Candidate hippocampal biomarkers of susceptibility and resilience to stress in a rat model of depression

DEFF Research Database (Denmark)

Henningsen, Kim; Palmfeldt, Johan; Christiansen, Sofie Friis

2012-01-01

-scale proteomics was used to map hippocampal protein alterations in different stress states. Membrane proteins were successfully captured by two-phase separation and peptide based proteomics. Using iTRAQ labeling coupled with mass spectrometry, more than 2000 proteins were quantified and 73 proteins were found......Susceptibility to stress plays a crucial role in the development of psychiatric disorders such as unipolar depression and post-traumatic stress disorder. In the present study the chronic mild stress rat model of depression was used to reveal stress-susceptible and stress-resilient rats. Large...... to be differentially expressed. Stress susceptibility was associated with increased expression of a sodium-channel protein (SCN9A) currently investigated as a potential antidepressant target. Differential protein profiling also indicated stress susceptibility to be associated with deficits in synaptic vesicle release...

Presynaptic plasticity as a hallmark of rat stress susceptibility and antidepressant response.

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Jose Luis Nieto-Gonzalez

Full Text Available Two main questions are important for understanding and treating affective disorders: why are certain individuals susceptible or resilient to stress, and what are the features of treatment response and resistance? To address these questions, we used a chronic mild stress (CMS rat model of depression. When exposed to stress, a fraction of rats develops anhedonic-like behavior, a core symptom of major depression, while another subgroup of rats is resilient to CMS. Furthermore, the anhedonic-like state is reversed in about half the animals in response to chronic escitalopram treatment (responders, while the remaining animals are resistant (non-responder animals. Electrophysiology in hippocampal brain slices was used to identify a synaptic hallmark characterizing these groups of animals. Presynaptic properties were investigated at GABAergic synapses onto single dentate gyrus granule cells. Stress-susceptible rats displayed a reduced probability of GABA release judged by an altered paired-pulse ratio of evoked inhibitory postsynaptic currents (IPSCs (1.48 ± 0.25 compared with control (0.81 ± 0.05 and stress-resilient rats (0.78 ± 0.03. Spontaneous IPSCs (sIPSCs occurred less frequently in stress-susceptible rats compared with control and resilient rats. Finally, a subset of stress-susceptible rats responding to selective serotonin reuptake inhibitor (SSRI treatment showed a normalization of the paired-pulse ratio (0.73 ± 0.06 whereas non-responder rats showed no normalization (1.2 ± 0.2. No changes in the number of parvalbumin-positive interneurons were observed. Thus, we provide evidence for a distinct GABAergic synaptopathy which associates closely with stress-susceptibility and treatment-resistance in an animal model of depression.

Genetic susceptibility markers for a breast-colorectal cancer phenotype: Exploratory results from genome-wide association studies

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Joon, Aron; Brewster, Abenaa M.; Chen, Wei V.; Eng, Cathy; Shete, Sanjay; Casey, Graham; Schumacher, Fredrick; Lin, Yi; Harrison, Tabitha A.; White, Emily; Ahsan, Habibul; Andrulis, Irene L.; Whittemore, Alice S.; Ko Win, Aung; Schmidt, Daniel F.; Kapuscinski, Miroslaw K.; Ochs-Balcom, Heather M.; Gallinger, Steven; Jenkins, Mark A.; Newcomb, Polly A.; Lindor, Noralane M.; Peters, Ulrike; Amos, Christopher I.; Lynch, Patrick M.

2018-01-01

Background Clustering of breast and colorectal cancer has been observed within some families and cannot be explained by chance or known high-risk mutations in major susceptibility genes. Potential shared genetic susceptibility between breast and colorectal cancer, not explained by high-penetrance genes, has been postulated. We hypothesized that yet undiscovered genetic variants predispose to a breast-colorectal cancer phenotype. Methods To identify variants associated with a breast-colorectal cancer phenotype, we analyzed genome-wide association study (GWAS) data from cases and controls that met the following criteria: cases (n = 985) were women with breast cancer who had one or more first- or second-degree relatives with colorectal cancer, men/women with colorectal cancer who had one or more first- or second-degree relatives with breast cancer, and women diagnosed with both breast and colorectal cancer. Controls (n = 1769), were unrelated, breast and colorectal cancer-free, and age- and sex- frequency-matched to cases. After imputation, 6,220,060 variants were analyzed using the discovery set and variants associated with the breast-colorectal cancer phenotype at Pcolorectal cancer phenotype in the discovery and replication data (most significant; rs7430339, Pdiscovery = 1.2E-04; rs7429100, Preplication = 2.8E-03). In meta-analysis of the discovery and replication data, the most significant association remained at rs7429100 (P = 1.84E-06). Conclusion The results of this exploratory analysis did not find clear evidence for a susceptibility locus with a pleiotropic effect on hereditary breast and colorectal cancer risk, although the suggestive association of genetic variation in the region of ROBO1, a potential tumor suppressor gene, merits further investigation. PMID:29698419

Disruption of the GDP-mannose synthesis pathway in Streptomyces coelicolor results in antibiotic hyper-susceptible phenotypes.

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Howlett, Robert; Anttonen, Katri; Read, Nicholas; Smith, Margaret C M

2018-04-01

Actinomycete bacteria use polyprenol phosphate mannose as a lipid linked sugar donor for extra-cytoplasmic glycosyl transferases that transfer mannose to cell envelope polymers, including glycoproteins and glycolipids. We showed recently that strains of Streptomyces coelicolor with mutations in the gene ppm1 encoding polyprenol phosphate mannose synthase were both resistant to phage φC31 and have greatly increased susceptibility to antibiotics that mostly act on cell wall biogenesis. Here we show that mutations in the genes encoding enzymes that act upstream of Ppm1 in the polyprenol phosphate mannose synthesis pathway can also confer phage resistance and antibiotic hyper-susceptibility. GDP-mannose is a substrate for Ppm1 and is synthesised by GDP-mannose pyrophosphorylase (GMP; ManC) which uses GTP and mannose-1-phosphate as substrates. Phosphomannomutase (PMM; ManB) converts mannose-6-phosphate to mannose-1-phosphate. S. coelicolor strains with knocked down GMP activity or with a mutation in sco3028 encoding PMM acquire phenotypes that resemble those of the ppm1 - mutants i.e. φC31 resistant and susceptible to antibiotics. Differences in the phenotypes of the strains were observed, however. While the ppm1 - strains have a small colony phenotype, the sco3028 :: Tn5062 mutants had an extremely small colony phenotype indicative of an even greater growth defect. Moreover we were unable to generate a strain in which GMP activity encoded by sco3039 and sco4238 is completely knocked out, indicating that GMP is also an important enzyme for growth. Possibly GDP-mannose is at a metabolic branch point that supplies alternative nucleotide sugar donors.

Growth, carcase and meat characteristics of stress susceptible and ...

African Journals Online (AJOL)

Growth, carcase and meat characteristics of stress susceptible and stress resistant. South African Landrace gilts. P.H. Heinze*. Animal and Dairy Science Research Institute, Private Bag X2, Irene, 1675Republic of South Africa. G. Mitchell. Department of Physiology, Medical School, University of the Witwatersrand, York ...

13 reasons why the brain is susceptible to oxidative stress

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James Nathan Cobley

2018-05-01

Full Text Available The human brain consumes 20% of the total basal oxygen (O2 budget to support ATP intensive neuronal activity. Without sufficient O2 to support ATP demands, neuronal activity fails, such that, even transient ischemia is neurodegenerative. While the essentiality of O2 to brain function is clear, how oxidative stress causes neurodegeneration is ambiguous. Ambiguity exists because many of the reasons why the brain is susceptible to oxidative stress remain obscure. Many are erroneously understood as the deleterious result of adventitious O2 derived free radical and non-radical species generation. To understand how many reasons underpin oxidative stress, one must first re-cast free radical and non-radical species in a positive light because their deliberate generation enables the brain to achieve critical functions (e.g. synaptic plasticity through redox signalling (i.e. positive functionality. Using free radicals and non-radical derivatives to signal sensitises the brain to oxidative stress when redox signalling goes awry (i.e. negative functionality. To advance mechanistic understanding, we rationalise 13 reasons why the brain is susceptible to oxidative stress. Key reasons include inter alia unsaturated lipid enrichment, mitochondria, calcium, glutamate, modest antioxidant defence, redox active transition metals and neurotransmitter auto-oxidation. We review RNA oxidation as an underappreciated cause of oxidative stress. The complex interplay between each reason dictates neuronal susceptibility to oxidative stress in a dynamic context and neural identity dependent manner. Our discourse sets the stage for investigators to interrogate the biochemical basis of oxidative stress in the brain in health and disease.

Neuronal substrates underlying stress resilience and susceptibility in rats

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Febbraro, Fabia; Svenningsen, Katrine; Thao Phuong Tran

2017-01-01

attention has been devoted to understand resiliency to stress. The aim of the present study was to identify changes in neuronal activity, associated with stress-resilient and stress-susceptible chronic mild stress endophenotypes, by examining c-Fos expression in 13 different brain areas. Changes in c...... responses was done by semi-automated profile counting procedures and design-based stereology. RESULTS: Exposure to chronic mild stress significantly altered c-Fos expression in a total of 6 out of 13 investigated areas. Chronic mild stress was found to suppress the c-Fos response within the magnocellular...

Genotyping using whole-genome sequencing is a realistic alternative to surveillance based on phenotypic antimicrobial susceptibility testing

DEFF Research Database (Denmark)

Zankari, Ea; Hasman, Henrik; Kaas, Rolf Sommer

2013-01-01

-genome sequencing (WGS) may soon be within reach even for routine surveillance and clinical diagnostics. The aim of this study was to evaluate WGS as a routine tool for surveillance of antimicrobial resistance compared with current phenotypic procedures. Methods: Antimicrobial susceptibility tests were performed...... to the categorizing of isolates as resistant and 2569 as susceptible. Seven cases of disagreement between tested and predicted susceptibility were observed, six of which were related to spectinomycin resistance in Escherichia coli. Correlation between MLST type and resistance profiles was only observed in Salmonella...

Machine Learning for High-Throughput Stress Phenotyping in Plants.

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Singh, Arti; Ganapathysubramanian, Baskar; Singh, Asheesh Kumar; Sarkar, Soumik

2016-02-01

Advances in automated and high-throughput imaging technologies have resulted in a deluge of high-resolution images and sensor data of plants. However, extracting patterns and features from this large corpus of data requires the use of machine learning (ML) tools to enable data assimilation and feature identification for stress phenotyping. Four stages of the decision cycle in plant stress phenotyping and plant breeding activities where different ML approaches can be deployed are (i) identification, (ii) classification, (iii) quantification, and (iv) prediction (ICQP). We provide here a comprehensive overview and user-friendly taxonomy of ML tools to enable the plant community to correctly and easily apply the appropriate ML tools and best-practice guidelines for various biotic and abiotic stress traits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Oxidative stress and hemoglobin-cholesterol adduct in renal patients with different LDL phenotypes.

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Miljkovic, Milica; Kotur-Stevuljevic, Jelena; Stefanovic, Aleksandra; Zeljkovic, Aleksandra; Vekic, Jelena; Gojkovic, Tamara; Bogavac-Stanojevic, Natasa; Nikolic, Milan; Simic-Ogrizovic, Sanja; Spasojevic-Kalimanovska, Vesna; Jelic-Ivanovic, Zorana

2016-10-01

Unfavorable lipid profile is a major risk factor for cardiovascular disease in renal pathology. In this study, we compared chronic renal patients and healthy controls with different LDL phenotypes (A or B) in respect of various biochemical parameters related to cardiovascular disease. Oxidative stress and anti-oxidative defense parameters [thiobarbituric acid-reacting substances (TBARS), total oxidative status (TOS), total anti-oxidative status (TAS), total protein sulfhydryl (-SH) groups], as well as red blood cell cholesterol distribution were assessed in 40 renal patients and 40 control subjects by standardized assays. LDL particle diameters were determined by polyacrylamide gradient gel electrophoresis. LDL particles are subdivided according to their size into large LDL A phenotype (diameter >25.5 nm) and small LDL B phenotype (diameter ≤25.5 nm). Renal patients with LDL A phenotype had increased oxidative stress (TOS: p LDL phenotype. A notable decrease in hemoglobin-cholesterol adduct was detected in patients with LDL A phenotype (p LDL B phenotype (p LDL B phenotype was characterized with increased TBARS (p LDL A phenotype in control group. Increased oxidative stress, decreased anti-oxidative defense followed with unfavorable changes in hemoglobin-cholesterol binding capacity, could have important influence on cardiovascular disease risk in renal patients regardless of LDL phenotype.

Response of Microcystis to copper stress - Do phenotypes of Microcystis make a difference in stress tolerance?

International Nuclear Information System (INIS)

Wu Zhongxing; Gan Nanqin; Huang Qun; Song Lirong

2007-01-01

To elucidate the role of phenotype in stress-tolerant bloom-forming cyanobacterium Microcystis, two phenotypes of M. aeruginosa - unicellular and colonial strains were selected to investigate how they responded to copper stress. Flow cytometry (FCM) examination indicated that the percents of viable cells in unicellular and colonial Microcystis were 1.92-2.83% and 72.3-97.51%, respectively, under 0.25 mg l -1 copper sulfate treatment for 24 h. Upon exposure to 0.25 mg l -1 copper sulfate, the activities of antioxidative enzyme, such as superoxide dismutase (SOD) and catalase (CAT), were significantly increased in colonial Microcystis compared to unicellular Microcystis. Meanwhile, the values of the photosynthetic parameters (F v /F m , ETR max , and oxygen evolution rate) decreased more rapidly in unicellular Microcystis than in colonial Microcystis. The results indicate that colonial Microcystis has a higher endurance to copper than unicellular Microcystis. This suggests that the efficient treatment concentration of copper sulfate as algaecides will be dependent on the phenotypes of Microcystis. - Stress-resistance ability in Microcystis is influenced by its phenotypes

Phenotypic heterogeneity in a bacteriophage population only appears as stress-induced mutagenesis.

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Yosef, Ido; Edgar, Rotem; Qimron, Udi

2016-11-01

Stress-induced mutagenesis has been studied in cancer cells, yeast, bacteria, and archaea, but not in viruses. In a recent publication, we present a bacteriophage model showing an apparent stress-induced mutagenesis. We show that the stress does not drive the mutagenesis, but only selects the fittest mutants. The mechanism underlying the observed phenomenon is a phenotypic heterogeneity that resembles persistence of the viral population. The new findings, the background for the ongoing debate on stress-induced mutagenesis, and the phenotypic heterogeneity underlying a novel phage infection strategy are discussed in this short manuscript.

Effects of thermal aging and stress triaxiality on PWSCC initiation susceptibility of nickel-based Alloy 600

Energy Technology Data Exchange (ETDEWEB)

Yoo, Seung Chang; Choi, Kyoung Joon; Kim, Tae Ho; Kim, Ji Hyun [Dept. of Nuclear Science and Engineering, School of Mechanical and Nuclear Engineering, Ulsan National Institute of Science and Technology, Ulsan (Korea, Republic of)

2016-10-15

In present study, effects of thermal aging and triaxial stress were investigated in terms of primary water stress corrosion cracking susceptibility. The thermal aging was applied via heat treatment at 400°C and triaxial stress was applied via notched tensile test specimen. The crack initiation time of each specimen were then measured by direct current potential drop method during slow strain rate test at primary water environment. Alloys with 10 years thermal aging exhibited the highest susceptibility to stress corrosion cracking and asreceived specimen shows lowest susceptibility. The trend was different with triaxial stress applied; 20 years thermal aging specimen shows highest susceptibility and as-received specimen shows lowest. It would be owing to change of precipitate morphology during thermal aging and different activated slip system in triaxial stress state.

Murine adipose tissue-derived stromal cell apoptosis and susceptibility to oxidative stress in vitro are regulated by genetic background.

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Robert Pazdro

Full Text Available Adipose tissue-derived stromal cells (ADSCs are of interest for regenerative medicine as they are isolated easily and can differentiate into multiple cell lineages. Studies of their in vitro proliferation, survival, and differentiation are common; however, genetic effects on these phenotypes remain unknown. To test if these phenotypes are genetically regulated, ADSCs were isolated from three genetically diverse inbred mouse strains--C57BL/6J (B6, BALB/cByJ (BALB, and DBA/2J (D2--in which genetic regulation of hematopoietic stem function is well known. ADSCs from all three strains differentiated into osteogenic and chondrogenic lineages in vitro. ADSCs from BALB grew least well in vitro, probably due to apoptotic cell death after several days in culture. BALB ADSCs were also the most susceptible to the free radical inducers menadione and H2O2. ADSCs from the three possible F1 hybrids were employed to further define genetic regulation of ADSC phenotypes. D2, but not B6, alleles stimulated ADSC expansion in BALB cells. In contrast, B6, but not D2, alleles rescued BALB H2O2 resistance. We conclude that low oxidative stress resistance does not limit BALB ADSC growth in vitro, as these phenotypes are genetically regulated independently. In addition, ADSCs from these strains are an appropriate model system to investigate genetic regulation of ADSC apoptosis and stress resistance in future studies. Such investigations are essential to optimize cell expansion and differentiation and thus, potential for regenerative medicine.

Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD.

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Robert P Young

2011-02-01

Full Text Available Epidemiological studies show that approximately 20-30% of chronic smokers develop chronic obstructive pulmonary disease (COPD while 10-15% develop lung cancer. COPD pre-exists lung cancer in 50-90% of cases and has a heritability of 40-77%, much greater than for lung cancer with heritability of 15-25%. These data suggest that smokers susceptible to COPD may also be susceptible to lung cancer. This study examines the association of several overlapping chromosomal loci, recently implicated by GWA studies in COPD, lung function and lung cancer, in (n = 1400 subjects sub-phenotyped for the presence of COPD and matched for smoking exposure. Using this approach we show; the 15q25 locus confers susceptibility to lung cancer and COPD, the 4q31 and 4q22 loci both confer a reduced risk to both COPD and lung cancer, the 6p21 locus confers susceptibility to lung cancer in smokers with pre-existing COPD, the 5p15 and 1q23 loci both confer susceptibility to lung cancer in those with no pre-existing COPD. We also show the 5q33 locus, previously associated with reduced FEV(1, appears to confer susceptibility to both COPD and lung cancer. The 6p21 locus previously linked to reduced FEV(1 is associated with COPD only. Larger studies will be needed to distinguish whether these COPD-related effects may reflect, in part, associations specific to different lung cancer histology. We demonstrate that when the "risk genotypes" derived from the univariate analysis are incorporated into an algorithm with clinical variables, independently associated with lung cancer in multivariate analysis, modest discrimination is possible on receiver operator curve analysis (AUC = 0.70. We suggest that genetic susceptibility to lung cancer includes genes conferring susceptibility to COPD and that sub-phenotyping with spirometry is critical to identifying genes underlying the development of lung cancer.

Distinguishing differential susceptibility from diathesis-stress: recommendations for evaluating interaction effects.

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Roisman, Glenn I; Newman, Daniel A; Fraley, R Chris; Haltigan, John D; Groh, Ashley M; Haydon, Katherine C

2012-05-01

This report describes the state of the art in distinguishing data generated by differential susceptibility from diathesis-stress models. We discuss several limitations of existing practices for probing interaction effects and offer solutions that are designed to better differentiate differential susceptibility from diathesis-stress models and quantify their corresponding implications. In addition, we demonstrate the utility of these methods by revisiting published evidence suggesting that temperamental difficulty serves as a marker of enhanced susceptibility to early maternal caregiving across a range of outcome domains in the NICHD Study of Early Child Care and Youth Development. We find that, with the exception of mother reports of psychopathology, there is consistent evidence in the Study of Early Child Care and Youth Development that the predictive significance of early sensitivity is moderated by difficult temperament over time. However, differential susceptibility effects emerged primarily for teacher reports of academic skills, social competence, and symptomatology. In contrast, effects more consistent with the diathesis-stress model were obtained for mother reports of social skills and objective tests of academic skills. We conclude by discussing the value of the application of this work to the next wave of Gene × Environment studies focused on early caregiving experiences.

Effect of tensile stress on the 3D reversible and irreversible differential magnetic susceptibilities

International Nuclear Information System (INIS)

Mao, Weihua; Atherton, David L.

2001-01-01

Magnetic hysteresis loops in three orthogonal directions are measured for a line pipe steel sample while the external magnetic field is applied in a direction perpendicular to the tensile stress direction. The total magnetization vector is calculated. This tends to the stress direction when tensile stress is applied. The reversible and irreversible differential magnetic susceptibilities are derived. It is found that the susceptibilities in all three directions are enhanced with increasing tensile stress, although the increase in the stress direction is much larger than in the other directions. [copyright] 2001 American Institute of Physics

Susceptibility to Stress Corrosion Cracking of 254SMO SS

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De Micheli Lorenzo

2002-01-01

Full Text Available The susceptibility to stress corrosion cracking (SCC of solubilized and sensitized 254SMO SS was studied in sodium chloride, and sodium fluoride solutions at 80 °C and sulfuric acid solutions in presence of sodium chloride at 25 °C. The influence of salt concentration, pH values and the addition of thiosulfate was examined. The susceptibility to SCC was evaluated by Slow Strain Rate Tests (SSRT, at 1.5 x 10-6 s-1 strain rate. The behavior of 254SMO was compared to those of AISI 316L SS and Hastelloy C276. 254SMO showed an excellent resistance to SCC in all conditions, except in the more acidic solutions (pH <= 1 where, in the sensitized conditions, intergranular stress corrosion cracking occurred.

[Emotional stress-induced Shanghuo syndrome increases disease susceptibility].

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Zhu, Si-Rui; Luo, Xiang; Li, Yi-Fang; Hiroshi, Kurihara; He, Rong-Rong

2018-04-01

Shanghuo(excessive internal heat) is a special organic state based on the concept of traditional Chinese medicine(TCM), commonly known as the abnormal heating syndrome of body in folks. With the acceleration of modern life rhythm and the increase of the social competition pressure, emotional stress has become an important cause for the spread of Shanghuo symptoms. What's more, Shanghuo can impact the body physiological functions to cause the onset, recurrence and progression of common diseases, harming the health of the body. According to the long-term research findings, the author found that Shanghuo referred to the imbalance of multiple physiological functions, such as nerve, immunity and metabolism, caused by emotional stress. "Shanghuo" is not a disease itself, but it can increase the susceptibility to a variety of diseases. This study reviewed the traditional medicine theory and the modern medical studies, and explored the relevance and correlation mechanisms between the Shanghuo symptoms and disease susceptibility, so as to provide a reference to improve the state of sub-health and prevent or treat modern diseases. Copyright© by the Chinese Pharmaceutical Association.

Genetic and Computational Approaches for Studying Plant Development and Abiotic Stress Responses Using Image-Based Phenotyping

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Campbell, M. T.; Walia, H.; Grondin, A.; Knecht, A.

2017-12-01

The development of abiotic stress tolerant crops (i.e. drought, salinity, or heat stress) requires the discovery of DNA sequence variants associated with stress tolerance-related traits. However, many traits underlying adaptation to abiotic stress involve a suite of physiological pathways that may be induced at different times throughout the duration of stress. Conventional single-point phenotyping approaches fail to fully capture these temporal responses, and thus downstream genetic analysis may only identify a subset of the genetic variants that are important for adaptation to sub-optimal environments. Although genomic resources for crops have advanced tremendously, the collection of phenotypic data for morphological and physiological traits is laborious and remains a significant bottleneck in bridging the phenotype-genotype gap. In recent years, the availability of automated, image-based phenotyping platforms has provided researchers with an opportunity to collect morphological and physiological traits non-destructively in a highly controlled environment. Moreover, these platforms allow abiotic stress responses to be recorded throughout the duration of the experiment, and have facilitated the use of function-valued traits for genetic analyses in major crops. We will present our approaches for addressing abiotic stress tolerance in cereals. This talk will focus on novel open-source software to process and extract biological meaningful data from images generated from these phenomics platforms. In addition, we will discuss the statistical approaches to model longitudinal phenotypes and dissect the genetic basis of dynamic responses to these abiotic stresses throughout development.

Reduced Slc6a15 in Nucleus Accumbens D2-Neurons Underlies Stress Susceptibility.

Science.gov (United States)

Chandra, Ramesh; Francis, T Chase; Nam, Hyungwoo; Riggs, Lace M; Engeln, Michel; Rudzinskas, Sarah; Konkalmatt, Prasad; Russo, Scott J; Turecki, Gustavo; Iniguez, Sergio D; Lobo, Mary Kay

2017-07-05

Previous research demonstrates that Slc6a15, a neutral amino acid transporter, is associated with depression susceptibility. However, no study examined Slc6a15 in the ventral striatum [nucleus accumbens (NAc)] in depression. Given our previous characterization of Slc6a15 as a striatal dopamine receptor 2 (D2)-neuron-enriched gene, we examined the role of Slc6a15 in NAc D2-neurons in mediating susceptibility to stress in male mice. First, we showed that Slc6a15 mRNA was reduced in NAc of mice susceptible to chronic social defeat stress (CSDS), a paradigm that produces behavioral and molecular adaptations that resemble clinical depression. Consistent with our preclinical data, we observed Slc6a15 mRNA reduction in NAc of individuals with major depressive disorder (MDD). The Slc6a15 reduction in NAc occurred selectively in D2-neurons. Next, we used Cre-inducible viruses combined with D2-Cre mice to reduce or overexpress Slc6a15 in NAc D2-neurons. Slc6a15 reduction in D2-neurons caused enhanced susceptibility to a subthreshold social defeat stress (SSDS) as observed by reduced social interaction, while a reduction in social interaction following CSDS was not observed when Slc6a15 expression in D2-neurons was restored. Finally, since both D2-medium spiny neurons (MSNs) and D2-expressing choline acetyltransferase (ChAT) interneurons express Slc6a15, we examined Slc6a15 protein in these interneurons after CSDS. Slc6a15 protein was unaltered in ChAT interneurons. Consistent with this, reducing Slc5a15 selectively in NAc D2-MSNs, using A2A-Cre mice that express Cre selectively in D2-MSNs, caused enhanced susceptibility to SSDS. Collectively, our data demonstrate that reduced Slc6a15 in NAc occurs in MDD individuals and that Slc6a15 reduction in NAc D2-neurons underlies stress susceptibility. SIGNIFICANCE STATEMENT Our study demonstrates a role for reduced Slc6a15, a neutral amino acid transporter, in nucleus accumbens (NAc) in depression and stress susceptibility. The

Multiple antibiotic susceptibility of polyphosphate kinase mutants (ppk1 and ppk2 from Pseudomonas aeruginosa PAO1 as revealed by global phenotypic analysis

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Javiera Ortiz-Severín

2015-01-01

Full Text Available BACKGROUND: Pseudomonas aeruginosa is known to be a multidrug resistant opportunistic pathogen. Particularly, P. aeruginosa PAO1 polyphosphate kinase mutant (ppk1 is deficient in motility, quorum sensing, biofilm formation and virulence FINDINGS: By using Phenotypic Microarrays (PM we analyzed near 2000 phenotypes of P. aeruginosa PAO1 polyP kinase mutants (ppk1 and ppk2. We found that both ppk mutants shared most of the phenotypic changes and interestingly many of them related to susceptibility toward numerous and different type of antibiotics such as Ciprofloxacin, Chloramphenicol and Rifampicin CONCLUSIONS: Combining the fact that ppk1 mutants have reduced virulence and are more susceptible to antibiotics, polyP synthesis and particularly PPK1, is a good target for the design of molecules with anti-virulence and anti-persistence properties.

A Mutator Phenotype Promoting the Emergence of Spontaneous Oxidative Stress-Resistant Mutants in Campylobacter jejuni.

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Dai, Lei; Sahin, Orhan; Tang, Yizhi; Zhang, Qijing

2017-12-15

Campylobacter jejuni is a leading cause of foodborne illnesses worldwide. As a microaerophilic organism, C. jejuni must be able to defend against oxidative stress encountered both in the host and in the environment. How Campylobacter utilizes a mutation-based mechanism for adaptation to oxidative stress is still unknown. Here we present a previously undescribed phenotypic and genetic mechanism that promotes the emergence of oxidative stress-resistant mutants. Specifically, we showed that a naturally occurring mutator phenotype, resulting from a loss of function mutation in the DNA repair enzyme MutY, increased oxidative stress resistance (OX R ) in C. jejuni We further demonstrated that MutY malfunction did not directly contribute to the OX R phenotype but increased the spontaneous mutation rate in the peroxide regulator gene perR , which functions as a repressor for multiple genes involved in oxidative stress resistance. Mutations in PerR resulted in loss of its DNA binding function and derepression of PerR-controlled oxidative stress defense genes, thereby conferring an OX R phenotype and facilitating Campylobacter survival under oxidative stress. These findings reveal a new mechanism that promotes the emergence of spontaneous OX R mutants in bacterial organisms. IMPORTANCE Although a mutator phenotype has been shown to promote antibiotic resistance in many bacterial species, little is known about its contribution to the emergence of OX R mutants. This work describes the link between a mutator phenotype and the enhanced emergence of OX R mutants as well as its underlying mechanism involving DNA repair and mutations in PerR. Since DNA repair systems and PerR are well conserved in many bacterial species, especially in Gram positives, the same mechanism may operate in multiple bacterial species. Additionally, we developed a novel method that allows for rapid quantification of spontaneous OX R mutants in a bacterial population. This method represents a technical

Phenotypic Resistance to Antibiotics

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Jose L. Martinez

2013-04-01

Full Text Available The development of antibiotic resistance is usually associated with genetic changes, either to the acquisition of resistance genes, or to mutations in elements relevant for the activity of the antibiotic. However, in some situations resistance can be achieved without any genetic alteration; this is called phenotypic resistance. Non-inherited resistance is associated to specific processes such as growth in biofilms, a stationary growth phase or persistence. These situations might occur during infection but they are not usually considered in classical susceptibility tests at the clinical microbiology laboratories. Recent work has also shown that the susceptibility to antibiotics is highly dependent on the bacterial metabolism and that global metabolic regulators can modulate this phenotype. This modulation includes situations in which bacteria can be more resistant or more susceptible to antibiotics. Understanding these processes will thus help in establishing novel therapeutic approaches based on the actual susceptibility shown by bacteria during infection, which might differ from that determined in the laboratory. In this review, we discuss different examples of phenotypic resistance and the mechanisms that regulate the crosstalk between bacterial metabolism and the susceptibility to antibiotics. Finally, information on strategies currently under development for diminishing the phenotypic resistance to antibiotics of bacterial pathogens is presented.

Cell-type-specific role for nucleus accumbens neuroligin-2 in depression and stress susceptibility.

Science.gov (United States)

Heshmati, Mitra; Aleyasin, Hossein; Menard, Caroline; Christoffel, Daniel J; Flanigan, Meghan E; Pfau, Madeline L; Hodes, Georgia E; Lepack, Ashley E; Bicks, Lucy K; Takahashi, Aki; Chandra, Ramesh; Turecki, Gustavo; Lobo, Mary Kay; Maze, Ian; Golden, Sam A; Russo, Scott J

2018-01-30

Behavioral coping strategies are critical for active resilience to stress and depression; here we describe a role for neuroligin-2 (NLGN-2) in the nucleus accumbens (NAc). Neuroligins (NLGN) are a family of neuronal postsynaptic cell adhesion proteins that are constituents of the excitatory and inhibitory synapse. Importantly, NLGN-3 and NLGN-4 mutations are strongly implicated as candidates underlying the development of neuropsychiatric disorders with social disturbances such as autism, but the role of NLGN-2 in neuropsychiatric disease states is unclear. Here we show a reduction in NLGN-2 gene expression in the NAc of patients with major depressive disorder. Chronic social defeat stress in mice also decreases NLGN-2 selectively in dopamine D1-positive cells, but not dopamine D2-positive cells, within the NAc of stress-susceptible mice. Functional NLGN-2 knockdown produces bidirectional, cell-type-specific effects: knockdown in dopamine D1-positive cells promotes subordination and stress susceptibility, whereas knockdown in dopamine D2-positive cells mediates active defensive behavior. These findings establish a behavioral role for NAc NLGN-2 in stress and depression; provide a basis for targeted, cell-type specific therapy; and highlight the role of active behavioral coping mechanisms in stress susceptibility.

Blood lactate kinetics in normal and stress-susceptible pigs

International Nuclear Information System (INIS)

Darrah, P.S.; Beitz, D.C.; Topel, D.G.; Christian, L.L.

1981-01-01

In vitro rates of lactate metabolism were determined in stress-susceptible (SS) and stress-resistant (SR) pigs. Three SR and three SS pigs were given 20 muCi of [U-/sup 14/C] L-lactate by a single injection method and resting blood lactate kinetics were measured. Seventeen blood samples were taken during the 60 min after injection. Lactate was separated from the deproteinized plasma by silicic acid column chromatography, and specific radioactivity was determined. Kinetic characteristics were calculated from plots of specific activity versus time. Pigs met steady-state requirements during the sampling period. There were no differences in kinetic characteristics of resting SS and SR pigs. Later, a second isotope injection was given after 5 min of electrical stress. Lactate pool sizes increased similarly in both types of pigs after stress; however, SS pigs had greater plasma lactate concentrations after stress. It is concluded that SS and SR pigs respond differently to stress but have similar capacities to metabolize lactate while resting

Diverse basal and stress-related phenotypes of Sprague Dawley rats from three vendors

NARCIS (Netherlands)

Pecoraro, Norman; Ginsberg, Abigail B.; Warne, James P.; Gomez, Francisca; la Fleur, Susanne E.; Dallman, Mary F.

2006-01-01

Based on observed phenotypic differences in growth and ACTH responses to stress in Sprague Dawley rats obtained from different vendors, we ran head-to-head comparisons on rats obtained from three different vendors, Harlan, Charles River, and Simonsen, with respect to baseline phenotypic differences

Field Phenotyping of Soybean Roots for Drought Stress Tolerance

Directory of Open Access Journals (Sweden)

Berhanu A. Fenta

2014-08-01

Full Text Available Root architecture was determined together with shoot parameters under well watered and drought conditions in the field in three soybean cultivars (A5409RG, Jackson and Prima 2000. Morphology parameters were used to classify the cultivars into different root phenotypes that could be important in conferring drought tolerance traits. A5409RG is a drought-sensitive cultivar with a shallow root phenotype and a root angle of <40°. In contrast, Jackson is a drought-escaping cultivar. It has a deep rooting phenotype with a root angle of >60°. Prima 2000 is an intermediate drought-tolerant cultivar with a root angle of 40°–60°. It has an intermediate root phenotype. Prima 2000 was the best performing cultivar under drought stress, having the greatest shoot biomass and grain yield under limited water availability. It had abundant root nodules even under drought conditions. A positive correlation was observed between nodule size, above-ground biomass and seed yield under well-watered and drought conditions. These findings demonstrate that root system phenotyping using markers that are easy-to-apply under field conditions can be used to determine genotypic differences in drought tolerance in soybean. The strong association between root and nodule parameters and whole plant productivity demonstrates the potential application of simple root phenotypic markers in screening for drought tolerance in soybean.

13 reasons why the brain is susceptible to oxidative stress

OpenAIRE

James Nathan Cobley; Maria Luisa Fiorello; Damian Miles Bailey

2018-01-01

The human brain consumes 20% of the total basal oxygen (O2) budget to support ATP intensive neuronal activity. Without sufficient O2 to support ATP demands, neuronal activity fails, such that, even transient ischemia is neurodegenerative. While the essentiality of O2 to brain function is clear, how oxidative stress causes neurodegeneration is ambiguous. Ambiguity exists because many of the reasons why the brain is susceptible to oxidative stress remain obscure. Many are erroneously understood...

Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.

Science.gov (United States)

Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Lorsch, Zachary S; Walker, Deena M; Wang, Junshi; Huang, Xiaojie; Schlüter, Oliver M; Maze, Ian; Peña, Catherine J; Heller, Elizabeth A; Issler, Orna; Wang, Minghui; Song, Won-Min; Stein, Jason L; Liu, Xiaochuan; Doyle, Marie A; Scobie, Kimberly N; Sun, Hao Sheng; Neve, Rachael L; Geschwind, Daniel; Dong, Yan; Shen, Li; Zhang, Bin; Nestler, Eric J

2016-06-01

Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

Differential GR Expression and Translocation in the Hippocampus Mediates Susceptibility vs. Resilience to Chronic Social Defeat Stress

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Qiu-Qin Han

2017-05-01

Full Text Available While social stress exposure is a common risk factor for affective disorders, most individuals exposed to it can maintain normal physical and psychological functioning. However, factors that determine susceptibility vs. resilience to social stress remain unclear. Here, the resident-intruder model of social defeat was used as a social stressor in male C57BL/6J mice to investigate the difference between susceptibility and resilience. As depression is often characterized by hyperactivity of the hypothalamic-pituitary-adrenal (HPA axis, we conducted the present study to further investigate the individual differences in the HPA axis response and glucocorticoid receptor (GR protein expression and translocation between susceptible mice and resilient mice. We found that hypercortisolemia, induced by social defeat stress occurred in susceptible mice, but not in resilient mice. Moreover, susceptible mice exhibited significantly less GR protein expression and nuclear translocation in the hippocampus than resilient mice. Treatment with escitalopram could decrease the serum corticosterone (CORT, increase GR protein expression as well as nuclear translocation in the hippocampus and ultimately reverse social withdrawal behaviors in susceptible mice. These results indicate that the up-regulation of GR and the enhancement of GR nuclear translocation in the hippocampus play an important role in resilience to chronic social defeat stress.

Shear Stress Induces Phenotypic Modulation of Vascular Smooth Muscle Cells via AMPK/mTOR/ULK1-Mediated Autophagy.

Science.gov (United States)

Sun, Liqian; Zhao, Manman; Liu, Aihua; Lv, Ming; Zhang, Jingbo; Li, Youxiang; Yang, Xinjian; Wu, Zhongxue

2018-03-01

Phenotypic modulation of vascular smooth muscle cells (VSMCs) is involved in the pathophysiological processes of the intracranial aneurysms (IAs). Although shear stress has been implicated in the proliferation, migration, and phenotypic conversion of VSMCs, the molecular mechanisms underlying these events are currently unknown. In this study, we investigated whether shear stress(SS)-induced VSMC phenotypic modulation was mediated by autophagy involved in adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/Unc-51-like kinase 1 (ULK1) pathway. The results show that shear stress could inhibit the expression of key VSMC contractile genes and induce pro-inflammatory/matrix-remodeling genes levels, contributing to VSMCs phenotypic switching from a contractile to a synthetic phenotype. More importantly, Shear stress also markedly increased the levels of the autophagy marker microtubule-associated protein light chain 3-II (LC3II), Beclin-1, and p62 degradation. The autophagy inhibitor 3-methyladenine (3-MA) significantly blocked shear-induced phenotypic modulation of VSMCs. To further explore the molecular mechanism involved in shear-induced autophagy, we found that shear stress could activate AMPK/mTOR/ULK1 signaling pathway in VSMCs. Compound C, a pharmacological inhibitor of AMPK, significantly reduced the levels of p-AMPK and p-ULK, enhanced p-mTOR level, and finally decreased LC3II and Beclin-1 level, which suggested that activated AMPK/mTOR/ULK1 signaling was related to shear-mediated autophagy. These results indicate that shear stress promotes VSMC phenotypic modulation through the induction of autophagy involved in activating the AMPK/mTOR/ULK1 pathway.

CHRONIC ALCOHOL NEUROADAPTATION AND STRESS CONTRIBUTE TO SUSCEPTIBILITY FOR ALCOHOL CRAVING AND RELAPSE

Science.gov (United States)

BREESE, GEORGE R.; SINHA, RAJITA; HEILIG, MARKUS

2010-01-01

Alcoholism is a chronic relapsing disorder. Major characteristics observed in alcoholics during an initial period of alcohol abstinence are altered physiological functions and a negative emotional state. Evidence suggests that a persistent, cumulative adaptation involving a kindling/allostasis-like process occurs during the course of repeated chronic alcohol exposures that is critical for the negative symptoms observed during alcohol withdrawal. Basic studies have provided evidence for specific neurotransmitters within identified brain sites being responsible for the negative emotion induced by the persistent cumulative adaptation following intermittent-alcohol exposures. After an extended period of abstinence, the cumulative alcohol adaptation increases susceptibility to stress- and alcohol cue-induced negative symptoms and alcohol seeking, both of which can facilitate excessive ingestion of alcohol. In the alcoholic, stressful imagery and alcohol cues alter physiological responses, enhance negative emotion, and induce craving. Brain fMRI imaging following stress and alcohol cues has documented neural changes in specific brain regions of alcoholics not observed in social drinkers. Such altered activity in brain of abstinent alcoholics to stress and alcohol cues is consistent with a continuing ethanol adaptation being responsible. Therapies in alcoholics found to block responses to stress and alcohol cues would presumably be potential treatments by which susceptibility for continued alcohol abuse can be reduced. By continuing to define the neurobiological basis of the sustained alcohol adaptation critical for the increased susceptibility of alcoholics to stress and alcohol cues that facilitate craving, a new era is expected to evolve in which the high rate of relapse in alcoholism is minimized. 250 PMID:20951730

Method of evaluation of stress corrosion cracking susceptibility of clad fuel tubes

International Nuclear Information System (INIS)

Takase, Iwao; Yoshida, Toshimi; Ikeda, Shinzo; Masaoka, Isao; Nakajima, Junjiro.

1986-01-01

Purpose: To determine, by an evaluation in out-pile test, the stress corrosion cracking susceptibility of clad fuel tubes in the reactor environment. Method: A plurality of electrodes are mounted in the circumferential direction on the entire surface of cladding tubes. Of the electrodes, electrodes at two adjacent places are used as measuring terminals and electrodes at another two places adjacent thereto are used as constant-current terminals. With a specific current flowing in the constant-current terminals, measurements are made of a potential difference between the terminals to be measured, and from a variation in the potential difference the depth of cracking of the cladding tube surface is presumed to determine the stress corrosion cracking susceptibility of the cladding tube. To check the entire surface of the cladding tube, the cladding tube is moved by each block in the circumferential direction by a contact changeover system, repeating the measurements of the potential difference. Contact type electrodes are secured with an insulator and held in uniform contact with the cladding tube by a spring. It is detachable by use of a locking system and movable as desired. Thus the stress corrosion cracking susceptibility can be determined without mounting the cladding tube through and also a fuel failure can be prevented. (Horiuchi, T.)

Effect of surface treatments on stress corrosion cracking susceptibility of nickel base alloys

International Nuclear Information System (INIS)

Iwanami, Masaru; Kaneda, Junya; Tamako, Hiroaki; Hato, Hisamitsu; Takamoto, Shinichi

2009-01-01

Effect of surface treatment on SCC susceptibility of Ni base alloys was investigated. Cracks were observed in all grinding specimens in a creviced bent beam (CBB) test. On the other hand, no cracks occurred in shot peening (SP), water jet peening (WJP) specimens. It was indicated that these surface treatments effectively reduced the SCC susceptibility of nickel-base alloys. As a result of a residual stress test, the surface of specimens with grinding had high tensile residual stress. However, SP and WJP improved surface residual stress to compressive stress. The depth of the compressive effect of WJP was almost the same as that of SP. However, the surface hardness of WJP specimens differed from that of SP and it was found that WJP had less impact on surface hardening. This difference was consistent with their surface microstructures. The surface of SP specimens had clearly the deformation region, but the surface of WJP specimens was localized. (author)

The relative stress-corrosion-cracking susceptibility of candidate aluminum-lithium alloys for aerospace applications

Science.gov (United States)

Pizzo, P. P.

1982-01-01

Stress corrosion tests of Al-Li-Cu powder metallurgy alloys are described. Alloys investigated were Al-2.6% Li-1.4% and Al-2.6% Li-1.4% Cu-1.6% Mg. The base properties of the alloys were characterized. Process, heat treatment, and size/orientational effects on the tensile and fracture behavior were investigated. Metallurgical and electrochemical conditions are identified which provide reproducible and controlled parameters for stress corrosion evaluation. Preliminary stress corrosion test results are reported. Both Al-Li-Cu alloys appear more susceptible to stress corrosion crack initiation than 7075-T6 aluminum, with the magnesium bearing alloy being the most susceptible. Tests to determine the threshold stress intensity for the base and magnesium bearing alloys are underway. Twelve each, bolt loaded DCB type specimens are under test (120 days) and limited crack growth in these precracked specimens has been observed. General corrosion in the aqueous sodium chloride environment is thought to be obscuring results through crack tip blunting.

Stress corrosion cracking susceptibility of selected materials for steam plant bolting applications

Energy Technology Data Exchange (ETDEWEB)

Mayer, P.; Noga, J.O.; Ogundele, G.

1996-12-01

The incidence of alloy steel bolting failure in nuclear and fossil fired generating plants was discussed. The problem manifests itself in the form of intergranular stress corrosion cracking. A study was conducted to rank the susceptibility of three materials (Alloy AISI, type 4140, Alloy ASTM A564-92AXM 13 and Inconel 718) to stress corrosion cracking and to determine threshold stress intensity factors of currently used and alternate alloys in service environments typically encountered in steam generating utility plants. Although most alloy steel bolting failures have involved Cr-Mo, failures have also been reported for all the above mentioned materials. Attempts to minimize the occurrence of stress corrosion cracking have involved a ban on molybdenum disulphide, limiting bolt tightening torque and placing an upper limit on bolt hardness, and by correlation on tensile strength. Slow strain rate and wedge opening-loading specimen tests were used to evaluate commonly used and superior alternative bolting materials. Electrochemical polarization tests were also conducted. Threshold stresses in a H{sub 2}S environment were determined according to NACE standard TM-01-77. Results showed that, to a certain degree, all tested materials were susceptible to stress corrosion cracking. They ranked as follows from best to worst performance: (1) the Inconel 718, (2) alloy SM 13, and (3) alloy 4140. 9 refs., 20 tabs., 34 figs.

Contrasting patterns of coral bleaching susceptibility in 2010 suggest an adaptive response to thermal stress.

Science.gov (United States)

Guest, James R; Baird, Andrew H; Maynard, Jeffrey A; Muttaqin, Efin; Edwards, Alasdair J; Campbell, Stuart J; Yewdall, Katie; Affendi, Yang Amri; Chou, Loke Ming

2012-01-01

Coral bleaching events vary in severity, however, to date, the hierarchy of susceptibility to bleaching among coral taxa has been consistent over a broad geographic range and among bleaching episodes. Here we examine the extent of spatial and temporal variation in thermal tolerance among scleractinian coral taxa and between locations during the 2010 thermally induced, large-scale bleaching event in South East Asia. Surveys to estimate the bleaching and mortality indices of coral genera were carried out at three locations with contrasting thermal and bleaching histories. Despite the magnitude of thermal stress being similar among locations in 2010, there was a remarkable contrast in the patterns of bleaching susceptibility. Comparisons of bleaching susceptibility within coral taxa and among locations revealed no significant differences between locations with similar thermal histories, but significant differences between locations with contrasting thermal histories (Friedman = 34.97; pBleaching was much less severe at locations that bleached during 1998, that had greater historical temperature variability and lower rates of warming. Remarkably, Acropora and Pocillopora, taxa that are typically highly susceptible, although among the most susceptible in Pulau Weh (Sumatra, Indonesia) where respectively, 94% and 87% of colonies died, were among the least susceptible in Singapore, where only 5% and 12% of colonies died. The pattern of susceptibility among coral genera documented here is unprecedented. A parsimonious explanation for these results is that coral populations that bleached during the last major warming event in 1998 have adapted and/or acclimatised to thermal stress. These data also lend support to the hypothesis that corals in regions subject to more variable temperature regimes are more resistant to thermal stress than those in less variable environments.

Evaluation of rice genotypes under salt stress at the seedling and reproductive stages using phenotypic and molecular markers

International Nuclear Information System (INIS)

Rubel, M.H.; Hassan, L.

2014-01-01

Salinity screening for 27 rice genotypes was performed at the seedling and reproductive stages respectively, in the hydroponic system and in sustained water bath. Three selected SSR markers were used to determine salinity tolerance in rice genotypes. Phenotyping of the germplasm was done at EC 12dS/m and 6dS/m at seedling and reproductive stages, respectively. Based on modified standard evaluation score for visual salt injury at seedling stage, eight genotypes were salt tolerant, four were moderately tolerant and the rest fifteen were susceptible. At the reproductive stage, six genotypes were tolerant to EC 6dS/m whereas eleven of them were susceptible. SSR based marker identified seven genotypes as tolerant but ten of them were susceptible for all three markers compared to two checks. Six genotypes were tolerant in both phenotypic and SSR screening. The indentified salt tolerant genotypes can be potential germplasm sources for future breeding program. (author)

Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice

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Allison R. Rogala

2018-02-01

Full Text Available Crohn's disease (CD represents a chronic inflammatory disorder of the intestinal tract. Several susceptibility genes have been linked to CD, though their precise role in the pathogenesis of this disorder remains unclear. Immunity-related GTPase M (IRGM is an established risk allele in CD. We have shown previously that conventionally raised (CV mice lacking the IRGM ortholog, Irgm1 exhibit abnormal Paneth cells (PCs and increased susceptibility to intestinal injury. In the present study, we sought to utilize this model system to determine if environmental conditions impact these phenotypes, as is thought to be the case in human CD. To accomplish this, wild-type and Irgm1−/− mice were rederived into specific pathogen-free (SPF and germ-free (GF conditions. We next assessed how these differential housing environments influenced intestinal injury patterns, and epithelial cell morphology and function in wild-type and Irgm1−/− mice. Remarkably, in contrast to CV mice, SPF Irgm1−/− mice showed only a slight increase in susceptibility to dextran sodium sulfate-induced inflammation. SPF Irgm1−/− mice also displayed minimal abnormalities in PC number and morphology, and in antimicrobial peptide expression. Goblet cell numbers and epithelial proliferation were also unaffected by Irgm1 in SPF conditions. No microbial differences were observed between wild-type and Irgm1−/− mice, but gut bacterial communities differed profoundly between CV and SPF mice. Specifically, Helicobacter sequences were significantly increased in CV mice; however, inoculating SPF Irgm1−/− mice with Helicobacter hepaticus was not sufficient to transmit a pro-inflammatory phenotype. In summary, our findings suggest the impact of Irgm1-deficiency on susceptibility to intestinal inflammation and epithelial function is critically dependent on environmental influences. This work establishes the importance of Irgm1−/− mice as a model to elucidate host

Phenotype, genotype, and antibiotic susceptibility of Swedish and Thai oral isolates of Staphylococcus aureus

Directory of Open Access Journals (Sweden)

Susanne Blomqvist

2015-04-01

Full Text Available Objective: The present study investigated phenotypes, virulence genotypes, and antibiotic susceptibility of oral Staphylococcus aureus strains in order to get more information on whether oral infections with this bacterium are associated with certain subtypes or related to an over-growth of the S. aureus variants normally found in the oral cavity of healthy carriers. Materials and methods: A total number of 157 S. aureus strains were investigated. Sixty-two strains were isolated from Swedish adults with oral infections, 25 strains were from saliva of healthy Swedish dental students, and 45 strains were from tongue scrapings of HIV-positive subjects in Thailand, and 25 Thai strains from non-HIV controls. The isolates were tested for coagulase, nitrate, arginine, and hemolysin, and for the presence of the virulence genes: hlg, clfA, can, sdrC, sdrD, sdrE, map/eap (adhesins and sea, seb, sec, tst, eta, etb, pvl (toxins. MIC90 and MIC50 were determined by E-test against penicillin V, oxacillin, amoxicillin, clindamycin, vancomycin, fusidic acid, and cefoxitin. Results: While the hemolytic phenotype was significantly (p<0.001 more common among the Thai strains compared to Swedish strains, the virulence genes were found in a similar frequency in the S. aureus strains isolated from all four subject groups. The Panton-Valentine leukocidin (PVL genotype was found in 73–100% of the strains. More than 10% of the strains from Swedish oral infections and from Thai HIV-positives showed low antibiotic susceptibility, most commonly for clindamycin. Only three methicillin-resistant S. aureus (MRSA strains were identified, two from oral infections and one from a Thai HIV patient. Conclusions: S. aureus is occasionally occurring in the oral cavity in both health and disease in Sweden and Thailand. It is therefore most likely that S. aureus in opportunistic oral infections originate from the oral microbiota. S. aureus should be considered in case of oral

In vitro susceptibility and resistance phenotypes in contemporary Enterobacter isolates in a university hospital in Crete, Greece.

