ambrose Alli University, Ekpoma, NigeriaAbstract: A four-year prospective study was carried out to determine the incidence and rate of development of resistance by common urinary tract infection (UTI pathogens to quinolone antimicrobial agents. Results show that there is high intrinsic resistance to the quinolones among strains of Pseudomonas aeruginosa (43.4%, Escherichia coli (26.3%, and Proteus spp. (17.1%. Over four years, rising rates of resistance were observed in P. aeruginosa (14.6% increase, Staphylococcus aureus (9.8%, and E. coli (9.7%. The highest potency was exhibited by ciprofloxacin (91.2%, levofloxacin (89.2%, and moxifloxacin (85.1%, while there were high rates of resistance to nalidixic acid (51.7% and pefloxacin (29.0%. Coliforms, particularly E. coli (>45%, remain the most prevalent causative agents of UTI while females within the age range of 20–50 years were most vulnerable to UTI.Keywords: UTI, microorganisms, antibiotics, resistance

Overexpression of a citrus NDR1 ortholog increases disease resistance in Arabidopsis

Science.gov (United States)

Emerging devastating diseases, such as Huanglongbing (HLB) and citrus canker, have caused tremendous losses to the citrus industry worldwide. Genetic engineering is a powerful approach that could allow us to increase citrus resistance against these diseases. The key to the success of this approach r...

42 CFR 93.221 - PHS support.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false PHS support. 93.221 Section 93.221 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.100 - General policy.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false General policy. 93.100 Section 93.100 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.202 - Charge letter.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Charge letter. 93.202 Section 93.202 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.209 - Funding component.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Funding component. 93.209 Section 93.209 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.105 - Time limitations.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Time limitations. 93.105 Section 93.105 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.50 - Special terms.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Special terms. 93.50 Section 93.50 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.103 - Research misconduct.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Research misconduct. 93.103 Section 93.103 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

42 CFR 93.224 - Research record.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Research record. 93.224 Section 93.224 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

9 CFR 93.106 - Quarantine requirements.

Science.gov (United States)

2010-01-01

... Section 93.106 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... other than ratites and hatching eggs of ratites. Each lot of pet birds, except as provided for in § 93.... (2) Physical plant requirements. The facility shall comply with the following requirements: (i...

28 CFR 93.2 - Statutory authority.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Statutory authority. 93.2 Section 93.2 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROVISIONS IMPLEMENTING THE VIOLENT CRIME CONTROL... under the Violent Crime Control and Law Enforcement Act of 1994, Title V, Public Law 103-322, 108 Stat...

Increasing antimicrobial resistance in clinical isolates of Staphylococcus intermedius group bacteria and emergence of MRSP in the UK.

Science.gov (United States)

Beever, L; Bond, R; Graham, P A; Jackson, B; Lloyd, D H; Loeffler, A

2015-02-14

Frequencies of antimicrobial resistance were determined amongst 14,555 clinical Staphylococcus intermedius group (SIG) isolates from UK dogs and cats to estimate resistance trends and quantify the occurrence of meticillin-resistant Staphylococcus pseudintermedius (MRSP). Reports from two diagnostic laboratories (13,313 general submissions, 1242 referral centre only submissions) were analysed retrospectively (2003/2006-2012). MRSP were defined by phenotypic resistance to meticillin and concurrent broad β-lactam resistance; a subset was confirmed genetically (SIG-specific nuc and mecA). Trends were analysed by Cochran-Armitage test. Resistance remained below 10 per cent for cefalexin, amoxicillin-clavulanic acid and the fluoroquinolones. Increasing resistance trends were seen in both laboratories for ampicillin/amoxicillin (both PResistance to cefalexin increased over time in referral hospital isolates (Presistance to important antimicrobials was identified overtime and the emergence of MRSP from UK clinical cases was confirmed. Attention to responsible use of antibacterial therapy in small animal practice is urgently needed. British Veterinary Association.

27 CFR 70.93 - Interest rate.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Interest rate. 70.93... Excise and Special (Occupational) Tax Interest § 70.93 Interest rate. (a) In general. The interest rate... annual percentage rate of interest will exceed the prescribed rate of interest. (b) Applicability of...

New approach to increasing rice lodging resistance and biomass yield through the use of high gibberellin producing varieties.

Science.gov (United States)

Okuno, Ayako; Hirano, Ko; Asano, Kenji; Takase, Wakana; Masuda, Reiko; Morinaka, Yoichi; Ueguchi-Tanaka, Miyako; Kitano, Hidemi; Matsuoka, Makoto

2014-01-01

Traditional breeding for high-yielding rice has been dependent on the widespread use of fertilizers and the cultivation of gibberellin (GA)-deficient semi-dwarf varieties. The use of semi-dwarf plants facilitates high grain yield since these varieties possess high levels of lodging resistance, and thus could support the high grain weight. Although this approach has been successful in increasing grain yield, it is desirable to further improve grain production and also to breed for high biomass. In this study, we re-examined the effect of GA on rice lodging resistance and biomass yield using several GA-deficient mutants (e.g. having defects in the biosynthesis or perception of GA), and high-GA producing line or mutant. GA-deficient mutants displayed improved bending-type lodging resistance due to their short stature; however they showed reduced breaking-type lodging resistance and reduced total biomass. In plants producing high amounts of GA, the bending-type lodging resistance was inferior to the original cultivars. The breaking-type lodging resistance was improved due to increased lignin accumulation and/or larger culm diameters. Further, these lines had an increase in total biomass weight. These results show that the use of rice cultivars producing high levels of GA would be a novel approach to create higher lodging resistance and biomass.

Excitation function and isomeric ratio of Tc-isotopes from the 93Nb(α, xn) reaction

International Nuclear Information System (INIS)

Kim, K.; Kim, G.N.; Naik, H.; Zaman, M.; Yang, S.-C.; Song, T.-Y.; Guin, R.; Das, S.K.

2015-01-01

The excitation functions of 94–96 Tc isotopes and independent isomeric ratios of 93m, g Tc, 94m, g Tc, and 95m, g Tc from the 93 Nb(α, xn) reaction within the energy range below 40 MeV have been determined by using a stacked-foil activation and an off-line γ-ray spectrometric technique at the Variable Energy Cyclotron Center, Kolkota, India. The excitation function of 94–96 Tc in the 93 Nb(α, xn) reaction was also calculated by using the computer code TALYS 1.6. The present data are found to be in general agreement with the literature data but have similar trend with some deviation from calculated data of the TALYS 1.6 code. The isomeric ratios of 93m, g Tc, 94m, g Tc, and 95m, g Tc in the 93 Nb(α, xn) reactions from the present work and literature data were compared with similar data in the 93 Nb( 3 He, xn) and 96 Mo(p, xn) reactions. In all the three reactions, the isomeric ratios increase with the increasing excitation energy. However, at all excitation energies, the isomeric ratios of 93m, g Tc, 94m, g Tc, and 95m, g Tc in the 93 Nb(α, xn) and 93 Nb( 3 He, xn) reactions are higher than those in the 96 Mo(p, xn) reactions, which indicate the role of input angular momentum besides excitation energy. Above the excitation energy of 35–55 MeV, the isomeric ratios of 95m, g Tc, 94m, g Tc, and 93m, g Tc decrease in all the 93 Nb(α, xn), 93 Nb( 3 He, xn) and 96 Mo(p, xn) reactions. This decreasing trend at higher excitation energy indicates the starting of pre-equilibrium reaction, which depends on the target, projectile, and type of reaction products

Microbial radio-resistance of Salmonella Typhimurium in egg increases due to repetitive irradiation with electron beam

Energy Technology Data Exchange (ETDEWEB)

Tesfai, Adiam T.; Beamer, Sarah K.; Matak, Kristen E. [West Virginia University, Division of Animal and Nutritional Sciences, PO Box 6108, Morgantown, WV 26508 (United States); Jaczynski, Jacek, E-mail: Jacek.Jaczynski@mail.wvu.ed [West Virginia University, Division of Animal and Nutritional Sciences, PO Box 6108, Morgantown, WV 26508 (United States)

2011-04-15

Ionizing radiation improves food safety. However, foodborne pathogens develop increased resistance in response to sub-lethal stresses such as heat, pH, antibiotics, etc. Therefore, it is hypothesized that foodborne pathogens may develop increased radio-resistance to electron beam (e-beam) radiation. The objective was to determine if D{sub 10}-value for Salmonella Typhimurium in de-shelled raw egg (egg white and yolk mixed together) increases due to repetitive processing with e-beam at sub-lethal doses. Survivors were enumerated on non-selective (TSA) and selective (XLD) media. Survivors from the highest dose were isolated and used in subsequent e-beam cycle. This process was repeated four times for a total of five e-beam cycles. D{sub 10}-values for S. Typhimurium enumerated on TSA and XLD following each e-beam cycle were calculated as inverse reciprocal of the slope of survivor curves. D{sub 10}-values for the ATCC strain were 0.59{+-}0.031 and 0.46{+-}0.022 kGy on TSA and XLD, respectively. However, following the fifth e-beam cycle, the respective D{sub 10}-values increased (P<0.05) to 0.69{+-}0.026 and 0.61{+-}0.029 kGy, respectively. S. Typhimurium showed a trend (P>0.05) to develop radio-resistance faster on selective media, likely due to facilitated selection of radio-resistant cells within microbial population following each e-beam cycle. For all five e-beam cycles, S. Typhimurium had higher (P<0.05) D{sub 10}-values on non-selective media, indicating that sub-lethal injury followed by cellular repair and recovery are important for radio-resistance and inactivation of this microorganism. This study demonstrated that e-beam efficiently inactivates S. Typhimurium in raw egg; however, similar to other inactivation techniques and factors affecting microbial growth, S. Typhimurium develops increased radio-resistance if repetitively processed with e-beam at sub-lethal doses.

Factors associated with acquisition of carbapenem-resistant Enterobacteriaceae

Directory of Open Access Journals (Sweden)

Lilian Silva Lavagnoli

2017-10-01

Full Text Available ABSTRACT Objective: to identify possible risk factors for acquisition of Enterobacterial strains with a marker for resistance to carbapenems. Methods: exploratory case-control study performed in hospital settings. The study sample consisted of patients with biological specimens that tested positive for carbapenem-resistant Enterobacteriaceae (cases, with the disk diffusion test and Etest, and controls with biological samples testing negative for carbapenem-resistant Enterobacteriaceae. In all, 65 patients were included: 13 (20% cases and 52 (80% controls. Results: the microorganisms isolated were Serratia marcescens (6, Klebsiella pneumoniae (4, and Enterobacter cloacae (3. Univariate analysis revealed that length of hospitalization prior to sample collection (p=0.002 and having a surgical procedure (p=0.006 were statistically significant. In the multivariable logistic regression model, both were still significant, with odds ratios of 0.93 (p = 0.009; 95% CI: 0.89 to 0.98 for length of hospitalization prior to sample collection, and 9.28 (p = 0.05; 95% CI: 1.01 to 85.14 for having a surgical procedure. Conclusion: shorter hospitalization times and increased surveillance of patients undergoing surgery could play a decisive role in reducing the spread of carbapenem-resistant microorganisms in hospital settings.

Aerobic exercise increases resistance to oxidative stress in sedentary older middle-aged adults. A pilot study.

Science.gov (United States)

Done, Aaron J; Traustadóttir, Tinna

2016-12-01

Older individuals who exercise regularly exhibit greater resistance to oxidative stress than their sedentary peers, suggesting that exercise can modify age-associated loss of resistance to oxidative stress. However, we recently demonstrated that a single bout of exercise confers protection against a subsequent oxidative challenge in young, but not older adults. We therefore hypothesized that repeated bouts of exercise would be needed to increase resistance to an oxidative challenge in sedentary older middle-aged adults. Sedentary older middle-aged men and women (50-63 years, n = 11) participated in an 8-week exercise intervention. Maximal oxygen consumption was measured before and after the intervention. The exercise intervention consisted of three sessions per week, for 45 min at an intensity corresponding to 70-85 % maximal heart rate (HR max ). Resistance to oxidative stress was measured by F 2 -isoprostane response to a forearm ischemia/reperfusion (I/R) trial. Each participant underwent the I/R trial before and after the exercise intervention. The intervention elicited a significant increase in maximal oxygen consumption (VO 2max ) (P exercise intervention (time-by-trial interaction, P = 0.043). Individual improvements in aerobic fitness were associated with greater improvements in the F 2 -isoprostane response (r = -0.761, P = 0.011), further supporting the role of aerobic fitness in resistance to oxidative stress. These data demonstrate that regular exercise with improved fitness leads to increased resistance to oxidative stress in older middle-aged adults and that this measure is modifiable in previously sedentary individuals.

29 CFR 1917.93 - Head protection.

Science.gov (United States)

2010-07-01

... 29 Labor 7 2010-07-01 2010-07-01 false Head protection. 1917.93 Section 1917.93 Labor Regulations... of the following consensus standards: (i) ANSI Z89.1-2003, “American National Standard for Industrial... constructed in accordance with one of the above consensus standards will be deemed to be in compliance with...

Rapid Increase of Genetically Diverse Methicillin-Resistant Staphylococcus aureus, Copenhagen, Denmark

DEFF Research Database (Denmark)

Bartels, Mette Damkjær; Boye, Kit; Larsen, Anders Rhod

2007-01-01

In Copenhagen, methicillin-resistant Staphylococcus aureus (MRSA) accounted for <15 isolates per year during 1980-2002. However, since 2003 an epidemic increase has been observed, with 33 MRSA cases in 2003 and 110 in 2004. We analyzed these 143 cases epidemiologically and characterized isolates ...... and soft tissue infections dominated. CO-MRSA with diverse genetic backgrounds is rapidly emerging in a low MRSA prevalence area. Udgivelsesdato: October...

9 CFR 93.326 - Horses for immediate slaughter.

Science.gov (United States)

2010-01-01

... CERTAIN ANIMALS, BIRDS, FISH, AND POULTRY, AND CERTAIN ANIMAL, BIRD, AND POULTRY PRODUCTS; REQUIREMENTS FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Horses Mexico 18 § 93.326 Horses for immediate slaughter. Horses may be imported from Mexico, subject to the applicable provisions of §§ 93.321, 93.322...

46 CFR 221.93 - Collection of civil penalties.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Collection of civil penalties. 221.93 Section 221.93... RELATED ACTIVITIES REGULATED TRANSACTIONS INVOLVING DOCUMENTED VESSELS AND OTHER MARITIME INTERESTS Civil Penalties § 221.93 Collection of civil penalties. Within 30 days after receipt of the Hearing Officer's...

Increase of the electrical resistance of thin aluminium film due to 14 MeV neutron irradiation

Energy Technology Data Exchange (ETDEWEB)

Agrawal, S K; Kumar, U; Singh, S P; Bhattacharya, S; Nigam, A K [Banaras Hindu Univ. (India). Dept. of Physics

1978-01-01

The effect of 14 MeV neutron bombardment on the electrical resistance of 500 A thick vacuum-coated Al film is investigated. In the beginning, a slow, then sharp and finally again slow increase is observed in the electrical resistance of the film. Transmission electron micrographs of the film after the same dose of neutron irradiation show a large number of defects produced in the film due to neutron irradiation, which seems to be the cause of this increase.

42 CFR 93.25 - Organization of this part.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Organization of this part. 93.25 Section 93.25 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND... RESEARCH MISCONDUCT § 93.25 Organization of this part. This part is subdivided into five subparts. Each...

Degradation Behavior of Lithium-Ion Batteries during Calendar Ageing – The Case of the Internal Resistance Increase

DEFF Research Database (Denmark)

Stroe, Daniel-Ioan; Swierczynski, Maciej Jozef; Kær, Søren Knudsen

2018-01-01

Lithium-ion batteries are regarded as the key energy storage technology for both e-mobility and stationary renewable energy storage applications. Nevertheless, the Lithium-ion batteries are complex energy storage devices, which are characterized by a complex degradation behavior, which affects both...... their capacity and internal resistance. This paper investigates, based on extended laboratory calendar ageing tests, the degradation of the internal resistance of a Lithium-ion battery. The dependence of the internal resistance increase on the temperature and state-of-charge level have been extensive studied...... and quantified. Based on the obtained laboratory results, an accurate semi-empirical lifetime model, which is able to predict with high accuracy the internal resistance increase of the Lithium-ion battery over a wide temperature range and for all state-of-charge levels was proposed and validated....

40 CFR 600.011-93 - Reference materials.

Science.gov (United States)

2010-07-01

... Density (Specific Gravity), or API Gravity of Crude Petroleum and Liquid Petroleum Products by Hydrometer... Petroleum and Liquid Petroleum Products by Hydrometer Method, IBR approved for §§ 600.113-93, 600.510-93...

Determination of 93Zr in nuclear power plant wastes

DEFF Research Database (Denmark)

Osváth, Szabolcs; Vajda, Nora; Molnar, Zsuzsa

2017-01-01

A radioanalytical method (based on separation using UTEVA columns and ICP-MS measurement) has been used for determination of 93Zr in 37 nuclear power plant samples. As 93Nb might affect the detection of 93Zr, Monte Carlo activation model was used to calculate the expected 93Zr/natZr mass ratio...

Heavy metals in liquid pig manure in light of bacterial antimicrobial resistance

Energy Technology Data Exchange (ETDEWEB)

Hoelzel, Christina S., E-mail: Christina.Hoelzel@wzw.tum.de [Chair of Animal Hygiene, Technische Universitaet Muenchen, Weihenstephaner Berg 3, 85354 Freising (Germany); Mueller, Christa [Institute for Agroecology, Organic Farming and Soil Protection, Bavarian State Research Center for Agriculture (LfL), Lange Point 12, 85354 Freising (Germany); Harms, Katrin S. [Chair of Animal Hygiene, Technische Universitaet Muenchen, Weihenstephaner Berg 3, 85354 Freising (Germany); Mikolajewski, Sabine [Department for Quality Assurance and Analytics, Bavarian State Research Center for Agriculture (LfL), Lange Point 4, 85354 Freising (Germany); Schaefer, Stefanie; Schwaiger, Karin; Bauer, Johann [Chair of Animal Hygiene, Technische Universitaet Muenchen, Weihenstephaner Berg 3, 85354 Freising (Germany)

2012-02-15

Heavy metals are regularly found in liquid pig manure, and might interact with bacterial antimicrobial resistance. Concentrations of heavy metals were determined by atomic spectroscopic methods in 305 pig manure samples and were connected to the phenotypic resistance of Escherichia coli (n=613) against 29 antimicrobial drugs. Concentrations of heavy metals (/kg dry matter) were 0.08-5.30 mg cadmium, 1.1-32.0 mg chrome, 22.4-3387.6 mg copper, <2.0-26.7 mg lead, <0.01-0.11 mg mercury, 3.1-97.3 mg nickel and 93.0-8239.0 mg zinc. Associated with the detection of copper and zinc, resistance rates against {beta}-lactams were significantly elevated. By contrast, the presence of mercury was significantly associated with low antimicrobial resistance rates of Escherichia coli against {beta}-lactams, aminoglycosides and other antibiotics. Effects of subinhibitory concentrations of mercury on bacterial resistance against penicillins, cephalosporins, aminoglycosides and doxycycline were also demonstrated in a laboratory trial. Antimicrobial resistance in the porcine microflora might be increased by copper and zinc. By contrast, the occurrence of mercury in the environment might, due to co-toxicity, act counter-selective against antimicrobial resistant strains.

HF diets increase hypothalamic PTP1B and induce leptin resistance through both leptin-dependent and -independent mechanisms

Science.gov (United States)

White, Christy L.; Whittington, Amy; Barnes, Maria J.; Wang, Zhong; Bray, George A.; Morrison, Christopher D.

2009-01-01

Protein tyrosine phosphatase 1B (PTP1B) contributes to leptin resistance by inhibiting intracellular leptin receptor signaling. Mice with whole body or neuron-specific deletion of PTP1B are hypersensitive to leptin and resistant to diet-induced obesity. Here we report a significant increase in PTP1B protein levels in the mediobasal hypothalamus (P = 0.003) and a concomitant reduction in leptin sensitivity following 28 days of high-fat (HF) feeding in rats. A significant increase in PTP1B mRNA levels was also observed in rats chronically infused with leptin (3 μg/day icv) for 14 days (P = 0.01) and in leptin-deficient ob/ob mice infused with leptin (5 μg/day sc for 14 days; P = 0.003). When saline-infused ob/ob mice were placed on a HF diet for 14 days, an increase in hypothalamic PTP1B mRNA expression was detected (P = 0.001) despite the absence of circulating leptin. In addition, although ob/ob mice were much more sensitive to leptin on a low-fat (LF) diet, a reduction in this sensitivity was still observed following exposure to a HF diet. Taken together, these data indicate that hypothalamic PTP1B is specifically increased during HF diet-induced leptin resistance. This increase in PTP1B is due in part to chronic hyperleptinemia, suggesting that hyperleptinemia is one mechanism contributing to the development of leptin resistance. However, these data also indicate that leptin is not required for the increase in hypothalamic PTP1B or the development of leptin resistance. Therefore, additional, leptin-independent mechanisms must exist that increase hypothalamic PTP1B and contribute to leptin resistance. PMID:19017730

Increase in resistance to extended-spectrum cephalosporins in Salmonella isolated from retail chicken products in Japan.

Science.gov (United States)

Noda, Tamie; Murakami, Koichi; Etoh, Yoshiki; Okamoto, Fuyuki; Yatsuyanagi, Jun; Sera, Nobuyuki; Furuta, Munenori; Onozuka, Daisuke; Oda, Takahiro; Asai, Tetsuo; Fujimoto, Shuji

2015-01-01

Extended-spectrum β-lactamase (ESBL)-producing Salmonella are one of the most important public health problems in developed countries. ESBL-producing Salmonella strains have been isolated from humans in Asian countries neighboring Japan, along with strains harboring the plasmid-mediated extended-spectrum cephalosporin (ESC)-resistance gene, ampC (pAmpC). However, only a few studies have investigated the prevalence of ESC-resistant Salmonella in chicken products in Japan, which are the main vehicle of Salmonella transmission. The aim of this study was to investigate the prevalence of ESBL-producing, pAmpC-harboring, or carbapenem-resistant Salmonella in chicken products in Japan. In total, 355 out of 779 (45.6%) chicken product samples collected from 1996-2010 contained Salmonella, resulting in 378 distinct isolates. Of these isolates, 373 were tested for resistance to ESCs, cephamycins, or carbapenems. Isolates that showed resistance to one or more of these antimicrobials were then examined by PCR and DNA sequence analysis for the presence of the bla(CMY), bla(CTX-M), bla(TEM), and bla(SHV) resistance genes. Thirty-five resistant isolates were detected, including 26 isolates that contained pAmpC (bla(CMY-2)), and nine ESBL-producing isolates harboring bla(CTX-M) (n = 4, consisting of two bla(CTX-M-2) and two bla(CTX-M-15 genes)), bla(TEM) (n = 4, consisting of one bla(TEM-20) and three bla(TEM-52) genes), and bla(SHV) (n = 1, bla(SHV-12)). All pAmpC-harboring and ESBL-producing Salmonella isolates were obtained from samples collected after 2005, and the percentage of resistant isolates increased significantly from 0% in 2004 to 27.9% in 2010 (P for trend = 0.006). This increase was caused in part by an increase in the number of Salmonella enterica subsp. enterica serovar Infantis strains harboring an approximately 280-kb plasmid containing bla(CMY-2) in proximity to ISEcp1. The dissemination of ESC-resistant Salmonella containing plasmid-mediated bla(CMY-2) in

Increase in resistance to extended-spectrum cephalosporins in Salmonella isolated from retail chicken products in Japan.

Directory of Open Access Journals (Sweden)

Tamie Noda

Full Text Available Extended-spectrum β-lactamase (ESBL-producing Salmonella are one of the most important public health problems in developed countries. ESBL-producing Salmonella strains have been isolated from humans in Asian countries neighboring Japan, along with strains harboring the plasmid-mediated extended-spectrum cephalosporin (ESC-resistance gene, ampC (pAmpC. However, only a few studies have investigated the prevalence of ESC-resistant Salmonella in chicken products in Japan, which are the main vehicle of Salmonella transmission. The aim of this study was to investigate the prevalence of ESBL-producing, pAmpC-harboring, or carbapenem-resistant Salmonella in chicken products in Japan. In total, 355 out of 779 (45.6% chicken product samples collected from 1996-2010 contained Salmonella, resulting in 378 distinct isolates. Of these isolates, 373 were tested for resistance to ESCs, cephamycins, or carbapenems. Isolates that showed resistance to one or more of these antimicrobials were then examined by PCR and DNA sequence analysis for the presence of the bla(CMY, bla(CTX-M, bla(TEM, and bla(SHV resistance genes. Thirty-five resistant isolates were detected, including 26 isolates that contained pAmpC (bla(CMY-2, and nine ESBL-producing isolates harboring bla(CTX-M (n = 4, consisting of two bla(CTX-M-2 and two bla(CTX-M-15 genes, bla(TEM (n = 4, consisting of one bla(TEM-20 and three bla(TEM-52 genes, and bla(SHV (n = 1, bla(SHV-12. All pAmpC-harboring and ESBL-producing Salmonella isolates were obtained from samples collected after 2005, and the percentage of resistant isolates increased significantly from 0% in 2004 to 27.9% in 2010 (P for trend = 0.006. This increase was caused in part by an increase in the number of Salmonella enterica subsp. enterica serovar Infantis strains harboring an approximately 280-kb plasmid containing bla(CMY-2 in proximity to ISEcp1. The dissemination of ESC-resistant Salmonella containing plasmid-mediated bla(CMY-2 in chicken

29 CFR 93.205 - Professional and technical services.

Science.gov (United States)

2010-07-01

... professional or technical discipline. For example, drafting of a legal document accompanying a bid or proposal... 29 Labor 1 2010-07-01 2010-07-01 true Professional and technical services. 93.205 Section 93.205... Professional and technical services. (a) The prohibition on the use of appropriated funds, in § 93.100 (a...

New approach to increasing rice lodging resistance and biomass yield through the use of high gibberellin producing varieties.