Science.gov (United States)

Maraki, Sofia; Vardakas, Konstantinos Z; Samonis, George; Perdikis, Dimitrios; Mavromanolaki, Viktoria Eirini; Kofteridis, Diamantis P; Falagas, Matthew E

2017-06-01

To study the evolution in the susceptibility of Enterobacter spp. in Crete, Greece from 2010 to 2015. Non-duplicate isolates were studied using automated systems. Phenotypic confirmatory tests were applied. A total of 939 Enterobacter isolates were included. Colistin was the most active antibiotic (97.9%) followed by imipenem (96.1%), gentamicin (95.7%), tigecycline (91.8%), cefepime (89.4%), chloramphenicol (85.8%), fosfomycin (85.5%), trimethoprim/sulfamethoxazole (83.3%) and piperacillin/tazobactam (73.3%). Antibiotic resistance did not increase during the study period for most antibiotics. Lower susceptibility was observed among multidrug-resistant strains and carbapenem-nonsusceptible isolates. AmpC was the most common resistant mechanism (21%); carbapenemases (3.7%) and aminoglycoside-modifying enzymes (6.5%) were also detected. A significant proportion of Enterobacter spp. was resistant to several antibiotics, most notably β-lactams.

Phenotyping of Arabidopsis Drought Stress Response Using Kinetic Chlorophyll Fluorescence and Multicolor Fluorescence Imaging

Directory of Open Access Journals (Sweden)

Jieni Yao

2018-05-01

Full Text Available Plant responses to drought stress are complex due to various mechanisms of drought avoidance and tolerance to maintain growth. Traditional plant phenotyping methods are labor-intensive, time-consuming, and subjective. Plant phenotyping by integrating kinetic chlorophyll fluorescence with multicolor fluorescence imaging can acquire plant morphological, physiological, and pathological traits related to photosynthesis as well as its secondary metabolites, which will provide a new means to promote the progress of breeding for drought tolerant accessions and gain economic benefit for global agriculture production. Combination of kinetic chlorophyll fluorescence and multicolor fluorescence imaging proved to be efficient for the early detection of drought stress responses in the Arabidopsis ecotype Col-0 and one of its most affected mutants called reduced hyperosmolality-induced [Ca2+]i increase 1. Kinetic chlorophyll fluorescence curves were useful for understanding the drought tolerance mechanism of Arabidopsis. Conventional fluorescence parameters provided qualitative information related to drought stress responses in different genotypes, and the corresponding images showed spatial heterogeneities of drought stress responses within the leaf and the canopy levels. Fluorescence parameters selected by sequential forward selection presented high correlations with physiological traits but not morphological traits. The optimal fluorescence traits combined with the support vector machine resulted in good classification accuracies of 93.3 and 99.1% for classifying the control plants from the drought-stressed ones with 3 and 7 days treatments, respectively. The results demonstrated that the combination of kinetic chlorophyll fluorescence and multicolor fluorescence imaging with the machine learning technique was capable of providing comprehensive information of drought stress effects on the photosynthesis and the secondary metabolisms. It is a promising

High-throughput behavioral phenotyping of drug and alcohol susceptibility traits in the expanded panel of BXD recombinant inbred strains

Energy Technology Data Exchange (ETDEWEB)

Philip, Vivek M [ORNL; Ansah, T [University of Tennessee Health Science Center, Memphis; Blaha, C, [University of Tennessee Health Science Center, Memphis; Cook, Melloni N. [University of Memphis; Hamre, Kristin M. [University of Tennessee Health Science Center, Memphis; Lariviere, William R [University of Pittsburgh; Matthews, Douglas B [Baylor University; Goldowitz, Daniel [University of British Columbia, Vancouver; Chesler, Elissa J [ORNL

2010-01-01

Genetic reference populations, particularly the BXD recombinant inbred strains, are a valuable resource for the discovery of the bio-molecular substrates and genetic drivers responsible for trait variation and co- ariation. This approach can be profitably applied in the analysis of susceptibility and mechanisms of drug and alcohol use disorders for which many predisposing behaviors may predict occurrence and manifestation of increased preference for these substances. Many of these traits are modeled by common mouse behavioral assays, facilitating the detection of patterns and sources of genetic co-regulation of predisposing phenotypes and substance consumption. Members of the Tennessee Mouse Genome Consortium have obtained behavioral phenotype data from 260 measures related to multiple behavioral assays across several domains: self-administration, response to, and withdrawal from cocaine, MDMA, morphine and alcohol; novelty seeking; behavioral despair and related neurological phenomena; pain sensitivity; stress sensitivity; anxiety; hyperactivity; and sleep/wake cycles. All traits have been measured in both sexes and the recently expanded panel of 69 additional BXD recombinant inbred strains (N=69). Sex differences and heritability estimates were obtained for each trait, and a comparison of early (N = 32) and recent BXD RI lines was performed. Primary data is publicly available for heritability, sex difference and genetic analyses using www.GeneNetwork.org. These analyses include QTL detection and genetic analysis of gene expression. Stored results from these analyses are available at http://ontologicaldiscovery.org for comparison to other genomic analysis results. Together with the results of related studies, these data form a public resource for integrative systems genetic analysis of neurobehavioral traits.

Comprehensive phenotypic analysis of rice (Oryza sativa) response to salinity stress

KAUST Repository

Pires, Inês S.

2015-07-22

Increase in soil salinity levels is becoming a major cause of crop yield losses worldwide. Rice (Oryza sativa) is the most salt-sensitive cereal crop, and many studies have focused on rice salinity tolerance, but a global understanding of this crop\\'s response to salinity is still lacking. We systematically analyzed phenotypic data previously collected for 56 rice genotypes to assess the extent to which rice uses three known salinity tolerance mechanisms: shoot-ion independent tolerance (or osmotic tolerance), ion exclusion, and tissue tolerance. In general, our analyses of different phenotypic traits agree with results of previous rice salinity tolerance studies. However, we also established that the three salinity tolerance mechanisms mentioned earlier appear among rice genotypes and that none of them is predominant. Against the pervasive view in the literature that the K+/Na+ ratio is the most important trait in salinity tolerance, we found that the K+ concentration was not significantly affected by salt stress in rice, which puts in question the importance of K+/Na+ when analyzing rice salt stress response. Not only do our results contribute to improve our global understanding of salt stress response in an important crop, but we also use our results together with an extensive literature research to highlight some issues commonly observed in salinity stress tolerance studies and to propose solutions for future experiments.

Potential predictors of susceptibility to occupational stress in Japanese novice nurses - a pilot study.

Science.gov (United States)

Okita, Shinobu; Daitoku, Satoshi; Abe, Masaharu; Arimura, Emi; Setoyama, Hitoshi; Koriyama, Chihaya; Ushikai, Miharu; Kawaguchi, Hiroaki; Horiuchi, Masahisa

2017-04-04

Occupational stress is a known factor behind employee resignations; thus, early identification of individuals prone to such stress is important. Accordingly, in this pilot study we evaluated potential predictors of susceptibility to occupational stress in Japanese novice nurses. Forty-two female novice nurses at Kagoshima University Hospital were recruited for the study population. Each underwent physical health and urinary examinations, and completed a lifestyle questionnaire at the time of job entry. Each also completed a Brief Job Stress Questionnaire (BJSQ), related to mental health status, at job entry and 5 months post-entry. Psychological stress, somatic symptoms, and combined BJSQ scores were determined for each time point. All three stress condition scores had significantly decreased at 5 months post-entry, suggesting occupational stress. Systolic blood pressure (r = -0.324, p stress condition scores were significantly low in subjects reporting substantial 1-year body weight change (≤ ± 3 kg) and short times between dinner and bedtimes (≤2 h), though baseline stress condition scores were not. Urinary sodium concentration, 1-year body weight change, and pre-sleep evening meals were then targeted for multivariate analysis, and confirmed as independent explanatory variables for post-entry stress condition scores. One-year body weight change, times between dinner and bedtimes, and urinary sodium concentration are promising potential predictors of susceptibility to occupational stress, and should be further investigated in future research. ISRCTN ISRCTN17516023. Retrospectively registered 7 December 2016.

Role of adult hippocampal neurogenesis in stress resilience

Directory of Open Access Journals (Sweden)

Brunno R. Levone

2015-01-01

Full Text Available There is a growing appreciation that adult hippocampal neurogenesis plays a role in emotional and cognitive processes related to psychiatric disorders. Although many studies have investigated the effects of stress on adult hippocampal neurogenesis, most have not focused on whether stress-induced changes in neurogenesis occur specifically in animals that are more resilient or more susceptible to the behavioural and neuroendocrine effects of stress. Thus, in the present review we explore whether there is a clear relationship between stress-induced changes in adult hippocampal neurogenesis, stress resilience and antidepressant-induced recovery from stress-induced changes in behaviour. Exposure to different stressors is known to reduce adult hippocampal neurogenesis, but some stressors have also been shown to exert opposite effects. Ablation of neurogenesis does not lead to a depressive phenotype, but it can enhance responsiveness to stress and affect stress susceptibility. Monoaminergic-targeted antidepressants, environmental enrichment and adrenalectomy are beneficial for reversing stress-induced changes in behaviour and have been shown to do so in a neurogenesis-dependant manner. In addition, stress and antidepressants can affect hippocampal neurogenesis, preferentially in the ventral hippocampus. Together, these data show that adult hippocampal neurogenesis may play a role in the neuroendocrine and behavioural responses to stress, although it is not yet fully clear under which circumstances neurogenesis promotes resilience or susceptibility to stress. It will be important that future studies carefully examine how adult hippocampal neurogenesis can contribute to stress resilience/susceptibility so that it may be appropriately exploited for the development of new and more effective treatments for stress-related psychiatric disorders.

Differential Response of Coral Assemblages to Thermal Stress Underscores the Complexity in Predicting Bleaching Susceptibility.

Science.gov (United States)

Chou, Loke Ming; Toh, Tai Chong; Toh, Kok Ben; Ng, Chin Soon Lionel; Cabaitan, Patrick; Tun, Karenne; Goh, Eugene; Afiq-Rosli, Lutfi; Taira, Daisuke; Du, Rosa Celia Poquita; Loke, Hai Xin; Khalis, Aizat; Li, Jinghan; Song, Tiancheng

2016-01-01

Coral bleaching events have been predicted to occur more frequently in the coming decades with global warming. The susceptibility of corals to bleaching during thermal stress episodes is dependent on many factors and an understanding of these underlying drivers is crucial for conservation management. In 2013, a mild bleaching episode ensued in response to elevated sea temperature on the sediment-burdened reefs in Singapore. Surveys of seven sites highlighted variable bleaching susceptibility among coral genera-Pachyseris and Podabacia were the most impacted (31% of colonies of both genera bleached). The most susceptible genera such as Acropora and Pocillopora, which were expected to bleach, did not. Susceptibility varied between less than 6% and more than 11% of the corals bleached, at four and three sites respectively. Analysis of four of the most bleached genera revealed that a statistical model that included a combination of the factors (genus, colony size and site) provided a better explanation of the observed bleaching patterns than any single factor alone. This underscored the complexity in predicting the coral susceptibility to future thermal stress events and the importance of monitoring coral bleaching episodes to facilitate more effective management of coral reefs under climate change.

Differential Response of Coral Assemblages to Thermal Stress Underscores the Complexity in Predicting Bleaching Susceptibility

Science.gov (United States)

Toh, Kok Ben; Ng, Chin Soon Lionel; Cabaitan, Patrick; Tun, Karenne; Goh, Eugene; Afiq-Rosli, Lutfi; Taira, Daisuke; Du, Rosa Celia Poquita; Loke, Hai Xin; Khalis, Aizat; Li, Jinghan; Song, Tiancheng

2016-01-01

Coral bleaching events have been predicted to occur more frequently in the coming decades with global warming. The susceptibility of corals to bleaching during thermal stress episodes is dependent on many factors and an understanding of these underlying drivers is crucial for conservation management. In 2013, a mild bleaching episode ensued in response to elevated sea temperature on the sediment-burdened reefs in Singapore. Surveys of seven sites highlighted variable bleaching susceptibility among coral genera–Pachyseris and Podabacia were the most impacted (31% of colonies of both genera bleached). The most susceptible genera such as Acropora and Pocillopora, which were expected to bleach, did not. Susceptibility varied between less than 6% and more than 11% of the corals bleached, at four and three sites respectively. Analysis of four of the most bleached genera revealed that a statistical model that included a combination of the factors (genus, colony size and site) provided a better explanation of the observed bleaching patterns than any single factor alone. This underscored the complexity in predicting the coral susceptibility to future thermal stress events and the importance of monitoring coral bleaching episodes to facilitate more effective management of coral reefs under climate change. PMID:27438593

Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice.

Science.gov (United States)

Iñiguez, Sergio D; Riggs, Lace M; Nieto, Steven J; Dayrit, Genesis; Zamora, Norma N; Shawhan, Kristi L; Cruz, Bryan; Warren, Brandon L

2014-05-01

Abstract Exposure to stress is highly correlated with the emergence of mood-related illnesses. Because major depressive disorder often emerges in adolescence, we assessed the effects of social defeat stress on responses to depressive-like behaviors in juvenile mice. To do this, postnatal day (PD) 35 male c57BL/6 mice were exposed to 10 days of social defeat stress (PD35-44), while control mice were handled daily. Twenty-four hours after the last episode of defeat (PD45), separate groups of mice were tested in the social interaction, forced swimming, sucrose preference, and elevated plus-maze behavioral assays (n = 7-12 per group). Also, we examined body weight gain across days of social defeat and levels of blood serum corticosterone 40 min after the last episode of defeat stress. Our data indicates that defeated mice exhibited a depressive-like phenotype as inferred from increased social avoidance, increased immobility in the forced swim test, and reduced sucrose preference (a measure of anhedonia), when compared to non-defeated controls. Defeated mice also displayed an anxiogenic-like phenotype when tested on the elevated plus-maze. Lastly, stressed mice displayed lower body weight gain, along with increased blood serum corticosterone levels, when compared to non-stressed controls. Overall, we show that in adolescent male c57BL/6 mice, social defeat stress induces a depression- and anxiety-like phenotype 24 h after the last episode of stress. These data suggest that the social defeat paradigm may be used to examine the etiology of stress-induced mood-related disorders during adolescence.

Contrasting Patterns of Coral Bleaching Susceptibility in 2010 Suggest an Adaptive Response to Thermal Stress

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Guest, James R.; Baird, Andrew H.; Maynard, Jeffrey A.; Muttaqin, Efin; Edwards, Alasdair J.; Campbell, Stuart J.; Yewdall, Katie; Affendi, Yang Amri; Chou, Loke Ming

2012-01-01

Background Coral bleaching events vary in severity, however, to date, the hierarchy of susceptibility to bleaching among coral taxa has been consistent over a broad geographic range and among bleaching episodes. Here we examine the extent of spatial and temporal variation in thermal tolerance among scleractinian coral taxa and between locations during the 2010 thermally induced, large-scale bleaching event in South East Asia. Methodology/Principal Findings Surveys to estimate the bleaching and mortality indices of coral genera were carried out at three locations with contrasting thermal and bleaching histories. Despite the magnitude of thermal stress being similar among locations in 2010, there was a remarkable contrast in the patterns of bleaching susceptibility. Comparisons of bleaching susceptibility within coral taxa and among locations revealed no significant differences between locations with similar thermal histories, but significant differences between locations with contrasting thermal histories (Friedman = 34.97; pSingapore, where only 5% and 12% of colonies died. Conclusions/Significance The pattern of susceptibility among coral genera documented here is unprecedented. A parsimonious explanation for these results is that coral populations that bleached during the last major warming event in 1998 have adapted and/or acclimatised to thermal stress. These data also lend support to the hypothesis that corals in regions subject to more variable temperature regimes are more resistant to thermal stress than those in less variable environments. PMID:22428027

Effects of cyclic tensile loading on stress corrosion cracking susceptibility for sensitized Type 304 stainless steel in 290 C high purity water

International Nuclear Information System (INIS)

Takaku, H.; Tokiwai, M.; Hirano, H.

1979-01-01

The effects of load waveform on intergranular stress corrosion cracking (IGSCC) susceptibility have been examined for sensitized Type 304 stainless steels in a 290 C high purity water loop. Concerning the strain rate in the trapezoidal stress waveform, it was found that IGSCC susceptibility was higher for smaller values of the strain rate. It was also shown that IGSCC susceptibility became higher when the holding time at the upper stress was prolonged, and when the upper stress was high. The occurrence of IGSCC for sensitized Type 304 stainless steel became easy due to the application of cyclic tensile stress in 290 C high purity water

Differential Response of Coral Assemblages to Thermal Stress Underscores the Complexity in Predicting Bleaching Susceptibility.

Directory of Open Access Journals (Sweden)

Loke Ming Chou

Full Text Available Coral bleaching events have been predicted to occur more frequently in the coming decades with global warming. The susceptibility of corals to bleaching during thermal stress episodes is dependent on many factors and an understanding of these underlying drivers is crucial for conservation management. In 2013, a mild bleaching episode ensued in response to elevated sea temperature on the sediment-burdened reefs in Singapore. Surveys of seven sites highlighted variable bleaching susceptibility among coral genera-Pachyseris and Podabacia were the most impacted (31% of colonies of both genera bleached. The most susceptible genera such as Acropora and Pocillopora, which were expected to bleach, did not. Susceptibility varied between less than 6% and more than 11% of the corals bleached, at four and three sites respectively. Analysis of four of the most bleached genera revealed that a statistical model that included a combination of the factors (genus, colony size and site provided a better explanation of the observed bleaching patterns than any single factor alone. This underscored the complexity in predicting the coral susceptibility to future thermal stress events and the importance of monitoring coral bleaching episodes to facilitate more effective management of coral reefs under climate change.

Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers.

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Alford, Sara K; van Beek, Edwin J R; McLennan, Geoffrey; Hoffman, Eric A

2010-04-20

Recent evidence suggests that endothelial dysfunction and pathology of pulmonary vascular responses may serve as a precursor to smoking-associated emphysema. Although it is known that emphysematous destruction leads to vasculature changes, less is known about early regional vascular dysfunction which may contribute to and precede emphysematous changes. We sought to test the hypothesis, via multidetector row CT (MDCT) perfusion imaging, that smokers showing early signs of emphysema susceptibility have a greater heterogeneity in regional perfusion parameters than emphysema-free smokers and persons who had never smoked (NS). Assuming that all smokers have a consistent inflammatory response, increased perfusion heterogeneity in emphysema-susceptible smokers would be consistent with the notion that these subjects may have the inability to block hypoxic vasoconstriction in patchy, small regions of inflammation. Dynamic ECG-gated MDCT perfusion scans with a central bolus injection of contrast were acquired in 17 NS, 12 smokers with normal CT imaging studies (SNI), and 12 smokers with subtle CT findings of centrilobular emphysema (SCE). All subjects had normal spirometry. Quantitative image analysis determined regional perfusion parameters, pulmonary blood flow (PBF), and mean transit time (MTT). Mean and coefficient of variation were calculated, and statistical differences were assessed with one-way ANOVA. MDCT-based MTT and PBF measurements demonstrate globally increased heterogeneity in SCE subjects compared with NS and SNI subjects but demonstrate similarity between NS and SNI subjects. These findings demonstrate a functional lung-imaging measure that provides a more mechanistically oriented phenotype that differentiates smokers with and without evidence of emphysema susceptibility.

Phenotypic characterization and colistin susceptibilities of carbapenem-resistant of Pseudomonas aeruginosa and Acinetobacter spp.

Science.gov (United States)

Mohanty, Srujana; Maurya, Vijeta; Gaind, Rajni; Deb, Monorama

2013-11-15

Pseudomonas aeruginosa and Acinetobcter spp. are important nosocomial pathogens and carbapenem resistance is an emerging threat. Therapeutic options for infections with these isolates include colistin. This study was conducted to determine the prevalence of carbapenem resistance in P. aeruginosa and Acinetobacter spp. bloodstream isolates, phenotypically characterize the resistance mechanisms and evaluate the in vitro activity of colistin. Consecutive 145 (95 P.aeruginosa and 50 Acinetobacter spp.) non-repeat isolates were included. Antibiotic susceptibility testing was performed per CLSI guidelines. MIC for carbapenems and colistin was performed using Etest. Isolates showing reduced susceptibility or resistance to the carbapenems were tested for metallo-β-lactamase (MBL) production using imipenem-EDTA combined disk and MBL Etest. Carbapenem resistance was observed in 40% P. aeruginosa and 66.0% Acinetobacter spp. Carbapenem-resistant (CA-R) isolates were significantly (p carbapenem-susceptible isolates. Approximately half of the CA-R strains were multidrug-resistant, and 3.1-5.5% were resistant to all antibiotics tested. MBL was found in 76.3% and 69.7% of the P. aeruginosa and Acinetobacter spp., respectively. Colistin resistance was observed in three (6.0%) Acinetobacter isolates and eight (8.4%) P. aeruginosa. MIC50 for carbapenems were two to four times higher for MBL-positive compared to MBL-negative isolates, but no difference was seen in MIC for colistin. Carbapenem resistance was observed to be mediated by MBL in a considerable number of isolates. Colistin is an alternative for infections caused by CA-R isolates; however, MIC testing should be performed whenever clinical use of colistin is considered.

The Role of Oxidative Stress in the Longevity and Insecticide Resistance Phenotype of the Major Malaria Vectors Anopheles arabiensis and Anopheles funestus.

Science.gov (United States)

Oliver, Shüné V; Brooke, Basil D

2016-01-01

Oxidative stress plays numerous biological roles, both functional and pathological. The role of oxidative stress in various epidemiologically relevant biological traits in Anopheles mosquitoes is not well established. In this study, the effects of oxidative stress on the longevity and insecticide resistance phenotype in the major malaria vector species An. arabiensis and An. funestus were examined. Responses to dietary copper sulphate and hydrogen peroxide were used as proxies for the oxidative stress phenotype by determining the effect of copper on longevity and hydrogen peroxide lethal dose. Glutathione peroxidase and catalase activities were determined colorimetrically. Oxidative burden was quantified as protein carbonyl content. Changes in insecticide resistance phenotype were monitored by WHO bioassay. Insecticide resistant individuals showed an increased capacity for coping with oxidative stress, mediated by increased glutathione peroxidase and catalase activity. This effect was observed in both species, as well as in laboratory strains and F1 individuals derived from wild-caught An. funestus mothers. Phenotypic capacity for coping with oxidative stress was greatest in strains with elevated Cytochrome P450 activity. Synergism of oxidative stress defence enzymes by dietary supplementation with haematin, 3-Amino-1, 2, 4-triazole and Sodium diethyldithiocarbamate significantly increased pyrethroid-induced mortality in An. arabiensis and An. funestus. It is therefore concluded that defence against oxidative stress underlies the augmentation of the insecticide resistance phenotype associated with multiple blood-feeding. This is because multiple blood-feeding ultimately leads to a reduction of oxidative stress in insecticide resistant females, and also reduces the oxidative burden induced by DDT and pyrethroids, by inducing increased glutathione peroxidase activity. This study highlights the importance of oxidative stress in the longevity and insecticide resistance

Inoculation stress hypothesis of environmental enrichment.

Science.gov (United States)

Crofton, Elizabeth J; Zhang, Yafang; Green, Thomas A

2015-02-01

One hallmark of psychiatric conditions is the vast continuum of individual differences in susceptibility vs. resilience resulting from the interaction of genetic and environmental factors. The environmental enrichment paradigm is an animal model that is useful for studying a range of psychiatric conditions, including protective phenotypes in addiction and depression models. The major question is how environmental enrichment, a non-drug and non-surgical manipulation, can produce such robust individual differences in such a wide range of behaviors. This paper draws from a variety of published sources to outline a coherent hypothesis of inoculation stress as a factor producing the protective enrichment phenotypes. The basic tenet suggests that chronic mild stress from living in a complex environment and interacting non-aggressively with conspecifics can inoculate enriched rats against subsequent stressors and/or drugs of abuse. This paper reviews the enrichment phenotypes, mulls the fundamental nature of environmental enrichment vs. isolation, discusses the most appropriate control for environmental enrichment, and challenges the idea that cortisol/corticosterone equals stress. The intent of the inoculation stress hypothesis of environmental enrichment is to provide a scaffold with which to build testable hypotheses for the elucidation of the molecular mechanisms underlying these protective phenotypes and thus provide new therapeutic targets to treat psychiatric/neurological conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Phenotypic and genotypic antimicrobial susceptibility pattern of Streptococcus spp. isolated from cases of clinical mastitis in dairy cattle in Poland.

Science.gov (United States)

Kaczorek, E; Małaczewska, J; Wójcik, R; Rękawek, W; Siwicki, A K

2017-08-01

Mastitis of dairy cattle is one of the most frequently diagnosed diseases worldwide. The main etiological agents of mastitis are bacteria of the genus Streptococcus spp., in which several antibiotic resistance mechanisms have been identified. However, detailed studies addressing this problem have not been conducted in northeastern Poland. Therefore, the aim of our study was to analyze, on phenotypic and genotypic levels, the antibiotic resistance pattern of Streptococcus spp. isolated from clinical cases of mastitis from dairy cattle in this region of Poland. The research was conducted using 135 strains of Streptococcus (Streptococcus uberis, n = 53; Streptococcus dysgalactiae, n = 41; Streptococcus agalactiae, n = 27; other streptococci, n = 14). The investigation of the antimicrobial susceptibility to 8 active substances applied in therapy in the analyzed region, as well as a selected bacteriocin (nisin), was performed using the minimum inhibitory concentration method. The presence of selected resistance genes (n = 14) was determined via PCR. We also investigated the correlation between the presence of resistance genes and the antimicrobial susceptibility of the examined strains in vitro. The highest observed resistance of Streptococcus spp. was toward gentamicin, kanamycin, and tetracycline, whereas the highest susceptibility occurred toward penicillin, enrofloxacin, and marbofloxacin. Additionally, the tested bacteriocin showed high efficacy. The presence of 13 analyzed resistance genes was observed in the examined strains [gene mef(A) was not detected]. In most strains, at least one resistance gene, mainly responsible for resistance to tetracyclines [tet(M), tet(K), tet(L)], was observed. However, a relationship between the presence of a given resistance gene and antimicrobial susceptibility on the phenotypic level was not always observed. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Prevalence in the USA of rilpivirine resistance-associated mutations in clinical samples and effects on phenotypic susceptibility to rilpivirine and etravirine.

Science.gov (United States)

Picchio, Gaston R; Rimsky, Laurence T; Van Eygen, Veerle; Haddad, Mojgan; Napolitano, Laura A; Vingerhoets, Johan

2014-01-01

The prevalence of rilpivirine resistance-associated mutations (RAMs) in the USA, and their effect on phenotypic susceptibility to rilpivirine and etravirine, was evaluated in clinical samples from HIV-1-infected patients. In total, 15,991 samples submitted to Monogram Biosciences (South San Francisco, CA, USA) for routine resistance testing between January 2010 and June 2011 were assessed for the presence of known rilpivirine RAMs K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L; non-nucleoside reverse transcriptase inhibitor (NNRTI) RAMs K103N, L100I and L100I+K103N; and the nucleoside reverse transcriptase inhibitor (NRTI) RAMs M184I/V and their combinations with rilpivirine RAMs. Phenotypic susceptibility (PhenoSenseGT(®) assay; Monogram Biosciences) was evaluated, with reduced susceptibility defined as fold change (FC) in 50% inhibitory concentration (IC50)>2.0 for rilpivirine and FC>2.9 for etravirine. Of the 15,991 samples, 17% harboured ≥1 rilpivirine RAMs. The prevalence of most rilpivirine RAMs and combinations of NNRTI RAMs of interest was low (≤3%), except for Y181C (7%). Rilpivirine RAMs were often associated with reduced rilpivirine phenotypic susceptibility. Median FC values >2.0 were observed for clinical isolates with rilpivirine RAMs K101P, E138Q/R, Y181C/I/V, Y188L or M230L, and for the combination of E138K with M184I/V, and K101E with M184I. Most rilpivirine FC values >2.0 were associated with etravirine FC values >2.9 for individual rilpivirine RAMs and those combined with M184I/V. There was no relationship between the presence of K103N and rilpivirine FC. However, the L100I+K103N combination (without rilpivirine RAMs), at 2.0. Based on 15,991 US clinical samples from HIV-1-infected patients, the frequency of most known rilpivirine RAMs apart from Y181C was low.

Lymnaea schirazensis, an Overlooked Snail Distorting Fascioliasis Data: Genotype, Phenotype, Ecology, Worldwide Spread, Susceptibility, Applicability

Science.gov (United States)

Bargues, María Dolores; Artigas, Patricio; Khoubbane, Messaoud; Flores, Rosmary; Glöer, Peter; Rojas-García, Raúl; Ashrafi, Keyhan; Falkner, Gerhard; Mas-Coma, Santiago

2011-01-01

Background Lymnaeid snails transmit medical and veterinary important trematodiases, mainly fascioliasis. Vector specificity of fasciolid parasites defines disease distribution and characteristics. Different lymnaeid species appear linked to different transmission and epidemiological patterns. Pronounced susceptibility differences to absolute resistance have been described among lymnaeid populations. When assessing disease characteristics in different endemic areas, unexpected results were obtained in studies on lymnaeid susceptibility to Fasciola. We undertook studies to understand this disease transmission heterogeneity. Methodology/Principal Findings A ten-year study in Iran, Egypt, Spain, the Dominican Republic, Mexico, Venezuela, Ecuador and Peru, demonstrated that such heterogeneity is not due to susceptibility differences, but to a hitherto overlooked cryptic species, Lymnaea schirazensis, confused with the main vector Galba truncatula and/or other Galba/Fossaria vectors. Nuclear rDNA and mtDNA sequences and phylogenetic reconstruction highlighted an old evolutionary divergence from other Galba/Fossaria species, and a low intraspecific variability suggesting a recent spread from one geographical source. Morphometry, anatomy and egg cluster analyses allowed for phenotypic differentiation. Selfing, egg laying, and habitat characteristics indicated a migration capacity by passive transport. Studies showed that it is not a vector species (n = 8572 field collected, 20 populations): snail finding and penetration by F. hepatica miracidium occur but never lead to cercarial production (n = 338 experimentally infected). Conclusions/Significance This species has been distorting fasciolid specificity/susceptibility and fascioliasis geographical distribution data. Hence, a large body of literature on G. truncatula should be revised. Its existence has henceforth to be considered in research. Genetic data on livestock, archeology and history along the 10,000-year

Lymnaea schirazensis, an overlooked snail distorting fascioliasis data: genotype, phenotype, ecology, worldwide spread, susceptibility, applicability.

Directory of Open Access Journals (Sweden)

María Dolores Bargues

Full Text Available BACKGROUND: Lymnaeid snails transmit medical and veterinary important trematodiases, mainly fascioliasis. Vector specificity of fasciolid parasites defines disease distribution and characteristics. Different lymnaeid species appear linked to different transmission and epidemiological patterns. Pronounced susceptibility differences to absolute resistance have been described among lymnaeid populations. When assessing disease characteristics in different endemic areas, unexpected results were obtained in studies on lymnaeid susceptibility to Fasciola. We undertook studies to understand this disease transmission heterogeneity. METHODOLOGY/PRINCIPAL FINDINGS: A ten-year study in Iran, Egypt, Spain, the Dominican Republic, Mexico, Venezuela, Ecuador and Peru, demonstrated that such heterogeneity is not due to susceptibility differences, but to a hitherto overlooked cryptic species, Lymnaea schirazensis, confused with the main vector Galba truncatula and/or other Galba/Fossaria vectors. Nuclear rDNA and mtDNA sequences and phylogenetic reconstruction highlighted an old evolutionary divergence from other Galba/Fossaria species, and a low intraspecific variability suggesting a recent spread from one geographical source. Morphometry, anatomy and egg cluster analyses allowed for phenotypic differentiation. Selfing, egg laying, and habitat characteristics indicated a migration capacity by passive transport. Studies showed that it is not a vector species (n = 8572 field collected, 20 populations: snail finding and penetration by F. hepatica miracidium occur but never lead to cercarial production (n = 338 experimentally infected. CONCLUSIONS/SIGNIFICANCE: This species has been distorting fasciolid specificity/susceptibility and fascioliasis geographical distribution data. Hence, a large body of literature on G. truncatula should be revised. Its existence has henceforth to be considered in research. Genetic data on livestock, archeology and history

The Role of Oxidative Stress in the Longevity and Insecticide Resistance Phenotype of the Major Malaria Vectors Anopheles arabiensis and Anopheles funestus.

Directory of Open Access Journals (Sweden)

Shüné V Oliver

Full Text Available Oxidative stress plays numerous biological roles, both functional and pathological. The role of oxidative stress in various epidemiologically relevant biological traits in Anopheles mosquitoes is not well established. In this study, the effects of oxidative stress on the longevity and insecticide resistance phenotype in the major malaria vector species An. arabiensis and An. funestus were examined. Responses to dietary copper sulphate and hydrogen peroxide were used as proxies for the oxidative stress phenotype by determining the effect of copper on longevity and hydrogen peroxide lethal dose. Glutathione peroxidase and catalase activities were determined colorimetrically. Oxidative burden was quantified as protein carbonyl content. Changes in insecticide resistance phenotype were monitored by WHO bioassay. Insecticide resistant individuals showed an increased capacity for coping with oxidative stress, mediated by increased glutathione peroxidase and catalase activity. This effect was observed in both species, as well as in laboratory strains and F1 individuals derived from wild-caught An. funestus mothers. Phenotypic capacity for coping with oxidative stress was greatest in strains with elevated Cytochrome P450 activity. Synergism of oxidative stress defence enzymes by dietary supplementation with haematin, 3-Amino-1, 2, 4-triazole and Sodium diethyldithiocarbamate significantly increased pyrethroid-induced mortality in An. arabiensis and An. funestus. It is therefore concluded that defence against oxidative stress underlies the augmentation of the insecticide resistance phenotype associated with multiple blood-feeding. This is because multiple blood-feeding ultimately leads to a reduction of oxidative stress in insecticide resistant females, and also reduces the oxidative burden induced by DDT and pyrethroids, by inducing increased glutathione peroxidase activity. This study highlights the importance of oxidative stress in the longevity and

ALS Patient Stem Cells for Unveiling Disease Signatures of Motoneuron Susceptibility: Perspectives on the Deadly Mitochondria, ER Stress and Calcium Triad

Science.gov (United States)

Kaus, Anjoscha; Sareen, Dhruv

2015-01-01

Amyotrophic lateral sclerosis (ALS) is a largely sporadic progressive neurodegenerative disease affecting upper and lower motoneurons (MNs) whose specific etiology is incompletely understood. Mutations in superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TARDBP/TDP-43) and C9orf72, have been identified in subsets of familial and sporadic patients. Key associated molecular and neuropathological features include ubiquitinated TDP-43 inclusions, stress granules, aggregated dipeptide proteins from mutant C9orf72 transcripts, altered mitochondrial ultrastructure, dysregulated calcium homeostasis, oxidative and endoplasmic reticulum (ER) stress, and an unfolded protein response (UPR). Such impairments have been documented in ALS animal models; however, whether these mechanisms are initiating factors or later consequential events leading to MN vulnerability in ALS patients is debatable. Human induced pluripotent stem cells (iPSCs) are a valuable tool that could resolve this “chicken or egg” causality dilemma. Relevant systems for probing pathophysiologically affected cells from large numbers of ALS patients and discovering phenotypic disease signatures of early MN susceptibility are described. Performing unbiased ‘OMICS and high-throughput screening in relevant neural cells from a cohort of ALS patient iPSCs, and rescuing mitochondrial and ER stress impairments, can identify targeted therapeutics for increasing MN longevity in ALS. PMID:26635528

Metabolomics reveals distinct neurochemical profiles associated with stress resilience

Directory of Open Access Journals (Sweden)

Brooke N. Dulka

2017-12-01

Full Text Available Acute social defeat represents a naturalistic form of conditioned fear and is an excellent model in which to investigate the biological basis of stress resilience. While there is growing interest in identifying biomarkers of stress resilience, until recently, it has not been feasible to associate levels of large numbers of neurochemicals and metabolites to stress-related phenotypes. The objective of the present study was to use an untargeted metabolomics approach to identify known and unknown neurochemicals in select brain regions that distinguish susceptible and resistant individuals in two rodent models of acute social defeat. In the first experiment, male mice were first phenotyped as resistant or susceptible. Then, mice were subjected to acute social defeat, and tissues were immediately collected from the ventromedial prefrontal cortex (vmPFC, basolateral/central amygdala (BLA/CeA, nucleus accumbens (NAc, and dorsal hippocampus (dHPC. Ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS was used for the detection of water-soluble neurochemicals. In the second experiment, male Syrian hamsters were paired in daily agonistic encounters for 2 weeks, during which they formed stable dominant-subordinate relationships. Then, 24 h after the last dominance encounter, animals were exposed to acute social defeat stress. Immediately after social defeat, tissue was collected from the vmPFC, BLA/CeA, NAc, and dHPC for analysis using UPLC-HRMS. Although no single biomarker characterized stress-related phenotypes in both species, commonalities were found. For instance, in both model systems, animals resistant to social defeat stress also show increased concentration of molecules to protect against oxidative stress in the NAc and vmPFC. Additionally, in both mice and hamsters, unidentified spectral features were preliminarily annotated as potential targets for future experiments. Overall, these findings

Metabolic mechanisms behind the type 2 diabetes susceptible phenotype in low birth weight individuals

DEFF Research Database (Denmark)

Ribel-Madsen, Amalie

Background and aims: Low birth weight (LBW) individuals have an increased risk of developing insulin resistance and type 2 diabetes compared with normal birth weight (NBW) individuals. Accordingly, young, healthy, LBW men of the study population examined in the present plasma metabolome studies...... show impaired hepatic insulin sensitivity and, in contrast to NBW men, develop impaired peripheral insulin sensitivity in response to a 5-day high-fat overfeeding. However, the metabolic mechanisms behind the type 2 diabetes susceptible phenotype in LBW individuals are not clear. Our primary aim...... available for lipogenesis, including the synthesis of lipotoxic lipids such as ceramides and diacylglycerols that impair insulin signalling. In the second study, we demonstrated that LBW men had higher plasma alanine, proline, methionine, citrulline, and total amino acid levels after the HFHC diet compared...

Behavioral phenotype relates to physiological differences in immunological and stress responsiveness in reactive and proactive birds.

Science.gov (United States)

Pusch, Elizabeth A; Navara, Kristen J

2018-05-15

It has now been demonstrated in many species that individuals display substantial variation in coping styles, generally separating into two major behavioral phenotypes that appear to be linked to the degree of physiological stress responsiveness. Laying hens are perfect examples of these dichotomous phenotypes; white laying hens are reactive, flighty, and exhibit large hormonal and behavioral responses to both acute and chronic stress, while brown laying hens are proactive, exploratory, and exhibit low hormonal and behavioral responses to stress. Given the linkages between stress physiology and many other body systems, we hypothesized that behavioral phenotype would correspond to additional physiological responses beyond the stress response, in this case, immunological responses. Because corticosterone is widely known to be immunosuppressive, we predicted that the reactive white hens would show more dampened immune responses than the proactive brown hens due to their exposure to higher levels of corticosterone throughout life. To assess immune function in white and brown hens, we compared febrile responses, corticosterone elevations, feed consumption, and egg production that occurred in response an injection of lipopolysaccharide (LPS) or saline, inflammatory responses to phytohemagglutinin (PHA) injection in the toe web, innate phagocytic activity in whole blood, and antibody responses to an injection of Sheep Red Blood Cells (SRBCs). Contrary to our predictions, white hens had significantly greater swelling of the toe web in response to PHA and showed a greater inhibition of feeding and reproductive output in response to LPS. These results indicated that reactive individuals are more reactive in both stress and immunological responsiveness. Copyright © 2018 Elsevier Inc. All rights reserved.

PON1 promoter polymorphisms contribute to PCOS susceptibility and phenotypic outcomes in Indian women.

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Dadachanji, Roshan; Shaikh, Nuzhat; Patil, Anushree; Shah, Nalini; Mukherjee, Srabani

2018-06-30

Polycystic ovary syndrome is a common endocrinopathy characterized by anovulatory infertility, hyperandrogenism, insulin resistance and oxidative stress, which predisposes affected women to reproductive and cardiometabolic complications in later life. We have investigated the association of PON1 promoter polymorphisms with PCOS susceptibility, PON1 activity and its related traits in Indian women. The genotypic and allelic frequency distribution of only -907G/C polymorphism in PON1 promoter showed significant difference between non-hyperandrogenic control and PCOS women, and was significantly associated with reduced susceptibility to PCOS, considering the recessive model. PON1 lactonase and arylesterase activities were also significantly decreased in women with PCOS compared to controls. Further, PON1 promoter polymorphisms were linked to altered insulin and testosterone levels in hyperandrogenic and non-hyperandrogenic women with PCOS. This study highlights PON1 as an important candidate gene influencing genetic pathophysiology of PCOS. Copyright © 2018 Elsevier B.V. All rights reserved.

Polygenic risk for alcohol consumption and its association with alcohol-related phenotypes: Do stress and life satisfaction moderate these relationships?

Science.gov (United States)

Mies, Gabry W; Verweij, Karin J H; Treur, Jorien L; Ligthart, Lannie; Fedko, Iryna O; Hottenga, Jouke Jan; Willemsen, Gonneke; Bartels, Meike; Boomsma, Dorret I; Vink, Jacqueline M

2018-02-01

Genetic and environmental factors contribute about equally to alcohol-related phenotypes in adulthood. In the present study, we examined whether more stress at home or low satisfaction with life might be associated with heavier drinking or more alcohol-related problems in individuals with a high genetic susceptibility to alcohol use. Information on polygenic scores and drinking behavior was available in 6705 adults (65% female; 18-83 years) registered with the Netherlands Twin Register. Polygenic risk scores (PRSs) were constructed for all subjects based on the summary statistics of a large genome-wide association meta-analysis on alcohol consumption (grams per day). Outcome measures were quantity of alcohol consumption and alcohol-related problems assessed with the Alcohol Use Disorders Identification Test (AUDIT). Stress at home and life satisfaction were moderating variables whose significance was tested by Generalized Estimating Equation analyses taking familial relatedness, age and sex into account. PRSs for alcohol were significantly associated with quantity of alcohol consumption and alcohol-related problems in the past year (R 2 =0.11% and 0.10% respectively). Participants who reported to have experienced more stress in the past year and lower life satisfaction, scored higher on alcohol-related problems (R 2 =0.27% and 0.29 respectively), but not on alcohol consumption. Stress and life satisfaction did not moderate the association between PRSs and the alcohol outcome measures. There were significant main effects of polygenic scores and of stress and life satisfaction on drinking behavior, but there was no support for PRS-by-stress or PRS-by-life satisfaction interactions on alcohol consumption and alcohol-related problems. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Stress corrosion cracking susceptibility of the earthquake resistant NOM B457 Mexican steel

International Nuclear Information System (INIS)

Arganis J, C.R.

1994-01-01

The Mexican construction code was modified after the Mexico city 1985 earthquake, substituted the medium carbon reinforced steel NOM B6 by the new micro alloyed steel NOM B457 in 42 Kg/mm 2 grade. The present study reports the evaluation of the NOM B457 steel behavior in mortar with and without 2% wt. in chlorides and in Ca(OH) 2 saturated solutions. The results are compared with the NOM B6 steel behavior in the same conditions. The Stress Corrosion Cracking (SCC) is not present in all the conditions used in this study and there are not susceptibility potential range to SCC when the material is evaluated by electrochemical Tests, Constant Extension Rate Tests (CERT) and Constant Load Test at 80 % of yield stress. A susceptibility potential range to Hydrogen Induced Cracking (HIC) is detected, below -900 mV. vs Standard Calomel Electrode (SCE) by CERT at constant potential

The Relationship between the Broader Autism Phenotype, Child Severity, and Stress and Depression in Parents of Children with Autism Spectrum Disorders

Science.gov (United States)

Ingersoll, Brooke; Hambrick, David Z.

2011-01-01

This study examined the relationship between child symptom severity, parent broader autism phenotype (BAP), and stress and depression in parents of children with ASD. One hundred and forty-nine parents of children with ASD completed a survey of parenting stress, depression, broader autism phenotype, coping styles, perceived social support, and…

Microstructural investigation of vintage pipeline steels highly susceptible to stress corrosion cracking

Science.gov (United States)

Torres, Monica

The use of pipelines for the transmission of gas offers not only efficiency, but a number of economic advantages. Nevertheless, pipelines are subject to aggressive operating conditions and environments which can lead to in-service degradation [1] and thus to failures. These failures can have catastrophic consequences, such as environmental damage and loss of life [2]. One of the most dangerous threats to pipeline integrity is stress corrosion cracking (SCC). Despite the substantial progress that has been achieved in the field, due to the complex nature of this phenomenon there is still not a complete understanding of this form of external corrosion. This makes its detection and prevention a challenge and therefore a risk to pipeline integrity, and most importantly, to the safety of the population. SCC cracks are the result of the interaction between a corrosive environment, applied stresses, and a susceptible microstructure. To date, what defines a susceptible microstructure remains ambiguous, as SCC has been observed in a range of steel grades, microstructures, chemical composition, and grain sizes. Therefore, in order to be able to accurately predict and prevent this hazardous form of corrosion, it is imperative to advance our knowledge on the subject and gain a better understanding on the microstructural features of highly susceptible pipeline materials, especially in the subsurface zone where crack nucleation must take place. Therefore, a microstructural characterization of the region near the surface layer was carried-out utilizing TEM. TEM analysis revealed the dislocation character, ferrite morphology, and apparent carbide precipitation in some grain boundaries. Furthermore, light microscopy, SEM, and hardness testing were performed to expand our knowledge on the microscopical features of highly SCC susceptible service components. This investigation presents a new approach to SCC characterization, which exposed the sub-surface region microscopical

Transgenerational Inheritance of Paternal Neurobehavioral Phenotypes: Stress, Addiction, Ageing and Metabolism.

Science.gov (United States)

Yuan, Ti-Fei; Li, Ang; Sun, Xin; Ouyang, Huan; Campos, Carlos; Rocha, Nuno B F; Arias-Carrión, Oscar; Machado, Sergio; Hou, Gonglin; So, Kwok Fai

2016-11-01

Epigenetic modulation is found to get involved in multiple neurobehavioral processes. It is believed that different types of environmental stimuli could alter the epigenome of the whole brain or related neural circuits, subsequently contributing to the long-lasting neural plasticity of certain behavioral phenotypes. While the maternal influence on the health of offsprings has been long recognized, recent findings highlight an alternative way for neurobehavioral phenotypes to be passed on to the next generation, i.e., through the male germ line. In this review, we focus specifically on the transgenerational modulation induced by environmental stress, drugs of abuse, and other physical or mental changes (e.g., ageing, metabolism, fear) in fathers, and recapitulate the underlying mechanisms potentially mediating the alterations in epigenome or gene expression of offsprings. Together, these findings suggest that the inheritance of phenotypic traits through male germ-line epigenome may represent the unique manner of adaptation during evolution. Hence, more attention should be paid to the paternal health, given its equivalently important role in affecting neurobehaviors of descendants.

Stress corrosion cracking susceptibility of steam generator tube materials in AVT (all volatile treatment) chemistry contaminated with lead

International Nuclear Information System (INIS)

Gomez Briceno, D.; Castano, M.L.; Garcia, M.S.

1996-01-01

Alloy 600 steam generator tubing has shown a high susceptibility to stress corrosion degradation at the operation conditions of pressurized water reactors. Several contaminants, such as lead, have been postulated as being responsible for producing the secondary side stress corrosion cracking that has occurred mainly at the location where these contaminants can concentrate. An extensive experimental work has been carried out in order to better understand the effects of lead on the stress corrosion cracking susceptibility of steam generator tube materials, namely Alloys 600, 690 and 800. This paper presents the experimental work conducted with a view to determining the influence of lead oxide concentration in AVT (all volatile treatment) conditions on the stress corrosion resistance of nickel alloys used in the fabrication of steam generator tubing. (orig.)

Neuropsychiatry phenotype in asthma: Psychological stress-induced alterations of the neuroendocrine-immune system in allergic airway inflammation

Directory of Open Access Journals (Sweden)

Isao Ohno

2017-09-01

Full Text Available Since the recognition of asthma as a syndrome with complex pathophysiological signs and symptoms, recent research has sought to classify asthma phenotypes based on its clinical and molecular pathological features. Psychological stress was first recognized as a potential immune system modulator of asthma at the end of the 19th century. The activation of the central nervous system (CNS upon exposure to psychological stress is integral for the initiation of signal transduction processes. The stress hormones, including glucocorticoids, epinephrine, and norepinephrine, which are secreted following CNS activation, are involved in the immunological alterations involved in psychological stress-induced asthma exacerbation. The mechanisms underlying this process may involve a pathological series of events from the brain to the lungs, which is attracting attention as a conceptually advanced phenotype in asthma pathogenesis. This review presents insights into the critical role of psychological stress in the development and exacerbation of allergic asthma, with a special focus on our own data that emphasizes on the continuity from the central sensing of psychological stress to enhanced eosinophilic airway inflammation.

Stress susceptibility as a determinant of endothelium-dependent vascular reactivity in rat mesenteric arteries.

NARCIS (Netherlands)

Riksen, N.P.; Ellenbroek, B.A.; Cools, A.R.; Siero, H.L.M.; Rongen, G.A.P.J.M.; Smits, B.W.; Russel, F.G.M.; Smits, P.

2003-01-01

In order to investigate the consequences of stress susceptibility on vascular function, the authors assessed the respective contributions of nitric oxide (NO), prostanoids, and endothelium-derived hyperpolarizing factor to the vascular tone in rats with a constitutionally determined high and low

Desipramine rescues age-related phenotypes in depression-like rats induced by chronic mild stress.

Science.gov (United States)

Xie, Xiaoxian; Chen, Yangyang; Wang, Qi; Shen, Qichen; Ma, Lingyan; Huang, Liangfeng; Wu, Tao; Fu, Zhengwei

2017-11-01

Our previous finding demonstrates that major depressive disorder can mediate accelerated aging in rats. Desipramine is a typical tricyclic antidepressant, and can provide neuroprotection and counteract depression-like behaviors. However, whether desipramine can rescue age-related phenotypes in depressed individuals is not understood. In the present study, we investigated the physiological function of desipramine on rescuing the age-related phenotypes in these animals. The rats were induced by chronic mild stress paradigm, and the depression-like behaviors of rats were detected by sucrose intake test, open field test (OFT) and forced swimming test (FST). Then the depressed rats were treated by desipramine. Desipramine administration was effective in counteracting depression-like behaviors by increasing the sucrose solution intake, reducing the immobility time in the FST, and increasing total distance travelled and numbers of grid line crossed in the OFT. Moreover, desipramine treatment was able to reduce the oxidative damage to rat liver, and to increase the expression of telomerase reverse transcriptase (TERT), leading to correspondingly restored telomerase activity. Our findings identify that one function of desipramine may partly be to rescue age-related phenotypes in depressed individuals induced by chronic stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Standard practice for determining cracking susceptibility of metals exposed under stress to a hot salt environment

CERN Document Server

American Society for Testing and Materials. Philadelphia

1990-01-01

1.1 This practice covers procedures for testing metals for embrittlement and cracking susceptibility when exposed under stress to a hot salt environment. This practice can be used for testing all metals for which service conditions dictate the need for such information. The test procedures described herein are generally applicable to all metal alloys; required adjustments in environmental variables (temperature, stress) to characterize a given materials system should be made. This practice describes the environmental conditions and degree of control required, and suggests means for obtaining this desired control. 1.2 This practice can be used both for alloy screening for determination of relative susceptibility to embrittlement and cracking, and for the determination of time-temperature-stress threshold levels for onset of embrittlement and cracking. However, certain specimen types are more suitable for each of these two types of characterizations. Note 1 This practice relates solely to the performance of ...

Knockdown of wfs1, a fly homolog of Wolfram syndrome 1, in the nervous system increases susceptibility to age- and stress-induced neuronal dysfunction and degeneration in Drosophila.

Science.gov (United States)

Sakakibara, Yasufumi; Sekiya, Michiko; Fujisaki, Naoki; Quan, Xiuming; Iijima, Koichi M

2018-01-01

Wolfram syndrome (WS), caused by loss-of-function mutations in the Wolfram syndrome 1 gene (WFS1), is characterized by juvenile-onset diabetes mellitus, bilateral optic atrophy, and a wide spectrum of neurological and psychiatric manifestations. WFS1 encodes an endoplasmic reticulum (ER)-resident transmembrane protein, and mutations in this gene lead to pancreatic β-cell death induced by high levels of ER stress. However, the mechanisms underlying neurodegeneration caused by WFS1 deficiency remain elusive. Here, we investigated the role of WFS1 in the maintenance of neuronal integrity in vivo by knocking down the expression of wfs1, the Drosophila homolog of WFS1, in the central nervous system. Neuronal knockdown of wfs1 caused age-dependent behavioral deficits and neurodegeneration in the fly brain. Knockdown of wfs1 in neurons and glial cells resulted in premature death and significantly exacerbated behavioral deficits in flies, suggesting that wfs1 has important functions in both cell types. Although wfs1 knockdown alone did not promote ER stress, it increased the susceptibility to oxidative stress-, excitotoxicity- or tauopathy-induced behavioral deficits, and neurodegeneration. The glutamate release inhibitor riluzole significantly suppressed premature death phenotypes induced by neuronal and glial knockdown of wfs1. This study highlights the protective role of wfs1 against age-associated neurodegeneration and furthers our understanding of potential disease-modifying factors that determine susceptibility and resilience to age-associated neurodegenerative diseases.

Knockdown of wfs1, a fly homolog of Wolfram syndrome 1, in the nervous system increases susceptibility to age- and stress-induced neuronal dysfunction and degeneration in Drosophila.

Directory of Open Access Journals (Sweden)

Yasufumi Sakakibara

2018-01-01

Full Text Available Wolfram syndrome (WS, caused by loss-of-function mutations in the Wolfram syndrome 1 gene (WFS1, is characterized by juvenile-onset diabetes mellitus, bilateral optic atrophy, and a wide spectrum of neurological and psychiatric manifestations. WFS1 encodes an endoplasmic reticulum (ER-resident transmembrane protein, and mutations in this gene lead to pancreatic β-cell death induced by high levels of ER stress. However, the mechanisms underlying neurodegeneration caused by WFS1 deficiency remain elusive. Here, we investigated the role of WFS1 in the maintenance of neuronal integrity in vivo by knocking down the expression of wfs1, the Drosophila homolog of WFS1, in the central nervous system. Neuronal knockdown of wfs1 caused age-dependent behavioral deficits and neurodegeneration in the fly brain. Knockdown of wfs1 in neurons and glial cells resulted in premature death and significantly exacerbated behavioral deficits in flies, suggesting that wfs1 has important functions in both cell types. Although wfs1 knockdown alone did not promote ER stress, it increased the susceptibility to oxidative stress-, excitotoxicity- or tauopathy-induced behavioral deficits, and neurodegeneration. The glutamate release inhibitor riluzole significantly suppressed premature death phenotypes induced by neuronal and glial knockdown of wfs1. This study highlights the protective role of wfs1 against age-associated neurodegeneration and furthers our understanding of potential disease-modifying factors that determine susceptibility and resilience to age-associated neurodegenerative diseases.

Genetic control of susceptibility to apoptosis of thymocytes

International Nuclear Information System (INIS)

Mori, N.; Okumoto, M.; Morimoto, J.; Imai, S.; Matsuyama, T.; Takamori, Y.; Yagasaki, O.

1992-01-01

Genetic control of the susceptibility of thymocytes to radiation-induced apoptosis in mice was investigated by counting dead cells in a selected area of thymic cortex on histological specimens after whole-body X-irradiation. The number of dead cells increased almost linearly with doses in BALB/cHeA and STS/A mice. However, dead cell counts in BALB/cHeA mice were more than twice those in STS/A mice at each dose. C57BL/6N and B10.BR mice exhibited a sensitive phenotype similar to BALB/cHeA mice, while C3H/HeMsNrs and NFS/N mice showed a resistant phenotype similar to STS/A mice. Sex difference in the susceptibility of thymocytes to cell death was not recognized in BALB/cHeA and STS/A mice. Resistance was dominant over susceptibility in the progenies of reciprocal crosses between the two strains, indicating an autosomal inheritance. The segregation ratio of susceptible to resistant phenotype in the backcrosses of (BALB/cHeA X STS/A)F 1 with BALB/cHeA was not significantly different from 1 : 1 and all backcrosses of (BALB/cHeA X STS/A)F 1 with STS/A exhibited a resistant phenotype. The results demonstrated that the difference in the susceptibility of thymocytes to radiation-induced apoptosis in the two strains of mice is due to one major autosomal allele. (author)

Evaluation of Virulence Factors In vitro, Resistance to Osmotic Stress and Antifungal Susceptibility of Candida tropicalis Isolated from the Coastal Environment of Northeast Brazil

Science.gov (United States)

Zuza-Alves, Diana L.; de Medeiros, Sayama S. T. Q.; de Souza, Luanda B. F. C.; Silva-Rocha, Walicyranison P.; Francisco, Elaine C.; de Araújo, Maria C. B.; Lima-Neto, Reginaldo G.; Neves, Rejane P.; Melo, Analy S. de Azevedo; Chaves, Guilherme M.

2016-01-01

Several studies have been developed regarding human health risks associated with the recreational use of beaches contaminated with domestic sewage. These wastes contain various micro-organisms, including Candida tropicalis. In this context, the objective of this study was to characterize C. tropicalis isolates from the sandy beach of Ponta Negra, Natal, Rio Grande do Norte, Brazil, regarding the expression of in vitro virulence factors, adaptation to osmotic stress and susceptibility to antifungal drugs. We analyzed 62 environmental isolates and observed a great variation among them for the various virulence factors evaluated. In general, environmental isolates were more adherent to human buccal epithelial cells (HBEC) than C. tropicalis ATCC13803 reference strain, and they also showed increased biofilm production. Most of the isolates presented wrinkled phenotypes on Spider medium (34 isolates, 54.8%). The majority of the isolates also showed higher proteinase production than control strains, but low phospholipase activity. In addition, 35 isolates (56.4%) had high hemolytic activity (hemolysis index > 0.55). With regard to C. tropicalis resistance to osmotic stress, 85.4% of the isolates were able to grow in a liquid medium containing 15% sodium chloride. The strains were highly resistant to the azoles tested (fluconazole, voriconazole and itraconazole). Fifteen strains were resistant to the three azoles tested (24.2%). Some strains were also resistant to amphotericin B (14 isolates; 22.6%), while all of them were susceptible for the echinocandins tested, except for a single strain of intermediate susceptibility to micafungin. Our results demonstrate that C. tropicalis isolated from the sand can fully express virulence attributes and showed a high persistence capacity on the coastal environment; in addition of showing high minimal inhibitory concentrations to several antifungal drugs used in current clinical practice, demonstrating that environmental isolates may

Use of Noninvasive Bone Structural Measurements to Evaluate Stress Fracture Susceptibility Among Female Recruits in U.S. Marine Corps Basic Training: Individual Profiles of Stress Fracture Susceptibility Among Female Recruits in U.S. Marine Corps Basic Training

National Research Council Canada - National Science Library

Shaffer, Rick

1996-01-01

The objective of this study was to derive predictive models of stress fracture susceptibility in female military recruits by administering a questionnaire highlighting exercise and health habits prior...

Grain boundary segregation and intergranular stress corrosion cracking susceptibility of austenitic stainless steels in high temperature water

International Nuclear Information System (INIS)

Shoji, T.; Yamaki, K.; Ballinger, R.G.; Hwang, I.S.

1992-01-01

The effects of grain boundary segregation on intergranular stress corrosion cracking of austenitic stainless steels in high temperature water have been examined as a function of heat treatment. The materials investigated were: (1) two commercial purity Type 304; (2) low sulfur Type 304; (3) nuclear grade Type 304; (4) ultra high purity Type 304L; and (5) Type 316L and Type 347L. Specimens were solution treated at 1050 degrees C for 0.5 hour and given a sensitization heat treatment at 650 degrees C for 50 hours. Some of the specimens were then subjected to an aging heat treatment at 850 degrees C for from one to ten hours to cause Cr recovery at the grain boundaries. The effects of heat treatments on degree of sensitization and grain boundary segregation were evaluated by Electrochemical Potentiokinetic Reactivation (EPR) and Coriou tests, respectively. The susceptibility to stress corrosion (SCC) was evaluated using slow strain rate tests technique (SSRT) in high temperature water. SSRT tests were performed in an aerated pure water (8 ppm dissolved oxygen) at 288 degrees C at a strain rate of 1.33 x 10 -6 /sec. Susceptibility to intergranular stress corrosion cracking was compared with degree of sensitization and grain boundary segregation. The results of the investigation indicate that EPR is not always an accurate indicator of SCC susceptibility. The Coriou test provides a more reliable measure of SCC susceptibility especially for 304L, 304NG, 316L, and 347L stainless steels. The results also indicate that grain boundary segregation as well as degree of sensitization must be considered in the determination of SCC susceptibility

Mesenchymal phenotype predisposes lung cancer cells to impaired proliferation and redox stress in response to glutaminase inhibition.

Directory of Open Access Journals (Sweden)

Danielle B Ulanet

Full Text Available Recent work has highlighted glutaminase (GLS as a key player in cancer cell metabolism, providing glutamine-derived carbon and nitrogen to pathways that support proliferation. There is significant interest in targeting GLS for cancer therapy, although the gene is not known to be mutated or amplified in tumors. As a result, identification of tractable markers that predict GLS dependence is needed for translation of GLS inhibitors to the clinic. Herein we validate a small molecule inhibitor of GLS and show that non-small cell lung cancer cells marked by low E-cadherin and high vimentin expression, hallmarks of a mesenchymal phenotype, are particularly sensitive to inhibition of the enzyme. Furthermore, lung cancer cells induced to undergo epithelial to mesenchymal transition (EMT acquire sensitivity to the GLS inhibitor. Metabolic studies suggest that the mesenchymal cells have a reduced capacity for oxidative phosphorylation and increased susceptibility to oxidative stress, rendering them unable to cope with the perturbations induced by GLS inhibition. These findings elucidate selective metabolic dependencies of mesenchymal lung cancer cells and suggest novel pathways as potential targets in this aggressive cancer type.

Effects of Cr and Nb contents on the susceptibility of Alloy 600 type Ni-base alloys to stress-corrosion cracking in a simulated BWR environment

International Nuclear Information System (INIS)

Akashi, Masatsune

1995-01-01

In order to discuss the effects of chromium and niobium contents on the susceptibility of Alloy 600 type nickel-base alloys to stress-corrosion cracking in the BWR primary coolant environment, a series of creviced bent-beam (CBB) tests were conducted in a high-temperature, high-purity water environment. Chromium, niobium, and titanium as alloying elements improved the resistivity to stress-corrosion cracking, whereas carbon enhanced the susceptibility to it. Alloy-chemistry-based correlations have been defined to predict the relative resistances of alloys to stress-corrosion cracking. A strong correlation was found, for several heats of alloys, between grain-boundary chromium depletion and the susceptibility to stress-corrosion cracking

Gene expression profiles deciphering rice phenotypic variation between Nipponbare (Japonica and 93-11 (Indica during oxidative stress.

Directory of Open Access Journals (Sweden)

Fengxia Liu

Full Text Available Rice is a very important food staple that feeds more than half the world's population. Two major Asian cultivated rice (Oryza sativa L. subspecies, japonica and indica, show significant phenotypic variation in their stress responses. However, the molecular mechanisms underlying this phenotypic variation are still largely unknown. A common link among different stresses is that they produce an oxidative burst and result in an increase of reactive oxygen species (ROS. In this study, methyl viologen (MV as a ROS agent was applied to investigate the rice oxidative stress response. We observed that 93-11 (indica seedlings exhibited leaf senescence with severe lesions under MV treatment compared to Nipponbare (japonica. Whole-genome microarray experiments were conducted, and 1,062 probe sets were identified with gene expression level polymorphisms between the two rice cultivars in addition to differential expression under MV treatment, which were assigned as Core Intersectional Probesets (CIPs. These CIPs were analyzed by gene ontology (GO and highlighted with enrichment GO terms related to toxin and oxidative stress responses as well as other responses. These GO term-enriched genes of the CIPs include glutathine S-transferases (GSTs, P450, plant defense genes, and secondary metabolism related genes such as chalcone synthase (CHS. Further insertion/deletion (InDel and regulatory element analyses for these identified CIPs suggested that there may be some eQTL hotspots related to oxidative stress in the rice genome, such as GST genes encoded on chromosome 10. In addition, we identified a group of marker genes individuating the japonica and indica subspecies. In summary, we developed a new strategy combining biological experiments and data mining to study the possible molecular mechanism of phenotypic variation during oxidative stress between Nipponbare and 93-11. This study will aid in the analysis of the molecular basis of quantitative traits.

MicroRNAs in Post-traumatic Stress Disorder.

Science.gov (United States)

Snijders, Clara; de Nijs, Laurence; Baker, Dewleen G; Hauger, Richard L; van den Hove, Daniel; Kenis, Gunter; Nievergelt, Caroline M; Boks, Marco P; Vermetten, Eric; Gage, Fred H; Rutten, Bart P F

2017-10-21

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop following exposure to or witnessing of a (potentially) threatening event. A critical issue is to pinpoint the (neuro)biological mechanisms underlying the susceptibility to stress-related disorder such as PTSD, which develops in the minority of ~15% of individuals exposed to trauma. Over the last few years, a first wave of epigenetic studies has been performed in an attempt to identify the molecular underpinnings of the long-lasting behavioral and mental effects of trauma exposure. The potential roles of non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) in moderating or mediating the impact of severe stress and trauma are increasingly gaining attention. To date, most studies focusing on the roles of miRNAs in PTSD have, however, been completed in animals, using cross-sectional study designs and focusing almost exclusively on subjects with susceptible phenotypes. Therefore, there is a strong need for new research comprising translational and cross-species approaches that use longitudinal designs for studying trajectories of change contrasting susceptible and resilient subjects. The present review offers a comprehensive overview of available studies of miRNAs in PTSD and discusses the current challenges, pitfalls, and future perspectives of this field.

Understanding susceptibility of in-core components to irradiation-assisted stress corrosion cracking

International Nuclear Information System (INIS)

Chung, H.M.; Ruther, W.E.; Sanecki, J.E.; Kassner, T.F.

1991-03-01

As nuclear plants age and accumulated fluences of core structural components increase, susceptibility of the components to irradiation-assisted stress corrosion cracking (IASCC) is also expected to increase. Irradiation-induced sensitization, commonly associated with an IASCC failure, was investigated in this study to provide a better understanding of long-term structural integrity of safety-significant in-core components. Irradiation-induced sensitization of high- and commercial-purity Type 304 stainless steels irradiated in BWRs was analyzed. 7 refs., 8 figs

Linking dynamic phenotyping with metabolite analysis to study natural variation in drought responses of Brachypodium distachyon

Directory of Open Access Journals (Sweden)

Lorraine H.C. Fisher

2016-11-01

Full Text Available Drought is an important environmental stress limiting the productivity of major crops worldwide. Understanding drought tolerance and possible mechanisms for improving drought resistance is therefore a prerequisite to develop drought-tolerant crops that produce significant yields with reduced amounts of water. Brachypodium distachyon (Brachypodium is a key model species for cereals, forage grasses and energy grasses. In this study, initial screening of a Brachypodium germplasm collection consisting of 138 different ecotypes exposed to progressive drought, highlighted the natural variation in morphology, biomass accumulation and responses to drought stress. A core set of ten ecotypes, classified as being either tolerant, susceptible or intermediate, in response to drought stress, were exposed to mild or severe (respectively 15% and 0% soil water content drought stress and phenomic parameters linked to growth and colour changes were assessed. When exposed to severe drought stress, phenotypic data and metabolite profiling combined with multivariate analysis revealed a remarkable consistency in separating the selected ecotypes into their different pre-defined drought tolerance groups. Increases in several metabolites, including for the phytohormones jasmonic acid and salicylic acid, and TCA-cycle intermediates, were positively correlated with biomass yield and with reduced yellow pixel counts; suggestive of delayed senescence, both key target traits for crop improvement to drought stress. While metabolite analysis also separated ecotypes into the distinct tolerance groupings after exposure to mild drought stress, similar analysis of the phenotypic data failed to do so, confirming the value of metabolomics to investigate early responses to drought stress. The results highlight the potential of combining the analyses of phenotypic and metabolic responses to identify key mechanisms and markers associated with drought tolerance in both the Brachypodium

Global Phenotypic Characterization of Effects of Fluoroquinolone Resistance Selection on the Metabolic Activities and Drug Susceptibilities of Clostridium perfringens Strains

Directory of Open Access Journals (Sweden)

Miseon Park

2014-01-01

Full Text Available Fluoroquinolone resistance affects toxin production of Clostridium perfringens strains differently. To investigate the effect of fluoroquinolone resistance selection on global changes in metabolic activities and drug susceptibilities, four C. perfringens strains and their norfloxacin-, ciprofloxacin-, and gatifloxacin-resistant mutants were compared in nearly 2000 assays, using phenotype microarray plates. Variations among mutant strains resulting from resistance selection were observed in all aspects of metabolism. Carbon utilization, pH range, osmotic tolerance, and chemical sensitivity of resistant strains were affected differently in the resistant mutants depending on both the bacterial genotype and the fluoroquinolone to which the bacterium was resistant. The susceptibilities to gentamicin and erythromycin of all resistant mutants except one increased, but some resistant strains were less susceptible to amoxicillin, cefoxitin, ceftriaxone, chloramphenicol, and metronidazole than their wild types. Sensitivity to ethidium bromide decreased in some resistant mutants and increased in others. Microarray analysis of two gatifloxacin-resistant mutants showed changes in metabolic activities that were correlated with altered expression of various genes. Both the chemical structures of fluoroquinolones and the genomic makeup of the wild types influenced the changes found in resistant mutants, which may explain some inconsistent reports of the effects of therapeutic use of fluoroquinolones on clinical isolates of bacteria.

ADRA2B deletion variant influences time-dependent effects of pre-learning stress on long-term memory.

Science.gov (United States)

Zoladz, Phillip R; Dailey, Alison M; Nagle, Hannah E; Fiely, Miranda K; Mosley, Brianne E; Brown, Callie M; Duffy, Tessa J; Scharf, Amanda R; Earley, McKenna B; Rorabaugh, Boyd R

2017-04-01

Extensive work over the past few decades has shown that certain genetic variations interact with life events to confer increased susceptibility for the development of psychological disorders. The deletion variant of the ADRA2B gene, which has been associated with enhanced emotional memory and heightened amygdala responses to emotional stimuli, might confer increased susceptibility for the development of post-traumatic stress disorder (PTSD) or related phenotypes by increasing the likelihood of traumatic memory formation. Thus, we examined whether this genetic variant would predict stress effects on learning and memory in a non-clinical sample. Two hundred and thirty-five individuals were exposed to the socially evaluated cold pressor test or a control condition immediately or 30min prior to learning a list of words that varied in emotional valence and arousal level. Participants' memory for the words was tested immediately (recall) and 24h after learning (recall and recognition), and saliva samples were collected to genotype participants for the ADRA2B deletion variant. Results showed that stress administered immediately before learning selectively enhanced long-term recall in deletion carriers. Stress administered 30min before learning impaired recognition memory in male deletion carriers, while enhancing recognition memory in female deletion carriers. These findings provide additional evidence to support the idea that ADRA2B deletion variant carriers retain a sensitized stress response system, which results in amplified effects of stress on learning and memory. The accumulating evidence regarding this genetic variant implicates it as a susceptibility factor for traumatic memory formation and PTSD-related phenotypes. Copyright © 2017 Elsevier Inc. All rights reserved.

AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON BRAIN OXIDATIVE STRESS PARAMETERS IN BROWN NORWAY RATS.

Science.gov (United States)

The influence of aging on susceptibility to environmental contaminants is poorly understood. The objectives of this study were to test whether oxidative stress (OS) is a potential toxicity pathway following toluene exposure and to determine if these effects are age-dependent. We ...

Endogenous and Exogenous KdpF Peptide Increases Susceptibility of Mycobacterium bovis BCG to Nitrosative Stress and Reduces Intramacrophage Replication

Science.gov (United States)

Rosas Olvera, Mariana; Vivès, Eric; Molle, Virginie; Blanc-Potard, Anne-Béatrice; Gannoun-Zaki, Laila

2017-01-01

Emerging antibiotic resistance in pathogenic bacteria like Mycobacterium sp., poses a threat to human health and therefore calls for the development of novel antibacterial strategies. We have recently discovered that bacterial membrane peptides, such as KdpF, possess anti-virulence properties when overproduced in pathogenic bacterial species. Overproduction of the KdpF peptide in Mycobacterium bovis BCG decreased bacterial replication within macrophages, without presenting antibacterial activity. We propose that KdpF functions as a regulatory molecule and interferes with bacterial virulence, potentially through interaction with the PDIM transporter MmpL7. We demonstrate here that KdpF overproduction in M. bovis BCG, increased bacterial susceptibility to nitrosative stress and thereby was responsible for lower replication rate within macrophages. Moreover, in a bacterial two-hybrid system, KdpF was able to interact not only with MmpL7 but also with two membrane proteins involved in nitrosative stress detoxification (NarI and NarK2), and a membrane protein of unknown function that is highly induced upon nitrosative stress (Rv2617c). Interestingly, we showed that the exogenous addition of KdpF synthetic peptide could affect the stability of proteins that interact with this peptide. Finally, the exogenous KdpF peptide presented similar biological effects as the endogenously expressed peptide including nitrosative stress susceptibility and reduced intramacrophage replication rate for M. bovis BCG. Taken together, our results establish a link between high levels of KdpF and nitrosative stress susceptibility to further highlight KdpF as a potent molecule with anti-virulence properties. PMID:28428950

A systems approach identifies networks and genes linking sleep and stress: implications for neuropsychiatric disorders.

Science.gov (United States)

Jiang, Peng; Scarpa, Joseph R; Fitzpatrick, Karrie; Losic, Bojan; Gao, Vance D; Hao, Ke; Summa, Keith C; Yang, He S; Zhang, Bin; Allada, Ravi; Vitaterna, Martha H; Turek, Fred W; Kasarskis, Andrew

2015-05-05

Sleep dysfunction and stress susceptibility are comorbid complex traits that often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multilevel organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J × A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type-specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests that the interplay among sleep, stress, and neuropathology emerges from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework for interrogating the mechanisms underlying sleep, stress susceptibility, and related neuropsychiatric disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Mechanisms of induced susceptibility to Diplodia tip blight in drought-stressed Austrian pine.

Science.gov (United States)

Sherwood, Patrick; Villari, Caterina; Capretti, Paolo; Bonello, Pierluigi

2015-05-01

Plants experiencing drought stress are frequently more susceptible to pathogens, likely via alterations in physiology that create favorable conditions for pathogens. Common plant responses to drought include the production of reactive oxygen species (ROS) and the accumulation of free amino acids (AAs), particularly proline. These same phenomena also frequently occur during pathogenic attack. Therefore, drought-induced perturbations in AA and ROS metabolism could potentially contribute to the observed enhanced susceptibility. Furthermore, nitrogen (N) availability can influence AA accumulation and affect plant resistance, but its contributions to drought-induced susceptibility are largely unexplored. Here we show that drought induces accumulation of hydrogen peroxide (H2O2) in Austrian pine (Pinus nigra Arnold) shoots, but that shoot infection by the blight and canker pathogen Diplodia sapinea (Fr.) Fuckel leads to large reductions in H2O2 levels in droughted plants. In in vitro assays, H2O2 was toxic to D. sapinea, and the fungus responded to this oxidative stress by increasing catalase and peroxidase activities, resulting in substantial H2O2 degradation. Proline increased in response to drought and infection when examined independently, but unlike all other AAs, proline further increased in infected shoots of droughted trees. In the same tissues, the proline precursor, glutamate, decreased significantly. Proline was found to protect D. sapinea from H2O2 damage, while also serving as a preferred N source in vitro. Fertilization increased constitutive and drought-induced levels of some AAs, but did not affect plant resistance. A new model integrating interactions of proline and H2O2 metabolism with drought and fungal infection of plants is proposed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of microstructure on the sulphide stress cracking susceptibility of a high strength pipeline steel

Energy Technology Data Exchange (ETDEWEB)

Ramirez, E. [Centro de Investigacion en Ingenieria y Ciencias Aplicadas-UAEM, Av. Universidad 1001, 62209-Cuernavaca, Mor. (Mexico); Gonzalez-Rodriguez, J.G. [Centro de Investigacion en Ingenieria y Ciencias Aplicadas-UAEM, Av. Universidad 1001, 62209-Cuernavaca, Mor. (Mexico)], E-mail: ggonzalez@uaem.mx; Torres-Islas, A.; Serna, S. [Centro de Investigacion en Ingenieria y Ciencias Aplicadas-UAEM, Av. Universidad 1001, 62209-Cuernavaca, Mor. (Mexico); Campillo, B. [Intituto de Ciencias Fisicas-Facultad de Quimicas-Universidad Nacional Autonoma de Mexico Cuernavaca, Mor. (Mexico); Dominguez-Patino, G. [Centro de Investigacion en Ingenieria y Ciencias Aplicadas-UAEM, Av. Universidad 1001, 62209-Cuernavaca, Mor. (Mexico); Juarez-Islas, J.A. [Instituto de Investigaciones en Materiales-Universidad Nacional Autonoma de Mexico, Circuito Exterior S/N, Cd. Universitaria, C.P. 04510, Mexico, D.F. (Mexico)

2008-12-15

The sulphide stress cracking (SSC) susceptibility of a newly developed high strength microalloyed steel with three different microstructures has been evaluated using the slow strain rate testing (SSRT) technique. Studies were complemented with potentiodynamic polarization curves and hydrogen permeation measurements. Material included a C-Mn steel having Ni, Cu, and Mo as main microalloying elements with three microstructures: martensitic, ferritic and ferritic + bainitic. Testing temperatures included 25, 50, 70 and 90 deg. C. Detailed SEM observations of the microstructure and fracture surfaces were done to identify possible degradation mechanisms. The results showed that in all cases, the corrosion rate, number of hydrogen atoms at the surface and the percentage reduction in area increased with temperature. The steel with a martensitic microstructure had the highest SSC susceptibility at all temperatures, whereas the ferritic steels were susceptible only at 25 deg. C, and the most likely mechanism is hydrogen embrittlement assisted by anodic dissolution.

Growth platform-dependent and -independent phenotypic and metabolic responses of Arabidopsis and its halophytic relative, Eutrema salsugineum, to salt stress.

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Kazachkova, Yana; Batushansky, Albert; Cisneros, Aroldo; Tel-Zur, Noemi; Fait, Aaron; Barak, Simon

2013-07-01

Comparative studies of the stress-tolerant Arabidopsis (Arabidopsis thaliana) halophytic relative, Eutrema salsugineum, have proven a fruitful approach to understanding natural stress tolerance. Here, we performed comparative phenotyping of Arabidopsis and E. salsugineum vegetative development under control and salt-stress conditions, and then compared the metabolic responses of the two species on different growth platforms in a defined leaf developmental stage. Our results reveal both growth platform-dependent and -independent phenotypes and metabolic responses. Leaf emergence was affected in a similar way in both species grown in vitro but the effects observed in Arabidopsis occurred at higher salt concentrations in E. salsugineum. No differences in leaf emergence were observed on soil. A new effect of a salt-mediated reduction in E. salsugineum leaf area was unmasked. On soil, leaf area reduction in E. salsugineum was mainly due to a fall in cell number, whereas both cell number and cell size contributed to the decrease in Arabidopsis leaf area. Common growth platform-independent leaf metabolic signatures such as high raffinose and malate, and low fumarate contents that could reflect core stress tolerance mechanisms, as well as growth platform-dependent metabolic responses were identified. In particular, the in vitro growth platform led to repression of accumulation of many metabolites including sugars, sugar phosphates, and amino acids in E. salsugineum compared with the soil system where these same metabolites accumulated to higher levels in E. salsugineum than in Arabidopsis. The observation that E. salsugineum maintains salt tolerance despite growth platform-specific phenotypes and metabolic responses suggests a considerable degree of phenotypic and metabolic adaptive plasticity in this extremophile.

Thermomechanical processing of 5083 aluminum to increase strength without increasing susceptibility to stress corrosion cracking

International Nuclear Information System (INIS)

Edstrom, C.M.; Blakeslee, J.J.

1980-01-01

5083 aluminium with 25% cold work must be processed above 215 0 C or below 70 0 C to avoid forming continuous precipitate in the grain boundaries which makes the material susceptible to stress corrosion cracking. Time at temperature above 215 0 C should be held to minimum (less than 30 min) to retain some strength from the 25% cold work

Susceptibility patterns and the role of extracellular DNA in Staphylococcus epidermidis biofilm resistance to physico-chemical stress exposure.

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Olwal, Charles Ochieng'; Ang'ienda, Paul Oyieng'; Onyango, David Miruka; Ochiel, Daniel Otieno

2018-05-02

Over 65% of human infections are ascribed to bacterial biofilms that are often highly resistant to antibiotics and host immunity. Staphylococcus epidermidis is the predominant cause of recurrent nosocomial and biofilm-related infections. However, the susceptibility patterns of S. epidermidis biofilms to physico-chemical stress induced by commonly recommended disinfectants [(heat, sodium chloride (NaCl), sodium hypochlorite (NaOCl) and hydrogen peroxide (H 2 O 2 )] in domestic and human healthcare settings remains largely unknown. Further, the molecular mechanisms of bacterial biofilms resistance to the physico-chemical stresses remain unclear. Growing evidence demonstrates that extracellular DNA (eDNA) protects bacterial biofilms against antibiotics. However, the role of eDNA as a potential mechanism underlying S. epidermidis biofilms resistance to physico-chemical stress exposure is yet to be understood. Therefore, this study aimed to evaluate the susceptibility patterns of and eDNA release by S. epidermidis biofilm and planktonic cells to physico-chemical stress exposure. S. epidermidis biofilms exposed to physico-chemical stress conditions commonly recommended for disinfection [heat (60 °C), 1.72 M NaCl, solution containing 150 μL of waterguard (0.178 M NaOCl) in 1 L of water or 1.77 M H 2 O 2 ] for 30 and 60 min exhibited lower log reductions of CFU/mL than the corresponding planktonic cells (p chemical stress induced by the four commonly recommended disinfectants than the analogous planktonic cells. Further, S. epidermidis biofilms enhanced eDNA release in response to the sub-lethal heat and oxidative stress exposure than the corresponding planktonic cells suggesting a role of eDNA in biofilms resistance to the physico-chemical stresses.

Effect of water content on the stress corrosion cracking susceptibility of Zircaloy-4 in iodine-alcoholic solutions

International Nuclear Information System (INIS)

Gomez Sanchez, Andrea; Farina, Silvia B.; Duffo, Gustavo S.

2005-01-01

The stress corrosion cracking (SCC) susceptibility of Zircaloy-4 (UNS R60804) was studied in 10 g/L iodine dissolved in various alcohols: methanol, ethanol, 1 propanol, 1-butanol, 1-pentanol and 1-octanol. SCC was observed in all the systems studied and it was found that the higher the size of alcohol molecule, the lower the SCC susceptibility. The existence of intergranular attack -controlled by the diffusion of the active species- is a condition for the SCC process to occur. In the present work the inhibiting effect of water on the SCC susceptibility of Zircaloy-4 in iodine-alcoholic solutions was also investigated and the results showed that the minimum water content to inhibit the SCC process depends on the type of alcohol used as a solvent. (author) [es

Stress corrosion cracking susceptibilities of various stainless steels in high temperature water

International Nuclear Information System (INIS)

Shoji, Saburo; Ohnaka, Noriyuki; Kikuchi, Eiji; Minato, Akira; Tanno, Kazuo.

1980-01-01

The intergranular stress corrosion cracking (IGSCC) behaviors of several austenitic stainless steels in high temperature water were evaluated using three types of SCC tests, i.e., single U-bend test in chloride containing water, uniaxial constant load and constant extension rate tests (CERT) in pure water. The steels used were SUS 304, 304L, 316, 316L, 321 and 347 and several heats of them to examine heat to heat variations. The three test methods gave the same relative ranking of the steels. The CERT is the most sensitive method to detect the relative IGSCC susceptibilities. The CERT result for relative ranking from poor to good is: SUS 304 - 0.07% C, 304 - 0.06% C, 304L - 0.028% C, 316 - 0.07% C. The IGSCC susceptibilities of SUS 304L - 0.020% C, 316L - 0.023% C, 321 and 347 were not detected. These test results suggest that the use of the low carbon, molybdenum bearing, or stabilized austenitic stainless steel is beneficial for eliminating the IGSCC problem in boiling water reactor environment. (author)

Stress-induced neuroinflammation is mediated by GSK3-dependent TLR4 signaling that promotes susceptibility to depression-like behavior.

Science.gov (United States)

Cheng, Yuyan; Pardo, Marta; Armini, Rubia de Souza; Martinez, Ana; Mouhsine, Hadley; Zagury, Jean-Francois; Jope, Richard S; Beurel, Eleonore

2016-03-01

Most psychiatric and neurological diseases are exacerbated by stress. Because this may partially result from stress-induced inflammation, we examined factors involved in this stress response. After a paradigm of inescapable foot shock stress that causes learned helplessness depression-like behavior, eighteen cytokines and chemokines increased in mouse hippocampus, peaking 6-12h after stress. A 24h prior pre-conditioning stress accelerated the rate of stress-induced hippocampal cytokine and chemokine increases, with most reaching peak levels after 1-3h, often without altering the maximal levels. Toll-like receptor 4 (TLR4) was involved in this response because most stress-induced hippocampal cytokines and chemokines were attenuated in TLR4 knockout mice. Stress activated glycogen synthase kinase-3 (GSK3) in wild-type mouse hippocampus, but not in TLR4 knockout mice. Administration of the antidepressant fluoxetine or the GSK3 inhibitor TDZD-8 reduced the stress-induced increases of most hippocampal cytokines and chemokines. Stress increased hippocampal levels of the danger-associated molecular pattern (DAMP) protein high mobility group box 1 (HMGB1), activated the inflammatory transcription factor NF-κB, and the NLRP3 inflammasome. Knockdown of HMGB1 blocked the acceleration of cytokine and chemokine increases in the hippocampus caused by two successive stresses. Fluoxetine treatment blocked stress-induced up-regulation of HMGB1 and subsequent NF-κB activation, whereas TDZD-8 administration attenuated NF-κB activation downstream of HMGB1. To test if stress-induced cytokines and chemokines contribute to depression-like behavior, the learned helplessness model was assessed. Antagonism of TNFα modestly reduced susceptibility to learned helplessness induction, whereas TLR4 knockout mice were resistant to learned helplessness. Thus, stress-induces a broad inflammatory response in mouse hippocampus that involves TLR4, GSK3, and downstream inflammatory signaling, and

Stress-induced neuroinflammation is mediated by GSK3-dependent TLR4 signaling that promotes susceptibility to depression-like behavior

Science.gov (United States)

Cheng, Yuyan; Pardo, Marta; de Souza Armini, Rubia; Martinez, Ana; Mouhsine, Hadley; Zagury, Jean-Francois; Jope, Richard S.; Beurel, Eleonore

2016-01-01

Most psychiatric and neurological diseases are exacerbated by stress. Because this may partially result from stress-induced inflammation, we examined factors involved in this stress response. After a paradigm of inescapable foot shock stress that causes learned helplessness depression-like behavior, eighteen cytokines and chemokines increased in mouse hippocampus, peaking 6 to 12 hr after stress. A 24 hr prior pre-conditioning stress accelerated the rate of stress-induced hippocampal cytokine and chemokine increases, with most reaching peak levels after 1 to 3 hr, often without altering the maximal levels. Toll-like receptor 4 (TLR4) was involved in this response because most stress-induced hippocampal cytokines and chemokines were attenuated in TLR4 knockout mice. Stress activated glycogen synthase kinase-3 (GSK3) in wild-type mouse hippocampus, but not in TLR4 knockout mice. Administration of the antidepressant fluoxetine or the GSK3 inhibitor TDZD-8 reduced the stress-induced increases of most hippocampal cytokines and chemokines. Stress increased hippocampal levels of the danger-associated molecular pattern (DAMP) protein high mobility group box 1 (HMGB1), activated the inflammatory transcription factor NF-κB, and the NLRP3 inflammasome. Knockdown of HMGB1 blocked the acceleration of cytokine and chemokine increases in the hippocampus caused by two successive stresses. Fluoxetine treatment blocked stress-induced up-regulation of HMGB1 and subsequent NF-κB activation, whereas TDZD-8 administration attenuated NF-κB activation downstream of HMGB1. To test if stress-induced cytokines and chemokines contribute to depression-like behavior, the learned helplessness model was assessed. Antagonism of TNFα modestly reduced susceptibility to learned helplessness induction, whereas TLR4 knockout mice were resistant to learned helplessness. Thus, stress-induces a broad inflammatory response in mouse hippocampus that involves TLR4, GSK3, and downstream inflammatory

Gene and stress history interplay in emergence of PTSD-like features.

Science.gov (United States)

Chakraborty, Nabarun; Meyerhoff, James; Gautam, Aarti; Muhie, Seid; Jibitu, Meskerem; De Lima, Thereza C M; Hammamieh, Rasha; Jett, Marti

2015-10-01

Systematically distinguishing genetic liability from other contributing factors is critical for designing a preventive strategy for post-traumatic stress disorder (PTSD). To address this issue, we investigated a murine model exposing C57BL/6j, DBA/2j and BALB/cj mice to repeated stress via exposure to conspecific aggressors (Agg-E). Naïve mice from each strain were subjected to the proximity of aggressor (Agg) mice for 6h using a 'cage-within-a-cage' paradigm, which was repeated for 5 or 10 days with intermittent and unpredictable direct contact with Agg mice. During the Agg-E stress, DBA/2j developed a different strategy to evade Agg mice, which potentially contributed to its phenotypic resilience to Agg-E stress. Although Agg mice inflicted C57BL/6j and BALB/cj with equivalent numbers of strikes, BALB/cj displayed a distinct behavioral phenotype with delayed exhibition of a number of PTSD-like features. By contrast, C57BL/6j mice displayed unique vulnerability to Agg-E stress induced myocardopathy, possibly attributable to their particular susceptibility to hypoxia. A group of genes (Bdnf, Ngf, Zwint, Cckbr, Slc6a4, Fkbp5) linked to PTSD and synaptic plasticity were significantly altered in C57BL/6j and BALB/cj Agg-E mice. Contributions of Agg-E stress history and genotypic heterogeneity emerged as the key mediators of PTSD-like features. Linking genetic components to specific phenotypic and pathological features could have potential clinical implications. Copyright © 2015 Elsevier B.V. All rights reserved.

DNA methyltransferase 3A gene polymorphism contributes to daily life stress susceptibility

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Barliana MI

2017-12-01

Full Text Available Melisa I Barliana,1,2 Shintya N Amalya,1 Ivan S Pradipta,3 Sofa D Alfian,3 Arif SW Kusuma,1,2 Tiana Milanda,1,4 Rizky Abdulah3,4 1Department of Biological Pharmacy, Biotechnology Pharmacy Laboratory, 2Pharmacy Services Development Research Center, 3Department of Pharmacology and Clinical Pharmacy, Clinical Pharmacy Laboratory, 4Center for Drug Discovery and Product Development, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, West Java, Indonesia Abstract: Daily life stress markedly affects the response toward stressful stimuli. DNA methy­lation is one of the factors that regulate this response, and is a normal mechanism of somatic cell growth, but its regulatory gene variations may cause alterations in the stress response. The aim of the present study was to investigate genotypic variants of the DNA methyltransferase 3A (DNMT3A gene in 129 healthy subjects and evaluate its association with daily life stress. Blood samples were collected, and genomic DNA was isolated. DNA was amplified using specific tetra primers for DNMT3A (C/T rs11683424 and visualized following 2% agarose gel electrophoresis. The association of DNMT3A genetic variants with daily life stress was analyzed using the Kessler Psychological Distress Scale (K10. We observed that the distribution of subjects with genotype CC (wild type, CT (heteromutant, and TT (homomutant was 13.95%, 81.4%, and 4.65%, respectively. Genetic variations significantly affected the daily life stress condition (p=0.04 in Indonesian healthy subjects, but most of the subjects with the CT phenotype were classified in a stress condition. Keywords: daily life stressor, DNA methylation, epigenetic, Kessler Psychological Distress Scale (K10, rs11683424, DNMT3A

Oxidative stress at high altitude: genotype–phenotype correlations

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Pandey P

2014-05-01

Full Text Available Priyanka Pandey,1,2 MA Qadar Pasha1,2 1CSIR-Institute of Genomics and Integrative Biology, Delhi, India; 2Department of Biotechnology, University of Pune, Ganeshkhind, Pune, India Abstract: It has been well-documented that the hypobaric hypoxic environment at high altitude (HA causes stress to both the permanent residents of HA and the sojourners. This oxidative stress primarily disturbs the oxygen-sensing and vascular homeostasis pathways, thereby upsetting normal human physiology, especially in sojourners. These environmental challenges have caused dynamic evolutionary changes within natives of HA, allowing them to develop adaptive plasticity. This review focuses on the genomic and biochemical features of the molecules involved in the oxygen-sensing and vascular homeostasis pathways with respect to HA pulmonary edema (HAPE and adaptation. We review the role of genetic markers such as HIF-prolyl hydroxylase 2, endothelial PAS domain-containing protein 1, endothelial nitric oxide synthase, endothelin 1, cytochrome b-245 alpha polypeptide, and glutathione S-transferase pi 1, as well as three circulatory biomarkers (nitric oxide, endothelin 1, and 8-iso-prostaglandin F2α, by highlighting approaches such as candidate gene and genome-wide, adopted in deciphering the pathways. A disagreement between the two approaches has also been highlighted. In addition, we discuss that an overrepresentation of wild-type alleles in HA natives and mutant alleles of same polymorphisms in HAPE patients implies that the allelic variants at the same locus are involved in adaptation and HAPE, respectively. Moreover, healthy sojourners present a number of genomic features similar to HA natives, further strengthening the concept of genetic predisposition. A trend in correlation between protective and risk alleles and altered levels of circulatory markers clearly documents the phenomenon of genotype–phenotype correlations. We conclude that the genetic and biochemical

Personality differences in the susceptibility to stress-eating: The influence of emotional control and impulsivity.

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Van Blyderveen, Sherry; Lafrance, Adele; Emond, Michael; Kosmerly, Stacey; O'Connor, Megan; Chang, Felicia

2016-12-01

Stress has been associated with deviations from typical eating patterns, with respect to both food choice and overall caloric intake. Both increases and decreases in dietary intake have been previously noted in response to stress. The purpose of the present study was to determine whether the affect regulation strategies of emotional control and impulsivity predict susceptibility to eating in response to stress. Specifically, it was anticipated that emotional suppression would predict decreases in caloric intake, whereas impulsivity would predict increases in caloric intake, in response to a stressor. Participants were randomly assigned to view either a video designed to elicit stress or a control video. Food was provided during the video and the amount and type of food consumed was measured. Participants' nutritional intake was greater in the stress condition than in the control condition. One aspect of affect regulation, impulsivity, moderated this relationship, with a tendency for greater impulsivity to be associated with greater caloric intake in the stress condition. The degree of negative affect that participants experienced in the stress condition predicted food choice and overall caloric intake. Both emotional control and impulsivity moderated the relationship between negative affect and both food choice and caloric intake in the stress condition. The present study highlights the importance of considering the personality attributes of both impulsivity and emotional suppression in understanding stress eating. Copyright © 2016. Published by Elsevier Ltd.

Maternal stress and diet may influence affective behavior and stress-response in offspring via epigenetic regulation of central peptidergic function.

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Thorsell, Annika; Nätt, Daniel

2016-08-01

It has been shown that maternal stress and malnutrition, or experience of other adverse events, during the perinatal period may alter susceptibility in the adult offspring in a time-of-exposure dependent manner. The mechanism underlying this may be epigenetic in nature. Here, we summarize some recent findings on the effects on gene-regulation following maternal malnutrition, focusing on epigenetic regulation of peptidergic activity. Numerous neuropeptides within the central nervous system are crucial components in regulation of homeostatic energy-balance, as well as affective health (i.e. health events related to affective disorders, psychiatric disorders also referred to as mood disorders). It is becoming evident that expression, and function, of these neuropeptides can be regulated via epigenetic mechanisms during fetal development, thereby contributing to the development of the adult phenotype and, possibly, modulating disease susceptibility. Here, we focus on two such neuropeptides, neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH), both involved in regulation of endocrine function, energy homeostasis, as well as affective health. While a number of published studies indicate the involvement of epigenetic mechanisms in CRH-dependent regulation of the offspring adult phenotype, NPY has been much less studied in this context and needs further work.

Stress corrosion cracking susceptibility of austenitic stainless steels in supercritical water conditions

International Nuclear Information System (INIS)

Novotny, R.; Haehner, P.; Ripplinger, S.; Siegl, J.; Penttilae, Sami; Toivonen, Aki

2009-01-01

Within the 6th Framework Program HPLWR-2 project (High Performance Light Water Reactor - Phase 2), stress corrosion cracking (SCC) susceptibilities of selected austenitic stainless steels, 316L and 316NG, were studied in supercritical water (SCW) with the aim to identify and describe the specific failure mechanisms prevailing during slow strain-rate tensile (SSRT) tests in ultra-pure demineralised SCW water solution. The SSRT tests were performed using a step-motor controlled loading device in an autoclave at 350 deg. C, 500 deg. C and 550 deg. C. Besides water temperature, the pressure, the oxygen content and the strain rate (resp. crosshead speed) were varied in the series of tests. The specimens SSRT tested to failure were subjected to fractographic analysis, in order to characterise the failure mechanisms. The fractography confirmed that failure was due to a combination of transgranular SCC and transgranular ductile fracture. The share of SCC and ductile fracture in the failure process of individual specimens was affected by the parameters of the SSRT tests, so that the environmental influence on SCC susceptibility could be assessed, in particular, the SCC sensitising effects of increasing oxygen content, decreasing strain rate and increasing test temperature. (author)

Mechanical massage and mental training programmes affect employees' anxiety, stress susceptibility and detachment-a randomised explorative pilot study.

Science.gov (United States)

Muller, Jasmin; Handlin, Linda; Harlén, Mikael; Lindmark, Ulrika; Ekström, Anette

2015-09-02

Working people's reduced ability to recover has been proposed as a key factor behind the increase in stress-related health problems. One not yet evidence-based preventive method designed to help employees keep healthy and be less stressed is an armchair with built-in mechanical massage and mental training programmes, This study aimed to evaluate possible effects on employees' experience of levels of "Anxiety", "Stress Susceptibility", "Detachment" and "Social Desirability" when using mechanical massage and mental training programmes, both separately and in combination, during working hours. Employees from four different workplaces were randomly assigned to one of the following groups: i) Massage and mental training (sitting in the armchair and receiving mechanical massage while listening to the mental training programmes, n=19), ii) Massage (sitting in the armchair and receiving mechanical massage only, n=19), iii) Mental training (sitting in the armchair and listening to the mental training programmes only, n=19), iv) Pause (sitting in the armchair but not receiving mechanical massage or listening to the mental training programmes, n=19), v) Control (not sitting in the armchair at all, n=17). In order to discover how the employees felt about their own health they were asked to respond to statements from the "Swedish Scale of Personality" (SSP), immediately before the randomisation, after four weeks and after eight weeks (end-of-study). There were no significant differences between the five study groups for any of the traits studied ("Somatic Trait Anxiety", "Psychic Trait Anxiety", "Stress Susceptibility", "Detachment" and "Social Desirability") at any of the occasions. However, the massage group showed a significant decrease in the subscale "Somatic Trait Anxiety" (p=0.032), during the entire study period. Significant decreases in the same subscale were also observed in the pause group between start and week eight (p=0.040) as well as between week four and week

Phenotypic, molecular characterization, antimicrobial susceptibility and draft genome sequence of Corynebacterium argentoratense strains isolated from clinical samples

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I. Fernández-Natal

2016-03-01

Full Text Available During a 12-year period we isolated five Corynebacterium argentoratense strains identified by phenotypic methods, including the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF and 16S rRNA gene sequencing. In addition, antimicrobial susceptibility was determined, and genome sequencing for the detection of antibiotic resistance genes was performed. The organisms were isolated from blood and throat cultures and could be identified by all methods used. All strains were resistant to cotrimoxazole, and resistance to β-lactams was partly present. Two strains were resistant to erythromycin and clindamycin. The draft genome sequences of theses isolates revealed the presence of the erm(X resistance gene that is embedded in the genetic structure of the transposable element Tn5423. Although rarely reported as a human pathogen, C. argentoratense can be involved in bacteraemia and probably in other infections. Our results also show that horizontal transfer of genes responsible for antibiotic resistance is occurring in this species.

Time-dependent miR-16 serum fluctuations together with reciprocal changes in the expression level of miR-16 in mesocortical circuit contribute to stress resilient phenotype in chronic mild stress - An animal model of depression.

Science.gov (United States)

Zurawek, Dariusz; Kusmider, Maciej; Faron-Gorecka, Agata; Gruca, Piotr; Pabian, Paulina; Kolasa, Magdalena; Solich, Joanna; Szafran-Pilch, Kinga; Papp, Mariusz; Dziedzicka-Wasylewska, Marta

2016-01-01

MicroRNAs (miRNAs) are involved in stress-related pathologies. However, the molecular mechanisms underlying stress resilience are elusive. Using chronic mild stress (CMS), an animal model of depression, we identified animals exhibiting a resilient phenotype. We investigated serum levels of corticosterone, melatonin and 376 mature miRNAs to find peripheral biomarkers associated with the resilient phenotype. miR-16, selected during screening step, was assayed in different brain regions in order to find potential relationship between brain and peripheral alterations in response to stress. Two CMS experiments that lasted for 2 and 7 consecutive weeks were performed. During both CMS procedures, sucrose consumption levels were significantly decreased in anhedonic-like animals (panimals, whereas the drinking profiles of resilient rats did not change despite the rats being stressed. Serum corticosterone measurements indicated that anhedonic-like animals had blunted hypothalamic-pituitary-adrenal (HPA) axis activity, whereas resilient animals exhibited dynamic responses to stress. miRNA profiling revealed that resilient animals had elevated serum levels of miR-16 after 7 weeks of CMS (adjusted p-valueanimals exhibited reciprocal changes in miR-16 expression level in mesocortical pathway after 2 weeks of CMS (panimals can actively cope with stress on a biochemical level and miR-16 may contribute to a "stress-resistant" behavioral phenotype by pleiotropic modulation of the expression of genes involved in the function of the nervous system. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Susceptibility of 17-4PH stainless steel to stress corrosion cracking in aqueous environments by electrochemical techniques

International Nuclear Information System (INIS)

Diaz S, A.C.

1997-01-01

The susceptibility of a 17-4PH type steel to Stress Corrosion Cracking (SCC) in low pressure steam turbine environments was assessed using slow strain rate test at 90 Centigrade and at 1.35x10 -6 seg -1 . Environments tested included different concentrated solutions of NaCl, NaOH and Na 2 SO 4 . It was concluded that this steel is susceptible to SCC in 20 % NaCl and pH=3 and in 20 % NaCl pH=neutral but under cathodic polarisation. The electrochemical potential noise of the specimen was monitored during the test. The naturally fluctuations in potential were arise due to spontaneous brake protective film and were characteristics of the kind of corrosion like pit or stress corrosion cracking. After that using Fast Fourier Transformer (FFT) the noise data set were analyzed to obtain power spectral density plots which showed differences between general corrosion and localized corrosion. Polarization curves were carry out at two different rates and them showed the general behavior of the systems. (Author)

Genetic variation in bacterial kidney disease (BKD) susceptibility in Lake Michigan Chinook Salmon and its progenitor population from the Puget Sound

Science.gov (United States)

Purcell, Maureen K.; Hard, Jeffrey J.; Neely, Kathleen G.; Park, Linda K.; Winton, James R.; Elliott, Diane G.