Directory of Open Access Journals (Sweden)

Ayako Okuno

Full Text Available Traditional breeding for high-yielding rice has been dependent on the widespread use of fertilizers and the cultivation of gibberellin (GA-deficient semi-dwarf varieties. The use of semi-dwarf plants facilitates high grain yield since these varieties possess high levels of lodging resistance, and thus could support the high grain weight. Although this approach has been successful in increasing grain yield, it is desirable to further improve grain production and also to breed for high biomass. In this study, we re-examined the effect of GA on rice lodging resistance and biomass yield using several GA-deficient mutants (e.g. having defects in the biosynthesis or perception of GA, and high-GA producing line or mutant. GA-deficient mutants displayed improved bending-type lodging resistance due to their short stature; however they showed reduced breaking-type lodging resistance and reduced total biomass. In plants producing high amounts of GA, the bending-type lodging resistance was inferior to the original cultivars. The breaking-type lodging resistance was improved due to increased lignin accumulation and/or larger culm diameters. Further, these lines had an increase in total biomass weight. These results show that the use of rice cultivars producing high levels of GA would be a novel approach to create higher lodging resistance and biomass.

Aromatic polymers of increased resistance to flow and molecular weight obtained by irradiation

International Nuclear Information System (INIS)

Staniland, P.A.; Jarrett, G.

1976-01-01

Aromatic polymers of increased resistance to flow and increased molecular weight are obtained by irradiation using β rays or gamma rays at temperatures up to 400 0 C of an aromatic polymer whose molecular chains comprise benzenoid groups and bivalent linking groups, and where irradiation is gamma rays by heating subsequent to irradiation at 200 0 C to 400 0 C. The polymeric materials having increased molecular weight are useful for coating non-cooking surfaces of cookware

Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats.

Science.gov (United States)

Ribeiro Júnior, Rogério Faustino; Marques, Vinicius Bermond; Nunes, Dieli Oliveira; Ronconi, Karoline de Sousa; de Araújo, Julia F P; Rodrigues, Paula Lopes; Padilha, Alessandra Simão; Vassallo, Dalton Valentim; Graceli, Jones B; Stefanon, Ivanita

2016-03-15

Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration-response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O2(-) production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. Copyright © 2016 Elsevier Inc. All rights reserved.

INC '93 overview

International Nuclear Information System (INIS)

Howe, Bruce

1993-01-01

At the close of the International Nuclear Congress, INC '93, held in Toronto in October 1993, Bruce Howe, then president of AECL, presented a 'Review and Conclusions' under the following headings: Introduction, Future Energy Requirements, Economics of electricity generation, Radioactive waste management, Reactor safety, Public acceptance, Technology developments, Future energy strategies, Conclusion

40 CFR 93.157 - Frequency of conformity determinations.

Science.gov (United States)

2010-07-01

... convenience of the user, the revised text is set forth as follows: § 93.157 Reevaluation of conformity. (a... were below the limits in § 93.153(b) and changes to the action would result in the total emissions from the action being above the limits in § 93.153(b), then the Federal agency must make a conformity...

Oral antimicrobials increase antimicrobial resistance in porcine E. coli--a systematic review.

Science.gov (United States)

Burow, E; Simoneit, C; Tenhagen, B-A; Käsbohrer, A

2014-03-01

Administration of antimicrobials to livestock increases the risk of antimicrobial resistance (AMR) in commensal bacteria. Antimicrobials in pig production are usually administered per pen via feed which implies treatment of sick alongside with healthy animals. The objective of this systematic literature review was to investigate the effect of orally administered antimicrobials on AMR in Escherichia coli of swine. Studies published in peer reviewed journals were retrieved from the international online databases ISI Web of Knowledge, PubMed, Scopus and the national electronic literature data base of Deutsches Institut für Medizinische Dokumentation und Information. The studies were assessed using the eligibility criteria English or German language, access to full paper version, defined treatment and control group (initial value or non-treatment) as well as administration and resistance testing of the same antimicrobial class. In the qualitative synthesis, only studies were included presenting the summary measures odds ratio or prevalence of resistance, the category of the applied antimicrobial and the dosage. An effect of the antimicrobial on AMR in E. coli was evaluated as an "increase", "no effect" or "decrease" if the odds or alternatively the prevalence ratio were >1.0, 1.0 or antimicrobial substance and dosage was missing in 4 and 5 of the 11 finally selected studies. The 36 identified trials were inhomogenous in usage and provision of information on sample size. Oral administration of antimicrobials increases the risk of AMR in E. coli from swine. There is however a lack of studies on the impact of dosage and longitudinal effects of treatment. The published studies have a number of issues concerning their scientific quality. More high quality research is needed to better address and quantifiy the effect of orally administered antimicrobials on AMR in swine. Copyright © 2014 Elsevier B.V. All rights reserved.

Has the emergence of community-associated methicillin-resistant Staphylococcus aureus increased trimethoprim-sulfamethoxazole use and resistance?: a 10-year time series analysis.

Science.gov (United States)

Wood, Jameson B; Smith, Donald B; Baker, Errol H; Brecher, Stephen M; Gupta, Kalpana

2012-11-01

There are an increasing number of indications for trimethoprim-sulfamethoxazole use, including skin and soft tissue infections due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Assessing the relationship between rates of use and antibiotic resistance is important for maintaining the expected efficacy of this drug for guideline-recommended conditions. Using interrupted time series analysis, we aimed to determine whether the 2005 emergence of CA-MRSA and recommendations of trimethoprim-sulfamethoxazole as the preferred therapy were associated with changes in trimethoprim-sulfamethoxazole use and susceptibility rates. The data from all VA Boston Health Care System facilities, including 118,863 inpatient admissions, 6,272,661 outpatient clinic visits, and 10,138 isolates were collected over a 10-year period. There was a significant (P = 0.02) increase in trimethoprim-sulfamethoxazole prescriptions in the post-CA-MRSA period (1,605/year) compared to the pre-CA-MRSA period (1,538/year). Although the overall susceptibility of Escherichia coli and Proteus spp. to trimethoprim-sulfamethoxazole decreased over the study period, the rate of change in the pre- versus the post-CA-MRSA period was not significantly different. The changes in susceptibility rates of S. aureus to trimethoprim-sulfamethoxazole and to methicillin were also not significantly different. The CA-MRSA period is associated with a significant increase in use of trimethoprim-sulfamethoxazole but not with significant changes in the rates of susceptibilities among clinical isolates. There is also no evidence for selection of organisms with increased resistance to other antimicrobials in relation to increased trimethoprim-sulfamethoxazole use.

Increased resistance to a generalist herbivore in a salinity-stressed non-halophytic plant.

Science.gov (United States)

Renault, Sylvie; Wolfe, Scott; Markham, John; Avila-Sakar, Germán

2016-01-01

Plants often grow under the combined stress of several factors. Salinity and herbivory, separately, can severely hinder plant growth and reproduction, but the combined effects of both factors are still not clearly understood. Salinity is known to reduce plant tissue nitrogen content and growth rates. Since herbivores prefer tissues with high N content, and biochemical pathways leading to resistance are commonly elicited by salt-stress, we hypothesized that plants growing in saline conditions would have enhanced resistance against herbivores. The non-halophyte, Brassica juncea, and the generalist herbivore Trichoplusia ni were used to test the prediction that plants subjected to salinity stress would be both more resistant and more tolerant to herbivory than those growing without salt stress. Plants were grown under different NaCl levels, and either exposed to herbivores and followed by removal of half of their leaves, or left intact. Plants were left to grow and reproduce until senescence. Tissue quality was assessed, seeds were counted and biomass of different organs measured. Plants exposed to salinity grew less, had reduced tissue nitrogen, protein and chlorophyll content, although proline levels increased. Specific leaf area, leaf water content, transpiration and root:shoot ratio remained unaffected. Plants growing under saline condition had greater constitutive resistance than unstressed plants. However, induced resistance and tolerance were not affected by salinity. These results support the hypothesis that plants growing under salt-stress are better defended against herbivores, although in B. juncea this may be mostly through resistance, and less through tolerance. Published by Oxford University Press on behalf of the Annals of Botany Company.

Freeing France: The Allies, the Resistance, and the JEDBURGHs

National Research Council Canada - National Science Library

Jones, Benjamin F

2008-01-01

.... The study below examines the Allied politics, the nature and the development of the French Resistance, and the actions of the German forces in France to evaluate how useful the deployment of 93...

Enzalutamide inhibits proliferation of gemcitabine-resistant bladder cancer cells with increased androgen receptor expression.

Science.gov (United States)

Kameyama, Koji; Horie, Kengo; Mizutani, Kosuke; Kato, Taku; Fujita, Yasunori; Kawakami, Kyojiro; Kojima, Toshio; Miyazaki, Tatsuhiko; Deguchi, Takashi; Ito, Masafumi

2017-01-01

Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In this study, we investigated the expression and role of AR in gemcitabine-resistant bladder cancer cells and also the potential of enzalutamide, an AR inhibitor, as a therapeutic for the chemoresistance. First of all, we established gemcitabine-resistant T24 cells (T24GR) from T24 bladder cancer cells and performed gene expression profiling. Microarray analysis revealed upregulation of AR expression in T24GR cells compared with T24 cells. AR mRNA and protein expression was confirmed to be increased in T24GR cells, respectively, by quantitative RT-PCR and western blot analysis, which was associated with more potent AR transcriptional activity as measured by luciferase reporter assay. The copy number of AR gene in T24GR cells determined by PCR was twice as many as that of T24 cells. AR silencing by siRNA transfection resulted in inhibition of proliferation of T24GR cells. Cell culture in charcoal-stripped serum and treatment with enzalutamide inhibited growth of T24GR cells, which was accompanied by cell cycle arrest. AR transcriptional activity was found to be reduced in T24GR cells by enzalutamide treatment. Lastly, enzalutamide also inhibited cell proliferation of HTB5 bladder cancer cells that express AR and possess intrinsic resistance to gemcitabine. Our results suggest that enzalutamide may have the potential to treat patients with advanced gemcitabine-resistant bladder cancer with increased AR expression.

FRMAC-93 lessons learned report

International Nuclear Information System (INIS)

Kerns, K.C.

1994-03-01

FRMAC-93 simulated a radiological accident at the Fort Calhoun nuclear power plant, 25 miles north of Omaha, Nebraska. The exercise involved the state Iowa and Nebraska, NRC as the lead Federal agency, FRMAC (Federal Radiological Monitoring and Assessment Center), and several federal agencies with statutory emergency responsibility. FRMAC-93 was a major 2-day field exercise designed to determine the effectiveness, coordination, and operations of a DOE-managed FRMAC. Other objectives were to ensure that appropriate priorities were established and assistance was provided to the states and the lead Federal agency by FRMAC. Day 1 involved the Fort Calhoun evaluated plume phase exercise. On Day 2, the flow of data, which was slow initially, improved so that confidence of states and other federal responders in FRMAC support capabilities was high. The impact and lessons learned from FRMAC-93 provided the necessary impetus to make organizational and operational changes to the FRMAC program, which were put into effect in the DOE exercise FREMONT at Hanford 3 months later

Failure to increase insulin secretory capacity during pregnancy-induced insulin resistance is associated with ethnicity and gestational diabetes.

Science.gov (United States)

Mørkrid, Kjersti; Jenum, Anne K; Sletner, Line; Vårdal, Mari H; Waage, Christin W; Nakstad, Britt; Vangen, Siri; Birkeland, Kåre I

2012-10-01

To assess changes in insulin resistance and β-cell function in a multiethnic cohort of women in Oslo, Norway, from early to 28 weeks' gestation and 3 months post partum and relate the findings to gestational diabetes mellitus (GDM). Population-based cohort study of 695 healthy pregnant women from Western Europe (41%), South Asia (25%), Middle East (15%), East Asia (6%) and elsewhere (13%). Blood samples and demographics were recorded at mean 15 (V1) and 28 (V2) weeks' gestation and 3 months post partum (V3). Universal screening was by 75 g oral glucose tolerance test at V2, GDM with modified IADPSG criteria (no 1-h measurement): fasting plasma glucose (PG) ≥5.1 or 2-h PG ≥8.5 mmol/l. Homeostatic model assessment (HOMA)-β (β-cell function) and HOMA-IR (insulin resistance) were calculated from fasting glucose and C-peptide. Characteristics were comparable across ethnic groups, except age (South Asians: younger, Pinsulin resistant than Western Europeans at V1. From V1 to V2, the increase in insulin resistance was similar across the ethnic groups, but the increase in β-cell function was significantly lower for the East and South Asians compared with Western Europeans. GDM women compared with non-GDM women were more insulin resistant at V1; from V1 to V2, their β-cell function increased significantly less and the percentage increase in β-cell function did not match the change in insulin resistance. Pregnant women from East Asia and South Asia were more insulin resistant and showed poorer HOMA-β-cell function than Western Europeans.

Study of the 93Mo nucleus

International Nuclear Information System (INIS)

Mittal, V.K.; Avasthi, D.K.; Kumar, A; Govil, I.M.

1981-01-01

The level structure of 93 Mo has been studied through 93 Nb(p,nγ) reaction at incident proton energy of 4.2 MeV. Spin assignments and multipole mixing ratios for various levels and transitions have been deduced from the analysis of angular distributions of singles γ-ray spectra. Lifetimes of various levels have been obtained using Doppler Shift Attenuation (DSA) method. (author)

Isobar separation of 93Zr and 93Nb at 24 MeV with a new multi-anode ionization chamber

International Nuclear Information System (INIS)

Martschini, Martin; Buchriegler, Josef; Collon, Philippe; Kutschera, Walter; Lachner, Johannes; Lu, Wenting; Priller, Alfred; Steier, Peter; Golser, Robin

2015-01-01

93 Zr with a half-life of 1.6 Ma is produced with high yield in nuclear fission, and thus should be present as a natural or anthropogenic trace isotope in all compartments of the general environment. Sensitive measurements of this isotope would immediately find numerous applications, however, its detection at sufficiently low levels has not yet been achieved. AMS measurements of 93 Zr suffer from the interference of the stable isobar 93 Nb. At the Vienna Environmental Research Accelerator VERA a new multi-anode ionization chamber was built. It is optimized for isobar separation in the medium mass range and is based on the experience from AMS experiments of 36 Cl at our 3-MV tandem accelerator facility. The design provides high flexibility in anode configuration and detector geometry. After validating the excellent energy resolution of the detector with 36 S, it was recently used to study iron–nickel and zirconium–niobium–molybdenum isobar separation. To our surprise, the separation of 94 Zr (Z = 40) from 94 Mo (Z = 42) was found to be much better than that of 58 Fe (Z = 26) from 58 Ni (Z = 28), despite the significantly larger ΔZ/Z of the latter pair. This clearly contradicts results from SRIM-simulations and suggests that differences in the stopping behavior may unexpectedly favor identification of 93 Zr. At 24 MeV particle energy, a 93 Nb (Z = 41) suppression factor of 1000 is expected based on a synthetic 93 Zr spectrum obtained by interpolation between experimental spectra from the two neighboring stable isotopes 92 Zr and 94 Zr. Assuming realistic numbers for chemical niobium reduction, a detection level of 93 Zr/Zr below 10 −9 seems feasible.

A Lipid Transfer Protein Increases the Glutathione Content and Enhances Arabidopsis Resistance to a Trichothecene Mycotoxin.

Directory of Open Access Journals (Sweden)

John E McLaughlin

Full Text Available Fusarium head blight (FHB or scab is one of the most important plant diseases worldwide, affecting wheat, barley and other small grains. Trichothecene mycotoxins such as deoxynivalenol (DON accumulate in the grain, presenting a food safety risk and health hazard to humans and animals. Despite considerable breeding efforts, highly resistant wheat or barley cultivars are not available. We screened an activation tagged Arabidopsis thaliana population for resistance to trichothecin (Tcin, a type B trichothecene in the same class as DON. Here we show that one of the resistant lines identified, trichothecene resistant 1 (trr1 contains a T-DNA insertion upstream of two nonspecific lipid transfer protein (nsLTP genes, AtLTP4.4 and AtLTP4.5. Expression of both nsLTP genes was induced in trr1 over 10-fold relative to wild type. Overexpression of AtLTP4.4 provided greater resistance to Tcin than AtLTP4.5 in Arabidopsis thaliana and in Saccharomyces cerevisiae relative to wild type or vector transformed lines, suggesting a conserved protection mechanism. Tcin treatment increased reactive oxygen species (ROS production in Arabidopsis and ROS stain was associated with the chloroplast, the cell wall and the apoplast. ROS levels were attenuated in Arabidopsis and in yeast overexpressing AtLTP4.4 relative to the controls. Exogenous addition of glutathione and other antioxidants enhanced resistance of Arabidopsis to Tcin while the addition of buthionine sulfoximine, an inhibitor of glutathione synthesis, increased sensitivity, suggesting that resistance was mediated by glutathione. Total glutathione content was significantly higher in Arabidopsis and in yeast overexpressing AtLTP4.4 relative to the controls, highlighting the importance of AtLTP4.4 in maintaining the redox state. These results demonstrate that trichothecenes cause ROS accumulation and overexpression of AtLTP4.4 protects against trichothecene-induced oxidative stress by increasing the glutathione

Increasing Prevalence of Pediatric Drug-Resistant Tuberculosis in Mumbai, India and its Outcome.

Science.gov (United States)

Shah, Miti A; Shah, Ira

2018-03-24

B.J.Wadia Hospital,Mumbai OBJECTIVE:: The prevalence and type of DR-TB was evaluated pre and post-2013 and outcome was studied. Descriptive retrospective study. Children were defined as having DR-TB on the basis of GeneXpert or LPA and/or drug susceptibility testing(DST) of MTB grown on culture or from contact's DST. The prevalence of DR-TB was 110 out of 1145 cases (9.6%) which showed an increase, compared to 5.6% pre-2010 and 7% in 2010-2013(p=0.014408). Twenty-two (20%) children had pulmonary-TB(PTB) and 88(80%) had extra-pulmonary-TB(EPTB) with disseminated-TB being the most common presentation in 31 children (28.18%). Ninety-six (87.3%) children were bacteriologically confirmed TB cases and 14 (12.7%) were clinically diagnosed-TB and treated as per contact DST. Eight (7.2%) cases were monoresistant, 7 (6.3%) polyresistant, MDR-TB seen in 28 (25.45%) patients, 32 (29.09%) had pre-XDR-TB, 9 (8.18%) had XDR-TB and 12 (10.9%) were rifampicin resistant. Ethionamide resistance increased from 26.1% pre-2013 to 60.8% post-2013(p=0.014408) and ofloxacin resistance rose from 30.4% pre-2010, to 47.6% in 2010-2013 and 56.9% post-2013(p=0.080863). Moxifloxacin resistance showed an acute rise from 8.7% pre-2010, to 46% in 2010-2013 and 57% post-2013(p=0.000275). Thirty-three (30%) patients had completed their treatment, 21(19.09%) were lost to follow up and 56(50.09%) patients are still on treatment.

METHODS OF INCREASING THE RESISTANCE OF A HEAVILY HOT TOOL LANDING BOLT HEADS

OpenAIRE

V. N. Fedoulov

2016-01-01

The present study focuses on increasing resistance of highly-loaded instrument (in particular, punches) for stud driving head diameter of 8 mm and 10 mm countersunk hex through the optimization of heat hardening process using a forged-rolled steel billet DI23 in its production.

An evaluation of the Nb-93(n,n')Nb-93m dosimeter reaction for ENDF/B-VI

International Nuclear Information System (INIS)

Smith, D.L.; Geraldo, L.P.

1990-01-01

The Nb-93(n,n')Nb-93m reaction plays an important role in nuclear energy applications. Because of its low threshold energy and relatively long half-life, it is a desirable reaction for long-term neutron fluence dosimetry in nuclear fission reactors. An evaluation of the differential cross section for this reaction was completed in 1985 by this laboratory as part of a comprehensive effort involving all neutron cross sections for niobium. The objective was to provide input for ENDF/B-VI. It was difficult to produce a reliable evaluation for this reaction in 1985 because the information available then was sparse and quite uncertain. In fact, that evaluation was based entirely on nuclear model calculations. The evaluated cross sections below 0.7 MeV were derived from calculations carried out in this laboratory, while the higher energy values were obtained from the work of Strohmaier and co-workers. In 1985 there was only one published experimental differential cross section value to consider for this reaction. Even the half-life of Nb-93m was in serious doubt. During the five years between the completion of the earlier evaluation and the finalization of ENDF/B-VI there have been some significant improvements and additions to the experimental database for this reaction. Also, new model calculations have been performed. Therefore, it was considered worthwhile to produce a new evaluation of Nb-93(n,n')Nb-93m for ENDF/B-VI which would supplant the one that had been completed in 1985

Antimicrobial resistance in clinical Escherichia coli isolates from poultry and livestock, China.

Directory of Open Access Journals (Sweden)

Afrah Kamal Yassin

Full Text Available Poultry and livestock are the most important reservoirs for pathogenic Escherichia coli and use of antimicrobials in animal farming is considered the most important factor promoting the emergence, selection and dissemination of antimicrobial-resistant microorganisms. The aim of our study was to investigate antimicrobial resistance in E. coli isolated from food animals in Jiangsu, China. The disc diffusion method was used to determine susceptibility to 18 antimicrobial agents in 862 clinical isolates collected from chickens, ducks, pigs, and cows between 2004 and 2012. Overall, 94% of the isolates showed resistance to at least one drug with 83% being resistance to at least three different classes of antimicrobials. The isolates from the different species were most commonly resistant to tetracycline, nalidixic acid, sulfamethoxazole, trimethoprim/sulfamethoxazole and ampicillin, and showed increasing resistance to amikacin, aztreonam, ceftazidime, cefotaxime, chloramphenicol, ciprofloxacin. They were least resistant to amoxicillin/clavulanic acid (3.4% and ertapenem (0.2%. MDR was most common in isolates from ducks (44/44, 100%, followed by chickens (568/644, 88.2%, pigs (93/113, 82.3% and cows (13/61, 21.3%. Our finding that clinical E. coli isolates from poultry and livestock are commonly resistant to multiple antibiotics should alert public health and veterinary authorities to limit and rationalize antimicrobial use in China.

Development of AMS procedure for measurement of 93Zr

Science.gov (United States)

Lu, Wenting; Collon, Philippe; Kashiv, Yoav; Bowers, Matthew; Robertson, Daniel; Schmitt, Christopher

2011-10-01

The procedure for measuring 93Zr (t1/2 = 1.5 Ma) by AMS is currently being developed at the Nuclear Science Lab at the University of Notre Dame and we report on first experiments performed in this direction. AMS detection of 93Zr can potentially be applied to address astrophysical and environmental issues: (1) the measurement of the 92Zr(n,γ)93Zr reaction cross-section at nucleosynthesis s-process relevant temperatures, (2) the search for potential live 93Zr from a supernova in deep sea sediments, (3) hydrological and radioactive waste tracing. The measurement of 93Zr requires adequate separation from its stable isobar 93Nb. We are currently working on optimizing this separation by using the GasFilled Magnet technique with additional multiple dE measurements in a focal plane ionization chamber.

Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats

International Nuclear Information System (INIS)

Ribeiro Júnior, Rogério Faustino; Marques, Vinicius Bermond; Nunes, Dieli Oliveira; Ronconi, Karoline de Sousa; Araújo, Julia F.P. de; Rodrigues, Paula Lopes; Padilha, Alessandra Simão; Vassallo, Dalton Valentim; Graceli, Jones B.; Stefanon, Ivanita

2016-01-01

Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration–response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT 1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O 2 − production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. - Highlights: • Tributyltin chloride reduces estrogen levels in female rats. • Treatment with TBT

Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats

Energy Technology Data Exchange (ETDEWEB)

Ribeiro Júnior, Rogério Faustino, E-mail: rogeriofaustinoribeiro@hotmail.com [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Marques, Vinicius Bermond; Nunes, Dieli Oliveira; Ronconi, Karoline de Sousa [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Araújo, Julia F.P. de [Department of Morphology, Federal University of Espírito Santo (Brazil); Rodrigues, Paula Lopes; Padilha, Alessandra Simão; Vassallo, Dalton Valentim [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Graceli, Jones B. [Department of Morphology, Federal University of Espírito Santo (Brazil); Stefanon, Ivanita [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil)

2016-03-15

Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration–response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT{sub 1} receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O{sub 2}{sup −} production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. - Highlights: • Tributyltin chloride reduces estrogen levels in female rats. �

Preclinical and Clinical Resistance Profile of EDP-239, a Novel Hepatitis C Virus NS5A Inhibitor.

Science.gov (United States)

Owens, Christopher M; Brasher, Bradley B; Polemeropoulos, Alex; Rhodin, Michael H J; McAllister, Nicole; Wong, Kelly A; Jones, Christopher T; Jiang, Lijuan; Lin, Kai; Or, Yat Sun

2016-10-01

EDP-239, a potent and selective hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor developed for the treatment of HCV infection, has been investigated in vitro and in vivo This study sought to characterize genotypic changes in the HCV NS5A sequence of genotype 1 (GT1) replicons and to compare those changes to GT1 viral RNA mutations isolated from clinical trial patients. Resistance selection experiments in vitro using a subgenomic replicon identified resistance-associated mutations (RAMs) at GT1a NS5A amino acid positions 24, 28, 30, 31, and 93 that confer various degrees of resistance to EDP-239. Key RAMs were similarly identified in GT1b NS5A at amino acid positions 31 and 93. Mutations F36L in GT1a and A92V in GT1b do not confer resistance to EDP-239 individually but were found to enhance the resistance of GT1a K24R and GT1b Y93H. RAMs were identified in GT1 patients at baseline or after dosing with EDP-239 that were similar to those detected in vitro Baseline RAMs identified at NS5A position 93 in GT1, or positions 28 or 30 in GT1a only, correlated with a reduced treatment response. RAMs at additional positions were also detected and may have contributed to reduced EDP-239 efficacy. The most common GT1a and GT1b RAMs found to persist up to weeks 12, 24, or 48 were those at NS5A positions 28, 30, 31, 58 (GT1a only), and 93. Those RAMs persisting at the highest frequencies up to weeks 24 or 48 were L31M and Q30H/R for GT1a and L31M and Y93H for GT1b. (This study has been registered at ClinicalTrials.gov under identifier NCT01856426.). Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Development and evaluation of a HEPA filter for increased strength and resistance to elevated temperature

International Nuclear Information System (INIS)

Gilbert, H.; Bergman, W.; Fretthold, J.K.