2014-01-01

Mass mortality events in wild fish due to infectious diseases are troubling, especially given the potential for long-term, population-level consequences. Evolutionary theory predicts that populations with sufficient genetic variation will adapt in response to pathogen pressure. Chinook Salmon Oncorhynchus tshawytscha were introduced into Lake Michigan in the late 1960s from a Washington State hatchery population. In the late 1980s, collapse of the forage base and nutritional stress in Lake Michigan were thought to contribute to die-offs of Chinook Salmon due to bacterial kidney disease (BKD). Previously, we demonstrated that Lake Michigan Chinook Salmon from a Wisconsin hatchery have greater survival following BKD challenge relative to their progenitor population. Here, we evaluated whether the phenotypic divergence of these populations in BKD susceptibility was due to selection rather than genetic drift. Comparison of the overall magnitude of quantitative trait to neutral marker divergence between the populations suggested selection had occurred but a direct test of quantitative trait divergence was not significant, preventing the rejection of the null hypothesis of differentiation through genetic drift. Estimates of phenotypic variation (VP), additive genetic variation (VA) and narrow-sense heritability (h2) were consistently higher in the Wisconsin relative to the Washington population. If selection had acted on the Wisconsin population there was no evidence of a concomitant loss of genetic variation in BKD susceptibility. The Renibacterium salmoninarum exposures were conducted at both 14°C and 9°C; the warmer temperature accelerated time to death in both populations and there was no evidence of phenotypic plasticity or a genotype-by-environment (G × E) interaction. High h2 estimates for BKD susceptibility in the Wisconsin population, combined with a lack of phenotypic plasticity, predicts that future adaptive gains in BKD resistance are still possible and

HLA Class II Alleles Susceptibility Markers of Type 1 Diabetes Fail to Specify Phenotypes of Ketosis-Prone Diabetes in Adult Tunisian Patients

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Lilia Laadhar

2011-01-01

Full Text Available We aimed to characterize the different subgroups of ketosis-prone diabetes (KPD in a sample of Tunisian patients using the Aβ scheme based on the presence or absence of β-cell autoantibodies (A+ or A− and β-cell functional reserve (β+ or β− and we investigated whether HLA class II alleles could contribute to distinct KPD phenotypes. We enrolled 43 adult patients with a first episode of ketosis. For all patients we evaluated clinical parameters, β-cell autoimmunity, β-cell function and HLA class II alleles. Frequency distribution of the 4 subgroups was 23.3% A+β−, 23.3% A−β−, 11.6% A+β+ and 41.9% A−β+. Patients from the group A+β− were significantly younger than those from the group A−β− (P=.002. HLA susceptibility markers were significantly more frequent in patients with autoantibodies (P=.003. These patients also had resistance alleles but they were more frequent in A+β+ than A+β− patients (P=.04. Insulin requirement was not associated to the presence or the absence of HLA susceptibility markers. HLA class II alleles associated with susceptibility to autoimmune diabetes have not allowed us to further define Tunisian KPD groups. However, high prevalence of HLA resistance alleles in our patients may reflect a particular genetic background of Tunisian KPD population.

Negative (but not Positive) Parenting Interacts with Infant Negative Affect to Predict Infant Approach: Evidence of Diathesis-Stress.

Science.gov (United States)

Holzman, Jacob B; Burt, Nicole M; Edwards, Erin S; Rosinski, Leanna D; Bridgett, David J

2018-01-01

Temperament by parenting interactions may reflect that individuals with greater risk are more likely to experience negative outcomes in adverse contexts (diathesis-stress) or that these individuals are more susceptible to contextual influences in a 'for better or for worse' pattern (differential susceptibility). Although such interactions have been identified for a variety of child outcomes, prior research has not examined approach characteristics - excitement and approach toward pleasurable activities - in the first year of life. Therefore, the current study investigated whether 6-month maternal reported infant negative affect - a phenotypic marker of risk/susceptibility - interacted with 8-month observed parenting behaviors (positive parenting, negative parenting) to predict 12-month infant behavioral approach. Based a sample of mothers and their infants ( N =150), results indicated that negative parenting was inversely associated with subsequent approach for infants with high, but not low, levels of early negative affect. Similar results did not occur regarding positive parenting. These findings better fit a diathesis-stress model rather than a differential susceptibility model. Implications and limitations of these findings are discussed.

Prenatal Stress as a Risk-and an Opportunity-Factor.

Science.gov (United States)

Hartman, Sarah; Freeman, Sara M; Bales, Karen L; Belsky, Jay

2018-04-01

Two separate lines of research indicate (a) that prenatal stress is associated with heightened behavioral and physiological reactivity and (b) that these postnatal phenotypes are associated with increased susceptibility to both positive and negative developmental experiences. Therefore, prenatal stress may increase sensitivity to the rearing environment. We tested this hypothesis by manipulating prenatal stress and rearing-environment quality, using a cross-fostering paradigm, in prairie voles. Results showed that prenatally stressed voles, as adults, displayed the highest behavioral and physiological reactivity when cross-fostered to low-contact (i.e., low-quality) rearing but the lowest behavioral and physiological reactivity when cross-fostered to high-contact (i.e., high-quality) rearing; non-prenatally stressed voles showed no effect of rearing condition. Additionally, while neither prenatal stress nor rearing condition affected oxytocin receptor binding, prenatally stressed voles cross-fostered to high-contact rearing showed the highest vasopressin-1a receptor binding in the amygdala. Results indicate that prenatal stress induces greater environmental sensitivity, making it both a risk and an opportunity factor.

Endoplasmic reticulum stress in amelogenesis imperfecta and phenotypic rescue using 4-phenylbutyrate.

Science.gov (United States)

Brookes, Steven J; Barron, Martin J; Boot-Handford, Ray; Kirkham, Jennifer; Dixon, Michael J

2014-05-01

Inherited diseases caused by genetic mutations can arise due to loss of protein function. Alternatively, mutated proteins may mis-fold, impairing endoplasmic reticulum (ER) trafficking, causing ER stress and triggering the unfolded protein response (UPR). The UPR attempts to restore proteostasis but if unsuccessful drives affected cells towards apoptosis. Previously, we reported that in mice, the p.Tyr64His mutation in the enamel extracellular matrix (EEM) protein amelogenin disrupts the secretory pathway in the enamel-forming ameloblasts, resulting in eruption of malformed tooth enamel that phenocopies human amelogenesis imperfecta (AI). Defective amelogenin post-secretory self-assembly and processing within the developing EEM has been suggested to underlie the pathogenesis of X chromosome-linked AI. Here, we challenge this concept by showing that AI pathogenesis associated with the p.Tyr64His amelogenin mutation involves ameloblast apoptosis induced by ER stress. Furthermore, we show that 4-phenylbutyrate can rescue the enamel phenotype in affected female mice by promoting cell survival over apoptosis such that they are able to complete enamel formation despite the presence of the mutation, offering a potential therapeutic option for patients with this form of AI and emphasizing the importance of ER stress in the pathogenesis of this inherited conformational disease.

Effect of fuel rod design on SCC susceptibility

International Nuclear Information System (INIS)

Wilson, H.W.; Yoon, K.K.; Baty, D.L.

1979-01-01

Laboratory tests were conducted to compare the relative susceptibility of three different zircaloy cladding types to iodine stress corrosion cracking. Two types of tests were conducted which had different characteristics. A substantial dependency of failure susceptibility on cladding type was noted. The differences in behavior were attributed to one or a combination of three cladding characteristics: cladding crystallographic texture, stress relaxation rates, and cladding inner diameter surface condition. The failure susceptibility was qualitatively consistent with the theoretical predictions of crystallographic texture dependencies. A separate series of tests were performed to quantify the differences in stress relaxation between the material types. Results of an analytical calculation are presented which evaluates the applicability of the test results to in-reactor performance

Standard Practice for Use of Mattsson's Solution of pH 7.2 to Evaluate the Stress- Corrosion Cracking Susceptibility of Copper-Zinc Alloys

CERN Document Server

American Society for Testing and Materials. Philadelphia

2011-01-01

1.1 This practice covers the preparation and use of Mattsson's solution of pH 7.2 as an accelerated stress-corrosion cracking test environment for brasses (copper-zinc base alloys). The variables (to the extent that these are known at present) that require control are described together with possible means for controlling and standardizing these variables. 1.2 This practice is recommended only for brasses (copper-zinc base alloys). The use of this test environment is not recommended for other copper alloys since the results may be erroneous, providing completely misleading rankings. This is particularly true of alloys containing aluminum or nickel as deliberate alloying additions. 1.3 This practice is intended primarily where the test objective is to determine the relative stress-corrosion cracking susceptibility of different brasses under the same or different stress conditions or to determine the absolute degree of stress corrosion cracking susceptibility, if any, of a particular brass or brass component ...

Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype.

LENUS (Irish Health Repository)

FitzGerald, Oliver

2015-05-07

This review focuses on the genetic features of psoriatic arthritis (PsA) and their relationship to phenotypic heterogeneity in the disease, and addresses three questions: what do the recent studies on human leukocyte antigen (HLA) tell us about the genetic relationship between cutaneous psoriasis (PsO) and PsA - that is, is PsO a unitary phenotype; is PsA a genetically heterogeneous or homogeneous entity; and do the genetic factors implicated in determining susceptibility to PsA predict clinical phenotype? We first discuss the results from comparing the HLA typing of two PsO cohorts: one cohort providing the dermatologic perspective, consisting of patients with PsO without evidence of arthritic disease; and the second cohort providing the rheumatologic perspective, consisting of patients with PsA. We show that these two cohorts differ considerably in their predominant HLA alleles, indicating the heterogeneity of the overall PsO phenotype. Moreover, the genotype of patients in the PsA cohort was shown to be heterogeneous with significant elevations in the frequency of haplotypes containing HLA-B*08, HLA-C*06:02, HLA-B*27, HLA-B*38 and HLA-B*39. Because different genetic susceptibility genes imply different disease mechanisms, and possibly different clinical courses and therapeutic responses, we then review the evidence for a phenotypic difference among patients with PsA who have inherited different HLA alleles. We provide evidence that different alleles and, more importantly, different haplotypes implicated in determining PsA susceptibility are associated with different phenotypic characteristics that appear to be subphenotypes. The implication of these findings for the overall pathophysiologic mechanisms involved in PsA is discussed with specific reference to their bearing on the discussion of whether PsA is conceptualised as an autoimmune process or one that is based on entheseal responses.

Murine Lupus Susceptibility Locus Sle2 Activates DNA-Reactive B Cells through Two Sub-Loci with Distinct Phenotypes

Science.gov (United States)

Zeumer, Leilani; Sang, Allison; Niu, Haitao; Morel, Laurence

2010-01-01

The NZM2410-derived Sle2 lupus susceptibility locus induces an abnormal B cell differentiation which most prominently leads to the expansion of autoreactive B1a cells. We have mapped the expansion of B1a cells to three Sle2 sub-loci, Sle2a, Sle2b, and Sle2c. Sle2 also enhances the breach of B cell tolerance to nuclear antigens in the 56R anti-DNA immunoglobulin transgenic (Tg) model. This study used the Sle2 sub-congenic strains to map the activation of 56R Tg B cells. Sle2c strongly sustained the breach of tolerance and the activation of anti-DNA B cells. The production of Tg-encoded anti-DNA antibodies was more modest in Sle2a expressing mice, but Sle2a was responsible for the recruitment for Tg B cells to the marginal zone, a phenotype that has been found for 56R Tg B cells in mice expressing the whole Sle2 interval. In addition, Sle2a promoted the production of endogenously encoded anti-DNA antibodies. Overall, this study showed that at least two Sle2 genes are involved in the activation of anti-DNA B cells, and excluded more than two-thirds of the Sle2 interval from contributing to this phenotype. This constitutes an important step toward the identification of novel genes that play a critical role in B cell tolerance. PMID:21270826

High-throughput phenotyping allows for QTL analysis of defense, symbiosis and development-related traits

DEFF Research Database (Denmark)

Hansen, Nina Eberhardtsen

-throughput phenotyping of whole plants. Additionally, a system for automated confocal microscopy aiming at automated detection of infection thread formation as well as detection of lateral root and nodule primordia is being developed. The objective was to use both systems in genome wide association studies and mutant...... the analysis. Additional phenotyping of defense mutants revealed that MLO, which confers susceptibility towards Blumeria graminis in barley, is also a prime candidate for a S. trifoliorum susceptibility gene in Lotus....

Rice Yellow Mottle Virus stress responsive genes from susceptible and tolerant rice genotypes

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Siré Christelle

2008-03-01

Full Text Available Abstract Background The effects of viral infection involve concomitant plant gene variations and cellular changes. A simple system is required to assess the complexity of host responses to viral infection. The genome of the Rice yellow mottle virus (RYMV is a single-stranded RNA with a simple organisation. It is the most well-known monocotyledon virus model. Several studies on its biology, structure and phylogeography have provided a suitable background for further genetic studies. 12 rice chromosome sequences are now available and provide strong support for genomic studies, particularly physical mapping and gene identification. Results The present data, obtained through the cDNA-AFLP technique, demonstrate differential responses to RYMV of two different rice cultivars, i.e. susceptible IR64 (Oryza sativa indica, and partially resistant Azucena (O. s. japonica. This RNA profiling provides a new original dataset that will enable us to gain greater insight into the RYMV/rice interaction and the specificity of the host response. Using the SIM4 subroutine, we took the intron/exon structure of the gene into account and mapped 281 RYMV stress responsive (RSR transcripts on 12 rice chromosomes corresponding to 234 RSR genes. We also mapped previously identified deregulated proteins and genes involved in partial resistance and thus constructed the first global physical map of the RYMV/rice interaction. RSR transcripts on rice chromosomes 4 and 10 were found to be not randomly distributed. Seven genes were identified in the susceptible and partially resistant cultivars, and transcripts were colocalized for these seven genes in both cultivars. During virus infection, many concomitant plant gene expression changes may be associated with host changes caused by the infection process, general stress or defence responses. We noted that some genes (e.g. ABC transporters were regulated throughout the kinetics of infection and differentiated susceptible and

[Association between 5-hydroxytryptamine 2A receptor gene polymorphisms and susceptibility to occupational stress in oilfield workers].

Science.gov (United States)

Jiang, Y; Palizhati, Abudoureyimu; Gao, X Y; Guan, S Z; Liu, J W

2016-10-20

Objective: To investigate the association between 5-hydroxytryptamine 2A (5-HT2A) receptor gene polymorphisms and occupational stress in oilfield workers. Methods: Cluster sampling was used to select 826 oilfield workers from January to August, 2013. The SNaPshot single nucleotide polymorphism (SNP) genotyping method was used to determine the genotypes of rs6313, rs1923884, and rs2070040 in 5-HT2A receptor gene, and the Occupational Stress Inventory-Revised Edition was used to analyze occupational stress in these workers. Results: There were no significant differences in occupational stress between groups with different individual characteristics ( P >0.05 ) . As for the comparison of occupational stress scores between workers with different genotypes of each SNP of 5-HT2A receptor gene, the workers with CC and CT genotypes of rs6313 had significantly higher role boundary scores than those with TT genotype ( P stress score than those with CT genotype ( P occupational role score than those with CC genotype ( P stress score than those with AA genotype ( P occupational stress ( OR =1.56, 95% CI 1.10~2.20) . Conclusion: CT genotype of rs1923884 in 5-HT2A receptor gene may be associated with the susceptibility to occupational stress in oilfield workers.

Susceptibility Genes in Thyroid Autoimmunity

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Yoshiyuki Ban

2005-01-01

Full Text Available The autoimmune thyroid diseases (AITD are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD and Hashimoto's thyroiditis (HT and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4 and thyroid specific genes (e.g. TSHR, Tg. Most likely, these loci interact and their interactions may influence disease phenotype and severity.

Investigation of irradiation induced inter-granular stress corrosion cracking susceptibility on austenitic stainless steels for PWR by simulated radiation induced segregation materials

Energy Technology Data Exchange (ETDEWEB)

Yonezawa, Toshio; Fujimoto, Koji; Kanasaki, Hiroshi; Iwamura, Toshihiko [Mitsubishi Heavy Industries Ltd., Takasago R and D Center, Takasago, Hyogo (Japan); Nakada, Shizuo; Ajiki, Kazuhide [Mitsubishi Heavy Industries Ltd., Kobe Shipyard and Machinery Works, Kobe, Hyogo (Japan); Urata, Sigeru [General Office of Nuclear and Fossil Power Production, Kansai Electric Power Co., Inc., Osaka (Japan)

2000-07-01

An Irradiation Assisted Stress Corrosion Cracking (IASCC) has not been found in Pressurized Water Reactors (PWRs). However, the authors have investigated on the possibility of IASCC so as to be able to estimate the degradation of PWR plants up to the end of their lifetime. In this study, the authors melted the test alloys whose bulk compositions simulated the grain boundary compositions of irradiated Type 304 and Type 316 CW stainless steels. Low chromium, high nickel and silicon (12%Cr-28%Ni-3%Si) steel showed high susceptibility to PWSCC (Primary Water Stress Corrosion Cracking) by SSRT (Slow Strain Rate Tensile) test in simulated PWR primary water. PWSCC susceptibility of the test steels increases with a decrease of chromium content and a increase of nickel and silicon contents. The aged test steel included coherent M{sub 23}C{sub 6} carbides with matrices at the grain boundaries showed low PWSCC susceptibility. This tendency is in very good agreement with that of the PWSCC susceptibility of nickel based alloys X-750 and 690. From these results, if there is the possibility of IASCC for austenitic stainless steels in PWRs, in the future, the IASCC shall be caused by the PWSCC as a result of irradiation induced grain boundary segregation. (author)

Improvements in the susceptibility to hydrogen attack and stress-relief cracking of 2 1/4Cr-1Mo steels

International Nuclear Information System (INIS)

Imanaka, T.; Sato, S.; Shimomura, J.; Aso, K.

1985-01-01

The influence of sulphur content at extremely low level on the susceptibility to hydrogen attack and stress-relief cracking in 2 1/4Cr-1Mo steels was studied. The reduction of sulphur content and/or the addition of REM (rare earth metal) or Ca in accordance with sulphur content remarkably improve the resistivity against hydrogen attack and stress-relief cracking. Micro-structural examination has showed that there exist Mn-REM-S-Al-O complex particles in the REM-added steels. It is concluded that the effect of REM on hydrogen attack and stress-relief cracking is to reduce ''the free sulphur'' in 2 1/4Cr-1Mo steels

Evaluation of SCC susceptibility of alloy 800 under CANDU SG secondary-side conditions

International Nuclear Information System (INIS)

Liu, S.; Lu, Y.

2006-01-01

As part of a coordinated program, AECL is developing a set of tools to aid with the prediction and management of steam generator performance. Although stress corrosion cracking (of Alloy 800) has not been detected in any operating steam generator, for life management it is necessary to develop mechanistic models to predict the conditions under which stress corrosion cracking is plausible. Therefore, constant extension rate tests were carried out for Alloy 800 under various steam generator crevice chemistry conditions at applied potentials. These tests were designed to evaluate the stress corrosion cracking susceptibility of Alloy 800 under CANDU( steam generator operating conditions. Based on the experimental results, the recommended electrochemical corrosion potential/pH zone for Alloy 800 determined by electrochemical polarization measurements was verified with the respect of stress corrosion cracking susceptibility. The effects of lead contamination on the stress corrosion cracking susceptibility of Alloy 800 tubing were also evaluated. The experimental results from constant extension rate tests obtained under applied potentials suggest that Alloy 800 has good performance inside much of a previously recommended electrochemical corrosion potential/pH zone determined by electrochemical analysis. Alloy 800 is not susceptible to stress corrosion cracking under normal CANDU steam generator operating conditions. However, Alloy 800 may be susceptible to stress corrosion cracking under near-neutral crevice chemistry conditions in the presence of oxidants. In addition, stress corrosion cracking susceptibility is increased by lead contamination. This observation suggests that the previously defined electrochemical corrosion potential limit under near-neutral crevice conditions could be modified to minimize stress corrosion cracking of Alloy 800. The test results from this work also suggest that the pH dependency of the stress corrosion cracking susceptibility of Alloy 800

Phenotype overlap in Xylella fastidiosa is controlled by the cyclic di-GMP phosphodiesterase Eal in response to antibiotic exposure and diffusible signal factor-mediated cell-cell signaling.

Science.gov (United States)

de Souza, Alessandra A; Ionescu, Michael; Baccari, Clelia; da Silva, Aline M; Lindow, Steven E

2013-06-01

Eal is an EAL domain protein in Xylella fastidiosa homologous to one involved in resistance to tobramycin in Pseudomonas aeruginosa. EAL and HD-GYP domain proteins are implicated in the hydrolysis of the secondary messenger bis-(3'-5')-cyclic dimeric GMP (cyclic di-GMP). Cell density-dependent communication mediated by a Diffusible Signal Factor (DSF) also modulates cyclic di-GMP levels in X. fastidiosa, thereby controlling the expression of virulence genes and genes involved in insect transmission. The possible linkage of Eal to both extrinsic factors such as antibiotics and intrinsic factors such as quorum sensing, and whether both affect virulence, was thus addressed. Expression of eal was induced by subinhibitory concentrations of tobramycin, and an eal deletion mutant was more susceptible to this antibiotic than the wild-type strain and exhibited phenotypes similar to those of an rpfF deletion mutant blocked in DSF production, such as hypermotility, reduced biofilm formation, and hypervirulence to grape. Consistent with that, the rpfF mutant was more susceptible than the wild-type strain to tobramycin. Therefore, we propose that cell-cell communication and antibiotic stress can apparently lead to similar modulations of cyclic di-GMP in X. fastidiosa, resulting in similar phenotypes. However, the effect of cell density is dominant compared to that of antibiotic stress, since eal is suppressed by RpfF, which may prevent inappropriate behavioral changes in response to antibiotic stress when DSF accumulates.

Water Stress Affects Development Time but Not Takeoff Performance in the Butterfly Pararge aegeria.

Science.gov (United States)

Lailvaux, Simon P; Breuker, Casper J; Van Damme, Raoul

Most organisms are limited in the amount and type of resources they are able to extract from the environment. The juvenile environment is particularly important in this regard, as conditions over ontogeny can influence the adult phenotype. Whole-organism performance traits, such as locomotion, are susceptible to such environmental effects, yet the specific biotic and abiotic factors driving performance plasticity have received little attention. We tested whether speckled wood Pararge aegeria L. butterflies reared under conditions of water stress exhibited poorer flight morphology and performance than control individuals. Despite large differences in mortality between treatments, we found no effects of water stress treatment on takeoff performance and only minor treatment effects on flight morphology. However, butterflies reared on water-stressed diets exhibited both significantly greater mortality and longer development times than did control individuals. Pararge aegeria larvae may compensate for this stress by prolonging development, resulting in similar realized performance capacities at least in takeoff performance in surviving adult butterflies; other measures of flight performance remain to be considered. Alternatively, the adult phenotype may be insulated from environmental effects at the larval stage in these insects.

Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster.

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Allison L Weber

Full Text Available Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress.We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genome-wide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67-79% and 56-66% of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis.We identified novel candidate genes associated with variation in resistance to oxidative stress that have context-dependent effects. These results form the basis for future translational studies to identify oxidative stress susceptibility/resistance genes that are evolutionary conserved and might play a role in human disease.

Thermotolerance, oxidative stress, apoptosis, heat-shock proteins and damages to reproductive cells of insecticide-susceptible and -resistant strains of the diamondback moth Plutella xylostella.

Science.gov (United States)

Zhang, L J; Chen, J L; Yang, B L; Kong, X G; Bourguet, D; Wu, G

2017-08-01

In this study, we investigated thermotolerance, several physiological responses and damage to reproductive cells in chlorpyrifos-resistant (Rc) and -susceptible (Sm) strains of the diamondback moth, Plutella xylostella subjected to heat stress. The chlorpyrifos resistance of these strains was mediated by a modified acetylcholinesterase encoded by an allele, ace1R, of the ace1 gene. Adults of the Rc strain were less heat resistant than those of the Sm strain; they also had lower levels of enzymatic activity against oxidative damage, higher reactive oxygen species contents, weaker upregulation of two heat shock protein (hsp) genes (hsp69s and hsp20), and stronger upregulation of two apoptotic genes (caspase-7 and -9). The damage to sperm and ovary cells was greater in Rc adults than in Sm adults and was temperature sensitive. The lower fitness of the resistant strain, compared with the susceptible strain, is probably due to higher levels of oxidative stress and apoptosis, which also have deleterious effects on several life history traits. The greater injury observed in conditions of heat stress may be due to both the stronger upregulation of caspase genes and weaker upregulation of hsp genes in resistant than in susceptible individuals.

Comprehensive assessment of rheumatoid arthritis susceptibility loci in a large psoriatic arthritis cohort.

LENUS (Irish Health Repository)

Bowes, John

2012-08-01

A number of rheumatoid arthritis (RA) susceptibility genes have been identified in recent years. Given the overlap in phenotypic expression of synovial joint inflammation between RA and psoriatic arthritis (PsA), the authors explored whether RA susceptibility genes are also associated with PsA.

Reduced left ventricular dimension and function following early life stress: A thrifty phenotype hypothesis engendering risk for mood and anxiety disorders

Directory of Open Access Journals (Sweden)

Jeremy D. Coplan

2018-02-01

Full Text Available Background: Early life stress (ELS in macaques in the form of insecure maternal attachment putatively induces epigenetic adaptations resulting in a “thrifty phenotype” throughout the life cycle. For instance, ELS induces persistent increases in insulin resistance, hippocampal and corpus callosum atrophy and reduced “behavioral plasticity”, which, taken together, engenders an increased risk for mood and anxiety disorders in humans but also a putative sparing of calories. Herein, we test the hypothesis whether a thrifty phenotype induced by ELS is peripherally evident as hypotrophy of cardiac structure and function, raising the possibility that certain mood disorders may represent maladaptive physiological and central thrift adaptations. Methods: 14 adult bonnet macaques (6 males exposed to the maternal variable foraging demand (VFD model of ELS were compared to 20 non-VFD adult subjects (6 males. Left ventricle end-diastolic dimension (LVEDD, Left ventricle end-systolic dimension (LVESD and stroke volume (SV were calculated using echocardiography. Blood pressure and heart rate were measured only in females. Previously obtained neurobehavioral correlates available only in males were analyzed in the context of cardiac parameters. Results: Reduced LVESD (p < 0.05 was observed when controlled for age, sex, body weight and crown-rump length whereas ejection fraction (EF (p = 0.037 was greater in VFD-reared versus non-VFD subjects. Pulse pressure was lower in VFD versus non-VFD females (p < 0.05. Male timidity in response to a human intruder was associated with reduced LVEDD (p < 0.05. Conclusions: ELS is associated with both structural and functional reductions of left ventricular measures, potentially implying a body-wide thrifty phenotype. Parallel “thrift” adaptations may occur in key brain areas following ELS and may play an unexplored role in mood and anxiety disorder susceptibility.

SUSCEPTIBILITY OF RESPIRATORY ISOLATES OF STREPTOCOCCUS PNEUMONIAE ISOLATED FROM CHILDREN HOSPITALIZED IN THE CLINICAL CENTER NIS.

Science.gov (United States)

Dinić, Marina M; Mladenović Antić, Snezana; Kocić, Branislava; Stanković Dordević, Dobrila; Vrbić, Miodrag; Bogdanović, Milena

2016-01-01

Streptococcus pneumoniae is one of the most common causes of respiratory infections. The aim was to study the susceptibility to antimicrobial agents of respiratory isolates ofStreptococcus pneumoniae obtained from hospitalized children. A total of 190 respiratory pneumococcal isolates obtained from children aged from 0 to 14 years were isolated and identified by using standard microbiological methods. Susceptibility to oxacillin, erythromycin, clindamycin, tetracycline, cotrimoxazole, ofloxacin and rifampicin was tested by disc diffusion method. Minimal inhibitory concentrations for amoxicillin and ceftriaxone were determined by means of E test. The macrolide-resistant phenotype was detected by double disc diffusion test. All tested isolates were susceptible to amoxicillin and ceftriaxone. The minimal amoxicillin concentration inhibiting the growth of 50% of isolates and of 90% of isolates was 0.50 microg/ml and 1.0 microg/ml, respectively and the minimal ceftriaxone concentration inhibiting the growth of 50% of isolates and of 90% of isolates was 0.25 microg/ml and 0.50 microg/ml, respectively. Susceptibility to erythromycin and clindamycin was observed in 21.6% and 29.47% of isolates, respectively. The resistence to macrolides-M phenotype was detected in 10.07% of isolates and constitutive macrolide-lincosamide-streptogramin phenotype (constitutive MLS phenotype) was found in 89.93% of isolates. All tested isolates were susceptible to ofloxacin and rifampicin. Amoxicillin could be the therapy of choice in pediatric practice. The macrolides should not be recommended for the empirical therapy of pneumococcal respiratory tract infection in our local area.

High susceptibility of activated lymphocytes to oxidative stress-induced cell death

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Giovanna R. Degasperi

2008-03-01

Full Text Available The present study provides evidence that activated spleen lymphocytes from Walker 256 tumor bearing rats are more susceptible than controls to tert-butyl hydroperoxide (t-BOOH-induced necrotic cell death in vitro. The iron chelator and antioxidant deferoxamine, the intracellular Ca2+ chelator BAPTA, the L-type Ca2+ channel antagonist nifedipine or the mitochondrial permeability transition inhibitor cyclosporin A, but not the calcineurin inhibitor FK-506, render control and activated lymphocytes equally resistant to the toxic effects of t-BOOH. Incubation of activated lymphocytes in the presence of t-BOOH resulted in a cyclosporin A-sensitive decrease in mitochondrial membrane potential. These results indicate that the higher cytosolic Ca2+ level in activated lymphocytes increases their susceptibility to oxidative stress-induced cell death in a mechanism involving the participation of mitochondrial permeability transition.O presente estudo demonstra que linfócitos ativados de baço de ratos portadores do tumor de Walker 256 são mais susceptíveis à morte celular necrótica induzida por tert-butil hidroperóxido (t-BOOH in vitro quando comparados aos controles. O quelante de ferro e antioxidante deferoxamina, o quelante intracelular de Ca2+ BAPTA, o antagonista de canal de Ca2+ nifedipina ou o inibidor da transição de permeabilidade mitocondrial ciclosporina-A, mas não o inibidor de calcineurina FK-506, inibiram de maneira similar a morte celular induzida por t-BOOH em linfócitos ativados e controles. Os linfócitos ativados apresentaram redução do potencial de membrana mitocondrial induzida por t-BOOH num mecanismo sensível a ciclosporina-A. Nossos resultados indicam que o aumento da concentração de Ca2+ citosólico em linfócitos ativados aumenta a susceptibilidade dos mesmos à morte celular induzida por estresse oxidativo, num mecanismo envolvendo a participação do poro de transição de permeabilidade mitocondrial.

Brain Potentials and Personality: A New Look at Stress Susceptibility.

Science.gov (United States)

1987-09-01

disinhibition (Dis) measures a hedonistic , extraverted lifestyle including drinking, parties, sex, and gambling; boredom susceptibility (BS) indicates an...adventure seeking; ES = Experience seeking; Dis = Disinhibition; BS = Boredom susceptibility. 1 14 I N i*5’ Table 4 Correlation of Auditory Evoked...20. aTAS = Thrill and adventure seeking; ES = Experience seeking; Dis = Disinhibition; BS = Boredom susceptibility. < .05. 15 I The present study

Stress, cortisol and well-being of caregivers and children in home-based child care: a case for differential susceptibility.

Science.gov (United States)

Groeneveld, M G; Vermeer, H J; van IJzendoorn, M H; Linting, M

2012-03-01

We examined whether children cared for by stressed caregivers show lower socio-emotional well-being and more stress, compared with children cared for by less stressed caregivers. Perceived stress and cortisol levels of professional caregivers (n = 44), and associations with children's (n = 44) well-being and cortisol levels in home-based child care were examined. Caregiver perceived stress and cortisol levels were related to children's well-being but not to children's cortisol levels. Children's social fearfulness acted as a moderator between caregivers' mean ratio of diurnal change in cortisol and children's well-being. When caregiver cortisol levels decreased, more fearful children were reported higher on well-being than less fearful peers. In contrast, when caregiver cortisol levels increased, more fearful children were reported lower on well-being. The findings point to differential susceptibility. Child care organizations and parents need to notice that a non-stressful child care environment is in particular important for children with a difficult temperament. © 2010 Blackwell Publishing Ltd.

De-anonymizing Genomic Databases Using Phenotypic Traits

Directory of Open Access Journals (Sweden)

Humbert Mathias

2015-06-01

Full Text Available People increasingly have their genomes sequenced and some of them share their genomic data online. They do so for various purposes, including to find relatives and to help advance genomic research. An individual’s genome carries very sensitive, private information such as its owner’s susceptibility to diseases, which could be used for discrimination. Therefore, genomic databases are often anonymized. However, an individual’s genotype is also linked to visible phenotypic traits, such as eye or hair color, which can be used to re-identify users in anonymized public genomic databases, thus raising severe privacy issues. For instance, an adversary can identify a target’s genome using known her phenotypic traits and subsequently infer her susceptibility to Alzheimer’s disease. In this paper, we quantify, based on various phenotypic traits, the extent of this threat in several scenarios by implementing de-anonymization attacks on a genomic database of OpenSNP users sequenced by 23andMe. Our experimental results show that the proportion of correct matches reaches 23% with a supervised approach in a database of 50 participants. Our approach outperforms the baseline by a factor of four, in terms of the proportion of correct matches, in most scenarios. We also evaluate the adversary’s ability to predict individuals’ predisposition to Alzheimer’s disease, and we observe that the inference error can be halved compared to the baseline. We also analyze the effect of the number of known phenotypic traits on the success rate of the attack. As progress is made in genomic research, especially for genotype-phenotype associations, the threat presented in this paper will become more serious.

Understanding Stress-Related Behavioral Phenotypes: Report from the 1st International Neuroscience Summer School and the 11th International “Stress and Behavior” Conference

Directory of Open Access Journals (Sweden)

J. L. LaPorte

2008-01-01

Full Text Available The 1st International Neuroscience Summer School and the 11th International Multidisciplinary Neuroscience and Biopsychiatry Conference on Stress and Behavior were held in St. Petersburg, Russia, during May 9–20, 2008. The summer school gathered 30 talented young scientists from 15 countries worldwide, and was dedicated to different topics of behavioral neuroscience. Many interactive courses were provided on neuropharmacology, animal phenotyping, and biopsychology. The conference's excellent scientific and social program attracted almost 500 delegates from 40 countries from many areas of stress research. The eclectic interaction between medical doctors, basic scientists, psychologists, and students made for a productive and collaborative environment, which contributed greatly to the success of the school and conference.

Current Status of Animal Models of Posttraumatic Stress Disorder: Behavioral and Biological Phenotypes, and Future Challenges in Improving Translation.

Science.gov (United States)

Deslauriers, Jessica; Toth, Mate; Der-Avakian, Andre; Risbrough, Victoria B

2018-05-15

Increasing predictability of animal models of posttraumatic stress disorder (PTSD) has required active collaboration between clinical and preclinical scientists. Modeling PTSD is challenging, as it is a heterogeneous disorder with ≥20 symptoms. Clinical research increasingly utilizes objective biological measures (e.g., imaging, peripheral biomarkers) or nonverbal behaviors and/or physiological responses to complement verbally reported symptoms. This shift toward more-objectively measurable phenotypes enables refinement of current animal models of PTSD, and it supports the incorporation of homologous measures across species. We reviewed >600 articles to examine the ability of current rodent models to probe biological phenotypes of PTSD (e.g., sleep disturbances, hippocampal and fear-circuit dysfunction, inflammation, glucocorticoid receptor hypersensitivity) in addition to behavioral phenotypes. Most models reliably produced enduring generalized anxiety-like or depression-like behaviors, as well as hyperactive fear circuits, glucocorticoid receptor hypersensitivity, and response to long-term selective serotonin reuptake inhibitors. Although a few paradigms probed fear conditioning/extinction or utilized peripheral immune, sleep, and noninvasive imaging measures, we argue that these should be incorporated more to enhance translation. Data on female subjects, on subjects at different ages across the life span, or on temporal trajectories of phenotypes after stress that can inform model validity and treatment study design are needed. Overall, preclinical (and clinical) PTSD researchers are increasingly incorporating homologous biological measures to assess markers of risk, response, and treatment outcome. This shift is exciting, as we and many others hope it not only will support translation of drug efficacy from animal models to clinical trials but also will potentially improve predictability of stage II for stage III clinical trials. Published by Elsevier Inc.

Phenotypical and Molecular Characterisation of Fusarium circinatum: Correlation with Virulence and Fungicide Sensitivity

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Martin Mullett

2017-11-01

Full Text Available Fusarium circinatum, causing pine pitch canker, is one of the most damaging pathogens of Pinus species. This study investigated the use of phenotypical and molecular characteristics to delineate groups in a worldwide collection of isolates. The groups correlated with virulence and fungicide sensitivity, which were tested in a subset of isolates. Virulence tests of twenty isolates on P. radiata, P. sylvestris and P. pinaster demonstrated differences in host susceptibility, with P. radiata most susceptible and P. sylvestris least susceptible. Sensitivity to the fungicides fludioxonil and pyraclostrobin varied considerably between isolates from highly effective (half-maximal effective concentration (EC50 < 0.1 ppm to ineffective (EC50 > 100 ppm. This study demonstrates the potential use of simply acquired phenotypical (cultural, morphological and molecular metrics to gain a preliminary estimate of virulence and sensitivity to certain fungicides. It also highlights the necessity of including a range of isolates in fungicide tests and host susceptibility assays, particularly of relevance to tree breeding programmes.

Phenotyping of sweet sorghum for tolerance to hydric stress through morphological characteristics

Directory of Open Access Journals (Sweden)

Luciano Rezende Moreira

2015-05-01

Full Text Available This study was conducted to identify the sweetsorghum cultivars presenting higher tolerance todrought as well as to phenotypically discriminatethe root morphological characteristics of thosegenotypes for environments with water deficit.The cultivars (Rio, Ramada, BRS 501 andBRS 506 were subjected to two treatments(Environments. The first one was an environmentnamed unrestricted water (AI -37.5 kPa, andthe second one, with hydric restriction, namedrestricted water (AR with a matrix pressurelower than the with CPA treatment, that is, -375kPa. The difference between the ideal weight ofthe treatment and the weight observed in thevase, before being irrigated, when compared withan identical vase used in the treatments withoutthe plant, provided an evapotranspiration ofthe cultivar during the period. The roots wereanalyzed by the WinRhizo system, in orderto obtain the following characteristics understudy: length, volume, superficial area, projectedarea and root diameter. For all characteristicsunder evaluation, the variance analysis showedno interaction (P> 0.05 between genotypeand environment. Separately, no variationswere observed (P> 0.05 in the genotypes and environments evaluated for the characteristicsunder study, except the root diameter. Thus,it was observed that the diameter of the rootswere higher (P <0.05 when the plants weresubmitted to higher drought stress conditions(AIR. Findings indicate that the cultivars didnot present significantly different characteristicsin the contrasting environments, which probablyoccurred because they are very tolerant to theimposed stress, the phenological stage underevaluation study was too initial, or the stress hadlow intensity to generate different activities in thecultivars..

Susceptibility or resilience? Prenatal stress predisposes male rats to social subordination, but facilitates adaptation to subordinate status.

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Scott, Karen A; de Kloet, Annette D; Smeltzer, Michael D; Krause, Eric G; Flak, Jonathan N; Melhorn, Susan J; Foster, Michelle T; Tamashiro, Kellie L K; Sakai, Randall R

2017-09-01

Mood disorders such as major depressive disorder (MDD) affect a significant proportion of the population. Although progress has been made in the development of therapeutics, a large number of individuals do not attain full remission of symptoms and adverse side effects affect treatment compliance for some. In order to develop new therapies, there is a push for new models that better reflect the multiple risk factors that likely contribute to the development of depressive illness. We hypothesized that early life stress would exacerbate the depressive-like phenotype that we have previously observed in socially subordinate (SUB) adult male rats in the visible burrow system (VBS), a semi-natural, ethologically relevant environment in which males in a colony form a dominance hierarchy. Dams were exposed to chronic variable stress (CVS) during the last week of gestation, resulting in a robust and non-habituating glucocorticoid response that did not alter maternal food intake, body weight or litter size and weight. As adults, one prenatal CVS (PCVS) and one non-stressed (NS) male were housed in the VBS with adult females. Although there were no overt differences between PCVS and NS male offspring prior to VBS housing, a greater percentage of PCVS males became SUB. However, the depressive-like phenotype of SUB males was not exacerbated in PCVS males; rather, they appeared to better cope with SUB status than NS SUB males. They had lower basal plasma corticosterone than NS SUB males at the end of VBS housing. In situ hybridization for CRH in the PVN and CeA did not reveal any prenatal treatment or status effects, while NPY expression was higher within the MeA of dominant and subordinate males exposed to the VBS in comparison with controls, but with no effect of prenatal treatment. These data suggest that prenatal chronic variable stress may confer resilience to offspring when exposed to social stress in adulthood. Copyright © 2017 Elsevier Inc. All rights reserved.

Air pollution, cardiovascular endpoints and susceptibility by stress and material resources: a systematic review of the evidence.

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Fuller, Christina H; Feeser, Karla R; Sarnat, Jeremy A; O'Neill, Marie S

2017-06-14

Evidence shows that both the physical and social environments play a role in the development of cardiovascular disease. The purpose of this systematic review is two-fold: First, we summarize research from the past 12 years from the growing number of studies focused on effect modification of the relationships between air pollution and cardiovascular disease (CVD) outcomes by socioeconomic position (SEP) and; second, we identify research gaps throughout the published literature on this topic and opportunities for addressing these gaps in future study designs. We identified 30 articles that examined the modifying effects of either material resources or psychosocial stress (both related to SEP) on associations between short and long-term air pollution exposure and CVD endpoints. Although 18 articles identified at least one interaction between an air pollutant and material resource indicator, 11 others did not. Support for susceptibility to air pollution by psychosocial stress was weaker; however, only three articles tested this hypothesis. Further studies are warranted to investigate how air pollution and SEP together may influence CVD. We recommend that such research include thorough assessment of air pollution and SEP correlations, including spatial correlation; investigate air pollution indices or multi-pollutant models; use standardized metrics of SEP to enhance comparability across studies; and evaluate potentially susceptible populations.

Phenotypic variation as an indicator of pesticide stress in gudgeon: Accounting for confounding factors in the wild.

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Shinn, Cândida; Blanchet, Simon; Loot, Géraldine; Lek, Sovan; Grenouillet, Gaël

2015-12-15

The response of organisms to environmental stress is currently used in the assessment of ecosystem health. Morphological changes integrate the multiple effects of one or several stress factors upon the development of the exposed organisms. In a natural environment, many factors determine the patterns of morphological differentiation between individuals. However, few studies have sought to distinguish and measure the independent effect of these factors (genetic diversity and structure, spatial structuring of populations, physical-chemical conditions, etc.). Here we investigated the relationship between pesticide levels measured at 11 sites sampled in rivers of the Garonne river basin (SW France) and morphological changes of a freshwater fish species, the gudgeon (Gobio gobio). Each individual sampled was genotyped using 8 microsatellite markers and their phenotype characterized via 17 morphological traits. Our analysis detected a link between population genetic structure (revealed by a Bayesian method) and morphometry (linear discriminant analysis) of the studied populations. We then developed an original method based on general linear models using distance matrices, an extension of the partial Mantel test beyond 3 matrices. This method was used to test the relationship between contamination (toxicity index) and morphometry (PST of morphometric traits), taking into account (1) genetic differentiation between populations (FST), (2) geographical distances between sites, (3) site catchment area, and (4) various physical-chemical parameters for each sampling site. Upon removal of confounding effects, 3 of the 17 morphological traits studied were significantly correlated with pesticide toxicity, suggesting a response of these traits to the anthropogenic stress. These results underline the importance of taking into account the different sources of phenotypic variability between organisms when identifying the stress factors involved. The separation and quantification of

Insecticide susceptibility of Anopheles mosquitoes changes in response to variations in the larval environment.

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Owusu, Henry F; Chitnis, Nakul; Müller, Pie

2017-06-16

Insecticide resistance threatens the success achieved through vector control in reducing the burden of malaria. An understanding of insecticide resistance mechanisms would help to develop novel tools and strategies to restore the efficacy of insecticides. Although we have substantially improved our understanding of the genetic basis of insecticide resistance over the last decade, we still know little of how environmental variations influence the mosquito phenotype. Here, we measured how variations in larval rearing conditions change the insecticide susceptibility phenotype of adult Anopheles mosquitoes. Anopheles gambiae and A. stephensi larvae were bred under different combinations of temperature, population density and nutrition, and the emerging adults were exposed to permethrin. Mosquitoes bred under different conditions showed considerable changes in mortality rates and body weight, with nutrition being the major factor. Weight is a strong predictor of insecticide susceptibility and bigger mosquitoes are more likely to survive insecticide treatment. The changes can be substantial, such that the same mosquito colony may be considered fully susceptible or highly resistant when judged by World Health Organization discriminatory concentrations. The results shown here emphasise the importance of the environmental background in developing insecticide resistance phenotypes, and caution for the interpretation of data generated by insecticide susceptibility assays.

Mapping of murine radiation-induced acute myeloid leukaemia susceptibility loci

International Nuclear Information System (INIS)

Darakhshan, F.

2001-01-01

Studies on radiation-induced AML have shown characteristic phenotypic variation in susceptibility amongst inbred mouse strains, suggesting the involvement of genetic factors in determining the development of AML post-irradiation exposure. The main objective of the present study therefore was to identify and map markers in linkage disequilibrium with gene variants associated with influencing susceptibility to radiation induced AML in mice. Given Chr 2 abnormalities are characteristic of AML in mice, this feature was exploited in an effort to overcome the long latency for AML development. Analysis of Chr 2 aberrations at 24 and 48 h following irradiation established a positive correlation between Chr 2 radiosensitivity and radiation-AML susceptibility thus validating the choice of substitute assay. The analysis also resulted in the identification of a further trait, additional to Chr 2 radiosensitivity, termed overall chromosome radiosensitivity. Genetic mapping of Chr 2 radiosensitivity using public domain microsatellite database information resulted in the definition of cluster regions on 7 different chromosomes. Further genotyping reduced the candidate regions to 3 specific regions of interest. A test of allelic association could not ascertain a conclusive link between markers at these regions and the Chr 2 radiosensitivity/radiation-AML susceptibility phenotype. However, a region on Chr 4 around D4Mit221 appears to be most strongly associated. Similar studies identified three chromosomal regions of interest (on Chrs 4, 8 and 16) associated with overall chromosome radiosensitivity trait. An independent mapping strategy using F3 RCS confirmed the likely involvement of two of the candidate Chr 2 radiosensitivity regions identified by the inbred analysis including that on Chr 4 and also highlighted phenotypic heterogeneity amongst resistant RC strains, suggesting the influence of multiple alleles in specific phenotypes. RFLP analysis of candidate genes, localised on

Stress-corrosion cracking susceptibility of V-15Cr-5Ti in pressurized water at 2880C

International Nuclear Information System (INIS)

Diercks, D.R.; Smith, D.L.

1987-07-01

The stress-corrosion cracking susceptibility of V-15Cr-5Ti in pressurized water at 288 0 C has been evaluated by means of constant extension rate tensile (CERT) tests in a refreshed autoclave system. The test environments included high-purity water as well as water containing SO 4 2- and NO 3 - impurities at a concentration of 10 wppM. Strain rates from 1 x 10 -6 to 5 x 10 -8 s -1 were employed, and dissolved oxygen levels ranged from <0.005 to 7.9 wppM. Test times were from 3.2 to 619 h. No stress corrosion cracking was observed under any of the test conditions. These results were analyzed using measured electrochemical potentials, available Pourbaix diagram information, and the observed oxidation behavior. 7 refs., 5 figs., 1 tab

Assessment of the effects of surface preparation and coatings on the susceptibility of line pipe to stress-corrosion cracking

International Nuclear Information System (INIS)

Beavers, J.A.

1992-01-01

Objectives were to evaluate susceptibility of pipeline steel to SCC when coated with coal-tar enamel, fusion-bonded epoxy (FBE), and polyethylene tape coatings. The tests included standard cathodic disbondment tests, potential gradients beneath disbonded coatings, electrochemical measurements, and SCC tests. It was concluded that factors affecting relative SCC susceptibility of pipelines with different coatings are the disbonding resistance of the coating and the ability of the coating to pass cathodic protection (CP) current. FBE coated pipelines would be expected to exhibit good SCC resistance, since the FBE coating had high cathodic disbonding resistance and could pass CP current. Grit blasting at levels used at coating mills may be beneficial or detrimental to SCC susceptibility. Excellent correlation was found between th Almen strip deflection and change in SCC threshold stress. It appears to be beneficial to remove as much mill scale as possible, and a white surface finish probably should also be specified. 50 figs, 10 tabs

Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda.

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Eshleman, Susan H; Laeyendecker, Oliver; Parkin, Neil; Huang, Wei; Chappey, Colombe; Paquet, Agnes C; Serwadda, David; Reynolds, Steven J; Kiwanuka, Noah; Quinn, Thomas C; Gray, Ronald; Wawer, Maria

2009-04-27

To analyze antiretroviral drug susceptibility in HIV from recently infected adults in Rakai, Uganda, prior to the availability of antiretroviral drug treatment. Samples obtained at the time of HIV seroconversion (1998-2003) were analyzed using the GeneSeq HIV and PhenoSense HIV assays (Monogram Biosciences, Inc., South San Francisco, California, USA). Test results were obtained for 104 samples (subtypes: 26A, 1C, 66D, 9A/D, 1C/D, 1 intersubtype recombinant). Mutations used for genotypic surveillance of transmitted antiretroviral drug resistance were identified in six samples: three had nucleoside reverse transcriptase inhibitor (NRTI) surveillance mutations (two had M41L, one had K219R), and three had protease inhibitor surveillance mutations (I47V, F53L, N88D); none had nonnucleoside reverse transcriptase inhibitor (NNRTI) surveillance mutations. Other resistance-associated mutations were identified in some samples. However, none of the samples had a sufficient number of mutations to predict reduced antiretroviral drug susceptibility. Ten (9.6%) of the samples had reduced phenotypic susceptibility to at least one drug (one had partial susceptibility to didanosine, one had nevirapine resistance, and eight had resistance or partial susceptibility to at least one protease inhibitor). Fifty-three (51%) of the samples had hypersusceptibility to at least one drug (seven had zidovudine hypersusceptibility, 28 had NNRTI hypersusceptibility, 34 had protease inhibitor hypersusceptibility). Delavirdine hypersusceptibility was more frequent in subtype A than D. In subtype D, efavirenz hypersusceptibility was associated with substitutions at codon 11 in HIV-reverse transcriptase. Phenotyping detected reduced antiretroviral drug susceptibility and hypersusceptibility in HIV from some antiretroviral-naive Ugandan adults that was not predicted by genotyping. Phenotyping may complement genotyping for analysis of antiretroviral drug susceptibility in populations with nonsubtype B

Evaluation of Post-Operative Antibiotic Administration on Phenotypic ...

African Journals Online (AJOL)

But baseline data to judge effects of long-term post-operative antibiotic administration in clinical and surgical canine health conditions are currently lacking in Nigeria. This study aimed at providing vital baseline antibiotic profiles of canine bacteria of veterinary and public health importance. Phenotypic antibiotic susceptibility ...

Susceptibility to stress corrosion in stainless steels type AISI 321 and 12X18H10T used in PWR type reactors (WWER)

International Nuclear Information System (INIS)

Matadamas C, N.