1992-01-01

We have developed an improved HEPA filter for increased strength and resistance to elevated temperature to improve the reliability of HEPA filters under accident conditions. The improvements to the HEPA filter consist of a silicone rubber sealant and a new HEPA medium reinforced with a glass cloth. Several prototype filters were built and evaluated for temperature and pressure resistance and resistance to rough handling. The temperature resistance test consisted of exposing the HEPA filter to 1,000 scan at 700 degrees F for five minutes. The pressure resistance test consisted of exposing the HEPA filter to a differential pressure of 10 in. w.g. using a water saturated air flow at 95 degrees F. For the rough handling test, we used a vibrating machine designated the Q110. DOP filter efficiency tests were performed before and after each of the environmental tests. In addition to following the standard practice of using a separate new filter for each environmental test, we also subjected the same filter to the elevated temperature test followed by the pressure resistance test. The efficiency test results show that the improved HEPA filter is significantly better than the standard HEPA filter

Variations of electric resistance and H2 and Rn emissions of concrete blocks under increasing uniaxial compression

Science.gov (United States)

King, C.-Y.; Luo, G.

1990-01-01

Electric resistance and emissions of hydrogen and radon isotopes of concrete (which is somewhat similar to fault-zone materials) under increasing uniaxial compression were continuously monitored to check whether they show any pre- and post-failure changes that may correspond to similar changes reported for earthquakes. The results show that all these parameters generally begin to increase when the applied stresses reach 20% to 90% of the corresponding failure stresses, probably due to the occurrence and growth of dilatant microcracks in the specimens. The prefailure changes have different patterns for different specimens, probably because of differences in spatial and temporal distributions of the microcracks. The resistance shows large co-failure increases, and the gas emissions show large post-failure increases. The post-failure increase of radon persists longer and stays at a higher level than that of hydrogen, suggesting a difference in the emission mechanisms for these two kinds of gases. The H2 increase may be mainly due to chemical reaction at the crack surfaces while they are fresh, whereas the Rn increases may be mainly the result of the increased emanation area of such surfaces. The results suggest that monitoring of resistivity and gas emissions may be useful for predicting earthquakes and failures of concrete structures. ?? 1990 Birkha??user Verlag.

Molecular markers of antifolate resistance in Plasmodium falciparum isolates from Luanda, Angola

Science.gov (United States)

2011-01-01

Background Plasmodium falciparum malaria remains a leading health problem in Africa and its control is seriously challenged by drug resistance. Although resistance to the sulphadoxine-pyrimethamine (SP) is widespread, this combination remains an important component of malaria control programmes as intermittent preventive therapy (IPT) for pregnant women and children. In Angola, resistance patterns have been poorly characterized, and IPT has been employed for pregnant women since 2006. The aim of this study was to assess the prevalence of key antifolate resistance mediating polymorphisms in the pfdhfr and pfdhps genes in P. falciparum samples from Angola. Methods Plasmodium falciparum samples collected in Luanda, in 2007, were genotyped by amplification and DNA forward and reverse sequencing of the pfdhfr and pfdhps genes. Results The most prevalent polymorphisms identified were pfdhfr 108N (100%), 51I (93%), 59R (57%) and pfdhps 437G (93%). Resistance-mediating polymorphisms in pfdhps less commonly observed in West Africa were also identified (540E in 10%, 581G in 7% of samples). Conclusion This study documents an important prevalence of 4 P. falciparum polymorphisms that predicts an antifolate resistance in Luanda. Further, some samples presented additional mutations associated to high-level resistance. These results suggest that the use of SP for IPT may no longer be warranted in Angola. PMID:21864379

Increased frequency of pink bollworm resistance to Bt toxin Cry1Ac in China.

Directory of Open Access Journals (Sweden)

Peng Wan

Full Text Available Transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt kill some key insect pests, but evolution of resistance by pests can reduce their efficacy. The main approach for delaying pest adaptation to Bt crops uses non-Bt host plants as "refuges" to increase survival of susceptible pests. To delay evolution of pest resistance to transgenic cotton producing Bt toxin Cry1Ac, the United States and some other countries have required refuges of non-Bt cotton, while farmers in China have relied on "natural" refuges of non-Bt host plants other than cotton. The "natural" refuge strategy focuses on cotton bollworm (Helicoverpa armigera, the primary target of Bt cotton in China that attacks many crops, but it does not apply to another major pest, pink bollworm (Pectinophora gossypiella, which feeds almost entirely on cotton in China. Here we report data showing field-evolved resistance to Cry1Ac by pink bollworm in the Yangtze River Valley of China. Laboratory bioassay data from 51 field-derived strains show that the susceptibility to Cry1Ac was significantly lower during 2008 to 2010 than 2005 to 2007. The percentage of field populations yielding one or more survivors at a diagnostic concentration of Cry1Ac increased from 0% in 2005-2007 to 56% in 2008-2010. However, the median survival at the diagnostic concentration was only 1.6% from 2008 to 2010 and failure of Bt cotton to control pink bollworm has not been reported in China. The early detection of resistance reported here may promote proactive countermeasures, such as a switch to transgenic cotton producing toxins distinct from Cry1A toxins, increased planting of non-Bt cotton, and integration of other management tactics together with Bt cotton.

9 CFR 93.806 - Animals refused entry.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Animals refused entry. 93.806 Section 93.806 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS IMPORTATION OF...

14 CFR 93.29 - International Arrival Authorizations.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false International Arrival Authorizations. 93.29... at Chicago O'Hare International Airport § 93.29 International Arrival Authorizations. (a) Except as... marketing arrangement unless the flight was predominately marketed, by contract, under the control of...

15 CFR 923.93 - Eligible implementation costs.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Eligible implementation costs. 923.93... MANAGEMENT COASTAL ZONE MANAGEMENT PROGRAM REGULATIONS Applications for Program Development or Implementation Grants § 923.93 Eligible implementation costs. (a) Costs claimed must be beneficial and necessary to the...

42 CFR 93.107 - Rule of interpretation.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Rule of interpretation. 93.107 Section 93.107 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON...

Anti-MRSA activities of Enterocins DD28 and DD93 and evidences on their role in the inhibition of biofilm formation

Directory of Open Access Journals (Sweden)

Ahmed Khassaf eAL ATYA

2016-05-01

Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA, along with other antibiotic resistant bacteria, has become a worrisome superbug worldwide. This work was aimed at studying the efficacies of two class IIb bacteriocins, enterocins DD28 and DD93, against MRSA-S1 grown in planktonic culture and embedded in biofilms. These bacteriocins were purified, from the cultures supernatants of Enterococcus faecalis 28 and 93, using a simplified purification procedure consisting in a cation exchange chromatography and a reversed-phase high-performance liquid chromatography. The anti-Staphylococcal activity of these bacteriocins was shown in-vitro by the assessment of the minimal inhibitory concentration (MIC. Afterwhich, a checkerboard and time-kill kinetics permitted unveiled a synergistic effect of these bacteriocins in combination with erythromycin and kanamycin against the clinical MRSA-S1. These bacteriocins alone or in combination with erythromycin and kanamycin were able to impede the formation of MRSA-S1 biofilms on stainless steel and glace devices as supported by the microbial cell counts, epifluorescence and Scanning Electron Microscope analyses.

Wear resistance increase of the modified coatings, deposited in the beam of relativistic electrons

International Nuclear Information System (INIS)

Poletika, I.M.; Perovskaya, M.V.; Balushkina, M.A.

2015-01-01

The 1.5-3 mm thickness coatings have been obtained by vacuum - free electron beam cladding of tungsten carbide on low - carbon steel sub state. The coatings have an increased hardness but low wear resistance. Adding both nickel and titanium carbide to the tungsten carbide results in essentially improving the wear resistance of the coatings due to austenite-promoting effect of nickel and precipitation of fine Tic particles resulting in the formation of the final and nano grain structure. In the layer of weld one can find 30-100 nm grain - size structures. (authors)

9 CFR 93.216 - Poultry from Canada.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Poultry from Canada. 93.216 Section 93... EXPORTATION AND IMPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS IMPORTATION OF CERTAIN ANIMALS, BIRDS, FISH, AND POULTRY, AND CERTAIN ANIMAL, BIRD, AND POULTRY PRODUCTS; REQUIREMENTS FOR MEANS OF...

42 CFR 93.227 - Secretary or HHS.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Secretary or HHS. 93.227 Section 93.227 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH...

Combined whole-body vibration, resistance exercise, and sustained vascular occlusion increases PGC-1α and VEGF mRNA abundances.

Science.gov (United States)

Item, Flurin; Nocito, Antonio; Thöny, Sandra; Bächler, Thomas; Boutellier, Urs; Wenger, Roland H; Toigo, Marco

2013-04-01

We previously reported that high load resistance exercise with superimposed whole-body vibration and sustained vascular occlusion (vibroX) markedly improves cycling endurance capacity, increases capillary-to-fibre ratio and skeletal muscle oxidative enzyme activity in untrained young women. These findings are intriguing, since increases in oxidative muscle phenotype and endurance capacity are typically induced by endurance but not heavy resistance exercise. Here, we tested the hypothesis that vibroX activates genes associated with mitochondrial biogenesis and angiogenesis. Eight healthy, recreationally resistance-trained young men performed either vibroX or resistance exercise (RES) in a randomised, cross-over design. Needle biopsies (M. vastus lateralis) were obtained at rest and 3 h post-exercise. Changes in relative gene expression levels were assessed by real-time quantitative PCR. After vibroX, vascular endothelial growth factor and peroxisome proliferator-activated receptor-γ coactivator 1α mRNA abundances increased to 2- and 4.4-fold, respectively, but did not significantly change above resting values after RES. Other genes involved in mitochondrial biogenesis were not affected by either exercise modality. While vibroX increased the expression of hexokinase II, xanthine dehydrogenase, and manganese superoxide dismutase mRNA, there were no changes in these transcripts after RES. This study demonstrates that high load resistance exercise with superimposed whole-body vibration and sustained vascular occlusion activates metabolic and angiogenic gene programs, which are usually activated after endurance but not resistance exercise. Thus, targeted modification of high load resistance exercise by vibration and vascular occlusion might represent a novel strategy to induce endurance-type muscle adaptations.

METHODS OF INCREASING THE RESISTANCE OF A HEAVILY HOT TOOL LANDING BOLT HEADS

Directory of Open Access Journals (Sweden)

V. N. Fedoulov

2016-01-01

Full Text Available The present study focuses on increasing resistance of highly-loaded instrument (in particular, punches for stud driving head diameter of 8 mm and 10 mm countersunk hex through the optimization of heat hardening process using a forged-rolled steel billet DI23 in its production.

Increasing awareness about antibiotic use and resistance: a hands-on project for high school students.

Science.gov (United States)

Fonseca, Maria João; Santos, Catarina L; Costa, Patrício; Lencastre, Leonor; Tavares, Fernando

2012-01-01

Health-promoting education is essential to foster an informed society able to make decisions about socio-scientific issues based on scientifically sustained criteria. Antibiotic resistance is currently a major public health issue. Considering that irrational antibiotic use has been associated with the development and widespread of antibiotic resistant bacteria, educational interventions to promote prudent antibiotic consumption are required. This study focuses on the outcomes of an interventional program implemented at the University of Porto, Portugal, to promote awareness about antibiotic resistance at high school levels (15-17 year old). The project Microbiology recipes: antibiotics à la carte articulates a set of wet and dry lab activities designed to promote the participants' understanding of concepts and processes underlying antibiotics' production and activity, such as the notion of mechanisms of action of antibiotics. Following a mix-method approach based on a pre-/post design, the effectiveness of this project was assessed by gathering data from surveys, direct observation and analysis of artifacts of 42 high school students (aged 15 and 16 years). The results indicate that the participants developed a more comprehensive picture of antibiotic resistance. The project was shown to promote more sophisticated conceptualizations of bacteria and antibiotics, increased awareness about the perils of antibiotic resistance, and enhanced consciousness towards measures that can be undertaken to mitigate the problem. The participants regarded their experiences as enjoyable and useful, and believed that the project contributed to improve their understanding and raise their interest about the issues discussed. Furthermore, there were also improvements in their procedural skills concerning the laboratory techniques performed. This study evidences the possibility of increasing high school students' awareness about the consequences of antibiotic resistance and the

Transgenic Pm3 multilines of wheat show increased powdery mildew resistance in the field.

Science.gov (United States)

Brunner, Susanne; Stirnweis, Daniel; Diaz Quijano, Carolina; Buesing, Gabriele; Herren, Gerhard; Parlange, Francis; Barret, Pierre; Tassy, Caroline; Sautter, Christof; Winzeler, Michael; Keller, Beat

2012-05-01

Resistance (R) genes protect plants very effectively from disease, but many of them are rapidly overcome when present in widely grown cultivars. To overcome this lack of durability, strategies that increase host resistance diversity have been proposed. Among them is the use of multilines composed of near-isogenic lines (NILs) containing different disease resistance genes. In contrast to classical R-gene introgression by recurrent backcrossing, a transgenic approach allows the development of lines with identical genetic background, differing only in a single R gene. We have used alleles of the resistance locus Pm3 in wheat, conferring race-specific resistance to wheat powdery mildew (Blumeria graminis f. sp. tritici), to develop transgenic wheat lines overexpressing Pm3a, Pm3c, Pm3d, Pm3f or Pm3g. In field experiments, all tested transgenic lines were significantly more resistant than their respective nontransformed sister lines. The resistance level of the transgenic Pm3 lines was determined mainly by the frequency of virulence to the particular Pm3 allele in the powdery mildew population, Pm3 expression levels and most likely also allele-specific properties. We created six two-way multilines by mixing seeds of the parental line Bobwhite and transgenic Pm3a, Pm3b and Pm3d lines. The Pm3 multilines were more resistant than their components when tested in the field. This demonstrates that the difference in a single R gene is sufficient to cause host-diversity effects and that multilines of transgenic Pm3 wheat lines represent a promising strategy for an effective and sustainable use of Pm3 alleles. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

Evaluation of the 93Nb (n,n')93mNb reaction cross section from the threshold up to 20 MeV

International Nuclear Information System (INIS)

Badikov, S.A.; Zolotarev, K.I.; Pashchenko, A.B.

1992-01-01

The data base comprising the results of the 93 Nb(n,n') 93m Nb reactions cross section measurements up to 1991 has been compiled. The experimental data have been renormalized to new values of standard cross-sections from the ENDF/B-6 and the IRDF-90 libraries. The evaluation of excitation function for the 93 Nb(n,n') 93m Nb reaction was carried out on the basis of procedure taking the correlation of experimental data into account. The files of evaluated cross-sections and covariance were prepared in the ENDF/B-6 format. The cross-section evaluations from present work and the IRDF-90 library are compared. 37 refs.; 3 figs.; 6 tabs

9 CFR 93.307 - Articles accompanying horses.

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2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Articles accompanying horses. 93.307... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Horses § 93.307 Articles accompanying horses. No..., blankets, or other things used for or about horses governed by the regulations this part, shall be landed...

Isolated cytochrome c oxidase deficiency in G93A SOD1 mice overexpressing CCS protein.

Science.gov (United States)

Son, Marjatta; Leary, Scot C; Romain, Nadine; Pierrel, Fabien; Winge, Dennis R; Haller, Ronald G; Elliott, Jeffrey L

2008-05-02

G93A SOD1 transgenic mice overexpressing CCS protein develop an accelerated disease course that is associated with enhanced mitochondrial pathology and increased mitochondrial localization of mutant SOD1. Because these results suggest an effect of mutant SOD1 on mitochondrial function, we assessed the enzymatic activities of mitochondrial respiratory chain complexes in the spinal cords of CCS/G93A SOD1 and control mice. CCS/G93A SOD1 mouse spinal cord demonstrates a 55% loss of complex IV (cytochrome c oxidase) activity compared with spinal cord from age-matched non-transgenic or G93A SOD1 mice. In contrast, CCS/G93A SOD1 spinal cord shows no reduction in the activities of complex I, II, or III. Blue native gel analysis further demonstrates a marked reduction in the levels of complex IV but not of complex I, II, III, or V in spinal cords of CCS/G93A SOD1 mice compared with non-transgenic, G93A SOD1, or CCS/WT SOD1 controls. With SDS-PAGE analysis, spinal cords from CCS/G93A SOD1 mice showed significant decreases in the levels of two structural subunits of cytochrome c oxidase, COX1 and COX5b, relative to controls. In contrast, CCS/G93A SOD1 mouse spinal cord showed no reduction in levels of selected subunits from complexes I, II, III, or V. Heme A analyses of spinal cord further support the existence of cytochrome c oxidase deficiency in CCS/G93A SOD1 mice. Collectively, these results establish that CCS/G93A SOD1 mice manifest an isolated complex IV deficiency which may underlie a substantial part of mutant SOD1-induced mitochondrial cytopathy.

Interactions of cullin3/KCTD5 complexes with both cytoplasmic and nuclear proteins: Evidence for a role in protein stabilization

Energy Technology Data Exchange (ETDEWEB)

Rutz, Natalja; Heilbronn, Regine; Weger, Stefan, E-mail: stefan.weger@charite.de

2015-08-28

Based on its specific interaction with cullin3 mediated by an N-terminal BTB/POZ homologous domain, KCTD5 has been proposed to function as substrate adapter for cullin3 based ubiquitin E3 ligases. In the present study we tried to validate this hypothesis through identification and characterization of additional KCTD5 interaction partners. For the replication protein MCM7, the zinc finger protein ZNF711 and FAM193B, a yet poorly characterized cytoplasmic protein, we could demonstrate specific interaction with KCTD5 both in yeast two-hybrid and co-precipitation studies in mammalian cells. Whereas trimeric complexes of cullin3 and KCTD5 with the respective KCTD5 binding partner were formed, KCTD5/cullin3 induced polyubiquitylation and/or proteasome-dependent degradation of these binding partners could not be demonstrated. On the contrary, KCTD5 or Cullin3 overexpression increased ZNF711 protein stability. - Highlights: • KCTD5 nuclear translocation depends upon M phase and protein oligomerization. • Identification of MCM7, ZNF711 and FAM193 as KCTD5 interaction partners. • Formation of trimeric complexes of KCTD5/cullin3 with MCM7, ZNF711 and FAM193B. • KCTD5 is not involved in polyubiquitylation of MCM7 replication factor. • The KCTD5/cullin3 complex stabilizes ZNF711 transcription factor.

Progressive resistance training increases strength after stroke but this may not carry over to activity: a systematic review.

Science.gov (United States)

Dorsch, Simone; Ada, Louise; Alloggia, Daniella

2018-04-01

Does progressive resistance training improve strength and activity after stroke? Does any increase in strength carry over to activity? Systematic review of randomised trials with meta-analysis. Adults who have had a stroke. Progressive resistance training compared with no intervention or placebo. The primary outcome was change in strength. This measurement had to be of maximum voluntary force production and performed in muscles congruent with the muscles trained in the intervention. The secondary outcome was change in activity. This measurement had to be a direct measure of performance that produced continuous or ordinal data, or with scales that produced ordinal data. Eleven studies involving 370 participants were included in this systematic review. The overall effect of progressive resistance training on strength was examined by pooling change scores from six studies with a mean PEDro score of 5.8, representing medium quality. The effect size of progressive resistance training on strength was 0.98 (95% CI 0.67 to 1.29, I 2 =0%). The overall effect of progressive resistance training on activity was examined by pooling change scores from the same six studies. The effect size of progressive resistance training on activity was 0.42 (95% CI -0.08 to 0.91, I 2 =54%). After stroke, progressive resistance training has a large effect on strength compared with no intervention or placebo. There is uncertainty about whether these large increases in strength carry over to improvements in activity. PROSPERO CRD42015025401. [Dorsch S, Ada L, Alloggia D (2018) Progressive resistance training increases strength after stroke but this may not carry over to activity: a systematic review. Journal of Physiotherapy 64: 84-90]. Copyright © 2018 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Heavy metals in liquid pig manure in light of bacterial antimicrobial resistance

International Nuclear Information System (INIS)

Hölzel, Christina S.; Müller, Christa; Harms, Katrin S.; Mikolajewski, Sabine; Schäfer, Stefanie; Schwaiger, Karin; Bauer, Johann

2012-01-01

Heavy metals are regularly found in liquid pig manure, and might interact with bacterial antimicrobial resistance. Concentrations of heavy metals were determined by atomic spectroscopic methods in 305 pig manure samples and were connected to the phenotypic resistance of Escherichia coli (n=613) against 29 antimicrobial drugs. Concentrations of heavy metals (/kg dry matter) were 0.08–5.30 mg cadmium, 1.1–32.0 mg chrome, 22.4–3387.6 mg copper, <2.0–26.7 mg lead, <0.01–0.11 mg mercury, 3.1–97.3 mg nickel and 93.0–8239.0 mg zinc. Associated with the detection of copper and zinc, resistance rates against β-lactams were significantly elevated. By contrast, the presence of mercury was significantly associated with low antimicrobial resistance rates of Escherichia coli against β-lactams, aminoglycosides and other antibiotics. Effects of subinhibitory concentrations of mercury on bacterial resistance against penicillins, cephalosporins, aminoglycosides and doxycycline were also demonstrated in a laboratory trial. Antimicrobial resistance in the porcine microflora might be increased by copper and zinc. By contrast, the occurrence of mercury in the environment might, due to co-toxicity, act counter-selective against antimicrobial resistant strains.

17 CFR 10.93 - Obtaining default order.

Science.gov (United States)

2010-04-01

... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Obtaining default order. 10.93... Disposition Without Full Hearing § 10.93 Obtaining default order. When a respondent has failed to (a) file an... enter findings and conclusions and a default order against that respondent based upon the matters set...

Intrahepatic upregulation of MRTF-A signaling contributes to increased hepatic vascular resistance in cirrhotic rats with portal hypertension.

Science.gov (United States)

Zheng, Lei; Qin, Jun; Sun, Longci; Gui, Liang; Zhang, Chihao; Huang, Yijun; Deng, Wensheng; Huang, An; Sun, Dong; Luo, Meng

2017-06-01

Portal hypertension in cirrhosis is mediated, in part, by increased intrahepatic resistance, reflecting massive structural changes associated with fibrosis and intrahepatic vasoconstriction. Activation of the Rho/MRTF/SRF signaling pathway is essential for the cellular regulatory network of fibrogenesis. The aim of this study was to investigate MRTF-A-mediated regulation of intrahepatic fibrogenesis in cirrhotic rats. Portal hypertension was induced in rats via an injection of CCl 4 oil. Hemodynamic measurements were obtained using a polyethylene PE-50 catheter and pressure transducers. Expression of hepatic fibrogenesis was measured using histological staining. Expression of protein was measured using western blotting. Upregulation of MRTF-A protein expression in the livers of rats with CCl 4 -induced cirrhosis was relevant to intrahepatic resistance and hepatic fibrogenesis in portal hypertensive rats with increased modeling time. Inhibition of MRTF-A by CCG-1423 decelerated hepatic fibrosis, decreased intrahepatic resistance and portal pressure, and alleviated portal hypertension. Increased intrahepatic resistance in rats with CCl 4 -induced portal hypertension is associated with an upregulation of MRTF-A signaling. Inhibition of this pathway in the liver can decrease hepatic fibrosis and intrahepatic resistance, as well as reduce portal pressure in cirrhotic rats with CCl 4 -induced portal hypertension. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Long-term exposure to benzalkonium chloride disinfectants results in change of microbial community structure and increased antimicrobial resistance.

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Tandukar, Madan; Oh, Seungdae; Tezel, Ulas; Konstantinidis, Konstantinos T; Pavlostathis, Spyros G

2013-09-03

The effect of benzalkonium chlorides (BACs), a widely used class of quaternary ammonium disinfectants, on microbial community structure and antimicrobial resistance was investigated using three aerobic microbial communities: BACs-unexposed (DP, fed a mixture of dextrin/peptone), BACs-exposed (DPB, fed a mixture of dextrin/peptone and BACs), and BACs-enriched (B, fed only BACs). Long-term exposure to BACs reduced community diversity and resulted in the enrichment of BAC-resistant species, predominantly Pseudomonas species. Exposure of the two microbial communities to BACs significantly decreased their susceptibility to BACs as well as three clinically relevant antibiotics (penicillin G, tetracycline, ciprofloxacin). Increased resistance to BACs and penicillin G of the two BACs-exposed communities is predominantly attributed to degradation or transformation of these compounds, whereas resistance to tetracycline and ciprofloxacin is largely due to the activity of efflux pumps. Quantification of several key multidrug resistance genes showed a much higher number of copies of these genes in the DPB and B microbial communities compared to the DP community. Collectively, our findings indicate that exposure of a microbial community to BACs results in increased antibiotic resistance, which has important implications for both human and environmental health.

Progranulin causes adipose insulin resistance via increased autophagy resulting from activated oxidative stress and endoplasmic reticulum stress.

Science.gov (United States)

Guo, Qinyue; Xu, Lin; Li, Huixia; Sun, Hongzhi; Liu, Jiali; Wu, Shufang; Zhou, Bo

2017-01-31

Progranulin (PGRN) has recently emerged as an important regulator for insulin resistance. However, the direct effect of progranulin in adipose insulin resistance associated with the autophagy mechanism is not fully understood. In the present study, progranulin was administered to 3T3-L1 adipocytes and C57BL/6 J mice with/without specific inhibitors of oxidative stress and endoplasmic reticulum stress, and metabolic parameters, oxidative stress, endoplasmic reticulum stress and autophagy markers were assessed. Progranulin treatment increased iNOS expression, NO synthesis and ROS generation, and elevated protein expressions of CHOP, GRP78 and the phosphorylation of PERK, and caused a significant increase in Atg7 and LC3-II protein expression and a decreased p62 expression, and decreased insulin-stimulated tyrosine phosphorylation of IRS-1 and glucose uptake, demonstrating that progranulin activated oxidative stress and ER stress, elevated autophagy and induced insulin insensitivity in adipocytes and adipose tissue of mice. Interestingly, inhibition of iNOS and ER stress both reversed progranulin-induced stress response and increased autophagy, protecting against insulin resistance in adipocytes. Furthermore, the administration of the ER stress inhibitor 4-phenyl butyric acid reversed the negative effect of progranulin in vivo. Our findings showed the clinical potential of the novel adipokine progranulin in the regulation of insulin resistance, suggesting that progranulin might mediate adipose insulin resistance, at least in part, by inducing autophagy via activated oxidative stress and ER stress.