1995-01-01

Titanium stabilized stainless steels have been utilized in sovietic pressurized water reactors (VVER) for avoid the susceptibility to Intergranular Corrosion (IGC) present in other austenitic stainless steels. However the Intergranular Corrosion resistance of this kind of materials has been questioned because of Intergranular Stress Corrosion Cracking failures (IGSCC) have been reported. This paper study the electrochemical behavior of the AISI 321 stainless steel in a H 3 BO 3 Solution contaminated with chlorides and its susceptibility to Intergranular Corrosion.Electrochemical prediction diagrams of the stainless steels AISI 321 and 12X18H10T (sovietic) sensitized (600 Centigrade, 3 h.) were compared. Cylindrical and conical samples were used in Slow Strain Rate Tests (SSRT), to determine the susceptibility to Stress Corrosion Cracking (SCC) in AISI 321 and 12X18H10T stainless steels. The results obtained showed that the temperature of the solution is a very important factor to detect this susceptibility. Fractography studies on the fracture surfaces of the samples obtained in the SSRT at high temperature were realized. Corrosion velocities of both AISI 321 and 12X18H10T stainless steels were determined using conical samples in the CERT system at high temperature. E.D.A.X. analysis was employed in both AISI 321 and 12X18H10T stainless steels in order to explain the degree of sensitization. (Author)

Effects of cold working ratio and stress intensity factor on intergranular stress corrosion cracking susceptibility of non-sensitized austenitic stainless steels in simulated BWR and PWR primary water

International Nuclear Information System (INIS)

Yaguchi, Seiji; Yonezawa, Toshio

2012-01-01

To evaluate the effects of cold working ratio, stress intensity factor and water chemistry on an IGSCC susceptibility of non-sensitized austenitic stainless steel, constant displacement DCB specimens were applied to SCC tests in simulated BWR and PWR primary water for the three types of austenitic stainless steels, Types 316L, 347 and 321. IGSCC was observed on the test specimens in simulated BWR and PWR primary water. The observed IGSCC was categorized into the following two types. The one is that the IGSCC observed on the same plane of the pre-fatigue crack plane, and the other is that the IGSCC observed on a plane perpendicular to the pre-fatigue crack plane. The later IGSCC fractured plane is parallel to the rolling plane of a cold rolled material. Two types of IGSCC fractured planes were changed according to the combination of the testing conditions (cold working ratio, stress intensity factor and simulated water). It seems to suggest that the most susceptible plane due to fabrication process of materials might play a significant role of IGSCC for non-sensitized cold worked austenitic stainless steels, especially, in simulated PWR primary water. Based upon evaluating on the reference crack growth rate (R-CGR) of the test specimens, the R-CGR seems to be mainly affected by cold working ratio. In case of simulated PWR primary water, it seems that the effect of metallurgical aspects dominates IGSCC susceptibility. (author)

Drought and Heat Differentially Affect XTH Expression and XET Activity and Action in 3-Day-Old Seedlings of Durum Wheat Cultivars with Different Stress Susceptibility.

Science.gov (United States)

Iurlaro, Andrea; De Caroli, Monica; Sabella, Erika; De Pascali, Mariarosaria; Rampino, Patrizia; De Bellis, Luigi; Perrotta, Carla; Dalessandro, Giuseppe; Piro, Gabriella; Fry, Stephen C; Lenucci, Marcello S

2016-01-01

Heat and drought stress have emerged as major constraints for durum wheat production. In the Mediterranean area, their negative effect on crop productivity is expected to be exacerbated by the occurring climate change. Xyloglucan endotransglucosylase/hydrolases (XTHs) are chief enzymes in cell wall remodeling, whose relevance in cell expansion and morphogenesis suggests a central role in stress responses. In this work the potential role of XTHs in abiotic stress tolerance was investigated in durum wheat. The separate effects of dehydration and heat exposure on XTH expression and its endotransglucosylase (XET) in vitro activity and in vivo action have been monitored, up to 24 h, in the apical and sub-apical root regions and shoots excised from 3-day-old seedlings of durum wheat cultivars differing in stress susceptibility/tolerance. Dehydration and heat stress differentially influence the XTH expression profiles and the activity and action of XET in the wheat seedlings, depending on the degree of susceptibility/tolerance of the cultivars, the organ, the topological region of the root and, within the root, on the gradient of cell differentiation. The root apical region was the zone mainly affected by both treatments in all assayed cultivars, while no change in XET activity was observed at shoot level, irrespective of susceptibility/tolerance, confirming the pivotal role of the root in stress perception, signaling, and response. Conflicting effects were observed depending on stress type: dehydration evoked an overall increase, at least in the apical region of the root, of XET activity and action, while a significant inhibition was caused by heat treatment in most cultivars. The data suggest that differential changes in XET action in defined portions of the root of young durum wheat seedlings may have a role as a response to drought and heat stress, thus contributing to seedling survival and crop establishment. A thorough understanding of the mechanisms underlying

Adolescent but not adult-born neurons are critical for susceptibility to chronic social defeat

Directory of Open Access Journals (Sweden)

Greer S Kirshenbaum

2014-08-01

Full Text Available Recent evidence implicates adult hippocampal neurogenesis in regulating behavioral and physiologic responses to stress. Hippocampal neurogenesis occurs across the lifespan, however the rate of cell birth is up to 300% higher in adolescent mice compared to adults. Adolescence is a sensitive period in development where emotional circuitry and stress reactivity undergo plasticity establishing life-long set points. Therefore neurogenesis occurring during adolescence may be particularly important for emotional behavior. However, little is known about the function of hippocampal neurons born during adolescence. In order to assess the contribution of neurons born in adolescence to the adult stress response and depression-related behavior, we transiently reduced cell proliferation either during adolescence, or during adulthood in GFAP-Tk mice. We found that the intervention in adolescence did not change baseline behavioral responses in the forced swim test, sucrose preference test or social affiliation test, and did not change corticosterone responses to an acute stressor. However following chronic social defeat, adult mice with reduced adolescent neurogenesis showed a resilient phenotype. A similar transient reduction in adult neurogenesis did not affect depression-like behaviors or stress induced corticosterone. Our study demonstrates that hippocampal neurons born during adolescence, but not in adulthood are important to confer susceptibility to chronic social defeat.

Stressful presentations: mild cold stress in laboratory mice influences phenotype of dendritic cells in naïve and tumor-bearing mice.

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Kokolus, Kathleen M; Spangler, Haley M; Povinelli, Benjamin J; Farren, Matthew R; Lee, Kelvin P; Repasky, Elizabeth A

2014-01-01

The ability of dendritic cells (DCs) to stimulate and regulate T cells is critical to effective anti-tumor immunity. Therefore, it is important to fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily to model immune responses. The goals of this report are to 1) briefly summarize previous work revealing how DCs respond to various forms of physiological stress and 2) to present new data highlighting the potential for chronic mild cold stress inherent to mice housed at the required standard ambient temperatures to influence baseline DCs properties in naïve and tumor-bearing mice. As recent data from our group shows that CD8(+) T cell function is significantly altered by chronic mild cold stress and since DC function is crucial for CD8(+) T cell activation, we wondered whether housing temperature may also be influencing DC function. Here we report that there are several significant phenotypical and functional differences among DC subsets in naïve and tumor-bearing mice housed at either standard housing temperature or at a thermoneutral ambient temperature, which significantly reduces the extent of cold stress. The new data presented here strongly suggests that, by itself, the housing temperature of mice can affect fundamental properties and functions of DCs. Therefore differences in basal levels of stress due to housing should be taken into consideration when interpreting experiments designed to evaluate the impact of additional variables, including other stressors on DC function.

Phosphoinositide 3-kinase/Akt signalling is responsible for the differential susceptibility of myoblasts and myotubes to menadione-induced oxidative stress.

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Lim, Jeong A; Woo, Joo Hong; Kim, Hye Sun

2008-09-01

In this study, it was found that undifferentiated myoblasts were more vulnerable to menadione-induced oxidative stress than differentiated myotubes. Cell death occurred with a relatively low concentration of menadione in myoblasts compared to myotubes. With the same concentration of menadione, the Bcl-2/Bax ratio decreased and nuclei containing condensed chromatin were observed in myoblasts to a greater extent than in myotubes. However, myotubes became increasingly susceptible to menadione when phosphoinositide 3-kinase (PI3-K) was blocked by pre-incubation with LY294002, a PI3-K inhibitor. Actually, PI3-K activity was reduced by menadione in myoblasts but not in myotubes. In addition, the phosphorylation of Akt, a downstream effector of PI3-K, was inhibited in myoblasts by menadione but increased in myotubes. Both LY294002 and API-2, an Akt inhibitor, decreased the Bcl-2/Bax ratio in menadione-exposed myotubes. These results suggest that the differential activity of PI3-K/Akt signalling is responsible for the differential susceptibility of myoblasts and myotubes to menadione-induced oxidative stress.

Host Genotype and Gut Microbiome Modulate Insulin Secretion and Diet-Induced Metabolic Phenotypes.

Science.gov (United States)

Kreznar, Julia H; Keller, Mark P; Traeger, Lindsay L; Rabaglia, Mary E; Schueler, Kathryn L; Stapleton, Donald S; Zhao, Wen; Vivas, Eugenio I; Yandell, Brian S; Broman, Aimee Teo; Hagenbuch, Bruno; Attie, Alan D; Rey, Federico E

2017-02-14

Genetic variation drives phenotypic diversity and influences the predisposition to metabolic disease. Here, we characterize the metabolic phenotypes of eight genetically distinct inbred mouse strains in response to a high-fat/high-sucrose diet. We found significant variation in diabetes-related phenotypes and gut microbiota composition among the different mouse strains in response to the dietary challenge and identified taxa associated with these traits. Follow-up microbiota transplant experiments showed that altering the composition of the gut microbiota modifies strain-specific susceptibility to diet-induced metabolic disease. Animals harboring microbial communities with enhanced capacity for processing dietary sugars and for generating hydrophobic bile acids showed increased susceptibility to metabolic disease. Notably, differences in glucose-stimulated insulin secretion between different mouse strains were partially recapitulated via gut microbiota transfer. Our results suggest that the gut microbiome contributes to the genetic and phenotypic diversity observed among mouse strains and provide a link between the gut microbiome and insulin secretion. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Biofluid metabotyping of occupationally exposed subjects to air pollution demonstrates high oxidative stress and deregulated amino acid metabolism

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Pradhan, Surya Narayan; Das, Aleena; Meena, Ramovatar; Nanda, Ranjan Kumar; Rajamani, Paulraj

2016-10-01

Occupational exposure to air pollution induces oxidative stress and prolonged exposure increases susceptibility to cardiovascular and respiratory diseases in several working groups. Biofluid of these subjects may reflect perturbed metabolic phenotypes. In this study we carried out a comparative molecular profiling study using parallel biofluids collected from subjects (n = 85) belonging to auto rickshaw drivers (ARD), traffic cops (TC) and office workers (OW). Higher levels of oxidative stress and inflammation markers in serum of ARD subjects were observed as compared to OW and TC. Uni and multivariate analyses of metabolites identified in urine by 1H NMR revealed 11 deregulated molecules in ARD subjects and involved in phenylalanine, histidine, arginine and proline metabolism. Despite contribution of confounding factors like exposure period, dietary factors including smoking and alcohol status, our results demonstrate existence of exposure specific metabotypes in biofluids of ARD, OW and TC groups. Monitoring serum oxidative stress and inflammation markers and urine metabolites by NMR may be useful to characterize perturbed metabolic phenotypes in populations exposed to urban traffic air pollution.

High-Dimensional Phenotyping Identifies Age-Emergent Cells in Human Mammary Epithelia

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Fanny A. Pelissier Vatter

2018-04-01

Full Text Available Summary: Aging is associated with tissue-level changes in cellular composition that are correlated with increased susceptibility to disease. Aging human mammary tissue shows skewed progenitor cell potency, resulting in diminished tumor-suppressive cell types and the accumulation of defective epithelial progenitors. Quantitative characterization of these age-emergent human cell subpopulations is lacking, impeding our understanding of the relationship between age and cancer susceptibility. We conducted single-cell resolution proteomic phenotyping of healthy breast epithelia from 57 women, aged 16–91 years, using mass cytometry. Remarkable heterogeneity was quantified within the two mammary epithelial lineages. Population partitioning identified a subset of aberrant basal-like luminal cells that accumulate with age and originate from age-altered progenitors. Quantification of age-emergent phenotypes enabled robust classification of breast tissues by age in healthy women. This high-resolution mapping highlighted specific epithelial subpopulations that change with age in a manner consistent with increased susceptibility to breast cancer. : Vatter et al. find that single-cell mass cytometry of human mammary epithelial cells from 57 women, from 16 to 91 years old, depicts an in-depth phenotyping of aging mammary epithelia. Subpopulations of altered luminal and progenitor cells that accumulate with age may be at increased risk for oncogenic transformation. Keywords: human mammary epithelia, aging, mass cytometry, single-cell analysis, heterogeneity, breast cancer

Correlation between passive film-induced stress and stress corrosion cracking of α-Ti in a methanol solution at various potentials

International Nuclear Information System (INIS)

Guo, X.Z.; Gao, K.W.; Chu, W.Y.; Qiao, L.J.

2003-01-01

The flow stress of a specimen of α-Ti before unloading is different with the yield stress of the same specimen after unloading and forming a passive film through immersing in a methanol solution at various constant potentials. The difference is the passive film-induced stress. The film-induced stress and susceptibility to stress corrosion cracking (SCC) in the methanol solution at various potentials were measured. At the stable open-circuit potential and under anodic polarization, both film-induced tensile stress σ p and susceptibility to SCC had a maximum value. The film-induced stress and SCC susceptibility, however, decreased steeply with a decrease in potential under cathodic polarization. When the potential V≤-280 mV SCE , the film-induced stress became compressive; correspondingly, susceptibility to SCC was zero. Therefore, the variation of film-induced stress with potential was consistent with that of susceptibility to SCC. A large film-induced tensile stress is the necessary condition for SCC of α-Ti in the methanol solution. The symbol and amount of the film-induced stress were related to the compositions of the passive film, which have been analyzed using the X-ray photoelectron spectrum (XPS)

IRGM Variants and Susceptibility to Inflammatory Bowel Disease in the German Population

Science.gov (United States)

Bues, Stephanie; Stallhofer, Johannes; Fries, Christoph; Olszak, Torsten; Tsekeri, Eleni; Wetzke, Martin; Beigel, Florian; Steib, Christian; Friedrich, Matthias; Göke, Burkhard; Diegelmann, Julia; Czamara, Darina; Brand, Stephan

2013-01-01

Background & Aims Genome-wide association studies identified the autophagy gene IRGM to be strongly associated with Crohn's disease (CD) but its impact in ulcerative colitis (UC), its phenotypic effects and potential epistatic interactions with other IBD susceptibility genes are less clear which we therefore analyzed in this study. Methodology/Principal Findings Genomic DNA from 2060 individuals including 817 CD patients, 283 UC patients, and 961 healthy, unrelated controls (all of Caucasian origin) was analyzed for six IRGM single nucleotide polymorphisms (SNPs) (rs13371189, rs10065172 = p.Leu105Leu, rs4958847, rs1000113, rs11747270, rs931058). In all patients, a detailed genotype-phenotype analysis and testing for epistasis with the three major CD susceptibility genes NOD2, IL23R and ATG16L1 were performed. Our analysis revealed an association of the IRGM SNPs rs13371189 (p = 0.02, OR 1.31 [95% CI 1.05–1.65]), rs10065172 = p.Leu105Leu (p = 0.016, OR 1.33 [95% CI 1.06–1.66]) and rs1000113 (p = 0.047, OR 1.27 [95% CI 1.01–1.61]) with CD susceptibility. There was linkage disequilibrium between these three IRGM SNPs. In UC, several IRGM haplotypes were weakly associated with UC susceptibility (passociations with a specific IBD phenotype or ileal CD involvement. There was evidence for weak gene-gene-interaction between several SNPs of the autophagy genes IRGM and ATG16L1 (p<0.05), which, however, did not remain significant after Bonferroni correction. Conclusions/Significance Our results confirm IRGM as susceptibility gene for CD in the German population, supporting a role for the autophagy genes IRGM and ATG16L1 in the pathogenesis of CD. PMID:23365659

Depression from childhood into late adolescence: Influence of gender, development, genetic susceptibility, and peer stress.

Science.gov (United States)

Hankin, Benjamin L; Young, Jami F; Abela, John R Z; Smolen, Andrew; Jenness, Jessica L; Gulley, Lauren D; Technow, Jessica R; Gottlieb, Andrea Barrocas; Cohen, Joseph R; Oppenheimer, Caroline W

2015-11-01

Depression is a debilitating mental illness with clear developmental patterns from childhood through late adolescence. Here, we present data from the Gene Environment Mood (GEM) study, which used an accelerated longitudinal cohort design with youth (N = 665) starting in 3rd, 6th, and 9th grades, and a caretaker, who were recruited from the general community, and were then assessed repeatedly through semistructured diagnostic interviews every 6 months over 3 years (7 waves of data) to establish and then predict trajectories of depression from age 8 to 18. First, we demonstrated that overall prevalence rates of depression over time, by age, gender, and pubertal status, in the GEM study closely match those trajectories previously obtained in past developmental epidemiological research. Second, we tested whether a genetic vulnerability-stress model involving 5-HTTLPR and chronic peer stress was moderated by developmental factors. Results showed that older aged adolescents with SS/SL genotype, who experienced higher peer chronic stress over 3 years, were the most likely to be diagnosed with a depressive episode over time. Girls experiencing greater peer chronic stress were the most likely to develop depression. This study used repeated assessments of diagnostic interviewing in a moderately large sample of youth over 3 years to show that depression rates increase in middle to late adolescence, or postpubertally, and that the gender difference in depression emerges earlier in adolescence (age 12.5), or postpubertally. Additionally, genetically susceptible older adolescents who experience chronic peer stress were the most likely to become depressed over time. (c) 2015 APA, all rights reserved).

Neonatal maternal separation increases susceptibility to experimental colitis and acute stress exposure in male mice

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Isabella M. Fuentes

2016-12-01

Full Text Available Experiencing early life stress can result in maladjusted stress response via dysregulation of the hypothalamic-pituitary-adrenal axis and serves as a risk factor for developing chronic pelvic pain disorders. We investigated whether neonatal maternal separation (NMS would increase susceptibility to experimental colitis or exposure to acute or chronic stress. Male mice underwent NMS from postnatal day 1–21 and as adults were assessed for open field behavior, hindpaw sensitivity, and visceromotor response (VMR to colorectal distension (CRD. VMR was also measured before and after treatment with intracolonic trinitrobenzene sulfonic acid (TNBS or exposure to acute or chronic water avoidance stress (WAS. Myeloperoxidase (MPO activity, proinflammatory gene and corticotropin-releasing factor (CRF receptor expression were measured in distal colon. Baseline VMR was not affected by NMS, but undergoing CRD increased anxiety-like behaviors and mechanical hindpaw sensitivity of NMS mice. Treatment with TNBS dose-dependently decreased body weight and survival only in NMS mice. Following TNBS treatment, IL-6 and artemin mRNA levels were decreased in the distal colon of NMS mice, despite increased MPO activity. A single WAS exposure increased VMR during CRD in NMS mice and increased IL-6 mRNA and CRF2 protein levels in the distal colon of naïve mice, whereas CRF2 protein levels were heightened in NMS colon both at baseline and post-WAS exposure. Taken together, these results suggest that NMS in mice disrupts inflammatory- and stress-induced gene expression in the colon, potentially contributing towards an exaggerated response to specific stressors later in life.

Modeling combined schizophrenia-related behavioral and metabolic phenotypes in rodents

NARCIS (Netherlands)

Sarnyai, Zoltán; Jashar, Cassandra; Olivier, Berend

2015-01-01

Schizophrenia is a chronic, debilitating disorder with a complex behavioral and cognitive phenotype underlined by a similarly complex etiology involving an interaction between susceptibility genes and environmental factors during early development. Limited progress has been made in developing novel

Parental smoking status, stress, anxiety, and depression are associated with susceptibility to smoking among non-smoking school adolescents in Malaysia.

Science.gov (United States)

Lim, Kuang Hock; Chong, Zhuolin; Khoo, Yi Yi; Kaur, Jasvindar

2014-09-01

Susceptibility to smoking is a reliable predictor of smoking initiation. This article describes its prevalence and associated factors among Malaysian school adolescents. Data were obtained from the Global School-Based Student Health Survey (GSHS) 2012, a nationwide representative sample of school adolescents. The overall prevalence of susceptibility to smoking was 6.0% and significantly higher among males (9.5%) compared with females (3.6%). Multivariable analyses revealed that males (adjusted odds ratio [aOR] 3.34, 95% confidence interval [CI] 2.70-4.18) and school adolescents of indigenous Sabahan or Sarawakian descents (aOR 1.62, 95%CI 1.21-2.18) were significantly more likely to be susceptible to smoking. Susceptible school adolescents had a slightly higher likelihood to have symptoms of stress (aOR 1.31, 95% CI 1.02-1.70), anxiety (aOR 1.19, 95% CI 1.01-1.40), depression (aOR 1.56, 95% CI 1.25-1.96), including those whose one or both parents/guardians were smokers (aOR 1.48, 95% CI 1.21-1.82; aOR 2.33, 95% CI 1.22-4.44, respectively). The findings from this study point out the need for proactive measures to reduce smoking initiation among Malaysian adolescents with particular attention toward factors associated with susceptibility to smoking. © 2014 APJPH.

Phenotypes of sleeplessness: stressing the need for psychodiagnostics in the assessment of insomnia.

Science.gov (United States)

van de Laar, Merijn; Leufkens, Tim; Bakker, Bart; Pevernagie, Dirk; Overeem, Sebastiaan

2017-09-01

Insomnia is a too general term for various subtypes that might have different etiologies and therefore require different types of treatment. In this explorative study we used cluster analysis to distinguish different phenotypes in 218 patients with insomnia, taking into account several factors including sleep variables and characteristics related to personality and psychiatric comorbidity. Three clusters emerged from the analysis. The 'moderate insomnia with low psychopathology'-cluster was characterized by relatively normal personality traits, as well as normal levels of anxiety and depressive symptoms in the presence of moderate insomnia severity. The 'severe insomnia with moderate psychopathology'-cluster showed relatively high scores on the Insomnia Severity Index and scores on the sleep log that were indicative for severe insomnia. Anxiety and depressive symptoms were slightly above the cut-off and they were characterized by below average self-sufficiency and less goal-directed behavior. The 'early onset insomnia with high psychopathology'-cluster showed a much younger age and earlier insomnia onset than the other two groups. Anxiety and depressive symptoms were well above the cut-off score and the group consisted of a higher percentage of subjects with comorbid psychiatric disorders. This cluster showed a 'typical psychiatric' personality profile. Our findings stress the need for psychodiagnostic procedures next to a sleep-related diagnostic approach, especially in the younger insomnia patients. Specific treatment suggestions are given based on the three phenotypes.

Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring.

Science.gov (United States)

Murthy, Krishna Dilip; George, Mitchel Constance; Ramasamy, Perumal; Mustapha, Zainal Arifin

2013-12-01

Mother-offspring interaction begins before birth. The foetus is particularly vulnerable to environmental insults and stress. The body responds by releasing excess of the stress hormone cortisol, which acts on glucocorticoid receptors. Hippocampus in the brain is rich in glucocorticoid receptors and therefore susceptible to stress. The stress effects are reduced when the animals are placed under a model wooden pyramid. The present study was to first explore the effects of prenatal restraint-stress on the plasma corticosterone levels and the dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the offspring. Further, to test whether the pyramid environment would alter these effects, as housing under a pyramid is known to reduce the stress effects, pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7 until parturition in a wire-mesh restrainer. Plasma corticosterone levels were found to be significantly increased. In addition, there was a significant reduction in the apical and the basal total dendritic branching points and intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest that, housing in the pyramid dramatically reduces prenatal stress effects in rats.

Maternal care affects the phenotype of a rat model for schizophrenia

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Ruben W M Van Vugt

2014-08-01

Full Text Available Schizophrenia is a complex mental disorder caused by an interplay between genetic and environmental factors, including early postnatal stressors. To explore this issue, we use two rat lines, apomorphine-susceptible (APO-SUS rats that display schizophrenia-relevant features and their phenotypic counterpart, apomorphine-unsusceptible (APO-UNSUS rats. These rat lines differ not only in their gnawing response to apomorphine, but also in their behavioral response to novelty (APO-SUS: high, APO-UNSUS: low. In this study, we examined the effects of early postnatal cross-fostering on maternal care and on the phenotypes of the cross-fostered APO-SUS and APO-UNSUS animals later in life. Cross-fostered APO-UNSUS animals showed decreased body weights as pups and decreased novelty-induced locomotor activity as adults (i.e., more extreme behavior, in accordance with the less appropriate maternal care provided by APO-SUS versus their own APO-UNSUS mothers (i.e., the APO-SUS mother displayed less non-arched-back nursing and more self-grooming, and was more away from its nest. In contrast, cross-fostered APO-SUS animals showed increased body weights as pups and reduced apomorphine-induced gnawing later in life (i.e., normalisation of their extreme behavior, in line with the more appropriate maternal care provided by APO-UNSUS relative to their own APO-SUS mothers (i.e., the APO-UNSUS mother displayed more non-arched-back nursing and similar self-grooming, and was not more away. Furthermore, we found that, in addition to arched-back nursing, non-arched-back nursing was an important feature of maternal care, and that cross-fostering APO-SUS mothers, but not cross-fostering APO-UNSUS mothers, displayed increased apomorphine-induced gnawing. Thus, cross-fostering not only causes early postnatal stress shaping the phenotypes of the cross-fostered animals later in life, but also affects the phenotypes of the cross-fostering mothers.

Effects of different aging statuses and strain rate on the adiabatic shear susceptibility of 2195 aluminum-lithium alloy

Energy Technology Data Exchange (ETDEWEB)

Yang, Y. [School of Materials Science and Engineering, Central South University, Changsha 410083, Hunan (China); State Key Laboratory of Explosion Science and Technology, Beijing 100081 (China); Tan, G.Y., E-mail: yangyanggroup@163.com [School of Materials Science and Engineering, Central South University, Changsha 410083, Hunan (China); Chen, P.X. [School of Materials Science and Engineering, Central South University, Changsha 410083, Hunan (China); Zhang, Q.M. [State Key Laboratory of Explosion Science and Technology, Beijing 100081 (China)

2012-06-01

The adiabatic shear susceptibility of 2195 aluminum-lithium alloy was investigated by means of split Hopkinson pressure bar. The stress collapse in true stress-true strain curves and true stress-time curves was observed. The adiabatic shear susceptibility of different aging statuses and strain rate were discussed by means of metallography observation. The critical strain, stress collapse time and formation energy of adiabatic shear bands were compared. The results show that different aging statuses and strain rate have significant influences on adiabatic shear behaviors of 2195 aluminum-lithium alloy. The peak-aged specimen has the highest adiabatic shearing susceptibility, while the under-aged specimen has the least adiabatic shear susceptibility. The susceptibility of adiabatic shearing increases with the increases of strain rate.

Lower susceptibility of female mice to acetaminophen hepatotoxicity: Role of mitochondrial glutathione, oxidant stress and c-jun N-terminal kinase

International Nuclear Information System (INIS)

Du, Kuo; Williams, C. David; McGill, Mitchell R.; Jaeschke, Hartmut

2014-01-01

Acetaminophen (APAP) overdose causes severe hepatotoxicity in animals and humans. However, the mechanisms underlying the gender differences in susceptibility to APAP overdose in mice have not been clarified. In our study, APAP (300 mg/kg) caused severe liver injury in male mice but 69–77% lower injury in females. No gender difference in metabolic activation of APAP was found. Hepatic glutathione (GSH) was rapidly depleted in both genders, while GSH recovery in female mice was 2.6 fold higher in the mitochondria at 4 h, and 2.5 and 3.3 fold higher in the total liver at 4 h and 6 h, respectively. This faster recovery of GSH, which correlated with greater induction of glutamate-cysteine ligase, attenuated mitochondrial oxidative stress in female mice, as suggested by a lower GSSG/GSH ratio at 6 h (3.8% in males vs. 1.4% in females) and minimal centrilobular nitrotyrosine staining. While c-jun N-terminal kinase (JNK) activation was similar at 2 and 4 h post-APAP, it was 3.1 fold lower at 6 h in female mice. However, female mice were still protected by the JNK inhibitor SP600125. 17β-Estradiol pretreatment moderately decreased liver injury and oxidative stress in male mice without affecting GSH recovery. Conclusion: The lower susceptibility of female mice is achieved by the improved detoxification of reactive oxygen due to accelerated recovery of mitochondrial GSH levels, which attenuates late JNK activation and liver injury. However, even the reduced injury in female mice was still dependent on JNK. While 17β-estradiol partially protects male mice, it does not affect hepatic GSH recovery. - Highlights: • Female mice are less susceptible to acetaminophen overdose than males. • GSH depletion and protein adduct formation are similar in both genders. • Recovery of hepatic GSH levels is faster in females and correlates with Gclc. • Reduced oxidant stress in females leads to reduced JNK activation. • JNK activation and mitochondrial translocation are critical

A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations

DEFF Research Database (Denmark)

Bønnelykke, Klaus; Sleiman, Patrick; Nielsen, Kasper

2014-01-01

Asthma exacerbations are among the most frequent causes of hospitalization during childhood, but the underlying mechanisms are poorly understood. We performed a genome-wide association study of a specific asthma phenotype characterized by recurrent, severe exacerbations occurring between 2 and 6......1RL1, were previously reported as asthma susceptibility loci, but the effect sizes for these loci in our cohort were considerably larger than in the previous genome-wide association studies of asthma. We also obtained strong evidence for a new susceptibility gene, CDHR3 (encoding cadherin......-related family member 3), which is highly expressed in airway epithelium. These results demonstrate the strength of applying specific phenotyping in the search for asthma susceptibility genes....

Effects of dissolved calcium and magnesium ions on lead-induced stress corrosion cracking susceptibility of nuclear steam generator tubing alloy in high temperature crevice solutions

International Nuclear Information System (INIS)

Lu, B.T.; Tian, L.P.; Zhu, R.K.; Luo, J.L.; Lu, Y.C.

2011-01-01

The effects of Ca 2+ and Mg 2+ ions on the stress corrosion cracking (SCC) susceptibility of UNS N08800 are investigated using constant extension rate tensile (CERT) tests at 300 o C in simulated crevice chemistries. The presence of lead contamination in the crevice chemistries increases significantly the SCC susceptibility of the alloy. The lead-assisted SCC (PbSCC) susceptibility is reduced markedly by the addition of Ca 2+ and Mg 2+ ions into the solution and this mitigating effect is enhanced by increasing the total concentration of Ca 2+ + Mg 2+ . The CERT test results are consistent with the types of fracture surfaces shown by Scanning Electron Microscopy (SEM). There is a reasonable correlation between the SCC susceptibility and the donor densities in the anodic films in accord with the role of lead-induced passivity degradation in PbSCC.

Standard test method for determining susceptibility to stress-corrosion cracking of 2XXX and 7XXX Aluminum alloy products

CERN Document Server

American Society for Testing and Materials. Philadelphia

1998-01-01

1.1 This test method covers a uniform procedure for characterizing the resistance to stress-corrosion cracking (SCC) of high-strength aluminum alloy wrought products for the guidance of those who perform stress-corrosion tests, for those who prepare stress-corrosion specifications, and for materials engineers. 1.2 This test method covers method of sampling, type of specimen, specimen preparation, test environment, and method of exposure for determining the susceptibility to SCC of 2XXX (with 1.8 to 7.0 % copper) and 7XXX (with 0.4 to 2.8 % copper) aluminum alloy products, particularly when stressed in the short-transverse direction relative to the grain structure. 1.3 The values stated in SI units are to be regarded as standard. The inch-pound units in parentheses are provided for information. This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and de...

Profile of antimicrobial susceptibility isolated microorganisms from hospitalized patients in PICU ward and detection of Methicillin-resistant Staphylococcus aureus and ESBL-producing bacteria by phenotypic methods

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Shahla Abbas Poor

2014-10-01

Full Text Available Background: Hospital-acquired infections are a major challenge to patient. A range of gram-negative organisms are responsible for hospital-acquired infections, the Enterobacteriaceae family being the most commonly identified group overall. Infections by ESBL producers are associated with severe adverse clinical outcomes that have led to increased mortality, prolonged hospitalization, and rising medical costs. The aim of this study was to survey profile of antimicrobial susceptibility isolated microorganisms from hospitalized patients in PICU ward and detection of methicillin-resistant Staphylococcus aureus and ESBL-producing bacteria by phenotypic methods. Material and Methods: In this study participants were patients hospitalized in PICU part of Bahrami Hospital, Tehran, with attention to involved organ. For isolation of bacteria from patient’s samples, culture performed on different selective and differential media. After confirmation of bacteria by biochemical tests, susceptibility testing was performed by disc diffusion method. Phenotypic detection of MRSA strains was performed using cefoxcitin disc. ESBL producing strains were detected by ceftazidime (CAZ and ceftazidime/clavulanic acid (CAZ/CLA discs. Results: Among all isolated organisms from clinical samples, the most common isolated organisms were Escherichia coli (24 cases, Pseudomonas areoginosa (9 cases and Staphylococcus aureus (8 cases, respectively. Among eight MRSA isolated strains from different clinical samples, six strains (75% were MRSA. Among 52 isolated gram negative organisms, 5 strains (9/6% were ESBL. Conclusion: Standard interventions to prevent the transmission of antimicrobial resistance in health care facilities include hand hygiene, using barrier precautions in the care of colonized and infected patients, using dedicated instruments and equipment for these patients. The colonized or infected patients should be isolated in single rooms, multibed rooms or areas

RNA-Mediated cis Regulation in Acinetobacter baumannii Modulates Stress-Induced Phenotypic Variation.

Science.gov (United States)

Ching, Carly; Gozzi, Kevin; Heinemann, Björn; Chai, Yunrong; Godoy, Veronica G

2017-06-01

In the nosocomial opportunistic pathogen Acinetobacter baumannii , RecA-dependent mutagenesis, which causes antibiotic resistance acquisition, is linked to the DNA damage response (DDR). Notably, unlike the Escherichia coli paradigm, recA and DDR gene expression in A. baumannii is bimodal. Namely, there is phenotypic variation upon DNA damage, which may provide a bet-hedging strategy for survival. Thus, understanding recA gene regulation is key to elucidate the yet unknown DDR regulation in A. baumannii Here, we identify a structured 5' untranslated region (UTR) in the recA transcript which serves as a cis -regulatory element. We show that a predicted stem-loop structure in this 5' UTR affects mRNA half-life and underlies bimodal gene expression and thus phenotypic variation in response to ciprofloxacin treatment. We furthermore show that the stem-loop structure of the recA 5' UTR influences intracellular RecA protein levels and, in vivo , impairing the formation of the stem-loop structure of the recA 5' UTR lowers cell survival of UV treatment and decreases rifampin resistance acquisition from DNA damage-induced mutagenesis. We hypothesize that the 5' UTR allows for stable recA transcripts during stress, including antibiotic treatment, enabling cells to maintain suitable RecA levels for survival. This innovative strategy to regulate the DDR in A. baumannii may contribute to its success as a pathogen. IMPORTANCE Acinetobacter baumannii is an opportunistic pathogen quickly gaining antibiotic resistances. Mutagenesis and antibiotic resistance acquisition are linked to the DNA damage response (DDR). However, how the DDR is regulated in A. baumannii remains unknown, since unlike most bacteria, A. baumannii does not follow the regulation of the Escherichia coli paradigm. In this study, we have started to uncover the mechanisms regulating the novel A. baumannii DDR. We have found that a cis -acting 5' UTR regulates recA transcript stability, RecA protein levels, and DNA

Stress Corrosion cracking susceptibility of reduced-activation martensitic steel F82H

Energy Technology Data Exchange (ETDEWEB)

Miwa, Y. [Nuclear Energy and Science Directorate, Japan Atomic Energy Agency, Tokai-mura, Ibaraki-ken (Japan); Jitsukawa, S.; Tsukada, T. [Japan Atomic Energy Agency, Tokai-mura, Naga-gun, Ibaraki-ken (Japan)

2007-07-01

Full text of publication follows: For fusion power source in near future, supercritical water-cooled type blanket system was planned in Japan Atomic Energy Agency. The blankest system was designed by the present knowledge base and a reasonable extrapolation in material and design technology. Reduced-activation martensitic steel, F82H, is one of the blanket system structural materials. Therefore durability of the F82H for corrosion and stress corrosion cracking (SCC) is one of the concerns for this water-cooling concept of the blanket system. In this paper, SCC susceptibility of F82H was studied after heat treatments simulating post weld heat treatment (PWHT) or neutron-irradiation at 493 K to a dose level of 2.2 dpa. In order to evaluate SCC susceptibility of F82H, slow strain rate testing (SSRT) in high-purity, circulating water was conducted at 513-603 K in an autoclave. The strain rate was 1.0- 2.0x10{sup -7} s{sup -1}. Concentration of dissolved oxygen and hydrogen of the circulating water was controlled by bubbling with these gases. Specimens were heat treated after normalization at 1313 K for 40 min and water quenching. Some of the specimens were tempered at 873-1073 K for 1 h. Since the temperature control during PWHT in vacuum vessel by remote handling will be difficult, it is expected the tempering temperature will be different at place to place. Some specimens after tempering at 1033 K for 1 h were irradiated at 493 K to 2.2 dpa in Japan Research Reactor No.3 at Japan Atomic Energy Agency. The SSRT results showed the as-normalized specimens failed by IGSCC in oxygenated temperature water at 573 K. SSRT results of specimens with other tempering temperature conditions will be presented at conference. In irradiated specimen, IGSCC did not occur in oxygenated water at 5113-603 K. IGSCC also did not occur in hydrogenated water at 573 K. However TGSCC occurred in the irradiated specimen with a round notch (radius= {approx}0.2 mm) in oxygenated water at 573 K

Lipid accumulation product as a marker of cardiometabolic susceptibility in women with different phenotypes of polycystic ovary syndrome.

Science.gov (United States)

Božić-Antić, Ivana; Ilić, Dušan; Bjekić-Macut, Jelica; Bogavac, Tamara; Vojnović-Milutinović, Danijela; Kastratovic-Kotlica, Biljana; Milić, Nataša; Stanojlović, Olivera; Andrić, Zoran; Macut, Djuro

2016-12-01

There are limited data on cardiometabolic risk factors and the prevalence of metabolic syndrome (MetS) across the different PCOS phenotypes in Caucasian population. Lipid accumulation product (LAP) is a clinical surrogate marker that could be used for evaluation of MetS in clinical practice. The aim of the study was to analyze metabolic characteristics and the ability of LAP to predict MetS in different PCOS phenotypes. Cross-sectional clinical study analyzing 365 women with PCOS divided into four phenotypes according to the ESHRE/ASRM criteria, and 125 healthy BMI-matched controls. In all subjects, LAP was determined and MetS was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III (NCEP-ATP III), the International Diabetes Federation (IDF) and the Joint Interim Statement (JIS) criteria. Logistic regression and ROC curve analyses were used to determine predictors of MetS in each PCOS phenotype. All analyses were performed with age and BMI adjustment. All PCOS phenotypes in comparison to controls had higher prevalence of MetS assessed by NCEP-ATP III criteria, and only classic phenotypes when IDF and JIS criteria were used. All phenotypes had the same prevalence of MetS irrespective of used definition. LAP and exhibited the highest diagnostic accuracy and was an independent predictor of MetS in all phenotypes. LAP is an independent and accurate clinical determinant of MetS in all PCOS phenotypes in our Caucasian population. All PCOS phenotypes, including non-classic ones, are metabolically challenged and with cardiovascular risk, particularly phenotype B. © 2016 European Society of Endocrinology.

Regulatory networks in pollen development under cold stress

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Kamal Dev Sharma

2016-03-01

Full Text Available Cold stress modifies anthers’ metabolic pathways to induce pollen sterility. Cold-tolerant plants, unlike the susceptible ones, produce high proportion of viable pollen. Anthers in susceptible plants, when exposed to cold stress, increase abscisic acid (ABA metabolism and reduce ABA catabolism. Increased ABA negatively regulates expression of tapetum cell wall bound invertase and monosaccharide transport genes resulting in distorted carbohydrate pool in anther. Cold-stress also reduces endogenous levels of the bioactive gibberellins (GAs, GA4 and GA7, in susceptible anthers by repression of the GA biosynthesis genes. Here we discuss recent findings on mechanisms of cold susceptibility in anthers which determine pollen sterility. We also discuss differences in regulatory pathways between cold-stressed anthers of susceptible and tolerant plants that decide pollen sterility or viability.

Effects of divorce on Dutch boys' and girls' externalizing behavior in Gene × Environment perspective: diathesis stress or differential susceptibility in the Dutch Tracking Adolescents' Individual Lives Survey study?

Science.gov (United States)

Nederhof, Esther; Belsky, Jay; Ormel, Johan; Oldehinkel, Albertine J

2012-08-01

The effects of divorce on children's behavioral development have proven to be quite varied across studies, and most developmental and family scholars today appreciate the great heterogeneity in divorce effects. Thus, this inquiry sought to determine whether select dopaminergic genes previously associated with externalizing behavior and/or found to moderate diverse environmental effects (dopamine receptors D2 and D4, catechol-O-methyltransferase) might moderate divorce effects on adolescent self-reported externalizing problems; and, if so, whether evidence of gene-environment (G × E) interaction would prove consistent with diathesis-stress or differential-susceptibility models of environmental action. Data from the first and third wave of the Dutch Tracking Adolescents' Individual Lives Survey (n = 1,134) revealed some evidence of G × E interaction reflecting diathesis-stress but not differential susceptibility. It is intriguing that some evidence pointed to "vantage sensitivity," which are benefits accruing to those with a specific genotype when their parents remained together, the exact opposite of diathesis-stress. The limits of this work are considered, especially with regard to the conditions for testing differential susceptibility, and future directions are outlined.

Phenotype, Genotype, and Drug Resistance in Subtype C HIV-1 Infection.

Science.gov (United States)

Derache, Anne; Wallis, Carole L; Vardhanabhuti, Saran; Bartlett, John; Kumarasamy, Nagalingeswaran; Katzenstein, David

2016-01-15

Virologic failure in subtype C is characterized by high resistance to first-line antiretroviral (ARV) drugs, including efavirenz, nevirapine, and lamivudine, with nucleoside resistance including type 2 thymidine analog mutations, K65R, a T69del, and M184V. However, genotypic algorithms predicting resistance are mainly based on subtype B viruses and may under- or overestimate drug resistance in non-B subtypes. To explore potential treatment strategies after first-line failure, we compared genotypic and phenotypic susceptibility of subtype C human immunodeficiency virus 1 (HIV-1) following first-line ARV failure. AIDS Clinical Trials Group 5230 evaluated patients failing an initial nonnucleoside reverse-transcriptase inhibitor (NNRTI) regimen in Africa and Asia, comparing the genotypic drug resistance and phenotypic profile from the PhenoSense (Monogram). Site-directed mutagenesis studies of K65R and T69del assessed the phenotypic impact of these mutations. Genotypic algorithms overestimated resistance to etravirine and rilpivirine, misclassifying 28% and 32%, respectively. Despite K65R with the T69del in 9 samples, tenofovir retained activity in >60%. Reversion of the K65R increased susceptibility to tenofovir and other nucleosides, while reversion of the T69del showed increased resistance to zidovudine, with little impact on other NRTI. Although genotype and phenotype were largely concordant for first-line drugs, estimates of genotypic resistance to etravirine and rilpivirine may misclassify subtype C isolates compared to phenotype. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Multiple Genetic Analysis System-Based Antibiotic Susceptibility Testing in Helicobacter pylori and High Eradication Rate With Phenotypic Resistance-Guided Quadruple Therapy.

Science.gov (United States)

Dong, Fangyuan; Ji, Danian; Huang, Renxiang; Zhang, Fan; Huang, Yiqin; Xiang, Ping; Kong, Mimi; Nan, Li; Zeng, Xianping; Wu, Yong; Bao, Zhijun

2015-11-01

Antibiotics resistance in Helicobacter pylori (H. pylori) is the major factor for eradication failure. Molecular tests including fluorescence in situ hybridization, PCR-restriction fragment length polymorphism, and dual priming oligonucleotide-PCR (DPO-PCR) play critical roles in the detection of antibiotic susceptibility; however, limited knowledge is known about application of multiple genetic analysis system (MGAS) in the area of H. pylori identification and antibiotics resistance detection.The aim of this study is to determine the antibiotics resistance using different molecular tests and evaluate the treatment outcomes of E-test-based genotypic resistance.A total of 297 patients with dyspepsia complaint were recruited for gastroscopies. Ninety patients with H. pylori culture positive were randomly divided into 2 groups (test group and control group). E-test, general PCR, and MGAS assay were performed in test group. Patients in control group were treated with empirical therapy (rabeprazole + bismuth potassium citrate + amoxicillin [AMX] + clarithromycin [CLR]), whereas patients in test group received quadruple therapy based on E-test results twice daily for 14 consecutive days. The eradication effect of H. pylori was confirmed by C-urea breath test after at least 4 weeks when treatment was finished.Rapid urease test showed 46.5% (128/297) patients with H. pylori infection, whereas 30.3% (90/297) patients were H. pylori culture positive. E-test showed that H. pylori primary resistance rate to CLR, AMX, metronidazole, tetracycline, and levofloxacin (LVX) was 40.0% (18/45), 4.4% (2/45), 53.3% (24/45), 0% (0/45), and 55.6% (25/45), respectively. In addition, there are many multidrug resistant (MDR) phenotypes, and the MDR strains have higher minimum inhibitory concentration than their single-drug resistant counterparts. Considering E-test as the reference test, the sensitivities of general PCR and MGAS in detecting CLR resistance were 83.3% (15/18) and 94.4% (17

Discovering susceptibility genes for allergic rhinitis and allergy using a genome-wide association study strategy.

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Li, Jingyun; Zhang, Yuan; Zhang, Luo

2015-02-01

Allergic rhinitis and allergy are complex conditions, in which both genetic and environmental factors contribute to the pathogenesis. Genome-wide association studies (GWASs) employing common single-nucleotide polymorphisms have accelerated the search for novel and interesting genes, and also confirmed the role of some previously described genes which may be involved in the cause of allergic rhinitis and allergy. The aim of this review is to provide an overview of the genetic basis of allergic rhinitis and the associated allergic phenotypes, with particular focus on GWASs. The last decade has been marked by the publication of more than 20 GWASs of allergic rhinitis and the associated allergic phenotypes. Allergic diseases and traits have been shown to share a large number of genetic susceptibility loci, of which IL33/IL1RL1, IL-13-RAD50 and C11orf30/LRRC32 appear to be important for more than two allergic phenotypes. GWASs have further reflected the genetic heterogeneity underlying allergic phenotypes. Large-scale genome-wide association strategies are underway to discover new susceptibility variants for allergic rhinitis and allergic phenotypes. Characterization of the underlying genetics provides us with an insight into the potential targets for future studies and the corresponding interventions.

Growth and physiological responses of two phenotypically distinct accessions of centipedegrass (Eremochloa ophiuroides (Munro) Hack.) to salt stress.

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Li, JianJian; Ma, Jingjing; Guo, Hailin; Zong, Junqin; Chen, Jingbo; Wang, Yi; Li, Dandan; Li, Ling; Wang, Jingjing; Liu, Jianxiu

2018-05-01

Salinity is one of the major abiotic environmental stress factors affecting plant growth and development. Centipedegrass (Eremochloa ophiuroides [Munro)] Hack.) is an important warm-season turfgrass species with low turf maintenance requirements, but is sensitive to salinity stress. To explore salt tolerant germplasms in centipedegrass and better understand the growth and physiological responses of centipedegrass to salinity, we conducted anatomic observation and phytochemical quantification, examined growth parameters, and investigated photosynthetic machinery and antioxidant system in two phenotypically distinct centipedegrass accessions under NaCl salt stress. The morphophenotypical difference of the stems in the two accessions mainly depends on whether or not a thickened epidermal horny layer with purple colour was formed, which was caused by anthocyanin accumulation in the tissue. Successive salinity treatment was found to result in an inhibition of leaf growth, a marked decrease in photosynthesis, chlorophyll contents, and the maximal photochemical efficiency of PSII (Fv/Fm). Under the same treatment, purple-stem accession (E092) showed a lower degree of inhibition or decrease than green-stem one (E092-1). With the exception of malondialdehyde level, both proline content and antioxidant enzymes were upregulated to a greater extent in E092 following exposure to salinity condition. Meanwhile, significant enhancements of anthocyanin accumulation and total protein synthesis were detected in E092 after salt treatment, but not in E092-1. These results demonstrated that E092 favor better accumulation of anthocyanins under salinity condition, which contribute to salt tolerance by adjusting physiological functions and osmotic balance, and better maintenance of high turf quality. Hence, genetic phenotype can be utilized as a key indicator in E. ophiuroides breeding for salt-tolerance. Copyright © 2018. Published by Elsevier Masson SAS.

Differences in Susceptibility to Heat Stress along the Chicken Intestine and the Protective Effects of Galacto-Oligosaccharides.

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Soheil Varasteh

Full Text Available High ambient temperatures negatively affect the human well-being as well as animal welfare and production. The gastrointestinal tract is predominantly responsive to heat stress. The currently available information about the multifaceted response to heat stress within different parts of the intestine is limited, especially in avian species. Hence, this study aims to evaluate the heat stress-induced sequence of events in the intestines of chickens. Furthermore, the gut health-promoting effect of dietary galacto-oligosaccharides (GOS was investigated in these heat stress-exposed chickens. Chickens were fed a control diet or diet supplemented with 1% or 2.5% GOS (6 days prior to and during a temperature challenge for 5 days (38-39°C, 8h per day. The parameters measured in different parts of the intestines included the genes (qPCR HSF1, HSF3, HSP70, HSP90, E-cadherin, claudin-1, claudin-5, ZO-1, occludin, TLR-2, TLR-4, IL-6, IL-8, HO-1, HIF-1α and their associated proteins HSP70, HSP90 and pan-cadherin (western blots. In addition, IL-6 and IL-8 plasma concentrations were measured by ELISA. In the jejunum, HSF3, HSP70, HSP90, E-cadherin, claudin-5, ZO-1, TLR-4, IL-6 and IL-8 mRNA expression and HSP70 protein expression were increased after heat stress exposure and a more pronounced increase in gene expression was observed in ileum after heat stress exposure, and in addition HSF1, claudin-1 and HIF-1α mRNA levels were upregulated. Furthermore, the IL-8 plasma levels were decreased in chickens exposed to heat stress. Interestingly, the heat stress-related effects in the jejunum were prevented in chickens fed a GOS diet, while dietary GOS did not alter these effects in ileum. In conclusion, our results demonstrate the differences in susceptibility to heat stress along the intestine, where the most obvious modification in gene expression is observed in ileum, while dietary GOS only prevent the heat stress-related changes in jejunum.

Evaluation of the CBL family gene expression under drought stress and virus attack in two susceptible and drought tolerant tomato cultivars using semi-quantitative PCR analysis

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Peyman Aghaie

2017-08-01

Full Text Available Eleven genes encoding Calcineurin B-Like proteins with a high degree of sequence conservation were identified using bioinformatics approaches in tomato. These proteins classified into five clusters including SlCBL1, SlCBL3, SlCBL4, SlCBL8 and SlCBL10 using orthology-based method of nomenclature. Sequence analysis showed that all five members of SlCBL1 and SlCBL4 contained a myristoylation conserved motif (MGXXXS/T at their N-terminals. Semi-quantitative RT-PCR showed that among the SlCBL1 members, SlCBL1-3 up-regulated under both drought and virus stresses, as well as the combined treatment. Although, both SlCBL3-1 and SlCBL3-2 up-regulated under both drought and virus stresses in both susceptive and resistant cultivars, the combined stress did not have any additional effect on the expression. Among SlCBL4 members, only SlCBL4-1 up-regulated under drought or virus attack. There was a diverse pattern of expression between the two SlCBL8 members under different stresses in both cultivars. SlCBL10 showed no change in expression pattern under drought or virus stresses in susceptive cultivar and this gene showed to be up-regulated under drought in resistant cultivar. Overall, it was concluded that changes in the expression pattern of CBL genes under biotic and abiotic stresses seemingly induced various CBL/CIPK patways in suseptive or resistant plants.

Stress-induced variation in evolution: from behavioural plasticity to genetic assimilation.