A hierarchical analysis of transcriptome alterations in intrauterine growth restriction (IUGR) reveals common pathophysiological pathways in mammals.

Science.gov (United States)

Buffat, C; Mondon, F; Rigourd, V; Boubred, F; Bessières, B; Fayol, L; Feuerstein, J-M; Gamerre, M; Jammes, H; Rebourcet, R; Miralles, F; Courbières, B; Basire, A; Dignat-Georges, F; Carbonne, B; Simeoni, U; Vaiman, D

2007-11-01

Intra-uterine growth restriction (IUGR) is a frequent disease, affecting up to 10% of human pregnancies and responsible for increased perinatal morbidity and mortality. Moreover, low birth weight is an important cause of the metabolic syndrome in the adult. Protein depletion during the gestation of rat females has been widely used as a model for human IUGR. By transcriptome analysis of control and protein-deprived rat placentas, we were able to identify 2543 transcripts modified more than 2.5 fold (1347 induced and 1196 repressed). Automatic functional classification enabled us to identify clusters of induced genes affecting chromosome structure, transcription, intracellular transport, protein modifications and apoptosis. In particular, we suggest the existence of a complex balance regulating apoptosis. Among repressed genes, we noted several groups of genes involved in immunity, signalling and degradation of noxious chemicals. These observations suggest that IUGR placentas have a decreased resistance to external aggression. The promoters of the most induced and most repressed genes were contrasted for their composition in putative transcription factor binding sites. There was an over-representation of Zn finger (ZNF) proteins and Pdx1 (pancreatic and duodenal homeobox protein 1) putative binding sites. Consistently, Pdx1 and a high proportion of ZNF genes were induced at the transcriptional level. A similar analysis of ZNF promoters showed an increased presence of putative binding sites for the Tata box binding protein (Tbp). Consistently again, we showed that the Tbp and TBP-associated factors (Tafs) were up-regulated in IUGR placentas. Also, samples of human IUGR and control placentas showed that human orthologous ZNFs and PDX1 were transcriptionally induced, especially in non-vascular IUGR. Immunohistochemistry revealed increased expression of PDX1 in IUGR human placentas. In conclusion, our approach permitted the proposition of hypotheses on a hierarchy of

Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity

International Nuclear Information System (INIS)

Powell, Ashley A; Akare, Sandeep; Qi, Wenqing; Herzer, Pascal; Jean-Louis, Samira; Feldman, Rebecca A; Martinez, Jesse D

2006-01-01

There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA. To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis. We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth. We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype

Drug resistance patterns of acinetobacter baumannii in makkah, saudi arabia

International Nuclear Information System (INIS)

Khan, M.A.; Ashshi, A.M.; Mahomed, M.F.

2012-01-01

Background: Acinetobacter baumannii causes infections of respiratory, urinary tract, blood stream and surgical sites. Its clinical significance has increased due to its rapidly developing resistance to major groups of antibiotics used for its treatment. There is limited data available on antimicrobial susceptibility of A. baumannii from Saudi Arabia. Objectives: To determine the patterns of drug resistance of Acinetobacter baumannii and predisposing factors for its acquisition.Subjects and Methods: In this descriptive study, 72 hospitalized patients infected with A baumannii were studied. The clinical and demographic data of the patients were collected using a predesigned questionnaire. Isolation and identification of A.baumannii from all clinical specimens were done using standard microbiological methods. Antibiotic susce ptibility testing was performed by disk diffusion method recommended by Clinical Laboratory Standards Institute. Results: Majority of the isolates (61.1%) were from respiratory tract infections. A.baumannii isolates showed high drug resistance to piperacil lin (93.1%), aztreonam (80.5%), ticarcillin, ampicillin, and tetracycline (76.4%, each) and cefotaxime (75%). Only amikacin showed low rate of resistance compared to other antibiotics (40.3%). About 36% patients had some underlying diseases with diabetes mellitus (11%) being the predominant underlying disease. Conclusions: High antimicrobial resistance to commonly used antibiotics was seen against A.baumannii isolates. Only amikacin was most effective against it. (author)

High prevalence of drug-resistant tuberculosis, Republic of Lithuania, 2002

DEFF Research Database (Denmark)

Dewan, P; Sosnovskaja, A; Thomsen, V

2005-01-01

BACKGROUND: Nations of the former Soviet Union have the world's highest reported levels of resistance to anti-tuberculosis drugs. We conducted the first national survey of anti-tuberculosis drug resistance in the Republic of Lithuania. METHODS: We tested Mycobacterium tuberculosis isolates from all...... isolates, 475 (41%) were resistant to at least one first-line drug, and 263 (23%) were resistant to at least INH and RMP (MDR); this included 76/818 (9.3%) from new patients and 187/345 (54%) from previously treated patients. Of 52 MDR isolates randomly selected for extended testing at an international...

27 CFR 4.93 - Approval of grape variety names.

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2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Approval of grape variety names. 4.93 Section 4.93 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE American Grape Variety Names § 4.93...

Increased incidences of multidrug-resistant gonorrhea in Taiwanese men: Experiences from a single institute

Directory of Open Access Journals (Sweden)

Yu-Hua Lin

2016-06-01

Conclusion: Genital discharge swab culture is a more effective method than urine culture to detect gonorrhea in patients with dysuria and urethral discharge. The increasing numbers of antibiotic-resistant N. gonorrhoeae strains is a major problem in treating gonococcal urethritis.

Increased tolerance and resistance to virus infections: a possible factor in the survival of Varroa destructor-resistant honey bees (Apis mellifera.

Directory of Open Access Journals (Sweden)

Barbara Locke

Full Text Available The honey bee ectoparasitic mite, Varroa destructor, has a world-wide distribution and inflicts more damage than all other known apicultural diseases. However, Varroa-induced colony mortality is more accurately a result of secondary virus infections vectored by the mite. This means that honey bee resistance to Varroa may include resistance or tolerance to virus infections. The aim of this study was to see if this is the case for a unique population of mite-resistant (MR European honey bees on the island of Gotland, Sweden. This population has survived uncontrolled mite infestation for over a decade, developing specific mite-related resistance traits to do so. Using RT-qPCR techniques, we monitored late season virus infections, Varroa mite infestation and honey bee colony population dynamics in the Gotland MR population and compared this to mite-susceptible (MS colonies in a close by apiary. From summer to autumn the deformed wing virus (DWV titres increased similarly between the MR and MS populations, while the black queen cell virus (BQCV and sacbrood virus (SBV titres decreased substantially in the MR population compared to the MS population by several orders of magnitude. The MR colonies all survived the following winter with high mite infestation, high DWV infection, small colony size and low proportions of autumn brood, while the MS colonies all perished. Possible explanations for these changes in virus titres and their relevance to Varroa resistance and colony winter survival are discussed.

Increasing Resistance to Extended-Spectrum Cephalosporins, Fluoroquinolone, and Carbapenem in Gram-Negative Bacilli and the Emergence of Carbapenem Non-Susceptibility in Klebsiella pneumoniae: Analysis of Korean Antimicrobial Resistance Monitoring System (KARMS) Data From 2013 to 2015.

Science.gov (United States)

Kim, Dokyun; Ahn, Ji Young; Lee, Chae Hoon; Jang, Sook Jin; Lee, Hyukmin; Yong, Dongeun; Jeong, Seok Hoon; Lee, Kyungwon

2017-05-01

National surveillance of antimicrobial resistance becomes more important for the control of antimicrobial resistance and determination of treatment guidelines. We analyzed Korean Antimicrobial Resistance Monitoring System (KARMS) data collected from 2013 to 2015. Of the KARMS participants, 16 secondary or tertiary hospitals consecutively reported antimicrobial resistance rates from 2013 to 2015. Data from duplicate isolates and institutions with fewer than 20 isolates were excluded. To determine the long-term trends, previous KARMS data from 2004 to 2012 were also considered. The prevalence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium from 2013 to 2015 was 66-72% and 29-31%, respectively. The resistance rates of Escherichia coli to cefotaxime and cefepime gradually increased to 35% and 31%, respectively, and fluoroquinolone resistance reached 48% in 2015. The resistance rates of Klebsiella pneumoniae to cefotaxime, cefepime, and carbapenem were 38-41%, 33-41%, and carbapenem susceptibility rates of E. coli and K. pneumoniae decreased from 100% and 99.3% in 2011 to 99.0% and 97.0% in 2015, respectively. The resistance rate of Pseudomonas aeruginosa to carbapenem increased to 35% and the prevalence of carbapenem-resistant Acinetobacter baumannii increased from 77% in 2013 to 85% in 2015. Between 2013 and 2015, the resistance rates of E. coli to third- and fourth-generation cephalosporins increased continuously, while carbapenem-susceptibility gradually decreased, particularly in K. pneumoniae. The prevalence of carbapenem-resistant P. aeruginosa and A. baumannii increased significantly; therefore, few treatment options remain for these resistant strains. © The Korean Society for Laboratory Medicine

Detection of macrolide resistance genes in culture-negative specimens from Bangladeshi children with invasive pneumococcal diseases.

Science.gov (United States)

Hasanuzzaman, Md; Malaker, Roly; Islam, Maksuda; Baqui, Abdullah H; Darmstadt, Gary L; Whitney, Cynthia G; Saha, Samir K

2017-03-01

In recent years, an increasing prevalence of macrolide resistance among pneumococci in Bangladesh has been observed. However, the scenario remains incomplete, as few isolates (80%) are culture-negative. This study optimised a triplex PCR method to detect macrolide resistance genes (MRGs) (mefA and ermB) and cpsA from culture-negative pneumococcal cases to predict the prevalence and level of macrolide resistance. The presence of MRGs among pneumococcal strains (n=153) with a wide range of erythromycin MICs (culture-negative clinical specimens and corresponding isolates. The known impact of the presence of specific MRG(s) on MICs of strains was used to predict the MICs of non-culturable strains based on the presence/absence of MRG(s) in the specimens. None of the erythromycin-susceptible isolates possessed any of the MRGs, and all non-susceptible strains had ≥1 MRG. MICs were 2-16mg/L and ≥256mg/L for 93% of strains with mefA and ermB, respectively, whereas 100% of isolates with both genes had MICs≥256mg/L. PCR for body fluids showed 100% concordance with corresponding isolates when tested for MRG(s) in parallel. Erythromycin MICs can be predicted for non-culturable strains with 93-100% precision based on detection of ermB and/or mefA. This method will be useful for establishing comprehensive surveillance for macrolide resistance among pneumococci, specifically in the population with prior antibiotic use. Copyright © 2017. Published by Elsevier Ltd.

Relationship between insulin resistance and tissue blood flow in preeclampsia.

Science.gov (United States)

Anim-Nyame, Nick; Gamble, John; Sooranna, Suren R; Johnson, Mark R; Steer, Philip J

2015-05-01

Preeclampsia is characterized by generalized endothelial dysfunction and impaired maternal tissue perfusion, and insulin resistance is a prominent feature of this disease. The aim of this study was to test the hypothesis that insulin resistance in preeclampsia is related to the reduced resting tissue blood flow. We used venous occlusion plethysmography to compare the resting calf muscle blood flow (measured as QaU) in 20 nulliparous women with preeclampsia and 20 normal pregnant controls matched for maternal age, gestational age, parity and BMI during the third trimester. Fasting blood samples were obtained to measure the plasma concentrations of insulin and glucose, and to calculate the fasting insulin resistance index (FIRI), a measure of insulin resistance in both groups of women. Calf blood flow was significantly reduced in the preeclampsia group (1.93 ± 0.86 QaU), compared with normal pregnant controls (3.94 ± 1.1 QaU, P insulin concentrations and Insulin Resistance Index were significantly higher in preeclampsia compared with normal pregnancy (P insulin concentrations (r = -0.57, P = 0.008) and FIRI (r = -0.59, P = 0.006) in preeclampsia, but not in normal pregnancy. These findings support our hypothesis and raise the possibility that reduced tissue blood flow may a play a role in the increased insulin resistance seen in preeclampsia.

Effects of drop sets with resistance training on increases in muscle CSA, strength, and endurance: a pilot study.

Science.gov (United States)

Ozaki, Hayao; Kubota, Atsushi; Natsume, Toshiharu; Loenneke, Jeremy P; Abe, Takashi; Machida, Shuichi; Naito, Hisashi

2018-03-01

To investigate the effects of a single high-load (80% of one repetition maximum [1RM]) set with additional drop sets descending to a low-load (30% 1RM) without recovery intervals on muscle strength, endurance, and size in untrained young men. Nine untrained young men performed dumbbell curls to concentric failure 2-3 days per week for 8 weeks. Each arm was randomly assigned to one of the following three conditions: 3 sets of high-load (HL, 80% 1RM) resistance exercise, 3 sets of low-load [LL, 30% 1RM] resistance exercise, and a single high-load (SDS) set with additional drop sets descending to a low-load. The mean training time per session, including recovery intervals, was lowest in the SDS condition. Elbow flexor muscle cross-sectional area (CSA) increased similarly in all three conditions. Maximum isometric and 1RM strength of the elbow flexors increased from pre to post only in the HL and SDS conditions. Muscular endurance measured by maximum repetitions at 30% 1RM increased only in the LL and SDS conditions. A SDS resistance training program can simultaneously increase muscle CSA, strength, and endurance in untrained young men, even with lower training time compared to typical resistance exercise protocols using only high- or low-loads.

Beta-lactam resistance in the gram negatives: increasing complexity of conditional, composite and multiply resistant phenotypes.

Science.gov (United States)

Iredell, Jon; Thomas, Lee; Espedido, Björn

2006-12-01

The greatest impact of microbiology data on clinical care is in the critically ill. Unfortunately, this is also the area in which microbiology laboratories are most often non-contributive. Attempts to move to rapid, culture-independent diagnostics are driven by the need to expedite urgent results. This is difficult in Gram-negative infection because of the complexity of the antibiotic resistance phenotype. Here, we discuss resistance to modern beta-lactams as a case in point. Recent outbreaks of transmissible carbapenem resistance among Gram-negative enteric pathogens in Sydney and Melbourne serve to illustrate the pitfalls of traditional phenotypical approaches. A better understanding of the epidemiology and mosaic nature of antibiotic resistance elements in the microflora is needed for us to move forward.

Functional promoter variant in zinc finger protein 202 predicts severe atherosclerosis and ischemic heart disease

DEFF Research Database (Denmark)

Frikke-Schmidt, R.; Nordestgaard, Børge; Grande, Peer

2008-01-01

Objectives This study was designed to test the hypotheses that single nucleotide polymorphisms ( SNPs), in zinc finger protein 202 ( ZNF202), predict severe atherosclerosis and ischemic heart disease ( IHD). Background ZNF202 is a transcriptional repressor controlling promoter elements in genes...... involved in vascular maintenance and lipid metabolism. Methods We first determined genotype association for 9 ZNF202 SNPs with severe atherosclerosis ( ankle brachial index >0.7 vs. ...,998 controls. Finally, we determined whether g. -660A>G altered transcriptional activity of the ZNF202 promoter in vitro. Results Cross-sectionally, ZNF202 g. -660 GG versus AA homozygosity predicted an odds ratio for severe atherosclerosis of 2.01 ( 95% confidence interval [CI]: 1.34 to 3.01). Prospectively...

Mutation of the Glucosinolate Biosynthesis Enzyme Cytochrome P450 83A1 Monooxygenase Increases Camalexin Accumulation and Powdery Mildew Resistance.

Science.gov (United States)

Liu, Simu; Bartnikas, Lisa M; Volko, Sigrid M; Ausubel, Frederick M; Tang, Dingzhong

2016-01-01

Small secondary metabolites, including glucosinolates and the major phytoalexin camalexin, play important roles in immunity in Arabidopsis thaliana. We isolated an Arabidopsis mutant with increased resistance to the powdery mildew fungus Golovinomyces cichoracearum and identified a mutation in the gene encoding cytochrome P450 83A1 monooxygenase (CYP83A1), which functions in glucosinolate biosynthesis. The cyp83a1-3 mutant exhibited enhanced defense responses to G. cichoracearum and double mutant analysis showed that this enhanced resistance requires NPR1, EDS1, and PAD4, but not SID2 or EDS5. In cyp83a1-3 mutants, the expression of genes related to camalexin synthesis increased upon G. cichoracearum infection. Significantly, the cyp83a1-3 mutant also accumulated higher levels of camalexin. Decreasing camalexin levels by mutation of the camalexin synthetase gene PAD3 or the camalexin synthesis regulator AtWRKY33 compromised the powdery mildew resistance in these mutants. Consistent with these observations, overexpression of PAD3 increased camalexin levels and enhanced resistance to G. cichoracearum. Taken together, our data indicate that accumulation of higher levels of camalexin contributes to increased resistance to powdery mildew.

Mutation of the glucosinolate biosynthesis enzyme cytochrome P450 83A1 monooxygenase increases camalexin accumulation and powdery mildew resistance

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Simu eLiu

2016-03-01

Full Text Available Small secondary metabolites, including glucosinolates and the major phytoalexin camalexin, play important roles in immunity in Arabidopsis thaliana. We isolated an Arabidopsis mutant with increased resistance to the powdery mildew fungus Golovinomyces cichoracearum and identified a mutation in the gene encoding cytochrome P450 83A1 monooxygenase (CYP83A1, which functions in glucosinolate biosynthesis. The cyp83a1-3 mutant exhibited enhanced defense responses to G. cichoracearum and double mutant analysis showed that this enhanced resistance requires NPR1, EDS1, and PAD4, but not SID2 or EDS5. In cyp83a1-3 mutants, the expression of genes related to camalexin synthesis increased upon G. cichoracearum infection. Significantly, the cyp83a1-3 mutant also accumulated higher levels of camalexin. Decreasing camalexin levels by mutation of the camalexin synthetase gene PAD3 or the camalexin synthesis regulator AtWRKY33 compromised the powdery mildew resistance in these mutants. Consistent with these observations, overexpression of PAD3 increased camalexin levels and enhanced resistance to G. cichoracearum. Taken together, our data indicate that accumulation of higher levels of camalexin contributes to increased resistance to powdery mildew.

Increased Abundance and Transferability of Resistance Genes after Field Application of Manure from Sulfadiazine-Treated Pigs

Science.gov (United States)

Jechalke, Sven; Kopmann, Christoph; Rosendahl, Ingrid; Groeneweg, Joost; Weichelt, Viola; Krögerrecklenfort, Ellen; Brandes, Nikola; Nordwig, Mathias; Ding, Guo-Chun; Siemens, Jan; Heuer, Holger

2013-01-01

Spreading manure containing antibiotics in agriculture is assumed to stimulate the dissemination of antibiotic resistance in soil bacterial populations. Plant roots influencing the soil environment and its microflora by exudation of growth substrates might considerably increase this effect. In this study, the effects of manure from pigs treated with sulfadiazine (SDZ), here called SDZ manure, on the abundance and transferability of sulfonamide resistance genes sul1 and sul2 in the rhizosphere of maize and grass were compared to the effects in bulk soil in a field experiment. In plots that repeatedly received SDZ manure, a significantly higher abundance of both sul genes was detected compared to that in plots where manure from untreated pigs was applied. Significantly lower abundances of sul genes relative to bacterial ribosomal genes were encountered in the rhizosphere than in bulk soil. However, in contrast to results for bulk soil, the sul gene abundance in the SDZ manure-treated rhizosphere constantly deviated from control treatments over a period of 6 weeks after manuring, suggesting ongoing antibiotic selection over this period. Transferability of sulfonamide resistance was analyzed by capturing resistance plasmids from soil communities into Escherichia coli. Increased rates of plasmid capture were observed in samples from SDZ manure-treated bulk soil and the rhizosphere of maize and grass. More than 97% of the captured plasmids belonged to the LowGC type (having low G+C content), giving further evidence for their important contribution to the environmental spread of antibiotic resistance. In conclusion, differences between bulk soil and rhizosphere need to be considered when assessing the risks associated with the spreading of antibiotic resistance. PMID:23315733

Increasing resistant coagulase negative staphylococci in bovine clinical mastitis.

Science.gov (United States)

Moniri, R; Dastehgoli, K; Akramian, A

2007-08-01

The aim of this study was to determine Coagulase Negative Staphylococci (CNS) and other bacteria for their resistance to antimicrobial agents approved for the control of pathogens involved in clinical bovine mastitis. This descriptive study was done on 106 milk samples obtained from clinical mastitis in dairy cattle husbandry from April 2006 through August 2006 in Kashan, Iran. From the total of 106 milk samples collected from clinical mastitis, 96 (90.6%) lead to positive culture. Coagulase negative Staphylococci isolated in 51 out of 96 samples (53.1%), Staphylococcus aureus isolated in 21 out of 96 (21.9%), gram negative bacilli isolated in 14 out of 96 (14.6%) and Enterococci isolated in 4 (4.2%). The highest rate of resistant CNS observed to penicillin (56.6%) and the highest rate of sensitivity to enrofloxacin 100%, followed by kanamycin, streptomycin and neomycin, 92.2, 82.3 and 82.3%, respectively. The highest rate of resistance S. aureus exhibited to penicillin (66.6%); while the highest rate of sensitivity showed to trimethoprim-sulphamethoxasole (81%), followed by kanamycin and enrofloxacin both at 76.2%. The highest rate of resistance gram negative bacilli exhibited to ampicillin and erythromycin at 71.4%. Their highest rate of sensitivity observed to enrofloxacin (78.6%), followed by kanamycin, (71.4%). In recent years, CNS is emerging as important minor mastitis pathogens and can be the cause of substantial economic losses. The high resistance rate to penicillin and other antibiotics found in this study emphasize the importance of identification of CNS when a bovine clinical mastitis is present.

Effect of zinc on grain characteristics of draught-resistant rice mutants

International Nuclear Information System (INIS)

Abo-Hegazi, A.M.T.; Rofail, N.B.; Eissa, E.A.; Hassan, A.M.

1996-01-01

Through the use of Instrumental Neutron Activation Analysis (INAA), zinc concentration was determined in kernels resulted on plants of six drought-resistant rice mutant lines fertilized with zinc sulphate. It was found that zinc fertilization increased zinc residues in the kernels with varying concentrations depending on the line, each line reacted and responded to zinc independently. Zinc content in the kernels ranged from 5.63 to 91.4 ppm in the unfertilized control lines. This range was enlarged due to zinc fertilization of the plants to be from 93.51 to 554.53 ppm. It was also noticed that zinc fertilization increased seed heaviness in varying degrees depending on the line itself. This increase may be due to the increase in kernel thickness rather than in kernel width or length. (author). 26 refs., 3 figs

Resistant starch in cassava products

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Bruna Letícia Buzati Pereira

2014-06-01

Full Text Available Found in different foods, starch is the most important source of carbohydrates in the diet. Some factors present in starchy foods influence the rate at which the starch is hydrolyzed and absorbed in vivo. Due the importance of cassava products in Brazilian diet, the objective of this study was to analyze total starch, resistant starch, and digestible starch contents in commercial cassava products. Thirty three commercial cassava products from different brands, classifications, and origin were analyzed. The method used for determination of resistant starch consisted of an enzymatic process to calculate the final content of resistant starch considering the concentration of glucose released and analyzed. The results showed significant differences between the products. Among the flours and seasoned flours analyzed, the highest levels of resistant starch were observed in the flour from Bahia state (2.21% and the seasoned flour from Paraná state (1.93%. Starch, tapioca, and sago showed levels of resistant starch ranging from 0.56 to 1.1%. The cassava products analyzed can be considered good sources of resistant starch; which make them beneficial products to the gastrointestinal tract.

A translational study of resistance emergence using sequential direct-acting antiviral agents for hepatitis C using ultra-deep sequencing.

Science.gov (United States)

Abe, Hiromi; Hayes, C Nelson; Hiraga, Nobuhiko; Imamura, Michio; Tsuge, Masataka; Miki, Daiki; Takahashi, Shoichi; Ochi, Hidenori; Chayama, Kazuaki

2013-09-01

Direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) have recently been developed and are ultimately hoped to replace interferon-based therapy. However, DAA monotherapy results in rapid emergence of resistant strains and DAAs must be used in combinations that present a high genetic barrier to resistance, although viral kinetics of multidrug-resistant strains remain poorly characterized. The aim of this study is to track the emergence and fitness of resistance using combinations of telaprevir and NS5A or NS5B inhibitors with genotype 1b clones. HCV-infected chimeric mice were treated with DAAs, and resistance was monitored using direct and ultra-deep sequencing. Combination therapy with telaprevir and BMS-788329 (NS5A inhibitor) reduced serum HCV RNA to undetectable levels. The presence of an NS3-V36A telaprevir resistance mutation resulted in poor response to telaprevir monotherapy but showed significant HCV reduction when telaprevir was combined with BMS-788329. However, a BMS-788329-resistant strain emerged at low frequency. Infection with a BMS-788329-resistant NS5A-L31V mutation rapidly resulted in gain of an additional NS5A-Y93A mutation that conferred telaprevir resistance during combination therapy. Infection with dual NS5AL31V/NS5AY93H mutations resulted in poor response to combination therapy and development of telaprevir resistance. Although HCV RNA became undetectable soon after the beginning of combination therapy with BMS-788329 and BMS-821095 (NS5B inhibitor), rebound with emergence of resistance against all three drugs occurred. Triple resistance also occurred following infection with the NS3V36A/NS5AL31V/NS5AY93H triple mutation. Resistant strains easily develop from cloned virus strains. Sequential use of DAAs should be avoided to prevent emergence of multidrug-resistant strains.

Utilization of the {sup 93}Nb(n,n'){sup 93}Nb{sup m} Reaction for for Reactor Neutron Dosimetry

Energy Technology Data Exchange (ETDEWEB)

Czock, K. H.; Houtermans, H. [International Atomic Energy Agency, Division of Research and Laboratories, Vienna (Austria)

1974-09-15

For the measurement of large ({Phi}>10{sup 18}n/cm{sup 2}) fast neutron fluences in research reactors, the reaction {sup 93}Nb(n,n'){sup 93}Nb{sup m} is fairly seldom used (Lloret, Hegedus). The reason is that the excitation function for the production of the {sup 93}Nb isomeric state (half-life{approx_equal}11.4 years) by inelastic neutron scattering is nearly unknown. Also the determination of the absolute {sup 93}Nb{sup m} activity is difficult, e.g. due to the bad knowledge of the conversion coefficients {alpha}{sub tot} and {alpha}{sub K}. But for neutron dosimetry purposes one does not necessarily need absolute activity values, if one irradiated niobium foil (e.g. 10 mm empty and 0.1 mm thick) is accepted to be a reference source to other irradiated niobium foils (of the same original material). If the cross section measurements and the fluence determinations are both based on the same reference source {sup 93}Nb{sup m} as an arbitrary activity standard, the possible inaccuracy of this activity value would not matter. Such an accepted reference source could be deposited at one central institution. Once the reference source activity is defined (at present within 30% of the true absolute activity value) niobium sources with activities determined relative to this reference source could be supplied together with non-irradiated niobium foils to interested laboratories. (author)

Blunted angiogenesis and hypertrophy are associated with increased fatigue resistance and unchanged aerobic capacity in old overloaded mouse muscle.

Science.gov (United States)

Ballak, Sam B; Busé-Pot, Tinelies; Harding, Peter J; Yap, Moi H; Deldicque, Louise; de Haan, Arnold; Jaspers, Richard T; Degens, Hans

2016-04-01

We hypothesize that the attenuated hypertrophic response in old mouse muscle is (1) partly due to a reduced capillarization and angiogenesis, which is (2) accompanied by a reduced oxidative capacity and fatigue resistance in old control and overloaded muscles, that (3) can be rescued by the antioxidant resveratrol. To investigate this, the hypertrophic response, capillarization, oxidative capacity, and fatigue resistance of m. plantaris were compared in 9- and 25-month-old non-treated and 25-month-old resveratrol-treated mice. Overload increased the local capillary-to-fiber ratio less in old (15 %) than in adult (59 %) muscle (P muscles of old mice had a higher succinate dehydrogenase (SDH) activity (P < 0.05) and a slower fiber type profile (P < 0.05), the isometric fatigue resistance was similar in 9- and 25-month-old mice. In both age groups, the fatigue resistance was increased to the same extent after overload (P < 0.01), without a significant change in SDH activity, but an increased capillary density (P < 0.05). Attenuated angiogenesis during overload may contribute to the attenuated hypertrophic response in old age. Neither was rescued by resveratrol supplementation. Changes in fatigue resistance with overload and aging were dissociated from changes in SDH activity, but paralleled those in capillarization. This suggests that capillarization plays a more important role in fatigue resistance than oxidative capacity.

Multiple mechanisms increase levels of resistance in Rapistrum rugosum to ALS herbicides

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Zhara M Hatami

2016-02-01

Full Text Available Rapistrum rugosum (turnip weed is a common weed of wheat fields in Iran, which is most often controlled by tribenuron-methyl (TM, a sulfonylurea (SU belonging to the acetolactate synthase (ALS inhibiting herbicides group. Several cases of unexplained control failure of R. rugosum by TM have been seen, especially in Golestan province-Iran. Hence, there is lack of research in evaluation of the level of resistance of the R. rugosum populations to TM, using whole plant dose–response and enzyme assays, then investigating some potential resistance mechanisms Results revealed that the resistance factor (RF for resistant (R populations was 2.5 to 6.6 fold higher than susceptible (S plant. Neither foliar retention, nor 14C-TM absorption and translocation were the mechanisms responsible for resistance in turnip weed. Metabolism of TM was the second resistant mechanism in two populations (Ag-R5 and G-1, in which three metabolites were found. The concentration of TM for 50% inhibition of ALS enzyme activity in vitro showed a high level of resistance to the herbicide (resistance factors were from 28 to 38 and cross-resistance to sulfonyl-aminocarbonyl-triazolinone (SCT, pyrimidinyl-thiobenzoate (PTB and triazolopyrimidine (TP, with no cross-resistance to imidazolinone (IMI. Substitution Pro 197 to Ser 197 provided resistance to four of five ALS-inhibiting herbicides including SU, TP, PTB and SCT with no resistance to IMI. These results documented the first case of R. rugosum resistant population worldwide and demonstrated that both RST and NRST mechanisms are involved to the resistance level to TM.

Successive increases in the resistance of Drosophila to viral infection through a transposon insertion followed by a Duplication.

Directory of Open Access Journals (Sweden)

Michael M Magwire

2011-10-01

Full Text Available To understand the molecular basis of how hosts evolve resistance to their parasites, we have investigated the genes that cause variation in the susceptibility of Drosophila melanogaster to viral infection. Using a host-specific pathogen of D. melanogaster called the sigma virus (Rhabdoviridae, we mapped a major-effect polymorphism to a region containing two paralogous genes called CHKov1 and CHKov2. In a panel of inbred fly lines, we found that a transposable element insertion in the protein coding sequence of CHKov1 is associated with increased resistance to infection. Previous research has shown that this insertion results in a truncated messenger RNA that encodes a far shorter protein than the susceptible allele. This resistant allele has rapidly increased in frequency under directional selection and is now the commonest form of the gene in natural populations. Using genetic mapping and site-specific recombination, we identified a third genotype with considerably greater resistance that is currently rare in the wild. In these flies there have been two duplications, resulting in three copies of both the truncated allele of CHKov1 and CHKov2 (one of which is also truncated. Remarkably, the truncated allele of CHKov1 has previously been found to confer resistance to organophosphate insecticides. As estimates of the age of this allele predate the use of insecticides, it is likely that this allele initially functioned as a defence against viruses and fortuitously "pre-adapted" flies to insecticides. These results demonstrate that strong selection by parasites for increased host resistance can result in major genetic changes and rapid shifts in allele frequencies; and, contrary to the prevailing view that resistance to pathogens can be a costly trait to evolve, the pleiotropic effects of these changes can have unexpected benefits.

Species interactions can maintain resistance of subtidal algal habitats to an increasingly modified world

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Laura J. Falkenberg

2015-07-01

Full Text Available Current trends in habitat loss have been forecast to accelerate under anticipated global change, thereby focusing conservation attention on identifying the circumstances under which key species interactions retard habitat loss. Urbanised coastlines are associated with broad-scale loss of kelp canopies and their replacement by less productive mats of algal turf, a trend predicted to accelerate under ocean acidification and warming (i.e. enhanced CO2 and temperature. Here we use kelp forests as a model system to test whether efforts to maintain key species interactions can maintain habitat integrity under forecasted conditions. First, we assessed whether increasing intensity of local human activity is associated with more extensive turf mats and sparser canopies via structured field observations. Second, we experimentally tested the hypothesis that intact canopies can resist turf expansion under enhanced CO2 and temperature in large mesocosms. In the field, there was a greater proportion of turf patches on urbanised coasts of South Australia than in agricultural and urban catchments in which there was a greater proportion of canopy-forming algae. Mesocosm experiments revealed this expansion of turfs is likely to accelerate under increases in CO2 and temperature, but may be limited by the presence of intact canopies. We note that even in the presence of canopy, increases in CO2 and temperature facilitate greater turf covers than occurs under contemporary conditions. The influence of canopy would likely be due to shading of the understorey turfs which, in turn, can modify their photosynthetic activity. These results suggest that resistance of habitat to change under human-dominated conditions may be managed via the retention of key species and their interactions. Management that directly reduces the disturbance of habitat-forming organisms (e.g. harvesting or reverses loss through restoration may, therefore, reinforce habitat resistance in an

Rapid increase in resistance to third generation cephalosporins, imipenem and co-resistance in Klebsiella pneumoniae from isolated from 7,140 blood-cultures (2010-2014) using EARS-Net data in Spain.

Science.gov (United States)

Aracil-García, Belén; Oteo-Iglesias, Jesús; Cuevas-Lobato, Óscar; Lara-Fuella, Noelia; Pérez-Grajera, Isabel; Fernández-Romero, Sara; Pérez-Vázquez, María; Campos, José

2017-10-01

An analysis was made about the evolution of resistance to 3rd generation cephalosporins, imipenem, and other antibiotics in invasive isolates of Klebsiella pneumoniae (K. pneumoniae) according to the Spanish EARS-Net database (2010-2014). Forty-two hospitals from 16 Autonomous Communities with an approximate population coverage of 33% participated. A total 7,140 pneumoniae corresponding to the same number of patients were studied. Overall resistance percentages (I+R) were: cefotaxime 15.8%, ceftazidime 13.7%, imipenem 1.7%, ciprofloxacin 20.1%, tobramycin 14.1%, gentamicin 10.4%, and amikacin 1.9%. Resistance to 3rd generation cephalosporins increased from 9.8% (2010) to 19% (2014); to ciprofloxacin from 15.4% (2010) to 19.6% (2014); to gentamicin from 6.2% (2010) to 10.3% (2014) and to tobramycin from 7.1% (2010) to 14.2% (2014) (presistance to 3rd generation cephalosporins, ciprofloxacin, and aminoglycosides increased from 3.3% (2010) to 9.7% (2014) (pResistance to imipenem also increased from 0.27% (2010) to 3.46% (2014) (presistant to imipenem, of which 104 (86%) produced carbapenemases: 74 OXA-48, 14 VIM, 9 KPC (6 KPC-2 and 3 KPC-3), 6 IMP, and 1 GES. Over the 5 year period (2010-2014), resistance to 3rd generation cephalosporins in invasive K. pneumoniae in Spain has doubled. The combined resistance to 3rd generation cephalosporins, ciprofloxacin, and aminoglycosides has tripled, and imipenem resistance has increased almost 13 times, mostly due to the spread of carbapenemase-producing isolates. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Analysis of Hepatitis C Virus Genotype 1b Resistance Variants in Japanese Patients Treated with Paritaprevir-Ritonavir and Ombitasvir.

Science.gov (United States)

Krishnan, Preethi; Schnell, Gretja; Tripathi, Rakesh; Beyer, Jill; Reisch, Thomas; Zhang, Xinyan; Setze, Carolyn; Rodrigues, Lino; Burroughs, Margaret; Redman, Rebecca; Chayama, Kazuaki; Kumada, Hiromitsu; Collins, Christine; Pilot-Matias, Tami

2016-02-01

Treatment of HCV genotype 1b (GT1b)-infected Japanese patients with paritaprevir (NS3/4A inhibitor boosted with ritonavir) and ombitasvir (NS5A inhibitor) in studies M12-536 and GIFT-I demonstrated high sustained virologic response (SVR) rates. The virologic failure rate was 3% (13/436) across the two studies. Analyses were conducted to evaluate the impact of baseline resistance-associated variants (RAVs) on treatment outcome and the emergence and persistence of RAVs in patients experiencing virologic failure. Baseline paritaprevir resistance-conferring variants in NS3 were infrequent, while Y93H in NS5A was the most prevalent ombitasvir resistance-conferring variant at baseline. A comparison of baseline prevalence of polymorphisms in Japanese and western patients showed that Q80L and S122G in NS3 and L28M, R30Q, and Y93H in NS5A were significantly more prevalent in Japanese patients. In the GIFT-I study, the prevalence of Y93H in NS5A varied between 13% and 21% depending on the deep-sequencing detection threshold. Among patients with Y93H comprising 40% of their preexisting viral population, the 24-week SVR (SVR24) rates were >99% (276/277), 93% (38/41), and 76% (25/33), respectively, indicating that the prevalence of Y93H within a patient's viral population is a good predictor of treatment response. The predominant RAVs at the time of virologic failure were D168A/V in NS3 and Y93H alone or in combination with other variants in NS5A. While levels of NS3 RAVs declined over time, NS5A RAVs persisted through posttreatment week 48. Results from these analyses are informative in understanding the resistance profile of an ombitasvir- plus paritaprevir/ritonavir-based regimen in Japanese GT1b-infected patients. Copyright © 2016 Krishnan et al.

Bioactive glass 13-93 as a subchondral substrate for tissue-engineered osteochondral constructs: a pilot study.

Science.gov (United States)

Jayabalan, Prakash; Tan, Andrea R; Rahaman, Mohammed N; Bal, B Sonny; Hung, Clark T; Cook, James L

2011-10-01

Replacement of diseased areas of the joint with tissue-engineered osteochondral grafts has shown potential in the treatment of osteoarthritis. Bioactive glasses are candidates for the osseous analog of these grafts. (1) Does Bioactive Glass 13-93 (BG 13-93) as a subchondral substrate improve collagen and glycosaminoglycan production in a tissue-engineered cartilage layer? (2) Does BG 13-93 as a culture medium supplement increase the collagen and glycosaminoglycan production and improve the mechanical properties in a tissue-engineered cartilage layer? In Study 1, bioactive glass samples (n = 4) were attached to a chondrocyte-seeded agarose layer to form an osteochondral construct, cultured for 6 weeks, and compared to controls. In Study 2, bioactive glass samples (n = 5) were cocultured with cell-seeded agarose for 6 weeks. The cell-seeded agarose layer was exposed to BG 13-93 either continuously or for the first or last 2 weeks in culture or had no exposure. Osteochondral constructs with a BG 13-93 base had improved glycosaminoglycan deposition but less collagen II content. Agarose scaffolds that had a temporal exposure to BG 13-93 within the culture medium had improved mechanical and biochemical properties compared to continuous or no exposure. When used as a subchondral substrate, BG 13-93 did not improve biochemical properties compared to controls. However, as a culture medium supplement, BG 13-93 improved the biochemical and mechanical properties of a tissue-engineered cartilage layer. BG 13-93 may not be suitable in osteochondral constructs but could have potential as a medium supplement for neocartilage formation.

Prevalence of antiseptic resistance genes increases in staphylococcal isolates from orthokeratology lens wearers over initial six-month period of use.

Science.gov (United States)

Guang-Sen, Shi; Boost, Maureen; Cho, Pauline

2016-06-01

The purpose of this study was to investigate the prevalence of antiseptic-resistance (QAC) genes in staphylococci colonizing periorbital tissues and accessories of orthokeratology (ortho-k) lens wearers over a 6-month period and determine the effect of their presence on minimum inhibitory (MIC) and bactericidal concentrations (MBC) of disinfectants and log reduction of multipurpose contact lens solutions (MPS). Staphylococci were isolated from periorbital tissues and accessories of patients before commencing ortho-k therapy and at two subsequent visits. Presence of QAC genes in 116 S. aureus and 67 CNS isolates was determined by PCR and association with period of ortho-k use determined. MICs and MBCs of staphylococci gene-positive were compared with gene-negative strains and the effectiveness of four MPS for rigid contact lenses investigated. S. aureus carriage rates in the conjunctiva decreased significantly from 41.2 % (baseline) to 11.8 % (3-months), and 13.3 % (6-months) (p trend 0.03), while CNS increased from 58.8 %(baseline) to 94.1 % (3-months), and 93.3 % (6-months) (p trend 0.02). Prevalence of qacA/B increased considerably over time (S. aureus: 4.4 % to 15.4 %, CNS: 6.7 % to 25 %), but frequency of smr was relatively stable. Only five CNS isolates harboured qacH. MICs and MBCs of gene-positive isolates were significantly increased and three MPS did not achieve a 3-log reduction of many QAC-positive strains. Ortho-k lens wear contributed to changes of staphylococcal carriage rates in the conjunctival sac. Use of MPS containing quaternary ammonium compounds may select for the carriage of organisms harbouring QAC genes, as the low concentration of disinfecting agents is not adequate for killing gene-positive strains.

The effect of different doses of vitamin D supplementation on insulin resistance during pregnancy.

Science.gov (United States)

Soheilykhah, Sedigheh; Mojibian, Mahdieh; Moghadam, Maryam Jannati; Shojaoddiny-Ardekani, Ahmad

2013-04-01

Low serum vitamin D levels are correlated with insulin resistance during pregnancy. We have assessed the effects of different doses of vitamin D on insulin resistance during pregnancy. A randomized clinical trial was done on 120 women with a gestational age of less than 12 weeks. The women were divided into three groups randomly. Group A received 200 IU vitamin D daily, group B 50,000 IU vitamin D monthly and group C 50,000 IU vitamin D every 2 weeks from 12 weeks of pregnancy until delivery. The serum levels of fasting blood sugar (FBS), insulin, calcium and 25-hydroxyvitamin D were measured before and after intervention. We used the homeostatic model assessment of insulin resistance (HOMA-IR) as a surrogate measure of insulin resistance. The mean ± standard deviation of serum 25-hydroxyvitamin D increased in group C from 7.3 ± 5.9 to 34.1 ± 11.5 ng/ml and in group B it increased from 7.3 ± 5.3 to 27.23 ± 10.7 ng/ml, but the level of vitamin D in group A increased from 8.3 ± 7.8 to 17.7 ± 9.3 ng/ml (p insulin and HOMA-IR before and after intervention in groups A and C were significant (p = 0.01, p = 0.02). This study has shown that supplementation of pregnant women with 50 000 IU vitamin D every 2 weeks improved insulin resistance significantly.

Increased STAT1 signaling in endocrine-resistant breast cancer.

Directory of Open Access Journals (Sweden)

Rui Huang

Full Text Available Proteomic profiling of the estrogen/tamoxifen-sensitive MCF-7 cell line and its partially sensitive (MCF-7/LCC1 and fully resistant (MCF-7/LCC9 variants was performed to identify modifiers of endocrine sensitivity in breast cancer. Analysis of the expression of 120 paired phosphorylated and non-phosphorylated epitopes in key oncogenic and tumor suppressor pathways revealed that STAT1 and several phosphorylated epitopes (phospho-STAT1(Tyr701 and phospho-STAT3(Ser727 were differentially expressed between endocrine resistant and parental controls, confirmed by qRT-PCR and western blotting. The STAT1 inhibitor EGCG was a more effective inhibitor of the endocrine resistant MCF-7/LCC1 and MCF-7/LCC9 lines than parental MCF-7 cells, while STAT3 inhibitors Stattic and WP1066 were equally effective in endocrine-resistant and parental lines. The effects of the STAT inhibitors were additive, rather than synergistic, when tested in combination with tamoxifen in vitro. Expression of STAT1 and STAT3 were measured by quantitative immunofluorescence in invasive breast cancers and matched lymph nodes. When lymph node expression was compared to its paired primary breast cancer expression, there was greater expression of cytoplasmic STAT1 (∼3.1 fold, phospho-STAT3(Ser727 (∼1.8 fold, and STAT5 (∼1.5 fold and nuclear phospho-STAT3(Ser727 (∼1.5 fold in the nodes. Expression levels of STAT1 and STAT3 transcript were analysed in 550 breast cancers from publicly available gene expression datasets (GSE2990, GSE12093, GSE6532. When treatment with tamoxifen was considered, STAT1 gene expression was nearly predictive of distant metastasis-free survival (DMFS, log-rank p = 0.067, while STAT3 gene expression was predictive of DMFS (log-rank p<0.0001. Analysis of STAT1 and STAT3 protein expression in a series of 546 breast cancers also indicated that high expression of STAT3 protein was associated with improved survival (DMFS, p = 0.006. These results suggest

Copper Pollution Increases the Resistance of Soil Archaeal Community to Changes in Water Regime.

Science.gov (United States)

Li, Jing; Liu, Yu-Rong; Cui, Li-Juan; Hu, Hang-Wei; Wang, Jun-Tao; He, Ji-Zheng

2017-11-01

Increasing efforts have been devoted to exploring the impact of environmental stresses on soil bacterial communities, but the work on the archaeal community is seldom. Here, we constructed microcosm experiments to investigate the responses of archaeal communities to the subsequent dry-rewetting (DW) disturbance in two contrasting soils (fluvo-aquic and red soil) after 6 years of copper pollution. Ten DW cycles were exerted on the two soils with different copper levels, followed by a 6-week recovery period. In both soils, archaeal diversity (Shannon index) in the high copper-level treatments increased over the incubation period, and archaeal community structure changed remarkably as revealed by the non-metric multidimensional scaling ordinations. In both soils, copper pollution altered the response of dominant operational taxonomic units (OTUs) to the DW disturbance. Throughout the incubation and recovery period, the resistance of archaeal abundance to the DW disturbance was higher in the copper-polluted soils than soils without pollution. Taken together, copper pollution altered the response of soil archaeal diversity and community composition to the DW disturbance and increased the resistance of the archaeal abundance. These findings have important implications for understanding soil microbial responses to ongoing environmental change.

LSD1 activates a lethal prostate cancer gene network independently of its demethylase function.

Science.gov (United States)

Sehrawat, Archana; Gao, Lina; Wang, Yuliang; Bankhead, Armand; McWeeney, Shannon K; King, Carly J; Schwartzman, Jacob; Urrutia, Joshua; Bisson, William H; Coleman, Daniel J; Joshi, Sunil K; Kim, Dae-Hwan; Sampson, David A; Weinmann, Sheila; Kallakury, Bhaskar V S; Berry, Deborah L; Haque, Reina; Van Den Eeden, Stephen K; Sharma, Sunil; Bearss, Jared; Beer, Tomasz M; Thomas, George V; Heiser, Laura M; Alumkal, Joshi J

2018-05-01

Medical castration that interferes with androgen receptor (AR) function is the principal treatment for advanced prostate cancer. However, clinical progression is universal, and tumors with AR-independent resistance mechanisms appear to be increasing in frequency. Consequently, there is an urgent need to develop new treatments targeting molecular pathways enriched in lethal prostate cancer. Lysine-specific demethylase 1 (LSD1) is a histone demethylase and an important regulator of gene expression. Here, we show that LSD1 promotes the survival of prostate cancer cells, including those that are castration-resistant, independently of its demethylase function and of the AR. Importantly, this effect is explained in part by activation of a lethal prostate cancer gene network in collaboration with LSD1's binding protein, ZNF217. Finally, that a small-molecule LSD1 inhibitor-SP-2509-blocks important demethylase-independent functions and suppresses castration-resistant prostate cancer cell viability demonstrates the potential of LSD1 inhibition in this disease.

Novel Functional Changes during Podocyte Differentiation: Increase of Oxidative Resistance and H-Ferritin Expression

Directory of Open Access Journals (Sweden)

Emese Bányai

2014-01-01

Full Text Available Podocytes are highly specialized, arborized epithelial cells covering the outer surface of the glomerular tuft in the kidney. Terminally differentiated podocytes are unable to go through cell division and hereby they are lacking a key property for regeneration after a toxic injury. Podocytes are long-lived cells but, to date, little is known about the mechanisms that support their stress resistance. Our aim was to investigate whether the well-known morphological changes during podocyte differentiation are accompanied by changes in oxidative resistance in a manner that could support their long-term survival. We used a conditionally immortalized human podocyte cell line to study the morphological and functional changes during differentiation. We followed the differentiation process for 14 days by time-lapse microscopy. During this period nondifferentiated podocytes gradually transformed into large, nonproliferating, frequently multinucleated cells, with enlarged nuclei and opened chromatin structure. We observed that differentiated podocytes were highly resistant to oxidants such as H2O2 and heme when applied separately or in combination, whereas undifferentiated cells were prone to such challenges. Elevated oxidative resistance of differentiated podocytes was associated with increased activities of antioxidant enzymes and H-ferritin expression. Immunohistochemical analysis of normal human kidney specimens revealed that podocytes highly express H-ferritin in vivo as well.

Development and evaluation of a HEPA filter for increased strength and resistance to elevated temperature

International Nuclear Information System (INIS)

Gilbert, H.; Bergman, W.; Fretthold, J.K.

1993-01-01

We have completed a preliminary study of an improved HEPA filter for increased strength and resistance to elevated temperature to improve the reliability of the standard deep pleated HEPA filter under accident conditions. The improvements to the HEPA filter consist of a silicone rubber sealant and a new HEPA medium reinforced with a glass cloth. Three prototype filters were built and evaluated for temperature and pressure resistance and resistance to rough handling. The temperature resistance test consisted of exposing the HEPA filter to 1,000 scan (1,700 m 3 /hr) at 700 degrees F (371 degrees C) for five minutes.The pressure resistance test consisted of exposing the HEPA filter to a differential pressure of 10 in. w.g. (2.5 kPa) using a water saturated air flow at 95 degrees F (35 degrees C). For the rough handling test, we used a vibrating machine designated the Q110. DOP filter efficiency tests were performed before and after each of the environmental tests. In addition to following the standard practice of using a separate new filter for each environmental test, we also subjected the same filter to the elevated temperature test followed by the pressure resistance test. The efficiency test results show that the improved HEPA filter is significantly better than the standard HEPA filter. Further studies are recommended to evaluate the improved HEPA filter and to assess its performance under more severe accident conditions

Phenotypic and molecular characterization of antimicrobial resistance in Enterobacter spp. isolates from companion animals in Japan.