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Badyaev, Alexander V

2005-05-07

Extreme environments are closely associated with phenotypic evolution, yet the mechanisms behind this relationship are poorly understood. Several themes and approaches in recent studies significantly further our understanding of the importance that stress-induced variation plays in evolution. First, stressful environments modify (and often reduce) the integration of neuroendocrinological, morphological and behavioural regulatory systems. Second, such reduced integration and subsequent accommodation of stress-induced variation by developmental systems enables organismal 'memory' of a stressful event as well as phenotypic and genetic assimilation of the response to a stressor. Third, in complex functional systems, a stress-induced increase in phenotypic and genetic variance is often directional, channelled by existing ontogenetic pathways. This accounts for similarity among individuals in stress-induced changes and thus significantly facilitates the rate of adaptive evolution. Fourth, accumulation of phenotypically neutral genetic variation might be a common property of locally adapted and complex organismal systems, and extreme environments facilitate the phenotypic expression of this variance. Finally, stress-induced effects and stress-resistance strategies often persist for several generations through maternal, ecological and cultural inheritance. These transgenerational effects, along with both the complexity of developmental systems and stressor recurrence, might facilitate genetic assimilation of stress-induced effects. Accumulation of phenotypically neutral genetic variance by developmental systems and phenotypic accommodation of stress-induced effects, together with the inheritance of stress-induced modifications, ensure the evolutionary persistence of stress-response strategies and provide a link between individual adaptability and evolutionary adaptation.

Downregulation of miR-205 modulates cell susceptibility to oxidative and endoplasmic reticulum stresses in renal tubular cells.

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Shiyo Muratsu-Ikeda

Full Text Available BACKGROUND: Oxidative stress and endoplasmic reticulum (ER stress play a crucial role in tubular damage in both acute kidney injury (AKI and chronic kidney disease (CKD. While the pathophysiological contribution of microRNAs (miRNA to renal damage has also been highlighted, the effect of miRNA on renal damage under oxidative and ER stresses conditions remains elusive. METHODS: We assessed changes in miRNA expression in the cultured renal tubular cell line HK-2 under hypoxia-reoxygenation-induced oxidative stress or ER stress using miRNA microarray assay and real-time RT-PCR. The pathophysiological effect of miRNA was evaluated by cell survival rate, intracellular reactive oxygen species (ROS level, and anti-oxidant enzyme expression in miRNA-inhibited HK-2 or miRNA-overexpressed HK-2 under these stress conditions. The target gene of miRNA was identified by 3'-UTR-luciferase assay. RESULTS: We identified 8 and 10 miRNAs whose expression was significantly altered by oxidative and ER stresses, respectively. Among these, expression of miR-205 was markedly decreased in both stress conditions. Functional analysis revealed that decreased miR-205 led to an increase in cell susceptibility to oxidative and ER stresses, and that this increase was associated with the induction of intracellular ROS and suppression of anti-oxidant enzymes. While increased miR-205 by itself made no change in cell growth or morphology, cell viability under oxidative or ER stress conditions was partially restored. Further, miR-205 bound to the 3'-UTR of the prolyl hydroxylase 1 (PHD1/EGLN2 gene and suppressed the transcription level of EGLN2, which modulates both intracellular ROS level and ER stress state. CONCLUSIONS: miR-205 serves a protective role against both oxidative and ER stresses via the suppression of EGLN2 and subsequent decrease in intracellular ROS. miR-205 may represent a novel therapeutic target in AKI and CKD associated with oxidative or ER stress in tubules.

Genetic, phenotypic and matrix-assisted laser desorption ionization time-of-flight mass spectrometry-based identification of anaerobic bacteria and determination of their antimicrobial susceptibility at a University Hospital in Japan.

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Yunoki, Tomoyuki; Matsumura, Yasufumi; Nakano, Satoshi; Kato, Karin; Hotta, Go; Noguchi, Taro; Yamamoto, Masaki; Nagao, Miki; Takakura, Shunji; Ichiyama, Satoshi

2016-05-01

The accuracies of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and the phenotypic method using VITEK 2 were compared to the accuracy of 16S rRNA sequence analysis for the identification of 170 clinically isolated anaerobes. The antimicrobial susceptibility of the isolates was also evaluated. Genetic analysis identified 21 Gram-positive species in 14 genera and 29 Gram-negative species in 11 genera. The most frequently isolated genera were Prevotella spp. (n = 46), Bacteroides spp. (n = 25) and Clostridium spp. (n = 25). MALDI-TOF MS correctly identified more isolates compared with VITEK 2 at the species (80 vs. 58%, respectively; p anaerobic agents indicated that the isolates of the three most frequently identified anaerobic genera exhibited good antimicrobial susceptibility. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Global changes in gene expression associated with phenotypic switching of wild yeast

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Stovicek, Vratislav; Váchová, Libuše; Begany, Markéta

2014-01-01

transitions that affect other properties of phenotypic strain-variants, such as resistance to the impact of environmental stress. Here we document the regulatory role of the histone deacetylase Hda1p in developing such a resistance. Conclusions : We provide detailed analysis of transcriptomic and phenotypic...... to this ability. Finally, we identify the importance of histone deacetylase Hda1p in strain resistance to stresses....

Canine susceptibility to visceral leishmaniasis: A systematic review upon genetic aspects, considering breed factors and immunological concepts.

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de Vasconcelos, Tassia Cristina Bello; Furtado, Marina Carvalho; Belo, Vínicus Silva; Morgado, Fernanda Nazaré; Figueiredo, Fabiano Borges

2017-10-05

Dogs have different susceptibility degrees to leishmaniasis; however, genetic research on this theme is scarce, manly on visceral form. The aims of this systematic review were to describe and discuss the existing scientific findings on genetic susceptibility to canine leishmaniasis, as well as to show the gaps of the existing knowledge. Twelve articles were selected, including breed immunological studies, genome wide associations or other gene polymorphism or gene sequencing studies, and transcription approaches. As main results of literature, there was a suggestion of genetic clinical resistance background for Ibizan Hound dogs, and alleles associated with protection or susceptibility to visceral leishmaniasis in Boxer dogs. Genetic markers can explain phenotypic variance in both pro- and anti-inflammatory cytokines and in cellular immune responses, including antigen presentation. Many gene segments are involved in canine visceral leishmaniasis phenotype, with Natural Resistance Associated Macrophage Protein 1 (NRAMP1) as the most studied. This was related to both protection and susceptibility. In comparison with murine and human genetic approaches, lack of knowledge in dogs is notorious, with many possibilities for new studies, revealing a wide field to be assessed on canine leishmaniasis susceptibility research. Copyright © 2017 Elsevier B.V. All rights reserved.

Susceptibility of bone marrow-derived macrophages to influenza virus infection is dependent on macrophage phenotype.

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Campbell, Gillian M; Nicol, Marlynne Q; Dransfield, Ian; Shaw, Darren J; Nash, Anthony A; Dutia, Bernadette M

2015-10-01

The role of the macrophage in influenza virus infection is complex. Macrophages are critical for resolution of influenza virus infections but implicated in morbidity and mortality in severe infections. They can be infected with influenza virus and consequently macrophage infection is likely to have an impact on the host immune response. Macrophages display a range of functional phenotypes, from the prototypical pro-inflammatory classically activated cell to alternatively activated anti-inflammatory macrophages involved in immune regulation and wound healing. We were interested in how macrophages of different phenotype respond to influenza virus infection and therefore studied the infection of bone marrow-derived macrophages (BMDMs) of classical and alternative phenotype in vitro. Our results show that alternatively activated macrophages are more readily infected and killed by the virus than classically activated. Classically activated BMDMs express the pro-inflammatory markers inducible nitric oxide synthase (iNOS) and TNF-α, and TNF-α expression was further upregulated following infection. Alternatively activated macrophages express Arginase-1 and CD206; however, following infection, expression of these markers was downregulated whilst expression of iNOS and TNF-α was upregulated. Thus, infection can override the anti-inflammatory state of alternatively activated macrophages. Importantly, however, this results in lower levels of pro-inflammatory markers than those produced by classically activated cells. Our results showed that macrophage phenotype affects the inflammatory macrophage response following infection, and indicated that modulating the macrophage phenotype may provide a route to develop novel strategies to prevent and treat influenza virus infection.

Truncated thioredoxin (Trx-80) promotes pro-inflammatory macrophages of the M1 phenotype and enhances atherosclerosis.

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Mahmood, Dler Faieeq Darweesh; Abderrazak, Amna; Couchie, Dominique; Lunov, Oleg; Diderot, Vimala; Syrovets, Tatiana; Slimane, Mohamed-Naceur; Gosselet, Fabien; Simmet, Thomas; Rouis, Mustapha; El Hadri, Khadija

2013-07-01

Vascular cells are particularly susceptible to oxidative stress that is believed to play a key role in the pathogenesis of cardiovascular disorders. Thioredoxin-1 (Trx-1) is an oxidative stress-limiting protein with anti-inflammatory and anti-apoptotic properties. In contrast, its truncated form (Trx-80) exerts pro-inflammatory effects. Here we analyzed whether Trx-80 might exert atherogenic effects by promoting macrophage differentiation into the M1 pro-inflammatory phenotype. Trx-80 at 1 µg/ml significantly attenuated the polarization of anti-inflammatory M2 macrophages induced by exposure to either IL-4 at 15 ng/ml or IL-4/IL-13 (10 ng/ml each) in vitro, as evidenced by the expression of the characteristic markers, CD206 and IL-10. By contrast, in LPS-challenged macrophages, Trx-80 significantly potentiated the differentiation into inflammatory M1 macrophages as indicated by the expression of the M1 cytokines, TNF-α and MCP-1. When Trx-80 was administered to hyperlipoproteinemic ApoE2.Ki mice at 30 µg/g body weight (b.w.) challenged either with LPS at 30 µg/30 g (b.w.) or IL-4 at 500 ng/30 g (b.w.), it significantly induced the M1 phenotype but inhibited differentiation of M2 macrophages in thymus and liver. When ApoE2.Ki mice were challenged once weekly with LPS for 5 weeks, they showed severe atherosclerotic lesions enriched with macrophages expressing predominantly M1 over M2 markers. Such effect was potentiated when mice received daily, in addition to LPS, the Trx-80. Moreover, the Trx-80 treatment led to a significantly increased aortic lesion area. The ability of Trx-80 to promote differentiation of macrophages into the classical proinflammatory phenotype may explain its atherogenic effects in cardiovascular diseases. Copyright © 2013 Wiley Periodicals, Inc.

Fetal Stress and Programming of Hypoxic/Ischemic-Sensitive Phenotype in the Neonatal Brain: Mechanisms and Possible Interventions

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Li, Yong; Gonzalez, Pablo; Zhang, Lubo

2012-01-01

Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxicischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other for brain disorders. PMID:22627492

Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible interventions.

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Li, Yong; Gonzalez, Pablo; Zhang, Lubo

2012-08-01

Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxic-ischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other brain disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

QTLs for tolerance of drought and breeding for tolerance of abiotic and biotic stress: an integrated approach.

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Shalabh Dixit

Full Text Available BACKGROUND: The coupling of biotic and abiotic stresses leads to high yield losses in rainfed rice (Oryza sativa L. growing areas. While several studies target these stresses independently, breeding strategies to combat multiple stresses seldom exist. This study reports an integrated strategy that combines QTL mapping and phenotypic selection to develop rice lines with high grain yield (GY under drought stress and non-stress conditions, and tolerance of rice blast. METHODOLOGY: A blast-tolerant BC2F3-derived population was developed from the cross of tropical japonica cultivar Moroberekan (blast- and drought-tolerant and high-yielding indica variety Swarna (blast- and drought-susceptible through phenotypic selection for blast tolerance at the BC2F2 generation. The population was studied for segregation distortion patterns and QTLs for GY under drought were identified along with study of epistatic interactions for the trait. RESULTS: Segregation distortion, in favour of Moroberekan, was observed at 50 of the 59 loci. Majority of these marker loci co-localized with known QTLs for blast tolerance or NBS-LRR disease resistance genes. Despite the presence of segregation distortion, high variation for DTF, PH and GY was observed and several QTLs were identified under drought stress and non-stress conditions for the three traits. Epistatic interactions were also detected for GY which explained a large proportion of phenotypic variance observed in the population. CONCLUSIONS: This strategy allowed us to identify QTLs for GY along with rapid development of high-yielding purelines tolerant to blast and drought with considerably reduced efforts. Apart from this, it also allowed us to study the effects of the selection cycle for blast tolerance. The developed lines were screened at IRRI and in the target environment, and drought and blast tolerant lines with high yield were identified. With tolerance to two major stresses and high yield potential, these

Stress-responsively modulated ymdAB-clsC operon plays a role in biofilm formation and apramycin susceptibility in Escherichia coli.

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Kim, Moonjeong; Kim, Kwang-Sun

2017-07-06

The YmdB protein, an inhibitor of biofilm formation and an inducer of apramycin susceptibility in Escherichia coli (E. coli), is part of a putative operon. However, transcription of this operon and its subsequent effects on biological pathways has not been fully studied. Here, we characterized the operon in terms of promoter activity, transcription and function. Promoter activity assays identified two new growth- and cold-shock-responsive upstream (PymdA) and inner (PclsC) promoters, respectively. Moreover, investigation of the operon-derived transcripts identified different polycistronic transcripts harboring multiple heterogeneous 3΄ ends. Overexpression of YmdA or ClsC proteins inhibited biofilm formation and affected apramycin susceptibility, a process dependent on the sucA gene, suggesting that the operon genes or their encoded proteins are functionally linked. Additional investigation of the effects of polycistronic transcripts on the response of E. coli cells to apramycin revealed that transcripts containing ymdA (-213 to +27) are required for apramycin susceptibility. Thus, ymdAB-clsC is a new stress-responsive operon that plays a role in inhibiting undesired biofilm forming and antibiotic-resistant bacterial populations. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Detection of oxacillin-susceptible mecA-positive Staphylococcus aureus isolates by use of chromogenic medium MRSA ID.

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Kumar, V Anil; Steffy, Katherin; Chatterjee, Maitrayee; Sugumar, Madhan; Dinesh, Kavitha R; Manoharan, Anand; Karim, Shamsul; Biswas, Raja

2013-01-01

Reports of oxacillin-susceptible mecA-positive Staphylococcus aureus strains are on the rise. Because of their susceptibility to oxacillin and cefoxitin, it is very difficult to detect them by using routine phenotypic methods. We describe two such isolates that were detected by chromogenic medium and confirmed by characterization of the mecA gene element.

Microstructure, local mechanical properties and stress corrosion cracking susceptibility of an SA508-52M-316LN safe-end dissimilar metal weld joint by GTAW

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Ming, Hongliang; Zhu, Ruolin [Key Laboratory of Nuclear Materials and Safety Assessment, Liaoning KeyLaboratory for Safety and Assessment Technique of Nuclear Materials, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049 (China); Zhang, Zhiming [Key Laboratory of Nuclear Materials and Safety Assessment, Liaoning KeyLaboratory for Safety and Assessment Technique of Nuclear Materials, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Wang, Jianqiu, E-mail: wangjianqiu@imr.ac.cn [Key Laboratory of Nuclear Materials and Safety Assessment, Liaoning KeyLaboratory for Safety and Assessment Technique of Nuclear Materials, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Han, En.-Hou.; Ke, Wei [Key Laboratory of Nuclear Materials and Safety Assessment, Liaoning KeyLaboratory for Safety and Assessment Technique of Nuclear Materials, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Su, Mingxing [Shanghai Research Center for Weld and Detection Engineering Technique of Nuclear Equipment, Shanghai 201306 (China)

2016-07-04

The microstructure, local mechanical properties and local stress corrosion cracking susceptibility of an SA508-52M-316LN domestic dissimilar metal welded safe-end joint used for AP1000 nuclear power plant prepared by automatic gas tungsten arc welding was studied in this work by optical microscopy, scanning electron microscopy (with electron back scattering diffraction and an energy dispersive X-ray spectroscopy system), micro-hardness testing, local mechanical tensile testing and local slow strain rate tests. The micro-hardness, local mechanical properties and stress corrosion cracking susceptibility across this dissimilar metal weld joint vary because of the complex microstructure across the fusion area and the dramatic chemical composition change across the fusion lines. Briefly, Type I boundaries and Type II boundaries exist in 52Mb near the SA508-52Mb interface, a microstructure transition was found in SA508 heat affected zone, the residual strain and grain boundary character distribution changes as a function of the distance from the fusion boundary in 316LN heat affected zone, micro-hardness distribution and local mechanical properties along the DMWJ are heterogeneous, and 52Mw-316LN interface has the highest SCC susceptibility in this DMWJ while 316LN base metal has the lowest one.

Correlation between phenotypic antibiotic susceptibility and the resistome in Pseudomonas aeruginosa.

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Jaillard, Magali; van Belkum, Alex; Cady, Kyle C; Creely, David; Shortridge, Dee; Blanc, Bernadette; Barbu, E Magda; Dunne, W Michael; Zambardi, Gilles; Enright, Mark; Mugnier, Nathalie; Le Priol, Christophe; Schicklin, Stéphane; Guigon, Ghislaine; Veyrieras, Jean-Baptiste

2017-08-01

Genetic determinants of antibiotic resistance (AR) have been extensively investigated. High-throughput sequencing allows for the assessment of the relationship between genotype and phenotype. A panel of 672 Pseudomonas aeruginosa strains was analysed, including representatives of globally disseminated multidrug-resistant and extensively drug-resistant clones; genomes and multiple antibiograms were available. This panel was annotated for AR gene presence and polymorphism, defining a resistome in which integrons were included. Integrons were present in >70 distinct cassettes, with In5 being the most prevalent. Some cassettes closely associated with clonal complexes, whereas others spread across the phylogenetic diversity, highlighting the importance of horizontal transfer. A resistome-wide association study (RWAS) was performed for clinically relevant antibiotics by correlating the variability in minimum inhibitory concentration (MIC) values with resistome data. Resistome annotation identified 147 loci associated with AR. These loci consisted mainly of acquired genomic elements and intrinsic genes. The RWAS allowed for correct identification of resistance mechanisms for meropenem, amikacin, levofloxacin and cefepime, and added 46 novel mutations. Among these, 29 were variants of the oprD gene associated with variation in meropenem MIC. Using genomic and MIC data, phenotypic AR was successfully correlated with molecular determinants at the whole-genome sequence level. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Lexical decisions in adults with low and high susceptibility to pattern-related visual stress: a preliminary investigation.

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James M Gilchrist

2015-04-01

Full Text Available Pattern-related visual stress (PRVS is a form of sensory hypersensitivity that some people experience when viewing high contrast repeating patterns, notably alternating dark and light stripes. Those susceptible to PRVS typically have a strong aversion to such stimuli, and this is often accompanied by experiences of visual discomfort and disturbance. The patterns most likely to elicit symptoms of PRVS have a square-wave grating configuration of spatial frequency ~ 3 cycles/degree. Such stimuli are characteristic of printed text in which lines of words and the spaces between them present a high contrast grating-like stimulus. Consequently, much printed reading material has the potential to elicit PRVS that may impair reading performance, and this problem is now thought to be common in individuals with reading difficulties including dyslexia. However, the manner in which PRVS affects reading ability is unknown. One possibility is that the early sensory visual stress may interfere with the later cognitive word recognition stage of the reading process, resulting in reading performance that is slower and/or less accurate.To explore the association of PRVS with word recognition ability, lexical decision performance (speed and accuracy to words and pronounceable non-words was measured in two groups of adults, having low and high susceptibility to PRVS. Results showed that lexical decisions were generally faster but less accurate in high-PRVS, and also that high-PRVS participants made decisions significantly faster for words than for non-words, revealing a strong lexicality effect that was not present in low-PRVS. These findings are novel and, as yet, unconfirmed by other studies. We consider possible interpretation in terms of cortical activity and perceptual mechanisms.

Phenotypic and genotypic analysis of anti-tuberculosis drug resistance in Mycobacterium tuberculosis isolates in Myanmar.

Science.gov (United States)

Aung, Wah Wah; Ei, Phyu Win; Nyunt, Wint Wint; Swe, Thyn Lei; Lwin, Thandar; Htwe, Mi Mi; Kim, Kyung Jun; Lee, Jong Seok; Kim, Chang Ki; Cho, Sang Nae; Song, Sun Dae; Chang, Chulhun L

2015-09-01

Tuberculosis (TB) is one of the most serious health problems in Myanmar. Because TB drug resistance is associated with genetic mutation(s) relevant to responses to each drug, genotypic methods for detecting these mutations have been proposed to overcome the limitations of classic phenotypic drug susceptibility testing (DST). We explored the current estimates of drug-resistant TB and evaluated the usefulness of genotypic DST in Myanmar. We determined the drug susceptibility of Mycobacterium tuberculosis isolated from sputum smear-positive patients with newly diagnosed pulmonary TB at two main TB centers in Myanmar during 2013 by using conventional phenotypic DST and the GenoType MTBDRplus assay (Hain Lifescience, Germany). Discrepant results were confirmed by sequencing the genes relevant to each type of resistance (rpoB for rifampicin; katG and inhA for isoniazid). Of 191 isolates, phenotypic DST showed that 27.7% (n=53) were resistant to at least one first-line drug and 20.9% (n=40) were resistant to two or more, including 18.3% (n=35) multidrug-resistant TB (MDR-TB) strains. Monoresistant strains accounted for 6.8% (n=13) of the samples. Genotypic assay of 189 isolates showed 17.5% (n=33) MDR-TB and 5.3% (n=10) isoniazid-monoresistant strains. Genotypic susceptibility results were 99.5% (n=188) concordant and agreed almost perfectly with phenotypic DST (kappa=0.99; 95% confidence interval 0.96-1.01). The results highlight the burden of TB drug resistance and prove the usefulness of the genotypic DST in Myanmar.

Exercise-Induced Rhabdomyolysis and Stress-Induced Malignant Hyperthermia Events, Association with Malignant Hyperthermia Susceptibility, and RYR1 Gene Sequence Variations

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Antonella Carsana

2013-01-01

Full Text Available Exertional rhabdomyolysis (ER and stress-induced malignant hyperthermia (MH events are syndromes that primarily afflict military recruits in basic training and athletes. Events similar to those occurring in ER and in stress-induced MH events are triggered after exposure to anesthetic agents in MH-susceptible (MHS patients. MH is an autosomal dominant hypermetabolic condition that occurs in genetically predisposed subjects during general anesthesia, induced by commonly used volatile anesthetics and/or the neuromuscular blocking agent succinylcholine. Triggering agents cause an altered intracellular calcium regulation. Mutations in RYR1 gene have been found in about 70% of MH families. The RYR1 gene encodes the skeletal muscle calcium release channel of the sarcoplasmic reticulum, commonly known as ryanodine receptor type 1 (RYR1. The present work reviews the documented cases of ER or of stress-induced MH events in which RYR1 sequence variations, associated or possibly associated to MHS status, have been identified.

Sex Differences in Nucleus Accumbens Transcriptome Profiles Associated with Susceptibility versus Resilience to Subchronic Variable Stress.

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Hodes, Georgia E; Pfau, Madeline L; Purushothaman, Immanuel; Ahn, H Francisca; Golden, Sam A; Christoffel, Daniel J; Magida, Jane; Brancato, Anna; Takahashi, Aki; Flanigan, Meghan E; Ménard, Caroline; Aleyasin, Hossein; Koo, Ja Wook; Lorsch, Zachary S; Feng, Jian; Heshmati, Mitra; Wang, Minghui; Turecki, Gustavo; Neve, Rachel; Zhang, Bin; Shen, Li; Nestler, Eric J; Russo, Scott J

2015-12-16

Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differences was DNA methyltransferase 3a (Dnmt3a), which shows a greater induction in females after SCVS. Interestingly, Dnmt3a expression levels were increased in the NAc of depressed humans, an effect seen in both males and females. Local overexpression of Dnmt3a in NAc rendered male mice more susceptible to SCVS, whereas Dnmt3a knock-out in this region rendered females more resilient, directly implicating this gene in stress responses. Associated with this enhanced resilience of female mice upon NAc knock-out of Dnmt3a was a partial shift of the NAc female transcriptome toward the male pattern after SCVS. These data indicate that males and females undergo different patterns of transcriptional regulation in response to stress and that a DNA methyltransferase in NAc contributes to sex differences in stress vulnerability. Women have a higher incidence of depression than men. However, preclinical models, the first step in developing new diagnostics and therapeutics, have been performed mainly on male subjects. Using a stress-based animal model of depression that causes behavioral effects in females but not males, we demonstrate a sex-specific transcriptional profile in brain reward circuitry. This transcriptional profile can be altered by removal of an epigenetic mechanism, which

Responses of nitrogen metabolism and seed nutrition to drought stress in soybean genotypes differing in slow-wilting phenotype

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Nacer eBellaloui

2013-12-01

Full Text Available Recent advances in soybean breeding have resulted in genotypes that express the slow-wilting phenotype (trait under drought stress conditions. The physiological mechanisms of this trait remain unknown due to the complexity of trait × environment interactions. The objective of this research was to investigate nitrogen metabolism and leaf and seed nutrients composition of the slow-wilting soybean genotypes under drought stress conditions. A repeated greenhouse experiment was conducted using check genotypes: NC-Roy (fast wilting, Boggs (intermediate in wilting; and NTCPR94-5157 and N04-9646 (slow-wilting, SLW genotypes. Plants were either well-watered or drought stressed. Results showed that under well-watered conditions, nitrogen fixation (NF, nitrogen assimilation (NA, and leaf and seed composition differed between genotypes. Under drought stress, NF and NA were higher in NTCPR94-5157 and N04-9646 than in NC-Roy and Boggs. Under severe water stress, however, NA was low in all genotypes. Leaf water potential was significantly lower in checks (-2.00 MPa than in the SLW genotypes (-1.68 MPa. Leaf and seed concentrations of K, P, Ca, Cu, Na, B were higher in SLW genotypes than in the checks under drought stress conditions. Seed protein, oleic acid, and sugars were higher in SLW genotypes, and oil, linoleic and linolenic acids were lower in SLW genotypes. This research demonstrated that K, P, Ca, Cu, Na, and B may be involved in SLW trait by maintaining homeostasis and osmotic regulation. Maintaining higher leaf water potential in NTCPR94-5157 and N04-9646 under drought stress could be a possible water conservation mechanism to maintain leaf turgor pressure. The increase in osmoregulators such as minerals, raffinose and stachyose, and oleic acid could be beneficial for soybean breeders in selecting for drought stress tolerance.

HEK293 in cell biology and cancer research: phenotype, karyotype, tumorigenicity, and stress-induced genome-phenotype evolution.

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Stepanenko, A A; Dmitrenko, V V

2015-09-15

293 cell line (widely known as the Human Embryonic Kidney 293 cells) and its derivatives were the most used cells after HeLa in cell biology studies and after CHO in biotechnology as a vehicle for the production of adenoviral vaccines and recombinant proteins, for analysis of the neuronal synapse formation, in electrophysiology and neuropharmacology. Despite the historically long-term productive exploitation, the origin, phenotype, karyotype, and tumorigenicity of 293 cells are still debated. 293 cells were considered the kidney epithelial cells or even fibroblasts. However, 293 cells demonstrate no evident tissue-specific gene expression signature and express the markers of renal progenitor cells, neuronal cells and adrenal gland. This complicates efforts to reveal the authentic cell type/tissue of origin. On the other hand, the potential to propagate the highly neurotropic viruses, inducible synaptogenesis, functionality of the endogenous neuron-specific voltage-gated channels, and response to the diverse agonists implicated in neuronal signaling give credibility to consider 293 cells of neuronal lineage phenotype. The compound phenotype of 293 cells can be due to heterogeneous, unstable karyotype. The mean chromosome number and chromosome aberrations differ between 293 cells and derivatives as well as between 293 cells from the different cell banks/labs. 293 cells are tumorigenic, whereas acute changes of expression of the cancer-associated genes aggravate tumorigenicity by promoting chromosome instability. Importantly, the procedure of a stable empty vector transfection can also impact karyotype and phenotype. The discussed issues caution against misinterpretations and pitfalls during the different experimental manipulations with 293 cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Neuropeptide Y and Stress

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Murat Gulsun

2012-03-01

Full Text Available The neurobiological aspects of stress and coping skills has been the focus of interest for many researchers. Some of the studies has shown that there is a significant relationship among genetically variables, stress response and life events. Neuropeptide Y is one of the systems regulating the stress response. Under the prolonged or repeated trauma neuropeptide Y is released from the brain's key areas. This system shows different levels of functioning in individuals with different levels of resilience. There is particular interest in the variations of genes that encode stress-sensitive signaling molecules during gene-environment interaction. This condition may contribute to susceptibility of stress or stress resilience. Neuropeptide Y system plays a key role in the adaptation to behavioral stress. The reduced levels of neuropeptide Y have also been observed in treatment-resistant depression and posttraumatic stress disorder. Lower level of neuropeptide Y expression and dysfunctional neuropeptide Y system in response to stress and resulting decreased stress resilience could increase susceptibility to stress-related disorders.

Comparative analysis of root transcriptome profiles between drought-tolerant and susceptible wheat genotypes in response to water stress.

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Hu, Ling; Xie, Yan; Fan, Shoujin; Wang, Zongshuai; Wang, Fahong; Zhang, Bin; Li, Haosheng; Song, Jie; Kong, Lingan

2018-07-01

Water deficit is one of the major factors limiting crop productivity worldwide. Plant roots play a key role in uptaking water, perceiving and transducing of water deficit signals to shoot. Although the mechanisms of drought-tolerance have been reported recently, the transcriptional regulatory network of wheat root response to water stress has not been fully understood. In this study, drought-tolerant cultivar JM-262 and susceptible cultivar LM-2 are planted to characterize the root transcriptional changes and physiological responses to water deficit. A total of 8197 drought tolerance-associated differentially expressed genes (DEGs) are identified, these genes are mainly mapped to carbon metabolism, flavonoid biosynthesis, and phytohormone signal transduction. The number and expression level of DEGs involved in antioxidative and antiosmotic stresses are more enhanced in JM-262 under water stress. Furthermore, we find the DEGs related to root development are much more induced in JM-262 in phytohormone signal transduction and carbon metabolism pathway. In conclusion, JM-262 may alleviate the damage of drought by producing more osmoprotectants, ROS scavengers, biomass and energy. Interestingly, hormone signaling and cross-talk probably play an important role in promoting JM-262 greater root systems to take up more water, higher capabilities to induce more drought-related DEGs and higher resisitance to oxidative stresse. Copyright © 2018 Elsevier B.V. All rights reserved.

High-Throughput Non-destructive Phenotyping of Traits that Contribute to Salinity Tolerance in Arabidopsis thaliana

KAUST Repository

Awlia, Mariam

2016-09-28

Reproducible and efficient high-throughput phenotyping approaches, combined with advances in genome sequencing, are facilitating the discovery of genes affecting plant performance. Salinity tolerance is a desirable trait that can be achieved through breeding, where most have aimed at selecting for plants that perform effective ion exclusion from the shoots. To determine overall plant performance under salt stress, it is helpful to investigate several plant traits collectively in one experimental setup. Hence, we developed a quantitative phenotyping protocol using a high-throughput phenotyping system, with RGB and chlorophyll fluorescence (ChlF) imaging, which captures the growth, morphology, color and photosynthetic performance of Arabidopsis thaliana plants in response to salt stress. We optimized our salt treatment by controlling the soil-water content prior to introducing salt stress. We investigated these traits over time in two accessions in soil at 150, 100, or 50 mM NaCl to find that the plants subjected to 100 mM NaCl showed the most prominent responses in the absence of symptoms of severe stress. In these plants, salt stress induced significant changes in rosette area and morphology, but less prominent changes in rosette coloring and photosystem II efficiency. Clustering of ChlF traits with plant growth of nine accessions maintained at 100 mM NaCl revealed that in the early stage of salt stress, salinity tolerance correlated with non-photochemical quenching processes and during the later stage, plant performance correlated with quantum yield. This integrative approach allows the simultaneous analysis of several phenotypic traits. In combination with various genetic resources, the phenotyping protocol described here is expected to increase our understanding of plant performance and stress responses, ultimately identifying genes that improve plant performance in salt stress conditions.

Phenotypic variations in osmotic lysis of Sahel goat erythrocytes in non-ionic glucose media.

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Igbokwe, Nanacha Afifi; Igbokwe, Ikechukwu Onyebuchi

2016-03-01

Erythrocyte osmotic lysis in deionised glucose media is regulated by glucose influx, cation efflux, and changes in cell volume after water diffusion. Transmembrane fluxes may be affected by varied expression of glucose transporter protein and susceptibility of membrane proteins to glucose-induced glycosylation and oxidation in various physiologic states. Variations in haemolysis of Sahel goat erythrocytes after incubation in hyposmotic non-ionic glucose media, associated with sex, age, late pregnancy, and lactation, were investigated. The osmotic fragility curve in glucose media was sigmoidal with erythrocytes from goats in late pregnancy (PRE) or lactation (LAC) or from kid (KGT) or middle-aged (MGT) goats. Non-sigmoidal phenotype occurred in yearlings (YGT) and old (OGT) goats. The composite fragility phenotype for males and non-pregnant dry (NPD) females was non-sigmoidal. Erythrocytes with non-sigmoidal curves were more stable than those with sigmoidal curves because of inflectional shift of the curve to the left. Erythrocytes tended to be more fragile with male than female sex, KGT and MGT than YGT and OGT, and LAC and PRE than NPD. Thus, sex, age, pregnancy, and lactation affected the haemolytic pattern of goat erythrocytes in glucose media. The physiologic state of the goat affected the in vitro interaction of glucose with erythrocytes, causing variations in osmotic stability with variants of fragility phenotype. Variations in the effect of high extracellular glucose concentrations on the functions of membrane-associated glucose transporter, aquaporins, and the cation cotransporter were presumed to be relevant in regulating the physical properties of goat erythrocytes under osmotic stress.

High susceptibility prevalence for F4+ and F18+Escherichia coli in Flemish pigs.

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Nguyen, Ut V; Coddens, Annelies; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Poucke, Mario Van; Peelman, Luc; Cox, Eric

2017-04-01

F4 and/or F18 enterotoxigenic Escherichia coli (F4 + /F18 + ETEC) are responsible for diarrhea while F18 + verotoxigenic E. coli (F18 + VTEC) cause edema disease in pigs. Both infections can result in severe economic losses, which are mainly the result of the medication, growth retardation and mortality. The susceptibility of piglets to these pathogens is determined by the presence of F4 and F18 receptors (F4R and F18R). Understanding the composition of the susceptibility phenotypes of pigs is useful for animal health and breeding management. This study aimed to determine the prevalence of the F4 ETEC susceptibility phenotypes and F18 + E. coli susceptibility among Flemish pig breeds by using the in vitro villous adhesion assay. In this study, seven F4 ETEC susceptibility phenotypes were found, namely A (F4 ab R + , ac R + , ad R + ; 59.16%), B (F4 ab R + , ac R + , ad R - ; 6.28%), C (F4 ab R + , ac R - , ad R + ; 2.62%), D (F4 ab R - , ac R - , ad R + ; 6.28%), E (F4 ab R - , ac R - , ad R - ; 24.08%), F (F4 ab R + , ac R - , ad R - ; 1.05%) and G (F4 ab R - , ac R + , ad R - ; 0.52%). F4ab and F4ac E. coli showed a stronger degree of adhesion to the intestinal villi (53.40% and 52.88% strong adhesion, respectively), compared to F4ad E. coli (43.46% strong adhesion). Furthermore, the correlation between F4ac and F4ab adhesion was higher (r=0.78) than between F4ac and F4ad adhesion (r=0.41) and between F4ab and F4ad adhesion (r=0.57). For F18 + E. coli susceptibility, seven out of 82 pigs were F18R negative (8.54%), but only two of these seven pigs (2.44%) were also negative for F4R. As such, the chance to identify a pig that is positive for a F4 ETEC variant or F18 + E. coli is 97.56%. Therefore, significant economic losses will arise due to F4 + and/or F18 + E. coli infections in the Flemish pig population due to the high susceptibility prevalence. Copyright © 2016 Elsevier B.V. All rights reserved.

Less Stress : Oxidative stress and glutathione kinetics in preterm infants

NARCIS (Netherlands)

D. Rook (Denise)

2013-01-01

textabstractDue to immature antioxidant defenses, preterm infants are at susceptible to oxidative stress, which is associated with bronchopulmonary dysplasia, retinopathy of prematurity and periventricular leukomalacia. The general aim of this thesis was to study oxidative stress in preterm infants

Behavioral and cognitive impact of early life stress: Insights from an animal model.

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Liu, Hesong; Atrooz, Fatin; Salvi, Ankita; Salim, Samina

2017-08-01

-like phenotype was evident only later on at PND90. Our findings suggest that early life stress caused co-occurrence of anxiety and depression-like behavior at PND32 (mimics human early-adolescent period). This co-occurrence was lost at PND60 with demonstration of anxiety- but not depression-like behavior. Later, depression but not anxiety-like behavior was observed at PND90. It seems that behavioral adaptations occur at the critical PND60 stage (mimics human late-adolescent period), where behavioral and cognitive switching occurs, thereby, expressing susceptible and resilient phenotypes. Published by Elsevier Inc.

Comparison of an antioxidant system in tolerant and susceptible wheat seedlings in response to salt stress

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Feki, K.; Tounsi, S.; Brini, F.

2017-07-01

It has been demonstrated previously that the physiological and molecular analysis of seedlings of the tolerant (Om Rabia3) and susceptible (Mahmoudi) Tunisian wheat genotypes were different at short and long-term response to salinity. In this study, we examined the antioxidant defence system in seedlings of these two cultivars at short-term response to different NaCl concentrations. The findings showed that high salinity tolerance of cv. Om Rabia3, as manifested by lower decrease in its dry biomass, was associated with lower malondialdehyde and hydrogen peroxide contents, lower accumulation of the superoxide (O2⎯) in the roots and the shoots, and also lower decrease in ascorbate content than those in cv. Mahmoudi. Moreover, the expression of some genes coding for antioxidant enzymes such as the catalase, the superoxide dismutase and the peroxidase were enhanced by NaCl stress especially in the salt-tolerant cultivar. In parallel, their activities were increased in response to the same condition of stress and especially in the cv. Om Rabia3. Taken together, these data suggested that the capacity to limit oxidative damage is important for NaCl tolerance of durum wheat.

Sex-Dependent Effects of Stress on Immobility Behavior and VTA Dopamine Neuron Activity: Modulation by Ketamine.

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Rincón-Cortés, Millie; Grace, Anthony A

2017-10-01

Stress constitutes a risk factor across several psychiatric disorders. Moreover, females are more susceptible to stress-related disorders, such as depression, than males. Although dopamine system underactivation is implicated in the pathophysiology of depression, little is known about the female dopamine system at baseline and post-stress. The effects of chronic mild stress were examined on ventral tegmental area dopamine neuron activity and forced swim test immobility by comparing male and female rats. The impact of a single dose of the rapid antidepressant ketamine (10 mg/kg, i.p.) on forced swim test immobility and ventral tegmental area function was then tested. Baseline ventral tegmental area dopamine activity was comparable in both sexes. At baseline, females exhibited roughly double the forced swim test immobility duration than males, which corresponded to ~50% decrease in ventral tegmental area dopamine population activity compared with similarly treated (i.e., post-forced swim test) males. Following chronic mild stress, there was greater immobility duration in both sexes and reduced ventral tegmental area dopamine neuron activity by approximately 50% in males and nearly 75% in females. Ketamine restored behavior and post-forced swim test ventral tegmental area dopamine activity for up to 7 days in females as well as in both male and female chronic mild stress-exposed rats. These data suggest increased female susceptibility to depression-like phenotypes (i.e., greater immobility, ventral tegmental area hypofunction) is associated with higher dopamine system sensitivity to both acute and repeated stress relative to males. Understanding the neural underpinnings of sex differences in stress vulnerability will provide insight into mechanisms of disease and optimizing therapeutic approaches in both sexes. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Genotypes in relation to phenotypic appearance and exposure to environmental factors in Graves' hyperthyroidism

NARCIS (Netherlands)

Vos, Xander G.; Endert, Erik; Tijssen, Jan G. P.; Wiersinga, Wilmar M.

2012-01-01

Background: Genetic polymorphisms and environmental factors are both involved in the pathogenesis of Graves' disease, but their interaction and effect on Graves' phenotypes have scarcely been investigated. Objective: To test the hypothesis that subjects with susceptibility genotypes develop more

High-throughput phenotyping and genomic selection: the frontiers of crop breeding converge.

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Cabrera-Bosquet, Llorenç; Crossa, José; von Zitzewitz, Jarislav; Serret, María Dolors; Araus, José Luis

2012-05-01

Genomic selection (GS) and high-throughput phenotyping have recently been captivating the interest of the crop breeding community from both the public and private sectors world-wide. Both approaches promise to revolutionize the prediction of complex traits, including growth, yield and adaptation to stress. Whereas high-throughput phenotyping may help to improve understanding of crop physiology, most powerful techniques for high-throughput field phenotyping are empirical rather than analytical and comparable to genomic selection. Despite the fact that the two methodological approaches represent the extremes of what is understood as the breeding process (phenotype versus genome), they both consider the targeted traits (e.g. grain yield, growth, phenology, plant adaptation to stress) as a black box instead of dissecting them as a set of secondary traits (i.e. physiological) putatively related to the target trait. Both GS and high-throughput phenotyping have in common their empirical approach enabling breeders to use genome profile or phenotype without understanding the underlying biology. This short review discusses the main aspects of both approaches and focuses on the case of genomic selection of maize flowering traits and near-infrared spectroscopy (NIRS) and plant spectral reflectance as high-throughput field phenotyping methods for complex traits such as crop growth and yield. © 2012 Institute of Botany, Chinese Academy of Sciences.

Metabolomic analysis of the selection response of Drosophila melanogaster to environmental stress: are there links to gene expression and phenotypic traits?

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Malmendal, Anders; Sørensen, Jesper Givskov; Overgaard, Johannes; Holmstrup, Martin; Nielsen, Niels Chr.; Loeschcke, Volker

2013-05-01

We investigated the global metabolite response to artificial selection for tolerance to stressful conditions such as cold, heat, starvation, and desiccation, and for longevity in Drosophila melanogaster. Our findings were compared to data from other levels of biological organization, including gene expression, physiological traits, and organismal stress tolerance phenotype. Overall, we found that selection for environmental stress tolerance changes the metabolomic 1H NMR fingerprint largely in a similar manner independent of the trait selected for, indicating that experimental evolution led to a general stress selection response at the metabolomic level. Integrative analyses across data sets showed little similarity when general correlations between selection effects at the level of the metabolome and gene expression were compared. This is likely due to the fact that the changes caused by these selection regimes were rather mild and/or that the dominating determinants for gene expression and metabolite levels were different. However, expression of a number of genes was correlated with the metabolite data. Many of the identified genes were general stress response genes that are down-regulated in response to selection for some of the stresses in this study. Overall, the results illustrate that selection markedly alters the metabolite profile and that the coupling between different levels of biological organization indeed is present though not very strong for stress selection at this level. The results highlight the extreme complexity of environmental stress adaptation and the difficulty of extrapolating and interpreting responses across levels of biological organization.

Transcriptome sequencing of two phenotypic mosaic Eucalyptus trees reveals large scale transcriptome re-modelling.

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Amanda Padovan

Full Text Available Phenotypic mosaic trees offer an ideal system for studying differential gene expression. We have investigated two mosaic eucalypt trees from two closely related species (Eucalyptus melliodora and E. sideroxylon, which each support two types of leaves: one part of the canopy is resistant to insect herbivory and the remaining leaves are susceptible. Driving this ecological distinction are differences in plant secondary metabolites. We used these phenotypic mosaics to investigate genome wide patterns of foliar gene expression with the aim of identifying patterns of differential gene expression and the somatic mutation(s that lead to this phenotypic mosaicism. We sequenced the mRNA pool from leaves of the resistant and susceptible ecotypes from both mosaic eucalypts using the Illumina HiSeq 2000 platform. We found large differences in pathway regulation and gene expression between the ecotypes of each mosaic. The expression of the genes in the MVA and MEP pathways is reflected by variation in leaf chemistry, however this is not the case for the terpene synthases. Apart from the terpene biosynthetic pathway, there are several other metabolic pathways that are differentially regulated between the two ecotypes, suggesting there is much more phenotypic diversity than has been described. Despite the close relationship between the two species, they show large differences in the global patterns of gene and pathway regulation.

Phenotypic, antimicrobial susceptibility profile and virulence factors of Klebsiella pneumoniae isolated from buffalo and cow mastitic milk.

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Osman, Kamelia M; Hassan, Hany M; Orabi, Ahmed; Abdelhafez, Ahmed S T

2014-06-01

Studies on the prevalence and virulence genes of Klebsiella mastitis pathogens in a buffalo population are undocumented. Also, the association of rmpA kfu, uge, magA, Aerobactin, K1 and K2 virulent factors with K. pneumoniae buffalo, and cow mastitis is unreported. The virulence of K. pneumoniae was evaluated through both phenotypic and molecular assays. In vivo virulence was assessed by the Vero cell cytotoxicity, suckling mouse assay and mice lethality test. Antimicrobial susceptibility was tested by disk diffusion method. The 45 K. pneumoniae isolates from buffalo (n = 10/232) and cow (n = 35/293) milk were isolated (45/525; 8.6%) and screened via PCR for seven virulence genes encoding uridine diphosphate galactose 4 epimerase encoding gene responsible for capsule and smooth lipopolysaccharide synthesis (uge), siderophores (kfu and aerobactin), protectines or invasins (rmpA and magA), and the capsule and hypermucoviscosity (K1 and K2). The most common virulence genes were rmpA, kfu, uge, and magA (77.8% each). Aerobactin and K1 genes were found at medium rates of 66.7% each and K2 (55.6%). The Vero cell cytotoxicity and LD (50) in mice were found in 100% of isolates. A multidrug resistance pattern was observed for 40% of the antimicrobials. The distribution of virulence profiles indicate a role of rmpA, kfu, uge, magA, Aerobactin, and K1 and K2 in pathogenicity of K. pneumoniae in udder infections and invasiveness, and constitutes a threat for vulnerable animals, even more if they are in combination with antibiotic resistance.

The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype.

NARCIS (Netherlands)

Rueda, B.; Broen, J.; Simeon, C.; Hesselstrand, R.; Diaz, B.; Suarez, H.; Ortego-Centeno, N.; Riemekasten, G.; Fonollosa, V.; Vonk, M.C.; Hoogen, F.H.J. van den; Sanchez-Roman, J.; Aguirre-Zamorano, M.A.; Garcia-Portales, R.; Pros, A.; Camps, M.T.; Gonzalez-Gay, M.A.; Coenen, M.J.H.; Airo, P.; Beretta, L.; Scorza, R.; Laar, J. van; Gonzalez-Escribano, M.F.; Nelson, J.L.; Radstake, T.R.D.J.; Martin, J.

2009-01-01

The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy

The resistome of Pseudomonas aeruginosa in relationship to phenotypic susceptibility.

Science.gov (United States)

Kos, Veronica N; Déraspe, Maxime; McLaughlin, Robert E; Whiteaker, James D; Roy, Paul H; Alm, Richard A; Corbeil, Jacques; Gardner, Humphrey

2015-01-01

Many clinical isolates of Pseudomonas aeruginosa cause infections that are difficult to eradicate due to their resistance to a wide variety of antibiotics. Key genetic determinants of resistance were identified through genome sequences of 390 clinical isolates of P. aeruginosa, obtained from diverse geographic locations collected between 2003 and 2012 and were related to microbiological susceptibility data for meropenem, levofloxacin, and amikacin. β-Lactamases and integron cassette arrangements were enriched in the established multidrug-resistant lineages of sequence types ST111 (predominantly O12) and ST235 (O11). This study demonstrates the utility of next-generation sequencing (NGS) in defining relevant resistance elements and highlights the diversity of resistance determinants within P. aeruginosa. This information is valuable in furthering the design of diagnostics and therapeutics for the treatment of P. aeruginosa infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Identification and Antimicrobial Susceptibility Testing of Anaerobic Bacteria: Rubik's Cube of Clinical Microbiology?

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Gajdács, Márió; Spengler, Gabriella; Urbán, Edit

2017-11-07

Anaerobic bacteria have pivotal roles in the microbiota of humans and they are significant infectious agents involved in many pathological processes, both in immunocompetent and immunocompromised individuals. Their isolation, cultivation and correct identification differs significantly from the workup of aerobic species, although the use of new technologies (e.g., matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, whole genome sequencing) changed anaerobic diagnostics dramatically. In the past, antimicrobial susceptibility of these microorganisms showed predictable patterns and empirical therapy could be safely administered but recently a steady and clear increase in the resistance for several important drugs (β-lactams, clindamycin) has been observed worldwide. For this reason, antimicrobial susceptibility testing of anaerobic isolates for surveillance purposes or otherwise is of paramount importance but the availability of these testing methods is usually limited. In this present review, our aim was to give an overview of the methods currently available for the identification (using phenotypic characteristics, biochemical testing, gas-liquid chromatography, MALDI-TOF MS and WGS) and antimicrobial susceptibility testing (agar dilution, broth microdilution, disk diffusion, gradient tests, automated systems, phenotypic and molecular resistance detection techniques) of anaerobes, when should these methods be used and what are the recent developments in resistance patterns of anaerobic bacteria.

Phenotypic characterisation of Saccharomyces spp. yeast for tolerance to stresses encountered during fermentation of lignocellulosic residues to produce bioethanol

Science.gov (United States)

2014-01-01

Background During industrial fermentation of lignocellulose residues to produce bioethanol, microorganisms are exposed to a number of factors that influence productivity. These include inhibitory compounds produced by the pre-treatment processes required to release constituent carbohydrates from biomass feed-stocks and during fermentation, exposure of the organisms to stressful conditions. In addition, for lignocellulosic bioethanol production, conversion of both pentose and hexose sugars is a pre-requisite for fermentative organisms for efficient and complete conversion. All these factors are important to maximise industrial efficiency, productivity and profit margins in order to make second-generation bioethanol an economically viable alternative to fossil fuels for future transport needs. Results The aim of the current study was to assess Saccharomyces yeasts for their capacity to tolerate osmotic, temperature and ethanol stresses and inhibitors that might typically be released during steam explosion of wheat straw. Phenotypic microarray analysis was used to measure tolerance as a function of growth and metabolic activity. Saccharomyces strains analysed in this study displayed natural variation to each stress condition common in bioethanol fermentations. In addition, many strains displayed tolerance to more than one stress, such as inhibitor tolerance combined with fermentation stresses. Conclusions Our results suggest that this study could identify a potential candidate strain or strains for efficient second generation bioethanol production. Knowledge of the Saccharomyces spp. strains grown in these conditions will aid the development of breeding programmes in order to generate more efficient strains for industrial fermentations. PMID:24670111

Evolution of the androgen-induced male phenotype.

Science.gov (United States)

Fuxjager, Matthew J; Miles, Meredith C; Schlinger, Barney A

2018-01-01

The masculine reproductive phenotype varies significantly across vertebrates. As a result, biologists have long recognized that many of the mechanisms that support these phenotypes-particularly the androgenic system-is evolutionarily labile, and thus susceptible to the effects of selection for different traits. However, exactly how androgenic signaling systems vary in a way which results in dramatically different functional outputs, remain largely unclear. We explore this topic here by outlining four key-but non-mutually exclusive-hypotheses that propose how the mechanisms of androgenic signaling might change over time to potentiate the emergence of phenotypical variation in masculine behavior and physiology. We anchor this framework in a review of our own studies of a tropical bird called the golden-collared manakin (Manacus vitellinus), which has evolved an exaggerated acrobatic courtship display that is heavily androgen-dependent. The result is an example of how the cellular basis of androgenic action can be modified to support a unique reproductive repertoire. We end this review by highlighting a broad pathway forward to further pursue the intricate ways by which the mechanisms of hormone action evolve to support processes of adaptation and animal design.

Genetic architecture for susceptibility to gout in the KARE cohort study.

Science.gov (United States)

Shin, Jimin; Kim, Younyoung; Kong, Minyoung; Lee, Chaeyoung

2012-06-01

This study aimed to identify functional associations of cis-regulatory regions with gout susceptibility using data resulted from a genome-wide association study (GWAS), and to show a genetic architecture for gout with interaction effects among genes within each of the identified functions. The GWAS was conducted with 8314 control subjects and 520 patients with gout in the Korea Association REsource cohort. However, genetic associations with any individual nucleotide variants were not discovered by Bonferroni multiple testing in the GWAS (P>1.42 × 10(-7)). Genomic regions enrichment analysis was employed to identify functional associations of cis-regulatory regions. This analysis revealed several biological processes associated with gout susceptibility, and they were quite different from those with serum uric acid level. Epistasis for susceptibility to gout was estimated using entropy decomposition with selected genes within each biological process identified by the genomic regions enrichment analysis. Some epistases among nucleotide sequence variants for gout susceptibility were found to be larger than their individual effects. This study provided the first evidence that genetic factors for gout susceptibility greatly differed from those for serum uric acid level, which may suggest that research endeavors for identifying genetic factors for gout susceptibility should not be heavily dependent on pathogenesis of uric acid. Interaction effects between genes should be examined to explain a large portion of phenotypic variability for gout susceptibility.

Absence of Wdr13 Gene Predisposes Mice to Mild Social Isolation – Chronic Stress, Leading to Depression-Like Phenotype Associated With Differential Expression of Synaptic Proteins

Science.gov (United States)

Mitra, Shiladitya; Sameer Kumar, Ghantasala S.; Jyothi Lakshmi, B.; Thakur, Suman; Kumar, Satish

2018-01-01

We earlier reported that the male mice lacking the Wdr13 gene (Wdr13-/0) showed mild anxiety, better memory retention, and up-regulation of synaptic proteins in the hippocampus. With increasing evidences from parallel studies in our laboratory about the possible role of Wdr13 in stress response, we investigated its role in brain. We observed that Wdr13 transcript gets up-regulated in the hippocampus of the wild-type mice exposed to stress. To further dissect its function, we analyzed the behavioral and molecular phenotypes of Wdr13-/0 mice when subjected to mild chronic psychological stress, namely; mild (attenuated) social isolation. We employed iTRAQ based quantitative proteomics, real time PCR and western blotting to investigate molecular changes. Three weeks of social isolation predisposed Wdr13-/0 mice to anhedonia, heightened anxiety-measured by Open field test (OFT), increased behavior despair- measured by Forced swim test (FST) and reduced dendritic branching along with decreased spine density of hippocampal CA1 neurons as compared to wild-type counterparts. This depression-like-phenotype was however ameliorated when treated with anti-depressant imipramine. Molecular analysis revealed that out of 1002 quantified proteins [1% False discovery rate (FDR), at-least two unique peptides], strikingly, a significant proportion of synaptic proteins including, SYN1, CAMK2A, and RAB3A were down-regulated in the socially isolated Wdr13-/0 mice as compared to its wild-type counterparts. This was in contrast to the elevated levels of these proteins in non-stressed mutants as compared to the controls. We hypothesized that a de-regulated transcription factor upstream of the synaptic genes might be responsible for the observed phenotype. Indeed, in the socially isolated Wdr13-/0 mice, there was an up-regulation of GATA1 – a transcription factor that negatively regulates synaptic genes and has been associated with Major Depression (MD) in humans. The present study

Do plants and animals differ in phenotypic plasticity?

Indian Academy of Sciences (India)

Unknown

fits, of a plastic versus non-plastic phenotype in plants and animals. [Renee M Borges ... polyphenol oxidase and other oxidative enzymes in the defence repertoire of .... males in response to environmental stress (Cremer and. Heinze 2003).

Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes

DEFF Research Database (Denmark)

Song, Yong; Schwager, Michelle J; Backer, Vibeke

2017-01-01

The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically...... separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-α, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-α), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit......-phenotype associations relating to bronchitis and allergy susceptibility are dependent on the environment and that environmental factors/lifestyles modify genetic predisposition and change the genetic effects on diseases....

Novel insight into antimicrobial resistance and sensitivity phenotypes associated to qac and norA genotypes in Staphylococcus aureus.

Science.gov (United States)

Marchi, Emmanuela; Furi, Leonardo; Arioli, Stefania; Morrissey, Ian; Di Lorenzo, Valeria; Mora, Diego; Giovannetti, Luciana; Oggioni, Marco Rinaldo; Viti, Carlo

2015-01-01

Staphylococcus aureus strains harboring QacA, QacB, QacC, QacG transporters and norA promoter up-regulating mutations were characterized by phenotype microarray (PM), standard methods for susceptibility testing, and ethidium bromide efflux assays, in order to increase knowledge on phenotypes associated to efflux pumps and their substrates. PM data and standard susceptibility testing lead to the identification of new potential efflux targets, such as guanidine hydrochloride or 8-hydroxyquinoline for QacA and QacC pumps, respectively. The identification of compounds to which the presence of efflux pumps induced increased susceptibility opens new perspectives for potential adjunct anti-resistance treatment (i.e. strains bearing QacB transporters showed increased susceptibility to thioridazine, amitriptyline and orphenadrine). Although the tested isolates were characterized by high degree of heterogeneity, a hallmark of clinical isolates, direct ethidium bromide efflux assays were effective in highlighting differences in efflux efficiency among strains. These data add to characterization of substrate specificity in the different classes of staphylococcal multidrug efflux systems conferring specific substrate profiles and efflux features to each of them. Copyright © 2014 Elsevier GmbH. All rights reserved.

The effect of multiple blood-feeding on the longevity and insecticide resistant phenotype in the major malaria vector Anopheles arabiensis (Diptera: Culicidae).

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Oliver, Shüné V; Brooke, Basil D

2014-08-23

Anopheles arabiensis is a major malaria vector in Africa. Adult females are likely to imbibe multiple blood meals during their lifetime. This results in regular exposure to potential toxins and blood-meal induced oxidative stress. Defence responses to these stressors may affect other factors of epidemiological significance, such as insecticide resistance and longevity. The aims of this study were to examine the effect of multiple blood-feeding on insecticide tolerance/resistance with increasing age, to assess the underlying biochemical mechanisms for the responses recorded, and to assess the effect of multiple blood-feeding on the life histories of adult females drawn from insecticide resistant and susceptible laboratory reared An. arabiensis. Laboratory reared An. arabiensis females from an insecticide resistant and an insecticide susceptible colony were offered either a single blood meal or multiple blood meals at 3-day intervals. Their tolerance or resistance to insecticide was then monitored by WHO bioassay four hours post blood-feeding. The biochemical basis of the phenotypic response was assessed by examining the effect of blood on detoxification enzyme activity and the effect of blood-meals on detoxification enzyme activity in ageing mosquitoes. Control cohorts that were not offered any blood meals showed steadily decreasing levels of insecticide tolerance/resistance with age, whereas a single blood meal significantly increased tolerance/resistance primarily at the age of three days. The expression of resistance/tolerance in those cohorts fed multiple blood meals generally showed the least variation with age. These results were consistent following exposure to DDT and pyrethroids but not to malathion. Multiple blood-meals also maintained the DDT and permethrin resistant phenotype, even after treatment females had stopped taking blood-meals. Biochemical analysis suggests that this phenotypic effect in resistant females may be mediated by the maintenance of

Standardized comparison of the relative impacts of HIV-1 reverse transcriptase (RT) mutations on nucleoside RT inhibitor susceptibility.

Science.gov (United States)

Melikian, George L; Rhee, Soo-Yon; Taylor, Jonathan; Fessel, W Jeffrey; Kaufman, David; Towner, William; Troia-Cancio, Paolo V; Zolopa, Andrew; Robbins, Gregory K; Kagan, Ron; Israelski, Dennis; Shafer, Robert W

2012-05-01

Determining the phenotypic impacts of reverse transcriptase (RT) mutations on individual nucleoside RT inhibitors (NRTIs) has remained a statistical challenge because clinical NRTI-resistant HIV-1 isolates usually contain multiple mutations, often in complex patterns, complicating the task of determining the relative contribution of each mutation to HIV drug resistance. Furthermore, the NRTIs have highly variable dynamic susceptibility ranges, making it difficult to determine the relative effect of an RT mutation on susceptibility to different NRTIs. In this study, we analyzed 1,273 genotyped HIV-1 isolates for which phenotypic results were obtained using the PhenoSense assay (Monogram, South San Francisco, CA). We used a parsimonious feature selection algorithm, LASSO, to assess the possible contributions of 177 mutations that occurred in 10 or more isolates in our data set. We then used least-squares regression to quantify the impact of each LASSO-selected mutation on each NRTI. Our study provides a comprehensive view of the most common NRTI resistance mutations. Because our results were standardized, the study provides the first analysis that quantifies the relative phenotypic effects of NRTI resistance mutations on each of the NRTIs. In addition, the study contains new findings on the relative impacts of thymidine analog mutations (TAMs) on susceptibility to abacavir and tenofovir; the impacts of several known but incompletely characterized mutations, including E40F, V75T, Y115F, and K219R; and a tentative role in reduced NRTI susceptibility for K64H, a novel NRTI resistance mutation.

The 'PhenoBox', a flexible, automated, open-source plant phenotyping solution.

Science.gov (United States)

Czedik-Eysenberg, Angelika; Seitner, Sebastian; Güldener, Ulrich; Koemeda, Stefanie; Jez, Jakub; Colombini, Martin; Djamei, Armin

2018-04-05

There is a need for flexible and affordable plant phenotyping solutions for basic research and plant breeding. We demonstrate our open source plant imaging and processing solution ('PhenoBox'/'PhenoPipe') and provide construction plans, source code and documentation to rebuild the system. Use of the PhenoBox is exemplified by studying infection of the model grass Brachypodium distachyon by the head smut fungus Ustilago bromivora, comparing phenotypic responses of maize to infection with a solopathogenic Ustilago maydis (corn smut) strain and effector deletion strains, and studying salt stress response in Nicotiana benthamiana. In U. bromivora-infected grass, phenotypic differences between infected and uninfected plants were detectable weeks before qualitative head smut symptoms. Based on this, we could predict the infection outcome for individual plants with high accuracy. Using a PhenoPipe module for calculation of multi-dimensional distances from phenotyping data, we observe a time after infection-dependent impact of U. maydis effector deletion strains on phenotypic response in maize. The PhenoBox/PhenoPipe system is able to detect established salt stress responses in N. benthamiana. We have developed an affordable, automated, open source imaging and data processing solution that can be adapted to various phenotyping applications in plant biology and beyond. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

[Phenotypic diversity of toxigenic Vibrio cholerae O1 El Tor strains identified in China].

Science.gov (United States)

Zhao, Xuan; Zhang, Li; Li, Jie; Kan, Biao; Liang, Weili

2014-05-01

To understand the phenotypic diversity of toxigenic Vibrio cholerae O1 El Tor strains isolated from different provinces in China during the last 50 years. Traditional biotyping testings including susceptibility to polymyxin B, sensitivity to group IV phage, Voges-Proskauer test and haemolysis of sheep erythrocytes were conducted. Data from Biotype-specific phenotype analysis revealed that only 133 isolates carried the typical El Tor phenotypes while the other 251 isolates displayed atypical El Tor phenotypes. Combined with ctxB, rstR genotypes and phenotypic characteristics, 64 isolates were identified as typical El Tor biotype, 21 were El Tor variants that showing the typical El Tor biotype-specific phenotype but with ctxB(class). 280 isolates were defined as the hybrid groups with traits of both classical and El Tor biotypes that could be further classified into 45 groups, based on the combination of genotypes of ctxB, rstR and phenotypic characteristics. Toxigenic Vibrio cholerae O1 El Tor strains that isolated from different provinces in China displayed high phenotypic diversity. The traditional biotype traits could not be used to correctly distinguish the two different biotypes.

Computer vision and machine learning for robust phenotyping in genome-wide studies.

Science.gov (United States)

Zhang, Jiaoping; Naik, Hsiang Sing; Assefa, Teshale; Sarkar, Soumik; Reddy, R V Chowda; Singh, Arti; Ganapathysubramanian, Baskar; Singh, Asheesh K

2017-03-08

Traditional evaluation of crop biotic and abiotic stresses are time-consuming and labor-intensive limiting the ability to dissect the genetic basis of quantitative traits. A machine learning (ML)-enabled image-phenotyping pipeline for the genetic studies of abiotic stress iron deficiency chlorosis (IDC) of soybean is reported. IDC classification and severity for an association panel of 461 diverse plant-introduction accessions was evaluated using an end-to-end phenotyping workflow. The workflow consisted of a multi-stage procedure including: (1) optimized protocols for consistent image capture across plant canopies, (2) canopy identification and registration from cluttered backgrounds, (3) extraction of domain expert informed features from the processed images to accurately represent IDC expression, and (4) supervised ML-based classifiers that linked the automatically extracted features with expert-rating equivalent IDC scores. ML-generated phenotypic data were subsequently utilized for the genome-wide association study and genomic prediction. The results illustrate the reliability and advantage of ML-enabled image-phenotyping pipeline by identifying previously reported locus and a novel locus harboring a gene homolog involved in iron acquisition. This study demonstrates a promising path for integrating the phenotyping pipeline into genomic prediction, and provides a systematic framework enabling robust and quicker phenotyping through ground-based systems.

The Aging Kidney: Increased Susceptibility to Nephrotoxicity

Science.gov (United States)

Wang, Xinhui; Bonventre, Joseph V.; Parrish, Alan R.

2014-01-01

Three decades have passed since a series of studies indicated that the aging kidney was characterized by increased susceptibility to nephrotoxic injury. Data from these experimental models is strengthened by clinical data demonstrating that the aging population has an increased incidence and severity of acute kidney injury (AKI). Since then a number of studies have focused on age-dependent alterations in pathways that predispose the kidney to acute insult. This review will focus on the mechanisms that are altered by aging in the kidney that may increase susceptibility to injury, including hemodynamics, oxidative stress, apoptosis, autophagy, inflammation and decreased repair. PMID:25257519

Differential gene expression of two extreme honey bee (Apis mellifera) colonies showing varroa tolerance and susceptibility.

Science.gov (United States)

Jiang, S; Robertson, T; Mostajeran, M; Robertson, A J; Qiu, X

2016-06-01

Varroa destructor, an ectoparasitic mite of honey bees (Apis mellifera), is the most serious pest threatening the apiculture industry. In our honey bee breeding programme, two honey bee colonies showing extreme phenotypes for varroa tolerance/resistance (S88) and susceptibility (G4) were identified by natural selection from a large gene pool over a 6-year period. To investigate potential defence mechanisms for honey bee tolerance to varroa infestation, we employed DNA microarray and real time quantitative (PCR) analyses to identify differentially expressed genes in the tolerant and susceptible colonies at pupa and adult stages. Our results showed that more differentially expressed genes were identified in the tolerant bees than in bees from the susceptible colony, indicating that the tolerant colony showed an increased genetic capacity to respond to varroa mite infestation. In both colonies, there were more differentially expressed genes identified at the pupa stage than at the adult stage, indicating that pupa bees are more responsive to varroa infestation than adult bees. Genes showing differential expression in the colony phenotypes were categorized into several groups based on their molecular functions, such as olfactory signalling, detoxification processes, exoskeleton formation, protein degradation and long-chain fatty acid metabolism, suggesting that these biological processes play roles in conferring varroa tolerance to naturally selected colonies. Identification of differentially expressed genes between the two colony phenotypes provides potential molecular markers for selecting and breeding varroa-tolerant honey bees. © 2016 The Royal Entomological Society.

Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes

Science.gov (United States)

Kalyan-Masih, Priya; Vega-Torres, Julio David; Haddad, Elizabeth; Rainsbury, Sabrina; Baghchechi, Mohsen

2016-01-01

Abstract Psychological trauma and obesity co-occur frequently and have been identified as major risk factors for psychiatric disorders. Surprisingly, preclinical studies examining how obesity disrupts the ability of the brain to cope with psychological trauma are lacking. The objective of this study was to determine whether an obesogenic Western-like high-fat diet (WD) predisposes rats to post-traumatic stress responsivity. Adolescent Lewis rats (postnatal day 28) were fed ad libitum for 8 weeks with either the experimental WD diet (41.4% kcal from fat) or the control diet (16.5% kcal from fat). We modeled psychological trauma by exposing young adult rats to a cat odor threat. The elevated plus maze and the open field test revealed increased psychological trauma-induced anxiety-like behaviors in the rats that consumed the WD when compared with control animals 1 week after undergoing traumatic stress (p < 0.05). Magnetic resonance imaging showed significant hippocampal atrophy (20% reduction) and lateral ventricular enlargement (50% increase) in the animals fed the WD when compared with controls. These volumetric abnormalities were associated with behavioral indices of anxiety, increased leptin and FK506-binding protein 51 (FKBP51) levels, and reduced hippocampal blood vessel density. We found asymmetric structural vulnerabilities to the WD, particularly the ventral and left hippocampus and lateral ventricle. This study highlights how WD consumption during adolescence impacts key substrates implicated in post-traumatic stress disorder. Understanding how consumption of a WD affects the developmental trajectories of the stress neurocircuitry is critical, as stress susceptibility imposes a marked vulnerability to neuropsychiatric disorders. PMID:27844058

Effect of Drought Stress on Antioxidant Enzymes and Cell Death Related Traits in Resistant and Susceptible Wheat Cultivars at Grain Filling Stage

Directory of Open Access Journals (Sweden)

H. Hasheminasab

2013-10-01

Full Text Available Drought is one of the major factors limiting crop production in Iran. Twenty Iranian wheat cultivars with wide range of sensitivity to drought, including 18 varieties of bread wheat and two varieties of durum wheat were used in two separate field experiments in 2009-2010 at the Experimental Station of College of Agricultural in Shiraz University. Each experiment was conducted as a randomized complete block design with three replications. The moisture level in one of the experiments was optimum (100% field capacity while the second experiment was conducted under drought stress (45% field capacity. Several biochemical components including antioxidant enzymes and hydrogen peroxide and some physiological traits were analyzed in the two conditions. Drought stress significantly increased antioxidant activity at the grain filling stage. Superoxide dismutase activity showed the highest increase. Lipid peroxidation, hydrogen peroxide, electrolyte leakage and cell death increased significantly under drought condition, however membrane stability index decreased. Resistant cultivars showed the highest antioxidant activity and the lowest lipid peroxidation, hydrogen peroxide, and electrolyte leakage. This trend was reversed in the susceptible cultivars. Peroxidase and superoxide dismutase had a significant correlation with yield stability index. Hydrogen peroxide and cell membrane stability indices showed the highest correlation with yield stability index. Also Pishtaz and Alamut were selected respectively as the most resistance and susceptible cultivars.

Effects of different aging statuses and strain rate on the adiabatic shear susceptibility of 2195 aluminum–lithium alloy

International Nuclear Information System (INIS)

Yang, Y.; Tan, G.Y.; Chen, P.X.; Zhang, Q.M.

2012-01-01

The adiabatic shear susceptibility of 2195 aluminum–lithium alloy was investigated by means of split Hopkinson pressure bar. The stress collapse in true stress–true strain curves and true stress–time curves was observed. The adiabatic shear susceptibility of different aging statuses and strain rate were discussed by means of metallography observation. The critical strain, stress collapse time and formation energy of adiabatic shear bands were compared. The results show that different aging statuses and strain rate have significant influences on adiabatic shear behaviors of 2195 aluminum–lithium alloy. The peak-aged specimen has the highest adiabatic shearing susceptibility, while the under-aged specimen has the least adiabatic shear susceptibility. The susceptibility of adiabatic shearing increases with the increases of strain rate.

Loss of elongation factor P disrupts bacterial outer membrane integrity

DEFF Research Database (Denmark)

Zou, S Betty; Hersch, Steven J; Roy, Hervé

2012-01-01

background ameliorates the detergent, antibiotic, and osmosensitivity phenotypes and restores wild-type permeability to NPN. Our data support a role for EF-P in the translational regulation of a limited number of proteins that, when perturbed, renders the cell susceptible to stress by the adventitious......Elongation factor P (EF-P) is posttranslationally modified at a conserved lysyl residue by the coordinated action of two enzymes, PoxA and YjeK. We have previously established the importance of this modification in Salmonella stress resistance. Here we report that, like poxA and yjeK mutants......, Salmonella strains lacking EF-P display increased susceptibility to hypoosmotic conditions, antibiotics, and detergents and enhanced resistance to the compound S-nitrosoglutathione. The susceptibility phenotypes are largely explained by the enhanced membrane permeability of the efp mutant, which exhibits...

Identification and Antimicrobial Susceptibility Testing of Anaerobic Bacteria: Rubik’s Cube of Clinical Microbiology?

Science.gov (United States)

Gajdács, Márió; Spengler, Gabriella; Urbán, Edit

2017-01-01

Anaerobic bacteria have pivotal roles in the microbiota of humans and they are significant infectious agents involved in many pathological processes, both in immunocompetent and immunocompromised individuals. Their isolation, cultivation and correct identification differs significantly from the workup of aerobic species, although the use of new technologies (e.g., matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, whole genome sequencing) changed anaerobic diagnostics dramatically. In the past, antimicrobial susceptibility of these microorganisms showed predictable patterns and empirical therapy could be safely administered but recently a steady and clear increase in the resistance for several important drugs (β-lactams, clindamycin) has been observed worldwide. For this reason, antimicrobial susceptibility testing of anaerobic isolates for surveillance purposes or otherwise is of paramount importance but the availability of these testing methods is usually limited. In this present review, our aim was to give an overview of the methods currently available for the identification (using phenotypic characteristics, biochemical testing, gas-liquid chromatography, MALDI-TOF MS and WGS) and antimicrobial susceptibility testing (agar dilution, broth microdilution, disk diffusion, gradient tests, automated systems, phenotypic and molecular resistance detection techniques) of anaerobes, when should these methods be used and what are the recent developments in resistance patterns of anaerobic bacteria. PMID:29112122

Understanding abiotic stress tolerance mechanisms in soybean: a comparative evaluation of soybean response to drought and flooding stress.

Science.gov (United States)

Mutava, Raymond N; Prince, Silvas Jebakumar K; Syed, Naeem Hasan; Song, Li; Valliyodan, Babu; Chen, Wei; Nguyen, Henry T

2015-01-01

Many sources of drought and flooding tolerance have been identified in soybean, however underlying molecular and physiological mechanisms are poorly understood. Therefore, it is important to illuminate different plant responses to these abiotic stresses and understand the mechanisms that confer tolerance. Towards this goal we used four contrasting soybean (Glycine max) genotypes (PI 567690--drought tolerant, Pana--drought susceptible, PI 408105A--flooding tolerant, S99-2281--flooding susceptible) grown under greenhouse conditions and compared genotypic responses to drought and flooding at the physiological, biochemical, and cellular level. We also quantified these variations and tried to infer their role in drought and flooding tolerance in soybean. Our results revealed that different mechanisms contribute to reduction in net photosynthesis under drought and flooding stress. Under drought stress, ABA and stomatal conductance are responsible for reduced photosynthetic rate; while under flooding stress, accumulation of starch granules played a major role. Drought tolerant genotypes PI 567690 and PI 408105A had higher plastoglobule numbers than the susceptible Pana and S99-2281. Drought stress increased the number and size of plastoglobules in most of the genotypes pointing to a possible role in stress tolerance. Interestingly, there were seven fibrillin proteins localized within the plastoglobules that were up-regulated in the drought and flooding tolerant genotypes PI 567690 and PI 408105A, respectively, but down-regulated in the drought susceptible genotype Pana. These results suggest a potential role of Fibrillin proteins, FBN1a, 1b and 7a in soybean response to drought and flooding stress. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The use of machine learning methodologies to analyse antibiotic and biocide susceptibility in Staphylococcus aureus.

Directory of Open Access Journals (Sweden)

Joana Rosado Coelho

Full Text Available BACKGROUND: The rise of antibiotic resistance in pathogenic bacteria is a significant problem for the treatment of infectious diseases. Resistance is usually selected by the antibiotic itself; however, biocides might also co-select for resistance to antibiotics. Although resistance to biocides is poorly defined, different in vitro studies have shown that mutants presenting low susceptibility to biocides also have reduced susceptibility to antibiotics. However, studies with natural bacterial isolates are more limited and there are no clear conclusions as to whether the use of biocides results in the development of multidrug resistant bacteria. METHODS: The main goal is to perform an unbiased blind-based evaluation of the relationship between antibiotic and biocide reduced susceptibility in natural isolates of Staphylococcus aureus. One of the largest data sets ever studied comprising 1632 human clinical isolates of S. aureus originated worldwide was analysed. The phenotypic characterization of 13 antibiotics and 4 biocides was performed for all the strains. Complex links between reduced susceptibility to biocides and antibiotics are difficult to elucidate using the standard statistical approaches in phenotypic data. Therefore, machine learning techniques were applied to explore the data. RESULTS: In this pioneer study, we demonstrated that reduced susceptibility to two common biocides, chlorhexidine and benzalkonium chloride, which belong to different structural families, is associated to multidrug resistance. We have consistently found that a minimum inhibitory concentration greater than 2 mg/L for both biocides is related to antibiotic non-susceptibility in S. aureus. CONCLUSIONS: Two important results emerged from our work, one methodological and one other with relevance in the field of antibiotic resistance. We could not conclude on whether the use of antibiotics selects for biocide resistance or vice versa. However, the observation of

Susceptibility of glucokinase-MODY mutants to inactivation by oxidative stress in pancreatic β-cells.

Science.gov (United States)

Cullen, Kirsty S; Matschinsky, Franz M; Agius, Loranne; Arden, Catherine

2011-12-01

The posttranslational regulation of glucokinase (GK) differs in hepatocytes and pancreatic β-cells. We tested the hypothesis that GK mutants that cause maturity-onset diabetes of the young (GK-MODY) show compromised activity and posttranslational regulation in β-cells. Activity and protein expression of GK-MODY and persistent hyperinsulinemic hypoglycemia of infancy (PHHI) mutants were studied in β-cell (MIN6) and non-β-cell (H4IIE) models. Binding of GK to phosphofructo-2-kinase, fructose-2,6-bisphosphatase (PFK2/FBPase2) was studied by bimolecular fluorescence complementation in cell-based models. Nine of 11 GK-MODY mutants that have minimal effect on enzyme kinetics in vitro showed decreased specific activity relative to wild type when expressed in β-cells. A subset of these were stable in non-β-cells but showed increased inactivation in conditions of oxidative stress and partial reversal of inactivation by dithiothreitol. Unlike the GK-MODY mutants, four of five GK-PHHI mutants had similar specific activity to wild type and Y214C had higher activity than wild type. The GK-binding protein PFK2/FBPase2 protected wild-type GK from oxidative inactivation and the decreased stability of GK-MODY mutants correlated with decreased interaction with PFK2/FBPase2. Several GK-MODY mutants show posttranslational defects in β-cells characterized by increased susceptibility to oxidative stress and/or protein instability. Regulation of GK activity through modulation of thiol status may be a physiological regulatory mechanism for the control of GK activity in β-cells.

Stress Corrosion Cracking Susceptibility of 304L Substrate and 308L Weld Metal Exposed to a Salt Spray

Directory of Open Access Journals (Sweden)

Chia-Hao Hsu

2017-02-01

Full Text Available 304 stainless steels (SS were considered as the materials for a dry storage canister. In this study, ER (Electrode Rod 308L was utilized as the filler metal for the groove and overlay welds of a 304L stainless steel substrate, which was prepared via a gas tungsten arc-welding process in multiple passes. The electron backscatter diffraction (EBSD map was used to identify the inherent microstructures in distinct specimens. U-bend and weight-loss tests were conducted by testing the 304L substrates and welds in a salt spray containing 5 wt % NaCl at 80 °C to evaluate their susceptibility to stress corrosion cracking (SCC. Generally, the weight loss of the ER 308L deposit was higher than that of the 304L substrate in a salt spray in the same sample-prepared condition. The dissolution of the skeletal structure in the fusion zone (FZ was responsible for a greater weight loss of the 308L deposit, especially for the cold-rolled and sensitized specimen. Cold rolling was detrimental and sensitization after cold rolling was very harmful to the SCC resistance of the 304L substrate and 308L deposit. Overall, the SCC susceptibility of each specimen was correlated with its weight loss in each group.

Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin.

Science.gov (United States)

Retta, Saverio Francesco; Glading, Angela J

2016-12-01

Cerebral Cavernous Malformation (CCM) is a vascular disease of proven genetic origin, which may arise sporadically or is inherited as an autosomal dominant condition with incomplete penetrance and highly variable expressivity. CCM lesions exhibit a range of different phenotypes, including wide inter-individual differences in lesion number, size, and susceptibility to intracerebral hemorrhage (ICH). Lesions may remain asymptomatic or result in pathological conditions of various type and severity at any age, with symptoms ranging from recurrent headaches to severe neurological deficits, seizures, and stroke. To date there are no direct therapeutic approaches for CCM disease besides the surgical removal of accessible lesions. Novel pharmacological strategies are particularly needed to limit disease progression and severity and prevent de novo formation of CCM lesions in susceptible individuals. Useful insights into innovative approaches for CCM disease prevention and treatment are emerging from a growing understanding of the biological functions of the three known CCM proteins, CCM1/KRIT1, CCM2 and CCM3/PDCD10. In particular, accumulating evidence indicates that these proteins play major roles in distinct signaling pathways, including those involved in cellular responses to oxidative stress, inflammation and angiogenesis, pointing to pathophysiological mechanisms whereby the function of CCM proteins may be relevant in preventing vascular dysfunctions triggered by these events. Indeed, emerging findings demonstrate that the pleiotropic roles of CCM proteins reflect their critical capacity to modulate the fine-tuned crosstalk between redox signaling and autophagy that govern cell homeostasis and stress responses, providing a novel mechanistic scenario that reconciles both the multiple signaling pathways linked to CCM proteins and the distinct therapeutic approaches proposed so far. In addition, recent studies in CCM patient cohorts suggest that genetic susceptibility

Personality traits modulate emotional and physiological responses to stress.

Science.gov (United States)

Childs, Emma; White, Tara L; de Wit, Harriet

2014-09-01

An individual's susceptibility to psychological and physical disorders associated with chronic stress exposure, for example, cardiovascular and infectious disease, may also be predicted by their reactivity to acute stress. One factor associated with both stress resilience and health outcomes is personality. An understanding of how personality influences responses to acute stress may shed light upon individual differences in susceptibility to chronic stress-linked disease. This study examined the relationships between personality and acute responses to stress in 125 healthy adults, using hierarchical linear regression. We assessed personality traits using the Multidimensional Personality Questionnaire (MPQ-BF), and responses to acute stress (cortisol, heart rate, blood pressure, mood) using a standardized laboratory psychosocial stress task, the Trier Social Stress Test. Individuals with high Negative Emotionality exhibited greater emotional distress and lower blood pressure responses to the Trier Social Stress Test. Individuals with high agentic Positive Emotionality exhibited prolonged heart rate responses to stress, whereas those with high communal Positive Emotionality exhibited smaller cortisol and blood pressure responses. Separate personality traits differentially predicted emotional, cardiovascular, and cortisol responses to a psychosocial stressor in healthy volunteers. Future research investigating the association of personality with chronic stress-related disease may provide further clues to the relationship between acute stress reactivity and susceptibility to disease.

Micro-evolutionary responses and adaptive costs of Caenorhabditis elegans populations exposed to environmental stress

International Nuclear Information System (INIS)

Dutilleul, M.

2013-01-01

The contemporary evolution of organisms is largely dependent on anthropogenic disturbances. In particular, pollution amplifies the intensity or the quantity of selection pressures on populations. However, these changes may have negative effects on the life, growth and reproduction of individuals, the demographics of the population, and its phenotypic and genetic characteristics over generations. Thus, micro-evolutionary changes are likely to occur in response to selection pressures. These phenomenon lead to collateral damages: adaptive costs. For example, a reduction of genetic diversity in a population entails a decrease in its potential to adapt to other stressors. Populations can be more susceptible to many environmental changes, especially with the increase of human activities. Hence in an ecological risk assessment, studying the mechanisms of action and immediate adverse effects of pollutants on organisms is no longer sufficient. It is also necessary to expand our knowledge on the evolution of populations in polluted environment. In this context, our study aims to determine the micro-evolutionary response of Caenorhabditis elegans populations exposed to environmental stressors, and to measure their costs of adaptation. Populations were experimentally exposed for 22 generations to a high concentration of uranium, sodium chloride or an alternation of both these pollutants. The analysis of phenotypic and genetic changes, observed through measures of life history traits, was accomplished using several quantitative genetics techniques. In particular, we confirmed the genetic differentiation between populations with an increase of resistance in populations exposed to different pollutions. The speed of evolutionary responses depended on the conditions of exposure and their effects on the expression of the genetic structure of traits (e.g. G matrix). Micro-evolutionary changes were linked to costs of adaptation, such as reduced fertility in stressful novel

Immunogenetics and genetic susceptibility in the pathogenesis of autoimmune hepatitis

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Das Anup K

2014-11-01

Full Text Available vAutoimmune hepatitis is a progressive liver disease. Its pathogenesis is unclear, but needs a ‘trigger’ to initiate the disease in a genetically susceptible person. The susceptibility is partly related to MHCII class genes, and more so with human leukocyte antigen (HLA. Several mechanisms have been proposed which, however, cannot fully explain the immunologic findings in autoimmune hepatitis. The susceptibility to any autoimmune disease is determined by several factors where genetic and immunological alterations, along with, environmental factor are active. MHCII antigens as a marker for AIH, or a predictor of treatment response and prognosis has been investigated. Since MHCII antigens show significant ethnic heterogeneity, mutations in MHCII may merely act as only precursors of the surface markers of immune cells, which can be of significance, because the changes in HLA and MHC are missing in certain populations. One such marker is the CTLA-4 (CD152 gene mutation, reported in the phenotypes representing susceptibility to AIH. Other candidate genes of cytokines, TNF, TGF-beta1 etc, have also been investigated but with unvalidated results. Paediatric AIH show differences in genetic susceptibility. Genetic susceptibility or resistance to AIH may be associated with polypeptides in DRB1 with certain amino-acid sequences. Understanding which genes are implicated in genesis and/or disease progression will obviously help to identify key pathways in AIH and provide better insights into its pathogenesis. But studies to identify responsible genes are complex because of the complex trait of AIH.

MTL genotypes, phenotypic switching, and susceptibility profiles of Candida parapsilosis species group compared to Lodderomyces elongisporus.

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Aylin Döğen

Full Text Available Reference isolates of Candida parapsilosis (n = 8, Candida metapsilosis (n = 6, Candida orthopsilosis (n = 7, and Lodderomyces elongisporus (n = 11 were analyzed to gain insight into their pathobiology and virulence mechanisms. Initial evaluation using BBL Chromagar Candida medium misidentified L. elongisporus isolates as C. albicans. Polymerase chain reaction analysis of isolate MTL idiomorphs revealed that all C. parapsilosis isolates were MTLa homozygous and no MTL α1, α2, a1, or a2 gene was detected in L. elongisporus isolates. For C. orthopsilosis, two isolates were MTLa homozygous and five were MTL-heterozygous. Similarly, one C. metapsilosis isolate was MTLα homozygous whereas five were MTL-heterozygous. Isolate phenotypic switching analysis revealed potential phenotypic switching in the MTLα homozygous C. metapsilosis isolate, resulting in concomitant elongated cell formation. Minimum inhibitory concentrations of fluconazole (FLC and FK506, alone or in combination, were determined by checkerboard assay, with data analyzed using the fractional inhibitory concentration index model. Synergistic or additive effects of these compounds were commonly observed in C. parapsilosis and L. elongisporus isolates. No killer activity was observed in the studied isolates, as determined phenotypically. No significant difference in virulence was seen for the four species in a Galleria mellonella model (P > 0.05. In conclusion, our results demonstrated phenotypic switching of C. metapsilosis CBS 2315 and that FLC and FK506 represent a promising drug combination against C. parapsilosis and L. elongisporus. The findings of the present study contribute to our understanding of the biology, diagnosis, and new possible treatments of the C. parapsilosis species group and L. elongisporus.

Does the oxytocin receptor polymorphism (rs2254298 confer 'vulnerability' for psychopathology or 'differential susceptibility'? insights from evolution

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Brüne Martin

2012-04-01

Full Text Available Abstract The diathesis-stress model of psychiatric conditions has recently been challenged by the view that it might be more accurate to speak of 'differential susceptibility' or 'plasticity' genes, rather than one-sidedly focusing on individual vulnerability. That is, the same allelic variation that predisposes to a psychiatric disorder if associated with (developmentally early environmental adversity may lead to a better-than-average functional outcome in the same domain under thriving (or favourable environmental conditions. Studies of polymorphic variations of the serotonin transporter gene, the monoamino-oxidase-inhibitor A coding gene or the dopamine D4 receptor gene indicate that the early environment plays a crucial role in the development of favourable versus unfavourable outcomes. Current evidence is limited, however, to establishing a link between genetic variation and behavioural phenotypes. In contrast, little is known about how plasticity may be expressed at the neuroanatomical level as a 'hard-wired' correlate of observable behaviour. The present review article seeks to further strengthen the argument in favour of the differential susceptibility theory by incorporating findings from behavioural and neuroanatomical studies in relation to genetic variation of the oxytocin receptor gene. It is suggested that polymorphic variation at the oxytocin receptor gene (rs2254298 is associated with sociability, amygdala volume and differential risk for psychiatric conditions including autism, depression and anxiety disorder, depending on the quality of early environmental experiences. Seeing genetic variation at the core of developmental plasticity can explain, in contrast to the diathesis-stress perspective, why evolution by natural selection has maintained such 'risk' alleles in the gene pool of a population. Please see related manuscript: http://www.biomedcentral.com/1741-7015/10/37

An Evolutionary Perspective on Family Studies: Differential Susceptibility to Environmental Influences.

Science.gov (United States)

Hartman, Sarah; Belsky, Jay

2016-12-01

An evolutionary perspective of human development provides the basis for the differential-susceptibility hypothesis which stipulates that individuals should differ in their susceptibility to environmental influences, with some being more affected than others by both positive and negative developmental experiences and environmental exposures. This paper reviews evidence consistent with this claim while revealing that temperamental and genetic characteristics play a role in distinguishing more and less susceptible individuals. The differential-susceptibility framework under consideration is contrasted to the traditional diathesis-stress view that "vulnerability" traits predispose some to being disproportionately affected by (only) adverse experiences. We raise several issues stimulated by the literature that need to be clarified in further research. Lastly, we suggest that therapy may differ in its effects depending on an individual's susceptibility. © 2015 Family Process Institute.

Variable antibiotic susceptibility patterns among Streptomyces species causing actinomycetoma in man and animals

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Hamid Mohamed E

2011-06-01

Full Text Available Abstract Background Drug therapy is recommended in conjunction with surgery in treatment of actinomycetoma. The specific prescription depends on the type of bacteria (actinomycetoma or fungi (eumycetoma causing the disease and their in vitro antimicrobial susceptibility. Objectives To investigate the antimicrobial susceptibility among isolates of Streptomyces spp. isolated from cases of actinomycetoma in man and animals in Sudan. Methods Streptomyces strains (n = 18 isolated from cases of actinomycetoma were tested in vitro against 15 commonly prescribed antibacterial agents using MIC agar dilution method as per standard guidelines. Results Streptomyces strains isolated from actinomycetoma fall into various phenotypic groups. All of the strains were inhibited by novobiocin (8 μg/mL, gentamycin (8, 32 μg/mL and doxycycline (32 μg/mL. Fusidic acid (64 μg/mL inhibited 94.4% of the strains; bacitracin, streptomycin, cephaloridine, clindamycin, ampicillin, rifampicin and tetracycline (64 μg/mL inhibited between 61.1 and 77.8% of the strains. All strains were found resistant to amphotericin B (64 μg/mL, penicillin (20 μg/mL and sulphamethoxazole (64 μg/mL. Conclusions Saprophytic Streptomyces spp. cause actinomycetoma in man and animal belong to separate phenotypes and have a wide range of susceptibility patterns to antimicrobial agents, which pose a lot of difficulties in selecting effective in vivo treatment for actinomycetoma.

Fluorometric assay for phenotypic differentiation of drug-resistant HIV mutants

Science.gov (United States)

Zhu, Qinchang; Yu, Zhiqiang; Kabashima, Tsutomu; Yin, Sheng; Dragusha, Shpend; El-Mahdy, Ahmed F. M.; Ejupi, Valon; Shibata, Takayuki; Kai, Masaaki

2015-01-01

Convenient drug-resistance testing of viral mutants is indispensable to effective treatment of viral infection. We developed a novel fluorometric assay for phenotypic differentiation of drug-resistant mutants of human immunodeficiency virus-I protease (HIV-PR) which uses enzymatic and peptide-specific fluorescence (FL) reactions and high-performance liquid chromatography (HPLC) of three HIV-PR substrates. This assay protocol enables use of non-purified enzyme sources and multiple substrates for the enzymatic reaction. In this study, susceptibility of HIV mutations to drugs was evaluated by selective formation of three FL products after the enzymatic HIV-PR reaction. This proof-of-concept study indicates that the present HPLC-FL method could be an alternative to current phenotypic assays for the evaluation of HIV drug resistance. PMID:25988960

Phenotypic, Genotypic, and Antibiotic Sensitivity Patterns of Strains Isolated from the Cholera Epidemic in Zimbabwe

NARCIS (Netherlands)

Islam, Mohammad S.; Mahmud, Zahid H.; Ansaruzzaman, Mohammad; Faruque, Shah M.; Talukder, Kaisar A.; Qadri, Firdausi; Alam, Munirul; Islam, Shafiqul; Bardhan, Pradip K.; Mazumder, Ramendra N.; Khan, Azharul I.; Ahmed, Sirajuddin; Iqbal, Anwarul; Chitsatso, Owen; Mudzori, James; Patel, Sheetal; Midzi, Stanley M.; Charimari, Lincoln; Endtz, Hubert P.; Cravioto, Alejandro

This paper details the phenotypic, genotypic, and antibiotic sensitivity patterns of 88 Vibrio cholerae strains from Zimbabwe. Of the 88 strains, 83 were classified as "altered El Tor" and 5 as "hybrid El Tor" strains. All of the strains were susceptible to tetracycline, doxycycline, ciprofloxacin,

Variation in phenotypic appearance of Graves' disease: effect of genetic anticipation and duration of complaints

NARCIS (Netherlands)

Vos, Xander; Smit, Natalie; Endert, Erik; Tijssen, Jan; Wiersinga, Wilmar

2009-01-01

Objective: Both genetic and environmental factors contribute to susceptibility of Graves' disease. In this study. we evaluated whether the duration of symptoms or a positive family history of autoimmune thyroid disease (AITD) are related to specific phenotypes in patients with a first episode of

Mechanical Stress Downregulates MHC Class I Expression on Human Cancer Cell Membrane

KAUST Repository

La Rocca, Rosanna

2014-12-26

In our body, cells are continuously exposed to physical forces that can regulate different cell functions such as cell proliferation, differentiation and death. In this work, we employed two different strategies to mechanically stress cancer cells. The cancer and healthy cell populations were treated either with mechanical stress delivered by a micropump (fabricated by deep X-ray nanolithography) or by ultrasound wave stimuli. A specific down-regulation of Major Histocompatibility Complex (MHC) class I molecules expression on cancer cell membrane compared to different kinds of healthy cells (fibroblasts, macrophages, dendritic and lymphocyte cells) was observed, stimulating the cells with forces in the range of nano-newton, and pressures between 1 and 10 bar (1 bar = 100.000 Pascal), depending on the devices used. Moreover, Raman spectroscopy analysis, after mechanical treatment, in the range between 700–1800 cm−1, indicated a relative concentration variation of MHC class I. PCA analysis was also performed to distinguish control and stressed cells within different cell lines. These mechanical induced phenotypic changes increase the tumor immunogenicity, as revealed by the related increased susceptibility to Natural Killer (NK) cells cytotoxic recognition.

Mechanical stress downregulates MHC class I expression on human cancer cell membrane.

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Rosanna La Rocca

Full Text Available In our body, cells are continuously exposed to physical forces that can regulate different cell functions such as cell proliferation, differentiation and death. In this work, we employed two different strategies to mechanically stress cancer cells. The cancer and healthy cell populations were treated either with mechanical stress delivered by a micropump (fabricated by deep X-ray nanolithography or by ultrasound wave stimuli. A specific down-regulation of Major Histocompatibility Complex (MHC class I molecules expression on cancer cell membrane compared to different kinds of healthy cells (fibroblasts, macrophages, dendritic and lymphocyte cells was observed, stimulating the cells with forces in the range of nano-newton, and pressures between 1 and 10 bar (1 bar = 100.000 Pascal, depending on the devices used. Moreover, Raman spectroscopy analysis, after mechanical treatment, in the range between 700-1800 cm(-1, indicated a relative concentration variation of MHC class I. PCA analysis was also performed to distinguish control and stressed cells within different cell lines. These mechanical induced phenotypic changes increase the tumor immunogenicity, as revealed by the related increased susceptibility to Natural Killer (NK cells cytotoxic recognition.

Cell-Based Phenotyping Reveals QTL for Membrane Potential Maintenance Associated with Hypoxia and Salinity Stress Tolerance in Barley

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Muhammad B. Gill

2017-11-01

Full Text Available Waterlogging and salinity are two major abiotic stresses that hamper crop production world-wide resulting in multibillion losses. Plant abiotic stress tolerance is conferred by many interrelated mechanisms. Amongst these, the cell’s ability to maintain membrane potential (MP is considered to be amongst the most crucial traits, a positive relationship between the ability of plants to maintain highly negative MP and its tolerance to both salinity and waterlogging stress. However, no attempts have been made to identify quantitative trait loci (QTL conferring this trait. In this study, the microelectrode MIFE technique was used to measure the plasma membrane potential of epidermal root cells of 150 double haploid (DH lines of barley (Hordeum vulgare L. from a cross between a Chinese landrace TX9425 and Japanese malting cultivar Naso Nijo under hypoxic conditions. A major QTL for the MP in the epidermal root cells in hypoxia-exposed plants was identified. This QTL was located on 2H, at a similar position to the QTL for waterlogging and salinity tolerance reported in previous studies. Further analysis confirmed that MP showed a significant contribution to both waterlogging and salinity tolerance. The fact that the QTL for MP was controlled by a single major QTL illustrates the power of the single-cell phenotyping approach and opens prospects for fine mapping this QTL and thus being more effective in marker assisted selection.

Reversion of High-level Mecillinam Resistance to Susceptibility in Escherichia coli During Growth in Urine

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Elisabeth Thulin

2017-09-01

This is the first example describing conditional resistance where a genetically stable antibiotic resistance can be phenotypically reverted to susceptibility by metabolites present in urine. These findings have several important clinical implications regarding the use of mecillinam to treat UTIs. First, they suggest that mecillinam can be used to treat also those clinical strains that are identified as MecR in standard laboratory tests. Second, the results suggest that testing of mecillinam susceptibility in the laboratory ought to be performed in media that mimics urine to obtain clinically relevant susceptibility testing results. Third, these findings imply that changes in patient behavior, such as increased water intake or use of diuretics to reduce urine osmolality and increased intake of cysteine, might induce antibiotic susceptibility in an infecting MecR E. coli strain and thereby increase treatment efficiency.

Phenotypes and enviromental factors: their influence in PCOS.

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Diamanti-Kandarakis, Evanthia; Christakou, Charikleia; Marinakis, Evangelos

2012-01-01

Polycystic ovary syndrome (PCOS) is a complex syndrome of unclear etiopathogenesis characterized by heterogeneity in phenotypic manifestations. The clinical phenotype of PCOS includes reproductive and hormonal aberrations, namely anovulation and hyperandrogenism, which coexist with metabolic disturbances. Reflecting the crosstalk between the reproductive system and metabolic tissues, obesity not only deteriorates the metabolic profile but also aggravates ovulatory dysfunction and hyperandrogenism. Although the pathogenesis of PCOS remains unclear, the syndrome appears to involve environmental and genetic components. Starting from early life and extending throughout lifecycle, environmental insults may affect susceptible women who finally demonstrate the clinical phenotype of PCOS. Diet emerges as the major environmental determinant of PCOS. Overnutrition leading to obesity is widely recognized to have an aggravating impact, while another detrimental dietary factor may be the high content of food in advanced glycated end products (AGEs). Environmental exposure to industrial products, particularly Bisphenol A (BPA), may also exacerbate the clinical course of PCOS. AGEs and BPA may act as endocrine disruptors in the pathogenesis of the syndrome. PCOS appears to mirror the harmful influence of the modern environment on the reproductive and metabolic balance of inherently predisposed individuals.

Genetic variability among the brown rust resistant and susceptible genotypes of sugarcane by RAPD technique

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Brown leaf rust in sugarcane is caused by Puccinia melanocephala (Syd. & P. Syd.), which is major cause of cultivar withdrawal. We attempted to analyze the RAPD diversity of two discrete phenotypic classes i.e. rust resistant (R) and rust susceptible (S) of six commercially available sugarcane elite...

A major QTL controls susceptibility to spinal curvature in the curveback guppy

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Dreyer Christine

2011-01-01

Full Text Available Abstract Background Understanding the genetic basis of heritable spinal curvature would benefit medicine and aquaculture. Heritable spinal curvature among otherwise healthy children (i.e. Idiopathic Scoliosis and Scheuermann kyphosis accounts for more than 80% of all spinal curvatures and imposes a substantial healthcare cost through bracing, hospitalizations, surgery, and chronic back pain. In aquaculture, the prevalence of heritable spinal curvature can reach as high as 80% of a stock, and thus imposes a substantial cost through production losses. The genetic basis of heritable spinal curvature is unknown and so the objective of this work is to identify quantitative trait loci (QTL affecting heritable spinal curvature in the curveback guppy. Prior work with curveback has demonstrated phenotypic parallels to human idiopathic-type scoliosis, suggesting shared biological pathways for the deformity. Results A major effect QTL that acts in a recessive manner and accounts for curve susceptibility was detected in an initial mapping cross on LG 14. In a second cross, we confirmed this susceptibility locus and fine mapped it to a 5 cM region that explains 82.6% of the total phenotypic variance. Conclusions We identify a major QTL that controls susceptibility to curvature. This locus contains over 100 genes, including MTNR1B, a candidate gene for human idiopathic scoliosis. The identification of genes associated with heritable spinal curvature in the curveback guppy has the potential to elucidate the biological basis of spinal curvature among humans and economically important teleosts.

Schizophrenia-Like Phenotype Inherited by the F2 Generation of a Gestational Disruption Model of Schizophrenia.

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Perez, Stephanie M; Aguilar, David D; Neary, Jennifer L; Carless, Melanie A; Giuffrida, Andrea; Lodge, Daniel J

2016-01-01

Both environmental and genetic factors contribute to schizophrenia; however, the exact etiology of this disorder is not known. Animal models are utilized to better understand the mechanisms associated with neuropsychiatric diseases, including schizophrenia. One of these involves gestational administration of methylazoxymethanol acetate (MAM) to induce a developmental disruption, which in turn produces a schizophrenia-like phenotype in post-pubertal rats. The mechanisms by which MAM produces this phenotype are not clear; however, we now demonstrate that MAM induces differential DNA methylation, which may be heritable. Here we demonstrate that a subset of both second (F2) and third (F3) filial generations of MAM-treated rats displays a schizophrenia-like phenotype and hypermethylation of the transcription factor, Sp5. Specifically, ventral tegmental area of dopamine neuron activity was examined using electrophysiology as a correlate for the dopamine hyperfunction thought to underlie psychosis in patients. Interestingly, only a subset of F2 and F3 MAM rats exhibited increases in dopamine neuron population activity, indicating that this may be a unique model with a susceptibility to develop a schizophrenia-like phenotype. An increase in dopamine system function in rodent models has been previously associated with decreases in hippocampal GABAergic transmission. In line with these observations, we found a significant correlation between hippocampal parvalbumin expression and dopamine neuron activity in F2 rats. These data therefore provide evidence that offspring born from MAM-treated rats possess a susceptibility to develop aspects of a schizophrenia-like phenotype and may provide a useful tool to investigate gene-environment interactions.

Stress Disrupts Context-Dependent Memory

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Schwabe, Lars; Bohringer, Andreas; Wolf, Oliver T.

2009-01-01

Memory is facilitated when the retrieval context resembles the learning context. The brain structures underlying contextual influences on memory are susceptible to stress. Whether stress interferes with context-dependent memory is still unknown. We exposed healthy adults to stress or a control procedure before they learned an object-location task…

Methodologies to assess PWSCC susceptibility of primary component Alloy 600 locations in pressurized water reactors

International Nuclear Information System (INIS)

Rao, G.V.