Science.gov (United States)

Harada, Kazuki; Shimizu, Takae; Mukai, Yujiro; Kuwajima, Ken; Sato, Tomomi; Kajino, Akari; Usui, Masaru; Tamura, Yutaka; Kimura, Yui; Miyamoto, Tadashi; Tsuyuki, Yuzo; Ohki, Asami; Kataoka, Yasushi

2017-01-01

The emergence of antimicrobial resistance among Enterobacter spp., including resistance to extended-spectrum cephalosporins (ESC), is of great concern in both human and veterinary medicine. In this study, we investigated the prevalence of antimicrobial resistance among 60 isolates of Enterobacter spp., including E. cloacae (n = 44), E. aerogenes (n = 10), and E. asburiae (n = 6), from clinical specimens of dogs and cats from 15 prefectures in Japan. Furthermore, we characterized the resistance mechanisms harbored by these isolates, including extended-spectrum β-lactamases (ESBLs) and plasmid-mediated quinolone resistance (PMQR); and assessed the genetic relatedness of ESC-resistant Enterobacter spp. strains by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Antimicrobial susceptibility testing demonstrated the resistance rates to ampicillin (93.3%), amoxicillin-clavulanic acid (93.3%), cefmetazole (93.3%), chloramphenicol (46.7%), ciprofloxacin (43.3%), tetracycline (40.0%), ceftazidime (33.3%), cefotaxime (33.3%), trimethoprim/sulfamethoxazole (28.3%), gentamicin (23.3%), and meropenem (0%). Phenotypic testing detected ESBLs in 16 of 18 ESC-resistant E. cloacae isolates but not in the other species. The most frequent ESBL was CTX-M-15 (n = 8), followed by SHV-12 (n = 7), and CTX-M-3 (n = 1). As for AmpC β-lactamases, CMY-2 (n = 2) and DHA-1 (n = 2) were identified in ESC-resistant E. cloacae strains with or without ESBLs. All of the ESC-resistant E. cloacae strains also harbored one or two PMQRs, including qnrB (n = 15), aac(6')-Ib-cr (n = 8), and qnrS (n = 2). Based on MLST and PFGE analysis, E. cloacae clones of ST591-SHV-12, ST171-CTX-M-15, and ST121-CTX-M-15 were detected in one or several hospitals. These results suggested intra- and inter-hospital dissemination of E. cloacae clones co-harboring ESBLs and PMQRs among companion animals. This is the first report on the large-scale monitoring of antimicrobial-resistant isolates

Rapid Increase in Prevalence of Carbapenem-Resistant Enterobacteriaceae (CRE) and Emergence of Colistin Resistance Gene mcr-1 in CRE in a Hospital in Henan, China.

Science.gov (United States)

Li, Yi; Sun, Qiao-Ling; Shen, Yingbo; Zhang, Yangjunna; Yang, Jun-Wen; Shu, Ling-Bin; Zhou, Hong-Wei; Wang, Yang; Wang, Bing; Zhang, Rong; Wang, Shaolin; Shen, Zhangqi

2018-04-01

The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is one of the most severe threats to human health in a clinical setting. The recent emergence of plasmid-mediated colistin resistance gene mcr-1 among CRE strains greatly compromises the use of colistin as a last resort for the treatment of infections caused by CRE. This study aimed to understand the current epidemiological trends and characteristics of CRE from a large hospital in Henan, the most populous province in China. From 2014 to 2016, a total of 7,249 Enterobacteriaceae isolates were collected from clinical samples, among which 18.1% (1,311/7,249) were carbapenem resistant. Carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Escherichia coli were the two most common CRE species, with Klebsiella pneumoniae carbapenemases (KPC) and New Delhi metallo-β-lactamases (NDM), respectively, responsible for the carbapenem resistance of the two species. Notably, >57.0% ( n = 589) of the K. pneumoniae isolates from the intensive care unit were carbapenem resistant. Furthermore, bla NDM-5 and mcr-1 were found to coexist in one E. coli isolate, which exhibited resistance to almost all tested antibiotics. Overall, we observed a significant increase in the prevalence of CRE isolates during the study period and suggest that carbapenems may no longer be considered to be an effective treatment for infections caused by K. pneumoniae in the studied hospital. Copyright © 2018 American Society for Microbiology.

9 CFR 93.305 - Declaration and other documents for horses.

Science.gov (United States)

2010-01-01

... horses. 93.305 Section 93.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE...; REQUIREMENTS FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Horses § 93.305 Declaration and other documents for horses. (a) The certificates, declarations, and affidavits required by the regulations in this...

40 CFR 600.113-93 - Fuel economy calculations.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Fuel economy calculations. 600.113-93... FUEL ECONOMY AND CARBON-RELATED EXHAUST EMISSIONS OF MOTOR VEHICLES Fuel Economy Regulations for 1978 and Later Model Year Automobiles-Test Procedures § 600.113-93 Fuel economy calculations. The...

Parity and increased risk of insulin resistance in postmenopausal women: the 2010 Korean National Health and Nutrition Examination Survey.

Science.gov (United States)

Kim, Jin Hwi; Lee, Sung Jong

2017-07-01

The objective of this study was to assess the association between parity and insulin resistance in nondiabetic, postmenopausal women. This cross-sectional study was conducted using data from the 2010 Korean National Health and Nutrition Examination Survey administered by the Korean Ministry of Health and Welfare. A total of 1,243 nondiabetic postmenopausal women were included in this study and subdivided into three groups according to parity (1-2, 3-4, and ≥5 live births). Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR) index. The relationship between parity and insulin resistance was investigated using analysis of covariance. HOMA-IR showed a positive relationship with parity. Mean HOMA-IR (geometric mean and 95% CI) increased according to increasing parity group (1-2, 3-4, and ≥5 live births) after adjustment for age, smoking, alcohol consumption, exercise, education, income, and body mass index as follows: 2.1 (2.0-2.2) insulin resistance was accompanied by obesity. The mean parity of the obese and insulin-resistant group was significantly higher than that of the nonobese insulin-sensitive group (3.6 ± 0.1 vs 3.2 ± 0.1, P = 0.047). Our study provides the first evidence that parity is significantly associated with insulin resistance in nondiabetic postmenopausal women. Further prospective longitudinal studies are needed to confirm the impact of parity on insulin resistance.

Fluoroquinolone resistance mechanisms in urinary tract pathogenic Escherichia coli isolated during rapidly increasing fluoroquinolone consumption in a low-use country

DEFF Research Database (Denmark)

Christiansen, Nina; Nielsen, Lene; Jakobsen, Lotte

2011-01-01

Resistance to ciprofloxacin in Escherichia coli from urinary tract infections (UTI) in Denmark is increasing parallel to increased use of fluoroquinolones both in Denmark and in other European countries. The objective was to investigate the occurrence of ciprofloxacin resistance mechanisms......, phenotypic coresistance, and if ciprofloxacin resistance was caused by clonal spread or to individual mutational events in a collection of consecutively obtained E. coli submitted to a clinical microbiology department at a Danish hospital. One hundred four UTI-related E. coli resistant toward nalidixic acid...

Annual accounts 1992-93

International Nuclear Information System (INIS)

1993-06-01

AEA Technology is the trading name of the United Kingdom Atomic Energy Authority. The principal activity is the provision of high quality scientific and engineering services, consultancy and specialist products across a broad range. During 1992-93, AEA achieved a profit of Pound 23.9M, representing a return of 12.2%. The detailed annual accounts are presented. (UK)

TOR signaling downregulation increases resistance to the cereal killer Fusarium graminearum.

Science.gov (United States)

Aznar, Néstor R; Consolo, V Fabiana; Salerno, Graciela L; Martínez-Noël, Giselle M A

2018-02-01

TOR is the master regulator of growth and development that senses energy availability. Biotic stress perturbs metabolic and energy homeostasis, making TOR a good candidate to participate in the plant response. Fusarium graminearum (Fusarium) produces important losses in many crops all over the world. To date, the role of TOR in Fusarium infection has remained unexplored. Here, we show that the resistance to the pathogen increases in different Arabidopsis mutants impaired in TOR complex or in wild-type plants treated with a TOR inhibitor. We conclude that TOR signaling is involved in plant defense against Fusarium.

Increased Prevalence of Activated Protein C Resistance During ...

African Journals Online (AJOL)

Background: Acquired resistance to protein C in pregnancy has been established as one of the factors associated with ..... diabetes, sickle cell disease, smoking, anti-phospholipid syndrome inherited thrombophilia, and previous history of.

9 CFR 93.312 - Manure from quarantined horses.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Manure from quarantined horses. 93.312... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Horses § 93.312 Manure from quarantined horses. No manure shall be removed from the quarantine premises until the release of the horses producing same. ...

28 CFR 0.93 - Bureau of Justice Statistics.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Bureau of Justice Statistics. 0.93...-Office of Justice Programs and Related Agencies § 0.93 Bureau of Justice Statistics. The Bureau of Justice Statistics is headed by a Director appointed by the President. Under the general authority of the...

9 CFR 93.319 - Import permit and declaration for horses.

Science.gov (United States)

2010-01-01

... horses. 93.319 Section 93.319 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE...; REQUIREMENTS FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Horses Central America and the West Indies 17 § 93.319 Import permit and declaration for horses. For all horses offered for importation from regions of...

9 CFR 93.315 - Import permit and declaration for horses.

Science.gov (United States)

2010-01-01

... horses. 93.315 Section 93.315 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE...; REQUIREMENTS FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Horses Canada 16 § 93.315 Import permit and declaration for horses. For all horses offered for importation from Canada, the importer or his or her agent...

AMS of 93Zr: Passive absorber versus gas-filled magnet

Science.gov (United States)

Hain, Karin; Deneva, Boyana; Faestermann, Thomas; Fimiani, Leticia; Gómez-Guzmán, José Manuel; Koll, Dominik; Korschinek, Gunther; Ludwig, Peter; Sergeyeva, Victoria; Thiollay, Nicolas

2018-05-01

Two different isobar separation techniques were tested for the detection of the long-lived fission product 93Zr (T1/2 = 1.64 · 106 a) using Accelerator Mass Spectrometry (AMS), i.e. a passive absorber and a gas-filled magnet, respectively. Both techniques were used in combination with a Time-of-Flight path for the identification of the stable neighboring isotopes 92Zr and 94Zr. The passive absorber was represented by a stack of silicon nitride foils for high flexibility regarding the thickness for optimal isobar separation. Ion beams with a large variety of energies, between 80 and 180 MeV, were provided for this experiment by the tandem accelerator at the Maier-Leibnitz Laboratory in Garching, Germany. With these beams, the stopping powers of 93Zr and 93Nb as a function of energy were determined experimentally and compared to the results obtained with the simulation program SRIM. Considerable discrepancies regarding the energy dependence of the two stopping power curves relative to each other were found. The lowest detection limit for 93Zr achieved with the passive absorber setup was 93Zr/Zr = 1 · 10-10. In comparison, by optimizing the gas-filled magnet set-up, 93Nb was suppressed by around six orders of magnitude and a detection limit of 93Zr/Zr = 5 · 10-11 was obtained. To our knowledge, these results represent the lowest detection limit achieved for 93Zr until now.

Energy 93, energy in Israel

International Nuclear Information System (INIS)

Shilo, D.; Bar Mashiah, D.; Er-El, J.

1993-01-01

For the first time this report includes a chapter entitles 'energy and peace'. Following is an overview of israel's energy economy and some principal initiatives in its various sectors during 1992/93 period. 46 figs, 13 tabs

76 FR 2799 - Amendment of Jet Route J-93; CA

Science.gov (United States)

2011-01-18

...; Airspace Docket No. 10-AWP-4] RIN 2120-AA66 Amendment of Jet Route J-93; CA AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action amends Jet Route J-93 in California between...) to amend J-93, (75 FR 66344). Interested parties were invited to participate in this rulemaking...

Structure and precursors of the 1992 / 93 drought in KwaZulu-Natal ...

African Journals Online (AJOL)

The historical context and potential causes and structure of the 1992/93 drought in KwaZulu-Natal are analysed using NCEP reanalysis data. The analysis indicates that increased westerly winds with surface marine lows and continental highs prevailed over Southern Africa. Anomalous divergence and subsidence occur ...

[Characterization of haemolysis of the Vibrio parahaemolyticus no.93].

Science.gov (United States)

Su, S C; Lee, C Y

1997-02-01

Vibrio parahaemolyticus is a causative bacterium of food poisoning, and the haemolysin produced by this organism has been considered as one of the important virulence factors. In order to understand the pathogenic mechanism of this bacterium, the characteristics of haemolysin from Vibrio parahaemolyticus isolated from Taiwan were studied. One of the clinical strains, V. parahaemolyticus No.93, presents a weak hemolytic zone on 7% NaCl-Wagatsuma medium. The DNA hybridization results show that V. parahemolyticus has neither tdh nor trh gene. V. parahaemolyticus No.93 shows obviously hemolytic zone on 3%-NaCl Wagatsuma medium (human blood). The crude extracellular protein of V. parahaemolyticus No. 93 was evaluated for its heat tolerance and enzyme activities by media assay. The results show that this crude extracellular protein is thermolabile. The crude extracellular protein of V. parahaemolyticus No.93 was analyzed on 10% SDS-PAGE and an apparent band of 64 kDa protein was observed. Furthermore, the crude extracellular protein was analyzed by running gelatin-SDS-PAGE and hemoglobin-SDS-PAGE, and three clear zones on 62 kDa, 52 kDa and 41 kDa were observed on both SDS-PAGEs. Thus we propose that the crude extracellular protein of the V. parahaemolyticus No.93 can degrade gelatin as well as hemoglobin. Whether these protease being the virulence factors of Vibrio parahaemolyticus No.93 needs to be further studied.

Assessing the oseltamivir-induced resistance risk and implications for influenza infection control strategies

Directory of Open Access Journals (Sweden)

Hsieh NH

2017-07-01

Full Text Available Nan-Hung Hsieh,1 Yi-Jun Lin,2 Ying-Fei Yang,2 Chung-Min Liao2 1Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA; 2Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan Background: Oseltamivir-resistant mutants with higher drug resistance rates and low transmission fitness costs have not accounted for influenza (subtype viruses. Predicting the impacts of neuraminidase inhibitor therapy on infection rates and transmission of drug-resistant viral strains requires further investigation.Objectives: The purpose of this study was to assess the potential risk of oseltamivir-induced resistance for influenza A (H1N1 and A (H3N2 viruses.Materials and methods: An immune-response-based virus dynamic model was used to best fit the oseltamivir-resistant A (H1N1 and A (H3N2 infection data. A probabilistic risk assessment model was developed by incorporating branching process-derived probability distribution of resistance to estimate oseltamivir-induced resistance risk.Results: Mutation rate and sensitive strain number were key determinants in assessing resistance risk. By increasing immune response, antiviral efficacy, and fitness cost, the spread of resistant strains for A (H1N1 and A (H3N2 were greatly decreased. Probability of resistance depends most strongly on the sensitive strain number described by a Poisson model. Risk of oseltamivir-induced resistance increased with increasing the mutation rate for A (H1N1 only. The ≥50% of resistance risk induced by A (H1N1 and A (H3N2 sensitive infected cells were 0.4 (95% CI: 0.28–0.43 and 0.95 (95% CI 0.93–0.99 at a mutation rate of 10−6, respectively. Antiviral drugs must be administrated within 1–1.5 days for A (H1N1 and 2–2.5 days for A (H3N2 virus infections to limit viral production.Conclusion: Probabilistic risk assessment of antiviral drug

Increased expression of the yeast multidrug resistance ABC transporter Pdr18 leads to increased ethanol tolerance and ethanol production in high gravity alcoholic fermentation

Directory of Open Access Journals (Sweden)

Teixeira Miguel C

2012-07-01

Full Text Available Abstract Background The understanding of the molecular basis of yeast tolerance to ethanol may guide the design of rational strategies to increase process performance in industrial alcoholic fermentations. A set of 21 genes encoding multidrug transporters from the ATP-Binding Cassette (ABC Superfamily and Major Facilitator Superfamily (MFS in S. cerevisiae were scrutinized for a role in ethanol stress resistance. Results A yeast multidrug resistance ABC transporter encoded by the PDR18 gene, proposed to play a role in the incorporation of ergosterol in the yeast plasma membrane, was found to confer resistance to growth inhibitory concentrations of ethanol. PDR18 expression was seen to contribute to decreased 3 H-ethanol intracellular concentrations and decreased plasma membrane permeabilization of yeast cells challenged with inhibitory ethanol concentrations. Given the increased tolerance to ethanol of cells expressing PDR18, the final concentration of ethanol produced during high gravity alcoholic fermentation by yeast cells devoid of PDR18 was lower than the final ethanol concentration produced by the corresponding parental strain. Moreover, an engineered yeast strain in which the PDR18 promoter was replaced in the genome by the stronger PDR5 promoter, leading to increased PDR18 mRNA levels during alcoholic fermentation, was able to attain a 6 % higher ethanol concentration and a 17 % higher ethanol production yield than the parental strain. The improved fermentative performance of yeast cells over-expressing PDR18 was found to correlate with their increased ethanol tolerance and ability to restrain plasma membrane permeabilization induced throughout high gravity fermentation. Conclusions PDR18 gene over-expression increases yeast ethanol tolerance and fermentation performance leading to the production of highly inhibitory concentrations of ethanol. PDR18 overexpression in industrial yeast strains appears to be a promising approach to

Enhanced mechanical properties and increased corrosion resistance of a biodegradable magnesium alloy by plasma electrolytic oxidation (PEO)

International Nuclear Information System (INIS)

White, Leon; Koo, Youngmi; Neralla, Sudheer; Sankar, Jagannathan; Yun, Yeoheung

2016-01-01

Highlights: • Plasma electrolytic oxidation (PEO) method was developed to control corrosion, porosity, and mechanical property. • Mechanical properties of PEO-coated AZ31 alloys were affected by the different electrolyte. • Mechanical properties and corrosion resistance of PEO-coated AZ31 alloys were compared with uncoated one. - Abstract: We report the enhanced mechanical properties of AZ31 magnesium alloys by plasma electrolytic oxidation (PEO) coating in NaOH, Na_2SiO_3, KF and NaH_2PO_4·2H_2O containing electrolytes. Mechanical properties including wear resistance, surface hardness and elastic modulus were increased for PEO-coated AZ31 Mg alloys (PEO-AZ31). DC polarization in Hank's solution indicating that the corrosion resistance significantly increased for PEO-coating in KF-contained electrolyte. Based on these results, the PEO coating method shows promising potential for use in biodegradable implant applications where tunable corrosion and mechanical properties are needed.

Enhanced mechanical properties and increased corrosion resistance of a biodegradable magnesium alloy by plasma electrolytic oxidation (PEO)

Energy Technology Data Exchange (ETDEWEB)

White, Leon; Koo, Youngmi [FIT BEST Laboratory, Engineering Research Center, Department of Chemical, Biological, and Bio Engineering, North Carolina A& T State University, Greensboro, NC 27411 (United States); Neralla, Sudheer [Jet-Hot LLC, Burlington, NC 27215 (United States); Sankar, Jagannathan [FIT BEST Laboratory, Engineering Research Center, Department of Chemical, Biological, and Bio Engineering, North Carolina A& T State University, Greensboro, NC 27411 (United States); Yun, Yeoheung, E-mail: yyun@ncat.edu [FIT BEST Laboratory, Engineering Research Center, Department of Chemical, Biological, and Bio Engineering, North Carolina A& T State University, Greensboro, NC 27411 (United States)

2016-06-15

Highlights: • Plasma electrolytic oxidation (PEO) method was developed to control corrosion, porosity, and mechanical property. • Mechanical properties of PEO-coated AZ31 alloys were affected by the different electrolyte. • Mechanical properties and corrosion resistance of PEO-coated AZ31 alloys were compared with uncoated one. - Abstract: We report the enhanced mechanical properties of AZ31 magnesium alloys by plasma electrolytic oxidation (PEO) coating in NaOH, Na{sub 2}SiO{sub 3}, KF and NaH{sub 2}PO{sub 4}·2H{sub 2}O containing electrolytes. Mechanical properties including wear resistance, surface hardness and elastic modulus were increased for PEO-coated AZ31 Mg alloys (PEO-AZ31). DC polarization in Hank's solution indicating that the corrosion resistance significantly increased for PEO-coating in KF-contained electrolyte. Based on these results, the PEO coating method shows promising potential for use in biodegradable implant applications where tunable corrosion and mechanical properties are needed.

Association between MLH1 -93G>a polymorphism and risk of colorectal cancer.

Directory of Open Access Journals (Sweden)

Ting Wang

Full Text Available The -93G>A (rs1800734 polymorphism located in the promoter of mismatch repair gene, MLH1, has been identified as a low-penetrance variant for cancer risk. Many published studies have evaluated the association between the MLH1 -93G>A polymorphism and colorectal cancer (CRC risk. However, the results remain conflicting rather than conclusive.The aim of this study was to assess the association between the MLH1 -93G>A polymorphism and the risk of CRC.To derive a more precise estimation of the association, a meta-analysis of six studies (17,791 cases and 13,782 controls was performed. Odds ratios (ORs and 95% confidence intervals (CIs were used to evaluate the strength of the association. Four of these published studies were performed on subjects of known microsatellite instability (MSI status. An additional analysis including 742 cases and 10,895 controls was used to assess the association between the MLH1 -93G>A polymorphism and the risk of MSI-CRC.The overall results indicated that the variant genotypes were associated with a significantly increased risk of CRC (AG versus GG: OR = 1.06, 95% CI = 1.01-1.11; AA/AG versus GG: OR = 1.06, 95% CI = 1.01-1.11. This increased risk was also found during stratified analysis of MSI status (AA versus GG: OR = 2.52, 95% CI = 1.94-3.28; AG versus GG: OR = 1.29, 95% CI = 1.10-1.52; AA/AG versus GG: OR = 1.45, 95% CI = 1.24-1.68; AA versusOR = 2.29, 95% CI = 1.78-2.96. Egger's test did not show any evidence of publication bias.Our results suggest that the MLH1 -93G>A polymorphism may contribute to individual susceptibility to CRC and act as a risk factor for MSI-CRC.

Decolonization of Staphylococcus aureus in patients with atopic dermatitis: a reason for increasing resistance to antibiotics?

Directory of Open Access Journals (Sweden)

Izabela Błażewicz

2017-12-01

Full Text Available Introduction : Exacerbation of atopic dermatitis can be associated with bacterial infection. The skin of patients is colonized with Staphylococcus aureus in 90% of cases. An attempt has been made to demonstrate that eradication significantly reduces the severity of the disease. Studies indicate the efficacy of topical antibiotics, topical corticosteroids and calcineurin inhibitors. Due to increasing resistance to drugs and the defective antimicrobial peptide profile, decolonization is virtually impossible. Aim : To determine the prevalence of S. aureus colonization among patients with atopic dermatitis and to assess antimicrobial susceptibility of isolated strains to antibiotics, especially fusidic acid and mupirocin. Material and methods : One hundred patients with atopic dermatitis and 50 healthy subjects were microbiologically assessed for the carriage of S. aureus . Antimicrobial susceptibility tests were performed using the broth-microdilution method for antibiotics: ampicillin, ciprofloxacin, daptomycin, erythromycin, fusidic acid, linezolid, lincomycin, mupirocin, tetracycline and vancomycin. Results : Staphylococcus aureus strains were isolated from the majority of our patients, either from the skin (71% or the anterior nares (67%. In the present study, 10% of isolations represented methicillin-resistant S. aureus (MRSA. Antibiotics exhibited diverse activities against clinical isolates of S. aureus . Among those tested, the highest rates of resistance were shown for ampicillin – 58.5%, lincomycin – 37.5% and erythromycin – 31.0%. Enhanced resistance levels were expressed to mupirocin (17.5% and fusidic acid (15.5%. Conclusions : According to the increasing rate of resistance and quick recolonization after discontinuation of the treatment, chronic use of topical antibiotics is not recommended and should be limited to exacerbation of atopic dermatitis with clinical signs of bacterial infection.

Enhanced mechanical properties and increased corrosion resistance of a biodegradable magnesium alloy by plasma electrolytic oxidation (PEO).

Science.gov (United States)

White, Leon; Koo, Youngmi; Neralla, Sudheer; Sankar, Jagannathan; Yun, Yeoheung

2016-06-01

We report the enhanced mechanical properties of AZ31 magnesium alloys by plasma electrolytic oxidation (PEO) coating in NaOH, Na 2 SiO 3 , KF and NaH 2 PO 4 ·2H 2 O containing electrolytes. Mechanical properties including wear resistance, surface hardness and elastic modulus were increased for PEO-coated AZ31 Mg alloys (PEO-AZ31). DC polarization in Hank's solution indicating that the corrosion resistance significantly increased for PEO-coating in KF-contained electrolyte. Based on these results, the PEO coating method shows promising potential for use in biodegradable implant applications where tunable corrosion and mechanical properties are needed.

Photo-neutron reaction cross-section for 93Nb in the end-point bremsstrahlung energies of 12–16 and 45–70 MeV

International Nuclear Information System (INIS)

Naik, H.; Kim, G.N.; Schwengner, R.; Kim, K.; Zaman, M.; Tatari, M.; Sahid, M.; Yang, S.C.; John, R.; Massarczyk, R.; Junghans, A.; Shin, S.G.; Key, Y.; Wagner, A.; Lee, M.W.; Goswami, A.; Cho, M.-H.

2013-01-01

The photo-neutron cross-sections of 93 Nb at the end-point bremsstrahlung energies of 12, 14 and 16 MeV as well as 45, 50, 55, 60 and 70 MeV have been determined by the activation and the off-line γ-ray spectrometric techniques using the 20 MeV electron linac (ELBE) at Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany, and 100 MeV electron linac at Pohang Accelerator Laboratory (PAL), Pohang, Korea. The 93 Nb(γ, xn, x=1–4) reaction cross-sections as a function of photon energy were also calculated using computer code TALYS 1.4. The flux-weighted average values were obtained from the experimental and the theoretical (TALYS) values based on mono-energetic photons. The experimental values of present work are in good agreement with the flux-weighted theoretical values of TALYS 1.4 but are slightly higher than the flux-weighted experimental data of mono-energetic photons. It was also found that the theoretical and the experimental values of present work and literature data for the 93 Nb(γ, xn) reaction cross-sections increase from the threshold values to a certain energy, where other reaction channels opens. However, the increase of 93 Nb(γ, n) and 93 Nb(γ, 2n) reaction cross-sections are sharper compared to 93 Nb(γ, 3n) and 93 Nb(γ, 4n) reaction cross-sections. The sharp increase of 93 Nb(γ, n) and 93 Nb(γ, 2n) reaction cross-sections from the threshold value up to 17–22 MeV is due to the Giant Dipole Resonance (GDR) effect besides the role of excitation energy. After a certain values, the individual 93 Nb(γ, xn) reaction cross-sections decrease with increase of bremsstrahlung energy due to opening of other reaction channels

9 CFR 93.311 - Milk from quarantined horses.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Milk from quarantined horses. 93.311... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Horses § 93.311 Milk from quarantined horses. Milk or cream from horses quarantined under the provisions of this part shall not be used by any person other...

7 CFR 27.93 - Bona fide spot markets.

Science.gov (United States)

2010-01-01

... Southwest Markets and the New Mexico counties of Union, Quay, Curry, Roosevelt and Lea. Desert Southwest The..., Hudspeth and El Paso, all New Mexico counties except those included in the West Texas market, all counties... 7 Agriculture 2 2010-01-01 2010-01-01 false Bona fide spot markets. 27.93 Section 27.93...

Increasing transmission of antibiotic resistance from animals to humans

DEFF Research Database (Denmark)

Aarestrup, Frank Møller; Frimodt-Møller, Niels

2011-01-01

usage of antibiotics which contributes most to resistance observed in humans, but also that the contribution from animals is large and larger than estimated just a few years ago. This indicates the need to implement restriction on antimicrobial usage for both humans and animals.......The importance of the animal reservoir for emergence of antimicrobial resistance in bacteria in humans is difficult to estimate. In this article we give our estimate of the importance and also highlight on which points we have become wiser during recent years. We conclude that it still is the human...

Increasing transmission of antibiotic resistance from animals to humans

DEFF Research Database (Denmark)

Aarestrup, Frank Møller; Frimodt-Møller, Niels

2011-01-01

The importance of the animal reservoir for emergence of antimicrobial resistance in bacteria in humans is difficult to estimate. In this article we give our estimate of the importance and also highlight on which points we have become wiser during recent years. We conclude that it still is the human...... usage of antibiotics which contributes most to resistance observed in humans, but also that the contribution from animals is large and larger than estimated just a few years ago. This indicates the need to implement restriction on antimicrobial usage for both humans and animals....

75 FR 66344 - Amendment of Jet Route J-93; CA

Science.gov (United States)

2010-10-28

...-1022; Airspace Docket No. 10-AWP-4] RIN 2120-AA66 Amendment of Jet Route J-93; CA AGENCY: Federal... proposes to amend Jet Route J-93 in California between the Julian VHF Omnidirectional Radio Range Tactical... is necessary to realign Jet Route J-93 with the revised location of the Penasco VOR. The Proposal The...

Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression.

Science.gov (United States)

Lomniczi, Alejandro; Wright, Hollis; Castellano, Juan Manuel; Matagne, Valerie; Toro, Carlos A; Ramaswamy, Suresh; Plant, Tony M; Ojeda, Sergio R

2015-12-16

In primates, puberty is unleashed by increased GnRH release from the hypothalamus following an interval of juvenile quiescence. GWAS implicates Zinc finger (ZNF) genes in timing human puberty. Here we show that hypothalamic expression of several ZNFs decreased in agonadal male monkeys in association with the pubertal reactivation of gonadotropin secretion. Expression of two of these ZNFs, GATAD1 and ZNF573, also decreases in peripubertal female monkeys. However, only GATAD1 abundance increases when gonadotropin secretion is suppressed during late infancy. Targeted delivery of GATAD1 or ZNF573 to the rat hypothalamus delays puberty by impairing the transition of a transcriptional network from an immature repressive epigenetic configuration to one of activation. GATAD1 represses transcription of two key puberty-related genes, KISS1 and TAC3, directly, and reduces the activating histone mark H3K4me2 at each promoter via recruitment of histone demethylase KDM1A. We conclude that GATAD1 epitomizes a subset of ZNFs involved in epigenetic repression of primate puberty.

Genetic characterisation of tigecycline-resistant Enterobacter spp. in blood isolates causing bacteraemia.

Science.gov (United States)

Cha, Min Kyeong; Kang, Cheol-In; Park, Ga Eun; Kim, So Hyun; Chung, Doo Ryeon; Peck, Kyong Ran; Song, Jae-Hoon

2018-01-05

Tigecycline (TIG) is one of the most important antimicrobial agents used to treat infections by multidrug-resistant bacteria. However, rates of TIG-resistant pathogens have increased recently. This study was conducted to identify the antimicrobial susceptibility profiles and to investigate the role of efflux pumps in high-level TIG-resistant Enterobacter spp. isolates causing bacteraemia. A total of 323 Enterobacter spp. causing bacteraemia were collected from eight hospitals in various regions of South Korea. Minimum inhibitory concentrations (MICs) were determined by the broth microdilution method and Etest. Expression levels of the efflux pump gene acrA and its regulators (ramA and rarA) were examined by quantitative real-time PCR. Isolate relatedness was determined by multilocus sequence typing (MLST). Among the 323 clinical isolates included in this study, 37 (11.5%) were TIG-non-susceptible, of which 8 isolates were highly resistant to TIG with MICs of 8mg/L (4 isolates) or 16mg/L (4 isolates). All high-level TIG-resistant isolates showed increased expression of acrA (0.93-13.3-fold) and ramA (1.4-8.2-fold). Isolates with a tigecycline MIC of 16mg/L also showed overexpression of rarA compared with TIG-susceptible isolates. In this study, overexpression of acrA, ramA and rarA was observed in high-level TIG-resistant Enterobacter spp. isolates. We suggest that rarA might be involved in the regulation of acrA overexpression in high-level TIG-resistant Enterobacter spp. isolates. Efflux pump-mediated resistance should be closely monitored because it could be indirectly attributed to the use of other antibiotics transported by the same efflux pump. Copyright © 2017. Published by Elsevier Ltd.

Coral resistance to ocean acidification linked to increased calcium at the site of calcification.

Science.gov (United States)

DeCarlo, T M; Comeau, S; Cornwall, C E; McCulloch, M T

2018-05-16

Ocean acidification threatens the persistence of biogenic calcium carbonate (CaCO 3 ) production on coral reefs. However, some coral genera show resistance to declines in seawater pH, potentially achieved by modulating the chemistry of the fluid where calcification occurs. We use two novel geochemical techniques based on boron systematics and Raman spectroscopy, which together provide the first constraints on the sensitivity of coral calcifying fluid calcium concentrations ([Formula: see text]) to changing seawater pH. In response to simulated end-of-century pH conditions, Pocillopora damicornis increased [Formula: see text] to as much as 25% above that of seawater and maintained constant calcification rates. Conversely, Acropora youngei displayed less control over [Formula: see text], and its calcification rates strongly declined at lower seawater pH. Although the role of [Formula: see text] in driving calcification has often been neglected, increasing [Formula: see text] may be a key mechanism enabling more resistant corals to cope with ocean acidification and continue to build CaCO 3 skeletons in a high-CO 2 world. © 2018 The Author(s).

Intense resistance exercise induces early and transient increases in ryanodine receptor 1 phosphorylation in human skeletal muscle.

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Sebastian Gehlert

Full Text Available BACKGROUND: While ryanodine receptor 1 (RyR1 critically contributes to skeletal muscle contraction abilities by mediating Ca²⁺ion oscillation between sarcoplasmatic and myofibrillar compartments, AMP-activated protein kinase (AMPK senses contraction-induced energetic stress by phosphorylation at Thr¹⁷². Phosphorylation of RyR1 at serine²⁸⁴³ (pRyR1Ser²⁸⁴³ results in leaky RyR1 channels and impaired Ca²⁺homeostasis. Because acute resistance exercise exerts decreased contraction performance in skeletal muscle, preceded by high rates of Ca²⁺-oscillation and energetic stress, intense myofiber contractions may induce increased RyR1 and AMPK phosphorylation. However, no data are available regarding the time-course and magnitude of early RyR1 and AMPK phosphorylation in human myofibers in response to acute resistance exercise. PURPOSE: Determine the effects and early time-course of resistance exercise on pRyR1Ser²⁸⁴³ and pAMPKThr¹⁷² in type I and II myofibers. METHODS: 7 male subjects (age 23±2 years, height: 185±7 cm, weight: 82±5 kg performed 3 sets of 8 repetitions of maximum eccentric knee extensions. Muscle biopsies were taken at rest, 15, 30 and 60 min post exercise. pRyR1Ser²⁸⁴³ and pAMPKThr¹⁷² levels were determined by western blot and semi-quantitative immunohistochemistry techniques. RESULTS: While total RyR1 and total AMPK levels remained unchanged, RyR1 was significantly more abundant in type II than type I myofibers. pRyR1Ser²⁸⁴³ increased 15 min and peaked 30 min (p<0.01 post exercise in both myofiber types. Type I fibers showed relatively higher increases in pRyR1Ser²⁸⁴³ levels than type II myofibers and remained elevated up to 60 min post resistance exercise (p<0.05. pAMPKThr¹⁷² also increased 15 to 30 min post exercise (p<0.01 in type I and II myofibers and in whole skeletal muscle. CONCLUSION: Resistance exercise induces acutely increased pRyR1Ser²⁸⁴³ and

Antibiotic resistance in Pseudomonas aeruginosa strains with increased mutation frequency due to inactivation of the DNA oxidative repair system

DEFF Research Database (Denmark)

Mandsberg, Lotte F; Ciofu, Oana; Kirkby, N

2009-01-01

,8-dihydro-8-oxodeoxyguanosine) than PAO1 after exposure to PMNs, and they developed resistance to antibiotics more frequently. The mechanisms of resistance were increased β-lactamase production and overexpression of the MexCD-OprJ efflux-pump. Mutations in either the mutT or the mutY gene were found...... in resistant HP clinical isolates from patients with CF, and complementation with wild-type genes reverted the phenotype. In conclusion, oxidative stress might be involved in the development of resistance to antibiotics. We therefore suggest the possible use of antioxidants for CF patients to prevent...

Characterization and Calibration of Large Area Resistive Strip Micromegas Detectors

CERN Document Server

AUTHOR|(INSPIRE)INSPIRE-00389527; The ATLAS collaboration

2016-01-01

Resistive strip Micromegas detectors are discharge tolerant. They have been tested extensively as small detectors of about 10 x 10 cm$^2$ in size and they work reliably at high rates of 100 kHz/cm$^2$ and above. Tracking resolution well below 100 $\\mu$m has been observed for 100 GeV muons and pions. Micromegas detectors are meanwhile proposed as large area muon precision trackers of 2-3 m$^2$ in size. To investigate possible differences between small and large detectors, a 1 m$^2$ detector with 2048 resistive strips at a pitch of 450 $\\mu$m was studied in the LMU Cosmic Ray Measurement Facility (CRMF) using two 4 $\\times$ 2.2 m$^2$ large Monitored Drift Tube (MDT) chambers for cosmic muon reference tracking. A segmentation of the resistive strip anode plane in 57.6 mm x 93 mm large areas has been realized by the readout of 128 strips with one APV25 chip each and by eleven 93 mm broad trigger scintillators placed along the readout strips. This allows for mapping of homogeneity in pulse height and efficiency, d...

Complementation of a pKM101 derivative that decreases resistance to UV killing but increases susceptibility to mutagenesis

International Nuclear Information System (INIS)

Langer, P.J.; Perry, K.L.; Walker, G.C.

1985-01-01

The drug resistance plasmid pKM101 makes Escherichia coli resistant to the lethal effects of ultraviolet (UV) irradiation and more susceptible to mutagenesis by a variety of agents. The plasmid operon responsible for increasing mutagenesis has been termed mucAB (Mutagenesis, UV and chemical). The authors have isolated a derivative of pKM101 called pGW1975 which makes cells more sensitive to killing by UV but which retains the ability of pKM101 to increase susceptibility to methyl methanesulfonate (MMS) mutagenesis. pGW1975 increases UV mutagenesis less than pKM101 in a uvrA + strain but more than pKM101 in a uvrA - strain. muc - point and insertion mutants of pKM101 and pGW1975 complement to restore the plasmid-mediated: (i) ability to reactivate UV-irradiated phage, (ii) resistance to killing by UV, and (iii) level of susceptibility to UV mutagenesis. They have identified a 2.0 kb region of pKM101 which is responsible for the complementation and which maps counterclockwise of mucAB. (Auth)

Molecular characterization of multidrug-resistant Shigella spp. of food origin.

Science.gov (United States)

Ahmed, Ashraf M; Shimamoto, Tadashi

2015-02-02

Shigella spp. are the causative agents of food-borne shigellosis, an acute enteric infection. The emergence of multidrug-resistant clinical isolates of Shigella presents an increasing challenge for clinicians in the treatment of shigellosis. Several studies worldwide have characterized the molecular basis of antibiotic resistance in clinical Shigella isolates of human origin, however, to date, no such characterization has been reported for Shigella spp. of food origin. In this study, we characterized the genetic basis of multidrug resistance in Shigella spp. isolated from 1600 food samples (800 meat products and 800 dairy products) collected from different street venders, butchers, retail markets, and slaughterhouses in Egypt. Twenty-four out of 27 Shigella isolates (88.9%) showed multidrug resistance phenotypes to at least three classes of antimicrobials. The multidrug-resistant Shigella spp. were as follows: Shigella flexneri (66.7%), Shigella sonnei (18.5%), and Shigella dysenteriae (3.7%). The highest resistance was to streptomycin (100.0%), then to kanamycin (95.8%), nalidixic acid (95.8%), tetracycline (95.8%), spectinomycin (93.6%), ampicillin (87.5%), and sulfamethoxazole/trimethoprim (87.5%). PCR and DNA sequencing were used to screen and characterize integrons and antibiotic resistance genes. Our results indicated that 11.1% and 74.1% of isolates were positive for class 1 and class 2 integrons, respectively. Beta-lactamase-encoding genes were identified in 77.8% of isolates, and plasmid-mediated quinolone resistance genes were identified in 44.4% of isolates. These data provide useful information to better understand the molecular basis of antimicrobial resistance in Shigella spp. To the best of our knowledge, this is the first report of the molecular characterization of antibiotic resistance in Shigella spp. isolated from food. Copyright © 2014 Elsevier B.V. All rights reserved.

Increased retinol-free RBP4 contributes to insulin resistance in gestational diabetes mellitus.

Science.gov (United States)

Chen, Yanmin; Lv, Ping; Du, Mengkai; Liang, Zhaoxia; Zhou, Menglin; Chen, Danqing

2017-07-01

Retinol-binding protein 4 (RBP4) is a circulating retinol transporter that is strongly associated with insulin resistance. The aim of this study was to evaluate the RBP4 and retinol level in rat model of gestational diabetes mellitus and the relationship between retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) and insulin resistance. Pregnant rats were administered streptozotocin to induce diabetes. The RBP4 and retinol levels were evaluated in GDM and normal pregnant rats. After then, normal pregnant rats were divided into two groups to receive either apo-RBP4 or vehicle injection. The metabolic parameters and insulin signaling in adipose tissue, skeletal muscle and liver were determined in apo-RBP4 and control groups. Primary human adipocytes were cultured in vitro with different proportions of apo-RBP4 and holo-RBP4 for 24 h. The interaction between RBP4 and STRA6 was assessed by co-immunoprecipitation, and the expression of JAK-STAT pathway and insulin signaling were detected by Western blotting and immunofluorescence. We found increases in serum RBP4 levels and the RBP4:retinol ratio but not in the retinol levels in GDM rats. Exogenous apo-RBP4 injection attenuated insulin sensitivity in pregnant rats. In vitro, a prolonged interaction between RBP4 and STRA6 was observed when apo-RBP4 was present. In response to increased apo-RBP4 levels, cells showed elevated activation of the JAK2/STAT5 cascade and SOCS3 expression, decreased phosphorylation of IR and IRS1, and attenuated GLUT4 translocation and glucose uptake upon insulin stimulation. Apo-RBP4 is a ligand that activates the STRA6 signaling cascade, inducing insulin resistance in GDM.

Increasing incidence of penicillin- and cefotaxime-resistant Streptococcus pneumoniae causing meningitis in India: Time for revision of treatment guidelines?

Science.gov (United States)

Verghese, Valsan Philip; Veeraraghavan, Balaji; Jayaraman, Ranjith; Varghese, Rosemol; Neeravi, Ayyanraj; Jayaraman, Yuvaraj; Thomas, Kurien; Mehendale, Sanjay M

2017-01-01

Pneumococcal meningitis is a life-threatening infection, requiring prompt diagnosis and effective treatment. Penicillin resistance in pneumococcal infections is a concern. Here, we present the antibiotic susceptibility profile of pneumococcal meningeal isolates from January 2008 to August 2016 to elucidate treatment guidelines for pneumococcal meningitis. Invasive pneumococcal isolates from all age groups, were included in this study. Minimum inhibitory concentrations for the isolates were identified by agar dilution technique and VITEK System 2. Serotyping of isolates was done by co-agglutination technique. Out of 830 invasive pneumococcal isolates, 167 (20.1%) isolates were from meningeal infections. Cumulative penicillin resistance in pneumococcal meningitis was 43.7% and cefotaxime non-susceptibility was 14.9%. Penicillin resistance amongst meningeal isolates in those younger than 5 years, 5-16 years of age and those aged 16 years and older was 59.7%, 50% and 27.3%, respectively, with non-susceptibility to cefotaxime in the same age groups being 18%, 22.2% and 10.4%. Penicillin resistance amongst pneumococcal meningeal isolates increased from 9.5% in 2008 to 42.8% in 2016, whereas cefotaxime non-susceptibility increased from 4.7% in 2008 to 28.5% in 2016. Serotypes 14, 19F, 6B, 6A, 23F, 9V and 5 were the most common serotypes causing meningitis, with the first five accounting for over 75% of resistant isolates. The present study reports increasing penicillin resistance and cefotaxime non-susceptibility to pneumococcal meningitis in our setting. This highlights the need for empiric therapy with third-generation cephalosporins and vancomycin for all patients with meningitis while awaiting results of culture and susceptibility testing.

Structure of the first PDZ domain of human PSD-93

DEFF Research Database (Denmark)

Fiorentini, Monica; Nielsen, Ann Kallehauge; Kristensen, Ole

2009-01-01

The crystal structure of the PDZ1 domain of human PSD-93 has been determined to 2.0 A resolution. The PDZ1 domain forms a crystallographic trimer that is also predicted to be stable in solution. The main contributions to the stabilization of the trimer seem to arise from interactions involving...... the PDZ1-PDZ2 linker region at the extreme C-terminus of PDZ1, implying that the oligomerization that is observed is not of biological significance in full-length PSD-93. Comparison of the structures of the binding cleft of PSD-93 PDZ1 with the previously reported structures of PSD-93 PDZ2 and PDZ3...

Survey of strain distribution and antibiotic resistance pattern of group B streptococci (Streptococcus agalactiae isolated from clinical specimens

Directory of Open Access Journals (Sweden)

Mousavi, Seyed Masoud

2016-09-01

Full Text Available Aim: The aims of the present study were to determine the antibiotic susceptibility profils with particular emphasis on susceptible or resistant strains to macrolides and lincosamids antibiotics and to determine possible antibiotic resistance mechanisms occurring in group B streptococci (GBS strains using PCR assay and disk diffusion method.Methods: A total of 62 clinical GBS strains were investigated. Antibacterial susceptibility testing was performed using the disk diffusion method and inducible resistance test for clindamycin by standard double disk diffusion or D-zone test for all isolates to differentiate macrolide resistance phenotype (M, constitutive macrolide-lincosamide-streptogramin B phenotype (cMLS and induced macrolide-lincosamide-streptogramin B phenotype (iMLS. In addition, minimum inhibitory concentrations (MIC of penicillin were determined for all isolates. Finally, possible existence of antibiotic resistance genes for erythromycin , and and for clindamycin were examined among isolates using PCR assay.Results: All 62 isolates were susceptible to penicillin, ampicillin, linezolid, cefazoline and vancomycin. However, 93.5% (n=58 of isolates showed an increased MIC to penicillin. The overall rate of erythromycin resistance was 35.5% (n=22. All erythromycin-resistant isolates displayed the M phenotype (100%, n=22. All three erythromycin resistance genes (i.e. , and were found in erythromycin-resistant isolates.Conclusion: It was concluded that prescribing antibiotic without antibacterial susceptibility tests should be prevented because of the high prevalence of erythromycin-resistant GBS strains and the fact that erythromycin-resistant GBS strains has shown an increased MIC to penicillin, as the drug of choice for treating GBS infections.

Induction of resistance to gray mold with benzothiadiazole modifies amino acid profile and increases proanthocyanidins in grape: primary versus secondary metabolism.

Science.gov (United States)

Iriti, Marcello; Rossoni, Mara; Borgo, Michele; Ferrara, Luigia; Faoro, Franco

2005-11-16

Field treatments of grapevine (cv. Merlot) with the plant activator benzothiadiazole (BTH, 0.3 mM) induced resistance against gray mold caused by Botrytis cinerea. Both incidence and severity of the disease were reduced. The resistance was associated with an increase of total polyphenols in berry skins, in particular, the proanthocyanidin fraction, that increased up to 36%. The amino acid profile of leaves was also modified by treatments, particularly lysine, that augmented 4-fold. Other amino acids involved in resistance mechanisms to either biotic or abiotic stress increased as well. These results indicate that BTH treatments can be used to control gray mold, thereby limiting an excessive use of fungicides, and could be exploited to increase the content of micronutrients of high nutritional value, arising from both primary and secondary metabolisms.

29 CFR 1915.93 - Utilities.

Science.gov (United States)

2010-07-01

... Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) OCCUPATIONAL SAFETY AND HEALTH STANDARDS FOR SHIPYARD EMPLOYMENT General Working Conditions § 1915.93 Utilities... a pressure not exceeding the safe working pressure of the vessel's system in its present condition...

Double mutation in eleusine indica alpha-tubulin increases the resistance of transgenic maize calli to dinitroaniline and phosphorothioamidate herbicides

Science.gov (United States)

Anthony; Hussey

1999-06-01

The repeated use of dinitroaniline herbicides on the cotton and soybean fields of the southern United States has resulted in the appearance of resistant biotypes of one of the world's worst weeds, Eleusine indica. Two biotypes have been characterized, a highly resistant (R) biotype and an intermediate resistant (I) biotype. In both cases the resistance has been attributed to a mutation in alpha-tubulin, a component of the alpha/beta tubulin dimer that is the major constituent of microtubules. We show here that the I-biotype mutation, like the R-biotype mutation shown in earlier work, can confer dinitroaniline resistance on transgenic maize calli. The level of resistance obtained is the same as that for E. indica I- or R-biotype seedlings. The combined I- and R-biotype mutations increase the herbicide tolerance of transgenic maize calli by a value close to the summation of the maximum herbicide tolerances of calli harbouring the single mutations. These data, taken together with the position of the two different mutations within the atomic structure of the alpha/beta tubulin dimer, imply that each mutation is likely to exert its effect by a different mechanism. These mechanisms may involve increasing the stability of microtubules against the depolymerizing effects of the herbicide or changing the conformation of the alpha/beta dimer so that herbicide binding is less effective, or a combination of both possibilities.

Increasing antibiotic resistance among uropathogens isolated during years 2006-2009: impact on the empirical management

Directory of Open Access Journals (Sweden)

Hamid Mohammad-Jafari

2012-02-01

Full Text Available Urinary tract infections (UTI are one of the most common infections with an increasing resistance to antimicrobial agents. PURPOSE: Empirical initial antibiotic treatment of UTI must rely on susceptible data from local studies. MATERIALS AND METHODS: Retrospective analysis of isolated bacteria from children with UTIs was performed at the university hospital during years 2006-2009. The findings were compared with data collected in a similar study carried out in 2002- 2003. RESULTS: A total of 1439 uropathogens were isolated. Escherichia coli (E.coli was the leading cause, followed by Enterobacter, and other gram negative bacilli. It was observed resistance of E.coli to ceftriaxone, cefexime, amikacin, gentamycin, and nalidixic acid; Enterobacter to cefexime; and the resistance of gram negative bacilli to gentamicin and cefexime increased significantly. The highest effective antibiotic was Imipenem, ciprofloxacin, and amikacin with 96.7%, 95% and 91% sensitivity rates , respectively, followed by ceftriaxone 77.2%, gentamicin 77%, nitrofurantoin 76.4%, nalidixic acid 74.3% and cefexime with 70%. CONCLUSION: The use of nitrofurantoin or nalidixic acid as initial empirical antibacterial therapy for cystitis seems appropriate. For cases of simple febrile UTI, the use of initial parenteral therapies with amikacin or ceftriaxone followed by an oral third generation cephalosporin also seemed appropriated, and in cases of severely ill patients or complicated UTI, imipenem as monotherapy or, a combination of Ceftriaxone with an aminoglycoside, are recommended.

Increasing penicillin resistance in pneumococci isolated from cerebrospinal fluid samples: Fifteen-year experience from a teaching hospital

Directory of Open Access Journals (Sweden)

Filiz Pehlivanoğlu

2014-12-01

Full Text Available Objective: There have been prominent changes in evaluation of resistance patterns of pneumococci and breakpoint values in recent years. We aimed to investigate the penicillin sensitivity of pneumococcal strains isolated from the ce­rebrospinal fluid specimens between the years 1997-2011 in our hospital and determine the MIC values under the light of these changes. Methods: Identification of pneumococci was made with conventional methods in patients with meningitis. MIC values for penicillin G were investigated by E test method in all strains. MIC values of pneumococci strains were evaluated ac­cording to values determined by CLSI for meningitis isolates in 2008. Results: A total of 57 strains were investigated in this study. The MIC range for penicillin was 0.016 - 0.75 μg/ml in S. pneumoniae strains. Seventy five percent of the strains were sensitive and eight strains (14% had resistance. MIC50 value was sensitive, and a MIC90 value was resistant. The first resistant strain was detected in 2000, and three strains were resistant in the last year. When examined over the years increased resistance was 5.3% in the first five-year period seems to be 28.6% in the last five-year period. Conclusions: Knowledge on penicillin resistance patterns and surveillance is very important in the empirical treatment in pneumococcal meningitis. J Microbiol Infect Dis 2014; 4(4: 136-140

Gas Plasma Pre-treatment Increases Antibiotic Sensitivity and Persister Eradication in Methicillin-Resistant Staphylococcus aureus

Science.gov (United States)

Guo, Li; Xu, Ruobing; Zhao, Yiming; Liu, Dingxin; Liu, Zhijie; Wang, Xiaohua; Chen, Hailan; Kong, Michael G.

2018-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of serious nosocomial infections, and recurrent MRSA infections primarily result from the survival of persister cells after antibiotic treatment. Gas plasma, a novel source of ROS (reactive oxygen species) and RNS (reactive nitrogen species) generation, not only inactivates pathogenic microbes but also restore the sensitivity of MRSA to antibiotics. This study further found that sublethal treatment of MRSA with both plasma and plasma-activated saline increased the antibiotic sensitivity and promoted the eradication of persister cells by tetracycline, gentamycin, clindamycin, chloramphenicol, ciprofloxacin, rifampicin, and vancomycin. The short-lived ROS and RNS generated by plasma played a primary role in the process and induced the increase of many species of ROS and RNS in MRSA cells. Thus, our data indicated that the plasma treatment could promote the effects of many different classes of antibiotics and act as an antibiotic sensitizer for the treatment of antibiotic-resistant bacteria involved in infectious diseases. PMID:29628915

A silver ion-doped calcium phosphate-based ceramic nanopowder-coated prosthesis increased infection resistance.

Science.gov (United States)

Kose, Nusret; Otuzbir, Ali; Pekşen, Ceren; Kiremitçi, Abdurrahman; Doğan, Aydin

2013-08-01

Despite progress in surgical techniques, 1% to 2% of joint arthroplasties become complicated by infection. Coating implant surfaces with antimicrobial agents have been attempted to prevent initial bacterial adhesion to implants with varying success rates. We developed a silver ion-containing calcium phosphate-based ceramic nanopowder coating to provide antibacterial activity for orthopaedic implants. We asked whether titanium prostheses coated with this nanopowder would show resistance to bacterial colonization as compared with uncoated prostheses. We inserted titanium implants (uncoated [n = 9], hydroxyapatite-coated [n = 9], silver-coated [n = 9]) simulating knee prostheses into 27 rabbits' knees. Before implantation, 5 × 10(2) colony-forming units of Staphylococcus aureus were inoculated into the femoral canal. Radiology, microbiology, and histology findings were quantified at Week 6 to define the infection, microbiologically by increased rate of implant colonization/positive cultures, histologically by leukocyte infiltration, necrosis, foreign-body granuloma, and devitalized bone, and radiographically by periosteal reaction, osteolysis, or sequestrum formation. Swab samples taken from medullary canals and implants revealed a lower proportion of positive culture in silver-coated implants (one of nine) than in uncoated (eight of nine) or hydroxyapatite-coated (five of nine) implants. Silver-coated implants also had a lower rate of colonization. No cellular inflammation or foreign-body granuloma was observed around the silver-coated prostheses. Silver ion-doped ceramic nanopowder coating of titanium implants led to an increase in resistance to bacterial colonization compared to uncoated implants. Silver-coated orthopaedic implants may be useful for resistance to local infection but will require in vivo confirmation.

Scottish Campaign to Resist the Atomic Menace annual report 1992/93

International Nuclear Information System (INIS)

1993-01-01

In a year which saw the Scottish Campaign to Resist the Atomic Menace (SCRAM) Safe Energy journal reach its 15th birthday, the Earth Summit in Rio was amongst the most important events. Though this historic international meeting failed to live up to the expectations of many, it was a step in the right direction. The activities of the many non-governmental organisations was particularly encouraging, and their continuing work on climate change in particular could be vital. The nuclear industry persists in claiming green credentials, but it has not had a good year. For SCRAM, founded to oppose the Torness nuclear power station, the Public Inquiry in December into Scottish Nuclear's plans for a dry store was of particular significance. Our pragmatic decision not to oppose the scheme did not go unnoticed. We were happy to provide registered objectors with information, including our report on dry storage. Having reached a landmark of fifteen years continuous publication, Safe Energy continues to be well received by a readership which includes concerned individuals, campaigners, politicians, environmentalists, government agencies, the media and the nuclear industry. SCRAM's main role is dissemination of information, and the journal is our main vehicle. We aim to deal with complex issues in a readable way, and are encouraged that such a broad range of people find it of use. (author)

Elevated carbon dioxide increases salicylic acid in Glycine max.

Science.gov (United States)

Casteel, Clare L; Segal, Lauren M; Niziolek, Olivia K; Berenbaum, May R; DeLucia, Evan H

2012-12-01

Concentrations of carbon dioxide (CO(2)) are increasing in the atmosphere, affecting soybean (Glycine max L.) phytohormone signaling and herbivore resistance. Whether the impact of elevated CO(2) on phytohormones and induced defenses is a generalized response within this species is an open question. We examined jasmonic acid (JA) and salicylic acid (SA) under ambient and elevated CO(2) concentrations with and without Japanese beetle (Popillia japonica Newman) damage and artificial damage across six soybean cultivars (HS93-4118, Pana, IA 3010, Loda, LN97-15076, and Dwight). Elevated CO(2) reduced constitutive levels of JA and related transcripts in some but not all soybean cultivars. In contrast to the variation in JA, constitutive levels of salicylic were increased universally among soybean cultivars grown under elevated CO(2). Variation in hormonal signaling may underpin observed variation in the response of insect herbivores and pathogens to plants grown under elevated CO(2).

STS-93 Commander Eileen Collins waves to her family

Science.gov (United States)

1999-01-01

STS-93 Commander Eileen M. Collins waves to her family nearby, a last meeting before launch of mission STS-93 on July 20. Liftoff is scheduled for 12:36 a.m. EDT. The primary mission of STS-93 is the release of the Chandra X-ray Observatory, which will allow scientists from around the world to study some of the most distant, powerful and dynamic objects in the universe. The new telescope is 20 to 50 times more sensitive than any previous X- ray telescope and is expected to unlock the secrets of supernovae, quasars and black holes. The STS-93 crew numbers five: Commander Collins, Pilot Jeffrey S. Ashby, and Mission Specialists Steven A. Hawley (Ph.D.), Catherine G. Coleman (Ph.D.) and Michel Tognini of France, with the Centre National d'Etudes Spatiales (CNES). Collins is the first woman to serve as commander of a shuttle mission.

Effects of Increased Respiratory Resistance on Maximal O2 Uptake and Anaerobic Threshold during Incremental Exercise Tests

OpenAIRE

ÖZÇELİK, Oğuz

2014-01-01

This study was undertaken to assess whether maximal O2 uptake (VO2max) can be used as an index of measuring aerobic capacity under the condition of increased respiratory resistance. Seven male subjects performed two incremental exercise tests on a cycle ergometer on different days: one control (C) and one breathing through an 8 mm bore diameter respiratory resistance (R). Ventilatory and gas exchange responses were measured with a turbine volume transducer and mass spectrometry, and processed...

Mining the Genus Solanum for Increasing Disease Resistance

NARCIS (Netherlands)

Vossen, J.H.; Kwang-Ryong Jo,; Vosman, B.J.

2014-01-01

Plant Breeding is the art of selecting and discarding genetic material to achieve crop improvement. Favourable alleles resulting in quality improvement or disease resistance must be added, while unfavourable alleles must be removed. The source for novel alleles can be other varieties, landraces or

9 CFR 93.323 - Inspection.

Science.gov (United States)

2010-01-01

..., BIRDS, FISH, AND POULTRY, AND CERTAIN ANIMAL, BIRD, AND POULTRY PRODUCTS; REQUIREMENTS FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Horses Mexico 18 § 93.323 Inspection. (a) All horses offered for entry from Mexico, including such horses intended for movement through the United States in bond for...

Brain Insulin Signaling Is Increased in Insulin-Resistant States and Decreases in FOXOs and PGC-1α and Increases in Aβ1-40/42 and Phospho-Tau May Abet Alzheimer Development.

Science.gov (United States)

Sajan, Mini; Hansen, Barbara; Ivey, Robert; Sajan, Joshua; Ari, Csilla; Song, Shijie; Braun, Ursula; Leitges, Michael; Farese-Higgs, Margaret; Farese, Robert V

2016-07-01

Increased coexistence of Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) suggests that insulin resistance abets neurodegenerative processes, but linkage mechanisms are obscure. Here, we examined insulin signaling factors in brains of insulin-resistant high-fat-fed mice, ob/ob mice, mice with genetically impaired muscle glucose transport, and monkeys with diet-dependent long-standing obesity/T2DM. In each model, the resting/basal activities of insulin-regulated brain protein kinases, Akt and atypical protein kinase C (aPKC), were maximally increased. Moreover, Akt hyperactivation was accompanied by hyperphosphorylation of substrates glycogen synthase kinase-3β and mammalian target of rapamycin and FOXO proteins FOXO1, FOXO3A, and FOXO4 and decreased peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression. Akt hyperactivation was confirmed in individual neurons of anterocortical and hippocampal regions that house cognition/memory centers. Remarkably, β-amyloid (Aβ1-40/42) peptide levels were as follows: increased in the short term by insulin in normal mice, increased basally in insulin-resistant mice and monkeys, and accompanied by diminished amyloid precursor protein in monkeys. Phosphorylated tau levels were increased in ob/ob mice and T2DM monkeys. Importantly, with correction of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, brain insulin signaling normalized. As FOXOs and PGC-1α are essential for memory and long-term neuronal function and regeneration and as Aβ1-40/42 and phospho-tau may increase interneuronal plaques and intraneuronal tangles, presently observed aberrations in hyperinsulinemic states may participate in linking insulin resistance to AD. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Curcumin increases the sensitivity of Paclitaxel-resistant NSCLC cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction.

Science.gov (United States)

Lu, Yimin; Wang, Jun; Liu, Lei; Yu, Lequn; Zhao, Nian; Zhou, Xingju; Lu, Xudong

2017-04-01

Non-small-cell lung cancer is one of the most lethal cancers in the worldwide. Although Paclitaxel-based combinational therapies have long been used as a standard treatment in aggressive non-small-cell lung cancers, Paclitaxel resistance emerges as a major clinical problem. It has been demonstrated that Curcumin from Curcuma longa as a traditional Chinese medicine can inhibit cancer cell proliferation. However, the role of Curcumin in Paclitaxel-resistant non-small-cell lung cancer cells is not clear. In this study, we investigated the effect of Curcumin on the Paclitaxel-resistant non-small-cell lung cancer cells and found that Curcumin treatment markedly increased the sensitivity of Paclitaxel-resistant non-small-cell lung cancer cells to Paclitaxel. Mechanically, the study revealed that Curcumin could reduce the expression of metastasis-associated gene 1 (MTA1) gene through upregulation of microRNA-30c in Paclitaxel-resistant non-small-cell lung cancer cells. During the course, MTA1 reduction sensitized Paclitaxel-resistant non-small-cell lung cancer cells and enhanced the effect of Paclitaxel. Taken together, our studies indicate that Curcumin increases the sensitivity of Paclitaxel-resistant non-small-cell lung cancer cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction. Curcumin might be a potential adjuvant for non-small-cell lung cancer patients during Paclitaxel treatment.

Resistance and the management of complicated skin and skin structure infections: the role of ceftobiprole

Directory of Open Access Journals (Sweden)

April Barbour

2010-09-01

Full Text Available April Barbour1, Hartmut Derendorf21GlaxoSmithKline, King of Prussia, PA, USA; 2Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USAAbstract: Antimicrobial resistant bacteria are an increasing concern due to the resulting increase in morbidity, mortality, and health-care costs associated with the administration of inadequate or delayed antimicrobial therapy. The implications of inadequate antimicrobial therapy in complicated skin and skin structure infections (cSSSIs have gained more attention recently, most likely due to the recent emergence of community-acquired methicillin resistant Staphylococcus aureus (MRSA and the already high prevalence of MRSA in the nosocomial setting. Due to the continuous threat of resistance arising and the limitations of currently available agents for the treatment of cSSSIs, it is necessary to develop new antimicrobials for this indication. Ceftobiprole medocaril, the prodrug of ceftobiprole, is a parental investigational cephalosporin for the treatment of cSSSIs displaying a wide-spectrum of activity against both Gram-positive and Gram-negative species, including MRSA. Ceftobiprole displays noncomplex linear pharmacokinetics, is eliminated primarily by glomerular filtration, and distributes to extracellular fluid. Additionally, it has been shown that the extent of distribution to the site of action with regard to cSSSIs, ie, the extracellular space fluid of subcutaneous adipose tissue and skeletal muscle, is expected to be efficacious, as free concentrations meet efficacy targets for most pathogens. Similar to other beta-lactams, it displays an excellent safety and tolerability profile with the primary adverse events being dysgeusia in healthy volunteers, resulting from the conversion of the prodrug to the active, and nausea in patients. Ceftobiprole has demonstrated noninferiority in two large-scale pivotal studies comparing it to vancomycin, clinical cure rates 93.3% vs

42 CFR 93.316 - Completing the research misconduct process.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Completing the research misconduct process. 93.316... POLICIES ON RESEARCH MISCONDUCT Responsibilities of Institutions The Institutional Investigation § 93.316 Completing the research misconduct process. (a) ORI expects institutions to carry inquiries and...

Salivary testosterone and immunoglobulin A were increased by resistance training in adults with Down syndrome

Directory of Open Access Journals (Sweden)

G. Fornieles

2014-04-01

Full Text Available This study was designed to assess the influence of resistance training on salivary immunoglobulin A (IgA levels and hormone profile in sedentary adults with Down syndrome (DS. A total of 40 male adults with DS were recruited for the trial through different community support groups for people with intellectual disabilities. All participants had medical approval for participation in physical activity. Twenty-four adults were randomly assigned to perform resistance training in a circuit with six stations, 3 days per week for 12 weeks. Training intensity was based on functioning in the eight-repetition maximum (8RM test for each exercise. The control group included 16 age-, gender-, and BMI-matched adults with DS. Salivary IgA, testosterone, and cortisol levels were measured by ELISA. Work task performance was assessed using the repetitive weighted-box-stacking test. Resistance training significantly increased salivary IgA concentration (P=0.0120; d=0.94 and testosterone levels (P=0.0088; d=1.57 in the exercising group. Furthermore, it also improved work task performance. No changes were seen in the controls who had not exercised. In conclusion, a short-term resistance training protocol improved mucosal immunity response as well as salivary testosterone levels in sedentary adults with DS.

TIMP-1 increases expression and phosphorylation of proteins associated with drug resistance in breast cancer cells

DEFF Research Database (Denmark)

Hekmat, Omid; Munk, Stephanie; Fogh, Louise

2013-01-01

may explain the resistance phenotype to topoisomerase inhibitors that was observed in cells with high TIMP-1 levels. Pathway analysis showed an enrichment of proteins from functional categories such as apoptosis, cell cycle, DNA repair, transcription factors, drug targets and proteins associated......Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a protein with a potential biological role in drug resistance. To elucidate the unknown molecular mechanisms underlying the association between high TIMP-1 levels and increased chemotherapy resistance, we employed SILAC-based quantitative mass...... spectrometry to analyze global proteome and phosphoproteome differences of MCF-7 breast cancer cells expressing high or low levels of TIMP-1. In TIMP-1 high expressing cells, 312 proteins and 452 phosphorylation sites were up-regulated. Among these were the cancer drug targets topoisomerase 1, 2A and 2B, which...

Relationship between increased serum tumor necrosis factor levels and insulin resistance in patients with essential hypertension

International Nuclear Information System (INIS)

Wang Weimin; Li Jinliang; Huang Yongqiang

2010-01-01

Objective: To investigate the relationship between serum tumor necrosis factor-α (TNF-α) levels and insulin resistance (IR) in patients with essential by pertension. Methods: Serum TNF-α and free insulin (fINS)levels were measured with RIA in 41 patients with essential hypertension and 38 controls. Insulin resistance was calculated with insulin resistance index (HOMA-IR). Results: The serum TNF-α levels were significantly higher in patients with essential hypertension than those in the controls (P<0.001). The HOMA-IR was also significantly higher in hypertension group than that in controls (P<0.001). Serum TNF-α levels was positively correlated with BMI, HOMA-IR and SBP both in hypertension group and control group (P<0.05). Conclusion: Serum TNF-α level was increased in hypertensive patients and positively correlated with obesity and IR. (authors)

9 CFR 93.102 - Ports designated for the importation of birds.

Science.gov (United States)

2010-01-01

... of birds. 93.102 Section 93.102 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PRODUCTS IMPORTATION OF CERTAIN ANIMALS, BIRDS, FISH, AND POULTRY, AND CERTAIN ANIMAL, BIRD, AND POULTRY PRODUCTS; REQUIREMENTS FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Birds § 93.102 Ports designated for...

40 CFR 81.93 - Hampton Roads Intrastate Air Quality Control Region.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 17 2010-07-01 2010-07-01 false Hampton Roads Intrastate Air Quality Control Region. 81.93 Section 81.93 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Quality Control Regions § 81.93 Hampton Roads Intrastate Air Quality Control Region. The Metropolitan...

Increasing the resistance of common bean to white mold through recurrent selection

Directory of Open Access Journals (Sweden)

Monik Evelin Leite

2016-02-01

Full Text Available ABSTRACT White mold, caused by Sclerotinea sclerotiorum (Lib. de Bary is one of the most important diseases of the common bean (Phaseolus vulgaris L. worldwide. Physiological resistance and traits related to disease avoidance such as architecture contribute to field resistance. The aim of this study was to verify the efficiency of recurrent selection in physiological resistance to white mold, “Carioca” grain type and upright habit in common bean. Thirteen common bean lines with partial resistance to white mold were intercrossed by means of a circulant diallel table, and seven recurrent selection cycles were obtained. Of these cycles, progenies of the S0:1, S0:2 and S0:3 generations of cycles III, IV, V and VI were evaluated. The best (8 to 10 progenies of the seven cycles were also evaluated, in two experiments, one in the greenhouse and one in the field. Lattice and/or randomized block experimental designs were used. The traits evaluated were: resistance to white mold by the straw test method, growth habit and grain type. The most resistant progenies were selected based on the average score of resistance to white mold. Subsequently, they were evaluated with regard to grain type and growth habit. Recurrent selection allowed for genetic progress of about 11 % per year for white mold resistance and about 15 % per year for the plant architecture. There was no gain among cycles for grain type. Progeny selection and recurrent selection were efficient for obtaining progenies with a high level of resistance to white mold with “Carioca” grain type and upright habit.

Brain Insulin Signaling Is Increased in Insulin-Resistant States and Decreases in FOXOs and PGC-1α and Increases in Aβ1–40/42 and Phospho-Tau May Abet Alzheimer Development

Science.gov (United States)

Sajan, Mini; Hansen, Barbara; Ivey, Robert; Sajan, Joshua; Ari, Csilla; Song, Shijie; Braun, Ursula; Leitges, Michael; Farese-Higgs, Margaret

2016-01-01

Increased coexistence of Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) suggests that insulin resistance abets neurodegenerative processes, but linkage mechanisms are obscure. Here, we examined insulin signaling factors in brains of insulin-resistant high-fat–fed mice, ob/ob mice, mice with genetically impaired muscle glucose transport, and monkeys with diet-dependent long-standing obesity/T2DM. In each model, the resting/basal activities of insulin-regulated brain protein kinases, Akt and atypical protein kinase C (aPKC), were maximally increased. Moreover, Akt hyperactivation was accompanied by hyperphosphorylation of substrates glycogen synthase kinase-3β and mammalian target of rapamycin and FOXO proteins FOXO1, FOXO3A, and FOXO4 and decreased peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α) expression. Akt hyperactivation was confirmed in individual neurons of anterocortical and hippocampal regions that house cognition/memory centers. Remarkably, β-amyloid (Aβ1–40/42) peptide levels were as follows: increased in the short term by insulin in normal mice, increased basally in insulin-resistant mice and monkeys, and accompanied by diminished amyloid precursor protein in monkeys. Phosphorylated tau levels were increased in ob/ob mice and T2DM monkeys. Importantly, with correction of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, brain insulin signaling normalized. As FOXOs and PGC-1α are essential for memory and long-term neuronal function and regeneration and as Aβ1–40/42 and phospho-tau may increase interneuronal plaques and intraneuronal tangles, presently observed aberrations in hyperinsulinemic states may participate in linking insulin resistance to AD. PMID:26895791

Calmodulin-like protein 3 is an estrogen receptor alpha coregulator for gene expression and drug response in a SNP, estrogen, and SERM-dependent fashion.

Science.gov (United States)

Qin, Sisi; Ingle, James N; Liu, Mohan; Yu, Jia; Wickerham, D Lawrence; Kubo, Michiaki; Weinshilboum, Richard M; Wang, Liewei

2017-08-18

We previously performed a case-control genome-wide association study in women treated with selective estrogen receptor modulators (SERMs) for breast cancer prevention and identified single nucleotide polymorphisms (SNPs) in ZNF423 as potential biomarkers for response to SERM therapy. The ZNF423rs9940645 SNP, which is approximately 200 bp away from the estrogen response elements, resulted in the SNP, estrogen, and SERM-dependent regulation of ZNF423 expression and, "downstream", that of BRCA1. Electrophoretic mobility shift assay-mass spectrometry was performed to identify proteins binding to the ZNF423 SNP and coordinating with estrogen receptor alpha (ERα). Clustered, regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing was applied to generate ZR75-1 breast cancer cells with different ZNF423 SNP genotypes. Both cultured cells and mouse xenograft models with different ZNF423 SNP genotypes were used to study the cellular responses to SERMs and poly(ADP-ribose) polymerase (PARP) inhibitors. We identified calmodulin-like protein 3 (CALML3) as a key sensor of this SNP and a coregulator of ERα, which contributes to differential gene transcription regulation in an estrogen and SERM-dependent fashion. Furthermore, using CRISPR/Cas9-engineered ZR75-1 breast cancer cells with different ZNF423 SNP genotypes, striking differences in cellular responses to SERMs and PARP inhibitors, alone or in combination, were observed not only in cells but also in a mouse xenograft model. Our results have demonstrated the mechanism by which the ZNF423 rs9940645 SNP might regulate gene expression and drug response as well as its potential role in achieving more highly individualized breast cancer therapy.

49 CFR 218.93 - Definitions.

Science.gov (United States)

2010-10-01

... § 214.353 of this chapter for the purpose of establishing on-track safety for roadway work groups... TRANSPORTATION RAILROAD OPERATING PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.93 Definitions... classification yard where rolling equipment is placed and made ready for an outgoing train movement. Employee...

45 CFR 2552.93 - What are grants management requirements?

Science.gov (United States)

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false What are grants management requirements? 2552.93... AND COMMUNITY SERVICE FOSTER GRANDPARENT PROGRAM Application and Fiscal Requirements § 2552.93 What are grants management requirements? What rules govern a sponsor's management of grants? (a) A sponsor...

The radiological spectrum of pulmonary multidrug-resistant tuberculosis: in HIV-Negative patients

International Nuclear Information System (INIS)

Zahirifard, S.; Amiri, M.V.; Bakhshayesh Karam, M.; Mirsaeidi, S.M.; Ehsanpour, A.; Masjedi, M.R.

2003-01-01

Background: Multidrug-resistant tuberculosis is a major worldwide health problem. In countries where tuberculosis is of moderate to high prevalence, the issue of Multidrug-resistant tuberculosis carries significant importance. Multidrug-resistant tuberculosis, similar to drug-sensitive tuberculosis, is contagious. Meanwhile its treatment is not only more difficult but also more expensive with lower success rates. Regarding clinical findings, there is no significant difference between Multidrug-resistant tuberculosis and drug-sensitive tuberculosis. Therefore determination of characteristic radiological findings in cases of Multidrug-resistant tuberculosis might be of help in early detection, and hence appropriate management of this disease condition. Objective: To explain the radiological spectrum of pulmonary Multidrug-resistant tuberculosis. Patients and methods: We retrospectively evaluated the radiographic images of 35 patients with clinically-and microbiologically- proven Multidrug-resistant tuberculosis admitted to our tertiary-care tuberculosis unit over a period of 13 months. The latest chest x-ray of all patients and the conventional chest CT scan without contrast of 15 patients were reviewed by three expert radiologists who rendered consensus opinion. Results: Of the 35 patients with imaging studies, 23 (66%) were male and 12 (34%) were female. The mean±SD age of participants was 38.2±17.3 (range: 16-20) years. 33 patients were known as secondary and only 2 had primary Multidrug-resistant tuberculosis. Chest radiography revealed cavitary lesion in 80% pulmonary infiltration in 89% and nodules in 80% of the cases. Pleurisy was the rarest finding observed in only 5 (14%) patients. All of 15 chest CT scans revealed cavitation, 93% of which were bilateral and multiple. Pleural involvement was seen in 93% of patients. Conclusion: Presence of multiple cavities, especially in both lungs, nodular and infiltrative lesions, and pleural effusion are main features

The small molecule triclabendazole decreases the intracellular level of cyclic AMP and increases resistance to stress in Saccharomyces cerevisiae.

Directory of Open Access Journals (Sweden)

Yong Joo Lee

Full Text Available The Ras-adenylyl cyclase-protein kinase A nutrient-sensing pathway controls metabolism, proliferation and resistance to stress in Saccharomyces cerevisiae. The genetic disruption of this pathway increases resistance to a variety of stresses. We show here that the pharmacological inhibition of this pathway by the drug triclabendazole increases resistance to oxidants, heat stress and extends the chronological life. Evidence is presented that triclabendazole decreases the intracellular level of cyclic AMP by inhibiting adenylyl cyclase and triggers the parallel rapid translocation of the stress-resistance transcription factor Msn2 from the cytosol into the nucleus, as deduced from experiments employing a strain in which MSN2 is replaced with MSN2-GFP (GFP, green fluorescent protein. Msn2 and Msn4 are responsible for activating the transcription of numerous genes that encode proteins that protect cells from stress. The results are consistent with triclabendazole either inhibiting the association of Ras with adenylyl cyclase or directly inhibiting adenylyl cyclase, which in turn triggers Msn2/4 to enter the nucleus and activate stress-responsible element gene expression.

42 CFR 93.401 - Interaction with other offices and interim actions.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Interaction with other offices and interim actions. 93.401 Section 93.401 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Human Services General Information § 93.401 Interaction with other offices and interim actions. (a) ORI...

27 CFR 6.93 - Combination packaging.

Science.gov (United States)

2010-04-01

..., DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Exceptions § 6.93 Combination packaging. The act by an industry member of packaging and distributing distilled spirits, wine, or malt beverages in combination...

45 CFR 2551.93 - What are grants management requirements?