1993-01-01

Methodologies to assess susceptibility to Primary Water Stress Corrosion Cracking (PWSCC) of Alloy 600 component locations in the Primary System of Pressurized Water Reactors are presented. The assessment methodologies are presented. The assessment methodologies are based on Relative Susceptibility Index (RSI) and Cumulative Susceptibility Index (CSI) models utilizing key contributing parameters such as service and residual stresses, yield strength, service temperature, material condition and microstructure, and the accumulated service time. To aid in the development of future inspection plans, a method of ranking of the assessed susceptibilities by 'bench marking' with respect to the susceptibility of a reference location of known PWSCC history of a reference location of known PWSCC history is presented. Means of utilizing the susceptibility ranking results in developing a prioritized inspection plan are discussed. A follow-up investigative plan to the initial inspection is proposed, which includes identification of critical sampling locations, sample extraction, sample investigations and testing to ensure that the potentially highest susceptibility locations are free from near term PWSCC and, further, to provide a basis for established schedules for future inspections. Finally, parametric considerations of the contributing factor are presented to help the utility choose suitable option to mitigate the PWSCC issue while minimizing the impact on continued service

Overexpression of the yeast frataxin homolog (Yfh1): contrasting effects on iron-sulfur cluster assembly, heme synthesis and resistance to oxidative stress

DEFF Research Database (Denmark)

Seguin, Alexandra; Bayot, Aurélien; Dancis, Andrew

2009-01-01

of 2muYFH1 cells compared to wild-type cells. To our knowledge, this work is the first description where major frataxin-related phenotypes ([Fe-S] cluster assembly and heme synthesis) can be split in vivo, suggesting that frataxin has independent roles in both processes, and that the optimal conditions......Friedreich's ataxia is generally associated with defects in [Fe-S] cluster assembly/stability and heme synthesis and strong susceptibility to oxidative stress. We used the yeast (Saccharomyces cerevisiae) model of Friedreich's ataxia to study the physiological consequences of modulating...... for these independent roles are different....

Strain, Sex, and Open-Field Behavior: Factors Underlying the Genetic Susceptibility to Helplessness

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Padilla, Eimeira; Barrett, Douglas W.; Shumake, Jason D.; Gonzalez-Lima, F.

2009-01-01

Learned helplessness represents a failure to escape after exposure to inescapable stress and may model human psychiatric disorders related to stress. Previous work has demonstrated individual differences in susceptibility to learned helplessness. In this study, we assessed different factors associated with this susceptibility, including strain, sex, and open-field behavior. Testing of three rat strains (Holtzman, Long-Evans, and Sprague-Dawley) revealed that Holtzman rats were the most susceptible to helplessness. Holtzman rats not only had the longest escape latencies following inescapable shock, but also showed spontaneous escape deficits in the absence of prior shock when tested with a fixed-ratio 2 (FR2) running response. Moreover, when tested with fixed-ratio 1 (FR1) running—an easy response normally unaffected by helplessness training in rats—inescapable shock significantly increased the escape latencies of Holtzman rats. Within the Holtzman strain, we confirmed recent findings that females showed superior escape performance and therefore appeared more resistant to helplessness than males. However, regression and covariance analyses suggest that this sex difference may be explained by more baseline ambulatory activity among females. In addition, some indices of novelty reactivity (greater exploration of novel vs. familiar open-field) predicted subsequent helpless behavior. In conclusion, Holtzman rats, and especially male Holtzman rats, have a strong predisposition to become immobile when stressed which interferes with their ability to learn active escape responses. The Holtzman strain therefore appears to be a commercially available model for studying susceptibility to helplessness in males, and novelty-seeking may be a marker of this susceptibility. PMID:19428642

SUSCEPTIBILITY TO OZONE-INDUCED INJURY AND ANTIOXIDANT COMPENSATION IN RAT MODELS OF CARDIOVASCULAR DISEASE

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Increased oxidative stress and compromised antioxidant status are common pathologic factors of cardiovascular diseases (CVD). It is hypothesized that individuals with chronic CVD are more susceptible to environmental exposures due to underlying oxidative stress. To determine the ...

Phenotypic evaluation of the resistance in F1 carnation populations to vascular wilt caused by Fusarium oxysporum f.sp. dianthi

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Johana Carolina Soto-Sedano

2012-08-01

Full Text Available One of the most important phytosanitary problems of the carnation crops in Colombia and in the entire world is vascular wilting produced by Fusarium oxysporum f.sp. dianthi. Currently, an effective treatment against the pathogen does not exist; the search for resistant varieties has been the most successful method for control of this disease. Breeding programs are vital to solving the problem of the carnation fusariosis. The objective of this research was the phenotypic evaluation of carnation F1 populations, products of contrasting crossing, resistant per susceptible to F. oxysporum f.sp. dianthi, in order to determine if the resistance is inherited in the lines. This information will contribute to the selection of material and to the successful introduction of the resistant characteristic, whose expression is commercially acceptable, to the gene pool. The methodology adopted was a phenotypic evaluation of the response to the parasite in the population (450 individuals and in the parental. This evaluation estimated the area under the curve (AU DPC, using a scale of symptoms reported for carnation vascular wilt. Three different phenotypes were established with this evaluation. The moderately susceptible one is the predominant phenotype and an analysis of phenotypic frequencies was carried out on it. The results show that the individuals of the evaluated F1 population were distributed between two extreme ranges, resistant and susceptible; this shows that there is segregation for the trait resistant to F. oxysporum f.sp dianthi. We did not observe clearly differentiated classes, i.e. with complete absence or presence of the disease, indicating a possible control of the resistance in the evaluated carnation material, governed by more than one gene and with a possible additive genetic action

Cluster-distinguishing genotypic and phenotypic diversity of carbapenem-resistant Gram-negative bacteria in solid-organ transplantation patients: a comparative study.

Science.gov (United States)

Karampatakis, Theodoros; Geladari, Anastasia; Politi, Lida; Antachopoulos, Charalampos; Iosifidis, Elias; Tsiatsiou, Olga; Karyoti, Aggeliki; Papanikolaou, Vasileios; Tsakris, Athanassios; Roilides, Emmanuel

2017-07-31

Solid-organ transplant recipients may display high rates of colonization and/or infection by multidrug-resistant bacteria. We analysed and compared the phenotypic and genotypic diversity of carbapenem-resistant (CR) strains of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii isolated from patients in the Solid Organ Transplantation department of our hospital. Between March 2012 and August 2013, 56 CR strains from various biological fluids underwent antimicrobial susceptibility testing with VITEK 2, molecular analysis by PCR amplification and genotypic analysis with pulsed-field gel electrophoresis (PFGE). They were clustered according to antimicrobial drug susceptibility and genotypic profiles. Diversity analyses were performed by calculating Simpson's diversity index and applying computed rarefaction curves.Results/Key findings. Among K. pneumoniae, KP-producers predominated (57.1 %). VIM and OXA-23 carbapenemases prevailed among P. aeruginosa and A. baumannii (89.4 and 88.9 %, respectively). KPC-producing K. pneumoniae and OXA-23 A. baumannii were assigned in single PFGE pulsotypes. VIM-producing P. aeruginosa generated multiple pulsotypes. CR K. pneumoniae strains displayed phenotypic diversity in tigecycline, colistin (CS), amikacin (AMK), gentamicin (GEN) and co-trimoxazole (SXT) (16 clusters); P. aeruginosa displayed phenotypic diversity in cefepime (FEP), ceftazidime, aztreonam, piperacillin, piperacillin-tazobactam, AMK, GEN and CS (9 clusters); and A. baumannii displayed phenotypic diversity in AMK, GEN, SXT, FEP, tobramycin and rifampicin (8 clusters). The Simpson diversity indices for the interpretative phenotype and PFGE analysis were 0.89 and 0.6, respectively, for K. pneumoniae strains (P<0.001); 0.77 and 0.6 for P. aeruginosa (P=0.22); and 0.86 and 0.19 for A. baumannii (P=0.004). The presence of different antimicrobial susceptibility profiles does not preclude the possibility that two CR K. pneumoniae or A. baumannii

Standard practice for determining the susceptibility of stainless steels and related Nickel-Chromium-Iron Alloys to stress-corrosion cracking in polythionic acids

CERN Document Server

American Society for Testing and Materials. Philadelphia

2010-01-01

1.1 This practice covers procedures for preparing and conducting the polythionic acid test at room temperature, 22 to 25°C (72 to 77°F), to determine the relative susceptibility of stainless steels or other related materials (nickel-chromiumiron alloys) to intergranular stress corrosion cracking. 1.2 This practice can be used to evaluate stainless steels or other materials in the “as received” condition or after being subjected to high-temperature service, 482 to 815°C (900 to 1500°F), for prolonged periods of time. 1.3 This practice can be applied to wrought products, castings, and weld metal of stainless steels or other related materials to be used in environments containing sulfur or sulfides. Other materials capable of being sensitized can also be tested in accordance with this test. 1.4 This practice may be used with a variety of stress corrosion test specimens, surface finishes, and methods of applying stress. 1.5 This standard does not purport to address all of the safety concerns, if any, ...

Effects of Social Defeat Stress on Sleep in Mice.

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Henderson, Fiona; Vialou, Vincent; El Mestikawy, Salah; Fabre, Véronique

2017-01-01

Stress plays a key role in the development of psychiatric disorders and has a negative impact on sleep integrity. In mice, chronic social defeat stress (CSDS) is an ethologically valid model of stress-related disorders but little is known about its effects on sleep regulation. Here, we investigated the immediate and long-term effects of 10 consecutive days of social defeat (SD) on vigilance states in C57Bl/6J male mice. Social behavior was assessed to identify susceptible mice, i.e., mice that develop long-lasting social avoidance, and unsusceptible mice. Sleep-wake stages in mice of both groups were analyzed by means of polysomnographic recordings at baseline, after the first, third, and tenth stress sessions and on the 5th recovery day (R5) following the 10-day CSDS. In susceptible mice, each SD session produced biphasic changes in sleep-wake states that were preserved all along 10-day CSDS. These sessions elicited a short-term enhancement of wake time while rapid eye-movement (REM) sleep was strongly inhibited. Concomitantly, delta power was increased during non REM (NREM) sleep. During the following dark period, an increase in total sleep time, as well as wake fragmentation, were observed after each analyzed SD session. Similar changes were observed in unsusceptible mice. At R5, elevated high-frequency EEG activity, as observed in insomniacs, emerged during NREM sleep in both susceptible and unsusceptible groups suggesting that CSDS impaired sleep quality. Furthermore, susceptible but not unsusceptible mice displayed stress-anticipatory arousal during recovery, a common feature of anxiety disorders. Altogether, our findings show that CSDS has profound impacts on vigilance states and further support that sleep is tightly regulated by exposure to stressful events. They also revealed that susceptibility to chronic psychological stress is associated with heightened arousal, a physiological feature of stress vulnerability.

Effects of Social Defeat Stress on Sleep in Mice

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Fiona Henderson

2017-11-01

Full Text Available Stress plays a key role in the development of psychiatric disorders and has a negative impact on sleep integrity. In mice, chronic social defeat stress (CSDS is an ethologically valid model of stress-related disorders but little is known about its effects on sleep regulation. Here, we investigated the immediate and long-term effects of 10 consecutive days of social defeat (SD on vigilance states in C57Bl/6J male mice. Social behavior was assessed to identify susceptible mice, i.e., mice that develop long-lasting social avoidance, and unsusceptible mice. Sleep-wake stages in mice of both groups were analyzed by means of polysomnographic recordings at baseline, after the first, third, and tenth stress sessions and on the 5th recovery day (R5 following the 10-day CSDS. In susceptible mice, each SD session produced biphasic changes in sleep-wake states that were preserved all along 10-day CSDS. These sessions elicited a short-term enhancement of wake time while rapid eye-movement (REM sleep was strongly inhibited. Concomitantly, delta power was increased during non REM (NREM sleep. During the following dark period, an increase in total sleep time, as well as wake fragmentation, were observed after each analyzed SD session. Similar changes were observed in unsusceptible mice. At R5, elevated high-frequency EEG activity, as observed in insomniacs, emerged during NREM sleep in both susceptible and unsusceptible groups suggesting that CSDS impaired sleep quality. Furthermore, susceptible but not unsusceptible mice displayed stress-anticipatory arousal during recovery, a common feature of anxiety disorders. Altogether, our findings show that CSDS has profound impacts on vigilance states and further support that sleep is tightly regulated by exposure to stressful events. They also revealed that susceptibility to chronic psychological stress is associated with heightened arousal, a physiological feature of stress vulnerability.

Susceptibility and tolerance of rice crop to salt threat: Physiological and metabolic inspections.

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Nyuk Ling Ma

Full Text Available Salinity threat is estimated to reduce global rice production by 50%. Comprehensive analysis of the physiological and metabolite changes in rice plants from salinity stress (i.e. tolerant versus susceptible plants is important to combat higher salinity conditions. In this study, we screened a total of 92 genotypes and selected the most salinity tolerant line (SS1-14 and most susceptible line (SS2-18 to conduct comparative physiological and metabolome inspections. We demonstrated that the tolerant line managed to maintain their water and chlorophyll content with lower incidence of sodium ion accumulation. We also examined the antioxidant activities of these lines: production of ascorbate peroxidase (APX and catalase (CAT were significantly higher in the sensitive line while superoxide dismutase (SOD was higher in the tolerant line. Partial least squares discriminant analysis (PLS-DA score plots show significantly different response for both lines after the exposure to salinity stress. In the tolerant line, there was an upregulation of non-polar metabolites and production of sucrose, GABA and acetic acid, suggesting an important role in salinity adaptation. In contrast, glutamine and putrescine were noticeably high in the susceptible rice. Coordination of different strategies in tolerant and susceptible lines show that they responded differently after exposure to salt stress. These findings can assist crop development in terms of developing tolerance mechanisms for rice crops.

A link between thrifty phenotype and maternal care across two generations of intercrossed mice.

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Bruno Sauce

Full Text Available Maternal effects are causal influences from mother to offspring beyond genetic information, and have lifelong consequences for multiple traits. Previously, we reported that mice whose mothers did not nurse properly had low birth weight followed by rapid fat accumulation and disturbed development of some organs. That pattern resembles metabolic syndromes known collectively as the thrifty phenotype, which is believed to be an adaptation to a stressful environment which prepares offspring for reduced nutrient supply. The potential link between maternal care, stress reactivity, and the thrifty phenotype, however, has been poorly explored in the human and animal literature: only a couple of studies even mention (much less, test these concepts under a cohesive framework. Here, we explored this link using mice of the parental inbred strains SM/J and LG/J-who differ dramatically in their maternal care-and the intercrossed generations F1 and F2. We measured individual differences in 15 phenotypes and used structural equation modeling to test our hypotheses. We found a remarkable relationship between thrifty phenotype and lower quality of maternal behaviors, including nest building, pup retrieval, grooming/licking, and nursing. To our knowledge, this is the first study to show, in any mammal, a clear connection between the natural variation in thrifty phenotype and maternal care. Both traits in the mother also had a substantial effect on survival rate in the F3 offspring. To our surprise, however, stress reactivity seemed to play no role in our models. Furthermore, the strain of maternal grandmother, but not of paternal grandmother, affected the variation of maternal care in F2 mice, and this effect was mediated by thrifty phenotype in F2. Since F1 animals were all genetically identical, this finding suggests that maternal effects pass down both maternal care and thrifty phenotype in these mice across generations via epigenetic transmission.

Down-regulation of miR-181a can reduce heat stress damage in PBMCs of Holstein cows.

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Chen, Kun-Lin; Fu, Yuan-Yuan; Shi, Min-Yan; Li, Hui-Xia

2016-09-01

Heat stress can weaken the immune system and even increase livestock's susceptibility to disease. MicroRNA (miR) is short non-coding RNA that functions in post-transcriptional regulation of gene expression and some phenotypes. Our recent study found that miR-181a is highly expressed in the serum of heat-stressed Holstein cows, but the potential function of miR-181a is still not clarified. In this study, peripheral blood mononuclear cells (PBMCs), isolated from Holstein cows' peripheral blood, were used to investigate the effects of miR-181a inhibitor on heat stress damage. Our results showed that significant apoptosis and oxidative damage were induced by heat stress in PBMCs. However, with apoptosis, the levels of reactive oxygen species (ROS) and content of malondialdehyde (MDA) were reduced, while the content of glutathione (GSH) and the activity of superoxide dismutase (SOD) were increased even under heat stress conditions after transfecting miR-181a inhibitors to PBMCs. Meanwhile, mRNA expression of bax and caspase-3 was significantly decreased, but mRNA expression of bcl-2 was increased in transfected PBMCs. In conclusion, our results demonstrated that down-regulation of miR-181a can reduce heat stress damage in PBMCs of Holstein cows.

Phenotypic Plasticity of Cuticular Hydrocarbon Profiles in Insects.

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Otte, Tobias; Hilker, Monika; Geiselhardt, Sven

2018-03-01

The insect integument is covered by cuticular hydrocarbons (CHCs) which provide protection against environmental stresses, but are also used for communication. Here we review current knowledge on environmental and insect-internal factors which shape phenotypic plasticity of solitary living insects, especially herbivorous ones. We address the dynamics of changes which may occur within minutes, but may also last weeks, depending on the species and conditions. Two different modes of changes are suggested, i.e. stepwise and gradual. A switch between two distinct environments (e.g. host plant switch by phytophagous insects) results in stepwise formation of two distinct adaptive phenotypes, while a gradual environmental change (e.g. temperature gradients) induces a gradual change of numerous adaptive CHC phenotypes. We further discuss the ecological and evolutionary consequences of phenotypic plasticity of insect CHC profiles by addressing the question at which conditions is CHC phenotypic plasticity beneficial. The high plasticity of CHC profiles might be a trade-off for insects using CHCs for communication. We discuss how insects cope with the challenge to produce and "understand" a highly plastic, environmentally dependent CHC pattern that conveys reliable and comprehensible information. Finally, we outline how phenotypic plasticity of CHC profiles may promote speciation in insects that rely on CHCs for mate recognition.

Evaluation of polymorphisms in pbp4 gene and genetic diversity in penicillin-resistant, ampicillin-susceptible Enterococcus faecalis from hospitals in different states in Brazil.

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Infante, Victor Hugo Pacagnelli; Conceição, Natália; de Oliveira, Adriana Gonçalves; Darini, Ana Lúcia da Costa

2016-04-01

The aim of the present study was to verify whether penicillin-resistant, ampicillin-susceptible Enterococcus faecalis (PRASEF) occurred in Brazil prior to the beginning of the 21st century, and to verify whether ampicillin susceptibility can predict susceptibility to other β-lactams in E. faecalis with this inconsistent phenotype. The presence of polymorphisms in the pbp4 gene and genetic diversity among the isolates were investigated. Of 21 PRASEF analyzed, 5 (23.8%) and 4 (19.0%) were imipenem and piperacillin resistant simultaneously by disk diffusion and broth dilution respectively, contradicting the current internationally accepted standards of susceptibility testing. Sequencing of pbp4 gene revealed an amino acid substitution (Asp-573→Glu) in all PRASEF isolates but not in the penicillin-susceptible, ampicillin-susceptible E. faecalis. Most PRASEF (90.5%) had related pulsed-field gel electrophoresis profiles, but were different from other PRASEF described to date. Results demonstrate that penicillin-resistant, ampicillin-susceptible phenotype was already a reality in the 1990s in E. faecalis isolates in different Brazilian states, and some of these isolates were also imipenem- and piperacillin-resistant; therefore, internationally accepted susceptibility criteria cannot be applied to these isolates. According to pbp4 gene sequencing, this study suggests that a specific amino acid substitution in pbp4 gene found in all PRASEF analyzed is associated with penicillin resistance. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Factor analysis in the Genetics of Asthma International Network family study identifies five major quantitative asthma phenotypes

NARCIS (Netherlands)

Pillai, S. G.; Tang, Y.; van den Oord, E.; Klotsman, M.; Barnes, K.; Carlsen, K.; Gerritsen, J.; Lenney, W.; Silverman, M.; Sly, P.; Sundy, J.; Tsanakas, J.; von Berg, A.; Whyte, M.; Ortega, H. G.; Anderson, W. H.; Helms, P. J.

Background Asthma is a clinically heterogeneous disease caused by a complex interaction between genetic susceptibility and diverse environmental factors. In common with other complex diseases the lack of a standardized scheme to evaluate the phenotypic variability poses challenges in identifying the

FKBP5 and specific microRNAs via glucocorticoid receptor in the basolateral amygdala involved in the susceptibility to depressive disorder in early adolescent stressed rats.

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Xu, Jingjing; Wang, Rui; Liu, Yuan; Liu, Dexiang; Jiang, Hong; Pan, Fang

2017-12-01

Exposure to stressful events induces depressive-like symptoms and increases susceptibility to depression. However, the molecular mechanisms are not fully understood. Studies reported that FK506 binding protein51 (FKBP5), the co-chaperone protein of glucocorticoid receptors (GR), plays a crucial role. Further, miR-124a and miR-18a are involved in the regulation of FKBP5/GR function. However, few studies have referred to effects of early life stress on depressive-like behaviours, GR and FKBP5, as well as miR-124a and miR-18a in the basolateral amygdala (BLA) from adolescence to adulthood. This study aimed to examine the dynamic alternations of depressive-like behaviours, GR and FKBP5, as well as miR-124a and miR-18a expressions in the BLA of chronic unpredictable mild stress (CUMS) rats and dexamethasone administration rats during the adolescent period. Meanwhile, the GR antagonist, RU486, was used as a means of intervention. We found that CUMS and dexamethasone administration in the adolescent period induced permanent depressive-like behaviours and memory impairment, decreased GR expression, and increased FKBP5 and miR-124a expression in the BLA of both adolescent and adult rats. However, increased miR-18a expression in the BLA was found only in adolescent rats. Depressive-like behaviours were positively correlated with the level of miR-124a, whereas GR levels were negatively correlated with those in both adolescent and adult rats. Our results suggested FKBP5/GR and miR-124a in the BLA were associated with susceptibility to depressive disorder in the presence of stressful experiences in early life. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differential Susceptibility to the Environment: Are Developmental Models Compatible with the Evidence from Twin Studies?

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Del Giudice, Marco

2016-01-01

According to models of differential susceptibility, the same neurobiological and temperamental traits that determine increased sensitivity to stress and adversity also confer enhanced responsivity to the positive aspects of the environment. Differential susceptibility models have expanded to include complex developmental processes in which genetic…

Identification and Characterization of Fluoroquinolone Non-susceptible Streptococcus pyogenes Clones Harboring Tetracycline and Macrolide Resistance in Shanghai, China

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Yinfang Shen

2018-03-01

Full Text Available Streptococcus pyogenes, also known as group A Streptococcus (GAS, is one of the top 10 infectious causes of death worldwide. Macrolide and tetracycline resistant GAS has emerged as a major health concern in China coinciding with an ongoing scarlet fever epidemic. Furthermore, increasing rates of fluoroquinolone (FQ non-susceptibility within GAS from geographical regions outside of China has also been reported. Fluoroquinolones are the third most commonly prescribed antibiotic in China and is an therapeutic alternative for multi-drug resistant GAS. The purpose of this study was to investigate the epidemiological and molecular features of GAS fluoroquinolone (FQ non-susceptibility in Shanghai, China. GAS (n = 2,258 recovered between 2011 and 2016 from children and adults were tested for FQ-non-susceptibility. Efflux phenotype and mutations in parC, parE, gyrA, and gyrB were investigated and genetic relationships were determined by emm typing, pulsed-field gel electrophoresis and phylogenetic analysis. The frequency of GAS FQ-non-susceptibility was 1.3% (30/2,258, with the phenotype more prevalent in GAS isolated from adults (14.3% than from children (1.2%. Eighty percent (24/30 of FQ-non-susceptible isolates were also resistant to both macrolides (ermB and tetracycline (tetM including the GAS sequence types emm12, emm6, emm11, and emm1. Genomic fingerprinting analysis of the 30 isolates revealed that non-susceptibility may arise in various genetic backgrounds even within a single emm type. No efflux phenotype was observed in FQ non-susceptible isolates, and molecular analysis of the quinolone resistance-determining regions (QRDRs identified several sequence polymorphisms in ParC and ParE, and none in GyrA and GyrB. Expansion of this analysis to 152 publically available GAS whole genome sequences from Hong Kong predicted 7.9% (12/152 of Hong Kong isolates harbored a S79F ParC mutation, of which 66.7% (8/12 were macrolide and tetracycline resistant

Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection

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Niu, Qingli; Hou, Wei; Churchyard, Gavin; Nitayaphan, Sorachai; Pitisuthithum, Punnee; Rerks-Ngarm, Supachai; Franchini, Genoveffa

2018-01-01

The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV in vitro. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination. PMID:29474461

Antibiotic Susceptibility Profile of Aeromonas Species Isolated from Wastewater Treatment Plant

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Isoken H. Igbinosa

2012-01-01

Full Text Available This study assessed the prevalence of antibiotic-resistant Aeromonas species isolated from Alice and Fort Beaufort wastewater treatment plant in the Eastern Cape Province of South Africa. Antibiotic susceptibility was determined using the disc diffusion method, and polymerase chain reaction (PCR assay was employed for the detection of antibiotics resistance genes. Variable susceptibilities were observed against ciprofloxacin, chloramphenicol, nalidixic acid, gentamicin, minocycline, among others. Aeromonas isolates from both locations were 100% resistant to penicillin, oxacillin, ampicillin, and vancomycin. Higher phenotypic resistance was observed in isolates from Fort Beaufort compared to isolates from Alice. Class A pse1 β-lactamase was detected in 20.8% of the isolates with a lower detection rate of 8.3% for blaTEM gene. Class 1 integron was present in 20.8% of Aeromonas isolates while class 2 integron and TetC gene were not detected in any isolate. The antibiotic resistance phenotypes observed in the isolates and the presence of β-lactamases genes detected in some isolates are of clinical and public health concern as this has consequences for antimicrobial chemotherapy of infections associated with Aeromonas species. This study further supports wastewater as potential reservoirs of antibiotic resistance determinants in the environment.

Sub-inhibitory stress with essential oil affects enterotoxins production and essential oil susceptibility in Staphylococcus aureus.

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Turchi, Barbara; Mancini, Simone; Pistelli, Luisa; Najar, Basma; Cerri, Domenico; Fratini, Filippo

2018-03-01

Fourteen wild strains of Staphylococcus aureus positive for gene sea were tested for enterotoxins production and the minimum inhibitory concentration of Leptospermum scoparium, Origanum majorana, Origanum vulgare, Satureja montana and Thymus vulgaris essential oils (EOs) were determined. After this trial, bacteria stressed with sub-inhibitory concentration of each EO were tested for enterotoxins production by an immunoenzymatic assay and resistance to the same EO. Oregano oil exhibited the highest antibacterial activity followed by manuka and thyme oils. After the exposure to a sub-inhibitory concentration of EOs, strains displayed an increased sensitivity in more than 95% of the cases. After treatment with oregano and marjoram EOs, few strains showed a modified enterotoxins production, while 43% of the strains were no longer able to produce enterotoxins after treatment with manuka EO. The results obtained in this study highlight that exposure to sub-inhibitory concentration of EO modifies strains enterotoxins production and EOs susceptibility profile.

Sex differences in stress-induced social withdrawal: independence from adult gonadal hormones and inhibition of female phenotype by corncob bedding.

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Trainor, Brian C; Takahashi, Elizabeth Y; Campi, Katharine L; Florez, Stefani A; Greenberg, Gian D; Laman-Maharg, Abigail; Laredo, Sarah A; Orr, Veronica N; Silva, Andrea L; Steinman, Michael Q

2013-03-01

There is compelling evidence for important sex differences in behavioral and hormonal responses to psychosocial stress. Here we examined the effects of gonadal hormones on behavioral responses to social defeat stress in monogamous California mice (Peromyscus californicus). Three episodes of social defeat induced social withdrawal in intact females but not males. Gonadectomy blocked corticosterone responses to defeat in females and sensitized male corticosterone responses. However, gonadectomy had no effects on social interaction behavior, suggesting that social withdrawal is not dependent on gonadal hormones in the adult California mouse. In contrast, defeat reduced exploratory behavior in the open field test for intact but not castrated males. We also examined the effects of social defeat on social interaction behavior when California mice were raised on corncob bedding, which has estrogenic properties. In this dataset of over 300 mice, we observed that social defeat did not induce social withdrawal when females were raised on corncob bedding. This finding suggests that the use of corncob in rodent studies could mask important sex differences in the effects of stress on brain and behavior. Although gonadal hormones do not affect social withdrawal behavior in adults, our data suggest that hormones may act earlier in development to induce a more resilient social phenotype. Copyright © 2013 Elsevier Inc. All rights reserved.

Vicarious social defeat stress: Bridging the gap between physical and emotional stress.

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Sial, Omar K; Warren, Brandon L; Alcantara, Lyonna F; Parise, Eric M; Bolaños-Guzmán, Carlos A

2016-01-30

Animal models capable of differentiating the neurobiological intricacies between physical and emotional stress are scarce. Current models rely primarily on physical stressors (e.g., chronic unpredictable or mild stress, social defeat, learned helplessness), and neglect the impact of psychological stress alone. This is surprising given extensive evidence that a traumatic event needs not be directly experienced to produce enduring perturbations on an individual's health and psychological well-being. Post-traumatic stress disorder (PTSD), a highly debilitating neuropsychiatric disorder characterized by intense fear of trauma-related stimuli, often occurs in individuals that have only witnessed a traumatic event. By modifying the chronic social defeat stress (CSDS) paradigm to include a witness component (witnessing the social defeat of another mouse), we demonstrate a novel behavioral paradigm capable of inducing a robust behavioral syndrome reminiscent of PTSD in emotionally stressed adult mice. We describe the vicarious social defeat stress (VSDS) model that is capable of inducing a host of behavioral deficits that include social avoidance and other depressive- and anxiety-like phenotypes in adult male mice. VSDS exposure induces weight loss and spike in serum corticosterone (CORT) levels. A month after stress, these mice retain the social avoidant phenotype and have an increased CORT response when exposed to subsequent stress. The VSDS is a novel paradigm capable of inducing emotional stress by isolating physical stress/confrontation in mice. The VSDS model can be used to study the short- and long-term neurobiological consequences of exposure to emotional stress in mice. Copyright © 2015 Elsevier B.V. All rights reserved.

Trypanosoma cruzi: in vivo evaluation of iron in skin employing X-ray fluorescence (XRF) in mouse strains that differ in their susceptibility to infection.

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Estevam, Marcelo; Appoloni, Carlos Roberto; Malvezi, Aparecida Donizette; Tatakihara, Vera Lúcia Hideko; Panis, Carolina; Cecchini, Rubens; Rizzo, Luiz Vicente; Pinge-Filho, Phileno

2012-04-01

Trypanosoma cruzi, the causative agent of Chagas' disease (CD), is a substantial public health concern in Latin America. Laboratory mice inoculated with T. cruzi have served as important animal models of acute CD. Host hypoferremic responses occur during T. cruzi infection; therefore, it has been hypothesized that T. cruzi requires iron for optimal growth in host cells and, unlike extracellular pathogens, may benefit from host hypoferremic responses. Recent technological improvements of X-ray fluorescence are useful for diagnostics or monitoring in biomedical applications. The goal of our study was to determine whether the iron availabilities in Swiss and C57BL/6 mice differ during the acute phase of T. cruzi infection and whether the availability correlates with oxidative stress in the susceptible and resistant phenotypes identified in these mice. Our results showed that the decrease in iron levels in the skin of resistant infected mice correlated with the increase in oxidative stress associated with anemia and the reduction in parasite burden. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Antimicrobial susceptibility among clinical Nocardia species identified by multilocus sequence analysis.

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McTaggart, Lisa R; Doucet, Jennifer; Witkowska, Maria; Richardson, Susan E

2015-01-01

Antimicrobial susceptibility patterns of 112 clinical isolates, 28 type strains, and 9 reference strains of Nocardia were determined using the Sensititre Rapmyco microdilution panel (Thermo Fisher, Inc.). Isolates were identified by highly discriminatory multilocus sequence analysis and were chosen to represent the diversity of species recovered from clinical specimens in Ontario, Canada. Susceptibility to the most commonly used drug, trimethoprim-sulfamethoxazole, was observed in 97% of isolates. Linezolid and amikacin were also highly effective; 100% and 99% of all isolates demonstrated a susceptible phenotype. For the remaining antimicrobials, resistance was species specific with isolates of Nocardia otitidiscaviarum, N. brasiliensis, N. abscessus complex, N. nova complex, N. transvalensis complex, N. farcinica, and N. cyriacigeorgica displaying the traditional characteristic drug pattern types. In addition, the antimicrobial susceptibility profiles of a variety of rarely encountered species isolated from clinical specimens are reported for the first time and were categorized into four additional drug pattern types. Finally, MICs for the control strains N. nova ATCC BAA-2227, N. asteroides ATCC 19247(T), and N. farcinica ATCC 23826 were robustly determined to demonstrate method reproducibility and suitability of the commercial Sensititre Rapmyco panel for antimicrobial susceptibility testing of Nocardia spp. isolated from clinical specimens. The reported values will facilitate quality control and standardization among laboratories. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Evaluation of the Clinical and Laboratory Standards Institute phenotypic confirmatory test to detect the presence of extended-spectrum β-lactamases from 4005 Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae and Proteus mirabilis isolates.

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Morrissey, Ian; Bouchillon, Samuel K; Hackel, Meredith; Biedenbach, Douglas J; Hawser, Stephen; Hoban, Daryl; Badal, Robert E

2014-04-01

A subset of Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae and Proteus mirabilis isolates collected for the Study for Monitoring Antimicrobial Resistance Trends that were positive for the Clinical and Laboratory Standards Institute (CLSI) extended-spectrum β-lactamase (ESBL) phenotypic confirmatory test (n = 3245) or had an ertapenem MIC of ≥0.5 µg ml(-1) (n = 293), or both (n = 467), were analysed for ESBL genes. Most ESBL phenotype E. coli or K. pneumoniae possessed an ESBL gene (95.8 and 88.4 %, respectively), and this was 93.1 % if carbapenem-non-susceptible K. pneumoniae were removed. This rate was lower for P. mirabilis (73.4 %) and K. oxytoca (62.5 %). Virtually all ESBL-positive isolates (99.5 %) were cefotaxime non-susceptible [CLSI or European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints)]. Fewer isolates (82 %) were ceftazidime non-susceptible (CLSI breakpoints). In addition, 21.1 % of E. coli, 25 % of K. oxytoca and 78.7 % of P. mirabilis isolates were ceftazidime susceptible but ESBL positive. This suggests that CLSI breakpoints for ceftazidime are too high to detect ESBLs. The lower EUCAST breakpoints detected ESBLs in E. coli and K. oxytoca better, but 59.6 % of ESBL-positive isolates of P. mirabilis were ceftazidime susceptible. For isolates with ertapenem MICs ≥0.5 µg ml(-1), more accurate ESBL phenotype analysis was observed for E. coli and K. pneumoniae (sensitivity >95 % for both, specificity 94.4 and 54.1 %, respectively). If carbapenemase-positive K. pneumoniae were excluded, the specificity increased to 78 %. The positive predictive values for the ESBL phenotypic test with E. coli and K. pneumoniae were 97.6 and 81.8 %, respectively, and negative predictive values were 75.9 and 95.2 %, respectively. We therefore suggest that it would be prudent to confirm phenotypic ESBL-positive P. mirabilis, K. pneumoniae and K. oxytoca with molecular analysis.

An explainable deep machine vision framework for plant stress phenotyping.

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Ghosal, Sambuddha; Blystone, David; Singh, Asheesh K; Ganapathysubramanian, Baskar; Singh, Arti; Sarkar, Soumik

2018-05-01

Current approaches for accurate identification, classification, and quantification of biotic and abiotic stresses in crop research and production are predominantly visual and require specialized training. However, such techniques are hindered by subjectivity resulting from inter- and intrarater cognitive variability. This translates to erroneous decisions and a significant waste of resources. Here, we demonstrate a machine learning framework's ability to identify and classify a diverse set of foliar stresses in soybean [ Glycine max (L.) Merr.] with remarkable accuracy. We also present an explanation mechanism, using the top-K high-resolution feature maps that isolate the visual symptoms used to make predictions. This unsupervised identification of visual symptoms provides a quantitative measure of stress severity, allowing for identification (type of foliar stress), classification (low, medium, or high stress), and quantification (stress severity) in a single framework without detailed symptom annotation by experts. We reliably identified and classified several biotic (bacterial and fungal diseases) and abiotic (chemical injury and nutrient deficiency) stresses by learning from over 25,000 images. The learned model is robust to input image perturbations, demonstrating viability for high-throughput deployment. We also noticed that the learned model appears to be agnostic to species, seemingly demonstrating an ability of transfer learning. The availability of an explainable model that can consistently, rapidly, and accurately identify and quantify foliar stresses would have significant implications in scientific research, plant breeding, and crop production. The trained model could be deployed in mobile platforms (e.g., unmanned air vehicles and automated ground scouts) for rapid, large-scale scouting or as a mobile application for real-time detection of stress by farmers and researchers. Copyright © 2018 the Author(s). Published by PNAS.

An explainable deep machine vision framework for plant stress phenotyping

Science.gov (United States)

Blystone, David; Ganapathysubramanian, Baskar; Singh, Arti; Sarkar, Soumik

2018-01-01

Current approaches for accurate identification, classification, and quantification of biotic and abiotic stresses in crop research and production are predominantly visual and require specialized training. However, such techniques are hindered by subjectivity resulting from inter- and intrarater cognitive variability. This translates to erroneous decisions and a significant waste of resources. Here, we demonstrate a machine learning framework’s ability to identify and classify a diverse set of foliar stresses in soybean [Glycine max (L.) Merr.] with remarkable accuracy. We also present an explanation mechanism, using the top-K high-resolution feature maps that isolate the visual symptoms used to make predictions. This unsupervised identification of visual symptoms provides a quantitative measure of stress severity, allowing for identification (type of foliar stress), classification (low, medium, or high stress), and quantification (stress severity) in a single framework without detailed symptom annotation by experts. We reliably identified and classified several biotic (bacterial and fungal diseases) and abiotic (chemical injury and nutrient deficiency) stresses by learning from over 25,000 images. The learned model is robust to input image perturbations, demonstrating viability for high-throughput deployment. We also noticed that the learned model appears to be agnostic to species, seemingly demonstrating an ability of transfer learning. The availability of an explainable model that can consistently, rapidly, and accurately identify and quantify foliar stresses would have significant implications in scientific research, plant breeding, and crop production. The trained model could be deployed in mobile platforms (e.g., unmanned air vehicles and automated ground scouts) for rapid, large-scale scouting or as a mobile application for real-time detection of stress by farmers and researchers. PMID:29666265

Antimony susceptibility of Leishmania isolates collected over a 30-year period in Algeria.

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Eddaikra, Naouel; Ait-Oudhia, Khatima; Kherrachi, Ihcen; Oury, Bruno; Moulti-Mati, Farida; Benikhlef, Razika; Harrat, Zoubir; Sereno, Denis

2018-03-01

In Algeria, the treatment of visceral and cutaneous leishmanioses (VL and CL) has been and continues to be based on antimony-containing drugs. It is suspected that high drug selective pressure might favor the emergence of chemoresistant parasites. Although treatment failure is frequently reported during antimonial therapy of both CL and VL, antimonial resistance has never been thoroughly investigated in Algeria. Determining the level of antimonial susceptibility, amongst Leishmania transmitted in Algeria, is of great importance for the development of public health policies. Within the framework of the knowledge about the epidemiology of VL and CL amassed during the last 30 years, we sampled Leishmania isolates to determine their susceptibility to antimony. We analyzed a total of 106 isolates including 88 isolates collected between 1976 and 2013 in Algeria from humans, dogs, rodents, and phlebotomines and 18 collected from dogs in France. All the Algerian isolates were collected in 14 localities where leishmaniasis is endemic. The 50% inhibitory concentrations (IC50) of potassium antimony tartrate (the trivalent form of antimony, Sb(III)) and sodium stibogluconate (the pentavalent form of antimony, Sb(V)) were determined in promastigotes and intramacrophage amastigotes, respectively. The epidemiological cutoff (ECOFF) that allowed us to differentiate between Leishmania species causing cutaneous or visceral leishmaniases that were susceptible (S+) or insusceptible (S-) to the trivalent form of antimony was determined. The computed IC50 cutoff values were 23.83 μg/mL and 15.91 μg/mL for VL and CL, respectively. We report a trend of increasing antimony susceptibility in VL isolates during the 30-year period. In contrast, an increase in the frequency of S- phenotypes in isolates causing CL was observed during the same period. In our study, the emergence of S- phenotypes correlates with the inclusion of L. killicki (syn: L. tropica) isolates that cause cutaneous

Interference fits and stress-corrosion failure. [aircraft parts fatigue life analysis

Science.gov (United States)

Hanagud, S.; Carter, A. E.

1976-01-01

It is pointed out that any proper design of interference fit fastener, interference fit bushings, or stress coining processes should consider both the stress-corrosion susceptibility and fatigue-life improvement together. Investigations leading to such a methodology are discussed. A service failure analysis of actual aircraft parts is considered along with the stress-corrosion susceptibility of cold-working interference fit bushings. The optimum design of the amount of interference is considered, giving attention to stress formulas and aspects of design methodology.

Abscisic Acid and Abiotic Stress Signaling

OpenAIRE

Tuteja, Narendra

2007-01-01

Abiotic stress is severe environmental stress, which impairs crop production on irrigated land worldwide. Overall, the susceptibility or tolerance to the stress in plants is a coordinated action of multiple stress responsive genes, which also cross-talk with other components of stress signal transduction pathways. Plant responses to abiotic stress can be determined by the severity of the stress and by the metabolic status of the plant. Abscisic acid (ABA) is a phytohormone critical for plant ...

Array-CGH Analysis in a Cohort of Phenotypically Well-Characterized Individuals with "Essential" Autism Spectrum Disorders

Science.gov (United States)

Napoli, Eleonora; Russo, Serena; Casula, Laura; Alesi, Viola; Amendola, Filomena Alessandra; Angioni, Adriano; Novelli, Antonio; Valeri, Giovanni; Menghini, Deny; Vicari, Stefano

2018-01-01

Copy-number variants (CNVs) are associated with susceptibility to autism spectrum disorder (ASD). To detect the presence of CNVs, we conducted an array-comparative genomic hybridization (array-CGH) analysis in 133 children with "essential" ASD phenotype. Genetic analyses documented that 12 children had causative CNVs (C-CNVs), 29…

Leaf phenotypic variation and developmental instability in relation to different light regimes

Directory of Open Access Journals (Sweden)

Henrique Venâncio

2016-06-01

Full Text Available ABSTRACT For pioneer plants, shaded habitats represent a stressful condition, where sunlight exposure is below the optimum level and so leaves expand in order to intercept a greater amount of light. We investigated changes in both phenotypic variation and stress of Bauhinia brevipes in sunny and shaded microhabitats. Leaf area was used as a measure of phenotypic variation, whereas leaf asymmetry (difference between right and left sides of leaves, was used as a measure of stress. We hypothesized an increase in leaf area and stress in shaded locations, which might indicate that B. brevipes was compensating for low light absorption, and elevated levels of stress, respectively. Plants in the sun fitted a fluctuating asymmetry pattern (normal distribution of right minus left sides, while shaded plants were clearly antisymmetric (bimodal distribution of leaf side differences. Leaf asymmetry and area were 5% and 26.8% higher in plants in the shade compared to plants in the sun, respectively. These results were expected since B. brevipes is found predominantly in open areas; so sunlight exposure is important for its development. The presence of antisymmetry is rare in studies of developmental instability, and here it might indicate higher stress compared to plants with fluctuating asymmetry.

Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats

Directory of Open Access Journals (Sweden)

Jane L. Tarry-Adkins

2016-10-01

Full Text Available ‘Developmental programming’, which occurs as a consequence of suboptimal in utero and early environments, can be associated with metabolic dysfunction in later life, including an increased incidence of cardiovascular disease and type 2 diabetes, and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these associations are poorly understood. Many conditions associated with developmental programming are also known to be associated with the aging process. We therefore utilized our well-established rat model of low birth weight and accelerated postnatal catch-up growth (termed ‘recuperated’ in this study to establish the effects of suboptimal maternal nutrition on age-associated factors in skeletal muscle. We demonstrated accelerated telomere shortening (a robust marker of cellular aging as evidenced by a reduced frequency of long telomeres (48.5-8.6 kb and an increased frequency of short telomeres (4.2-1.3 kb in vastus lateralis muscle from aged recuperated offspring compared to controls. This was associated with increased protein expression of the DNA-damage-repair marker 8-oxoguanine-glycosylase (OGG1 in recuperated offspring. Recuperated animals also demonstrated an oxidative stress phenotype, with decreased citrate synthase activity, increased electron-transport-complex activities of complex I, complex II-III and complex IV (all markers of functional mitochondria, and increased xanthine oxidase (XO, p67phox and nuclear-factor kappa-light-chain-enhancer of activated B-cells (NF-κB. Recuperated offspring also demonstrated increased antioxidant defense capacity, with increased protein expression of manganese superoxide dismutase (MnSOD, copper-zinc superoxide dismutase (CuZnSOD, catalase and heme oxygenase-1 (HO1, all of which are known targets of NF-κB and can be upregulated as a consequence of oxidative stress. Recuperated offspring also had a pro-inflammatory phenotype, as evidenced by

Links between early baseline cortisol, attachment classification, and problem behaviors: A test of differential susceptibility versus diathesis-stress.

Science.gov (United States)

Fong, Michelle C; Measelle, Jeffrey; Conradt, Elisabeth; Ablow, Jennifer C

2017-02-01

The purpose of the current study was to predict concurrent levels of problem behaviors from young children's baseline cortisol and attachment classification, a proxy for the quality of caregiving experienced. In a sample of 58 children living at or below the federal poverty threshold, children's baseline cortisol levels, attachment classification, and problem behaviors were assessed at 17 months of age. We hypothesized that an interaction between baseline cortisol and attachment classification would predict problem behaviors above and beyond any main effects of baseline cortisol and attachment. However, based on limited prior research, we did not predict whether or not this interaction would be more consistent with diathesis-stress or differential susceptibility models. Consistent with diathesis-stress theory, the results indicated no significant differences in problem behavior levels among children with high baseline cortisol. In contrast, children with low baseline cortisol had the highest level of problem behaviors in the context of a disorganized attachment relationship. However, in the context of a secure attachment relationship, children with low baseline cortisol looked no different, with respect to problem behavior levels, then children with high cortisol levels. These findings have substantive implications for the socioemotional development of children reared in poverty. Copyright © 2017 Elsevier Inc. All rights reserved.

Mitochondrial genetic background modulates bioenergetics and susceptibility to acute cardiac volume overload.

Science.gov (United States)

Fetterman, Jessica L; Zelickson, Blake R; Johnson, Larry W; Moellering, Douglas R; Westbrook, David G; Pompilius, Melissa; Sammy, Melissa J; Johnson, Michelle; Dunham-Snary, Kimberly J; Cao, Xuemei; Bradley, Wayne E; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G; Kesterson, Robert A; Dell'italia, Louis J; Darley-Usmar, Victor M; Welch, Danny R; Ballinger, Scott W

2013-10-15

Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mtDNA sequence variation contributes to disease susceptibility. In the present study we show a novel animal model of mtDNA polymorphisms, the MNX (mitochondrial-nuclear exchange) mouse, in which the mtDNA from the C3H/HeN mouse has been inserted on to the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harbouring the C57/BL6J mtDNA generate more ROS (reactive oxygen species) and have a higher mitochondrial membrane potential relative to those with C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the 'mitochondrial paradigm' for the development of disease susceptibility, and show that the mtDNA modulates cellular bioenergetics, mitochondrial ROS generation and susceptibility to cardiac stress.

Phenotypic and genotypic characterization of vancomycin-resistant Enterococcus faecium clinical isolates from two hospitals in Mexico: First detection of VanB phenotype-vanA genotype.

Science.gov (United States)

Bocanegra-Ibarias, Paola; Flores-Treviño, Samantha; Camacho-Ortiz, Adrián; Morfin-Otero, Rayo; Villarreal-Treviño, Licet; Llaca-Díaz, Jorge; Martínez-Landeros, Erik Alan; Rodríguez-Noriega, Eduardo; Calzada-Güereca, Andrés; Maldonado-Garza, Héctor Jesús; Garza-González, Elvira

2016-01-01

Enterococcus faecium has emerged as a multidrug-resistant nosocomial pathogen involved in outbreaks worldwide. Our aim was to determine the antimicrobial susceptibility, biofilm production, and clonal relatedness of vancomycin-resistant E. faecium (VREF) clinical isolates from two hospitals in Mexico. Consecutive clinical isolates (n=56) were collected in two tertiary care hospitals in Mexico from 2011 to 2014. VREF isolates were characterized by phenotypic and molecular methods including pulsed-field gel electrophoresis (PFGE). VREF isolates were highly resistant to vancomycin, erythromycin, norfloxacin, high-level streptomycin, and teicoplanin, and showed lower resistance to tetracycline, nitrofurantoin and quinupristin-dalfopristin. None of the isolates were resistant to linezolid. The vanA gene was detected in all isolates. Two VanB phenotype-vanA genotype isolates, highly resistant to vancomycin and susceptible to teicoplanin, were detected. Furthermore, 17.9% of the isolates were classified as biofilm producers, and the espfm gene was found in 98.2% of the isolates. A total of 37 distinct PFGE patterns and 6 clones (25% of the isolates as clone A, 5.4% as clone B, and 3.6% each as clone C, D, E, and F) were detected. Clone A was detected in 5 different wards of the same hospital during 14 months of surveillance. The high resistance to most antimicrobial agents and the moderate cross-transmission of VREF detected accentuates the need for continuous surveillance of E. faecium in the hospital setting. This is also the first reported incidence of the E. faecium VanB phenotype-vanA genotype in the Americas. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Multidimensionality of behavioural phenotypes in Atlantic cod, Gadus morhua.

Science.gov (United States)

Meager, Justin J; Fernö, Anders; Skjæraasen, Jon Egil; Järvi, Torbjörn; Rodewald, Petra; Sverdrup, Gisle; Winberg, Svante; Mayer, Ian

2012-06-25

Much of the inter-individual variation observed in animal behaviour is now attributed to the existence of behavioural phenotypes or animal personalities. Such phenotypes may be fundamental to fisheries and aquaculture, yet there have been few detailed studies of this phenomenon in exploited marine animals. We investigated the behavioural and neuroendocrine responses of Atlantic cod (Gadus morhua L.), to situations reflecting critical ecological challenges: predator attacks and territorial challenges. Both hatchery-reared and wild fish were tested and behavioural profiles were compared with baseline conditions. We then used an objective, multivariate approach, rather than assigning individuals along one-dimensional behavioural axes, to examine whether distinct behavioural phenotypes were present. Our results indicate that two distinct behavioural phenotypes were evident in fish from each background. In hatchery-reared fish, phenotypes displayed divergent locomotor activity, sheltering, brain monoamine concentrations and responses to competitive challenges. In wild fish, phenotypes were distinguished primarily by locomotor activity, sheltering and responsiveness to predator stimuli. Hatcheries presumably represent a more stressful social environment, and social behaviour and neuroendocrine responses were important in discerning behavioural phenotypes in hatchery fish, whereas antipredator responses were important in discerning phenotypes in wild fish that have previously encountered predators. In both fish types, behavioural and physiological traits that classified individuals into phenotypes were not the same as those that were correlated across situations. These results highlight the multidimensionality of animal personalities, and that the processes that regulate one suite of behavioural traits may be very different to the processes that regulate other behaviours. Copyright © 2012 Elsevier Inc. All rights reserved.

Transgenerational effects of stress exposure on offspring phenotypes in apomictic dandelion

NARCIS (Netherlands)

Verhoeven, K.J.F.; Van Gurp, T.P.

2012-01-01

Heritable epigenetic modulation of gene expression is a candidate mechanism to explain parental environmental effects on offspring phenotypes, but current evidence for environment-induced epigenetic changes that persist in offspring generations is scarce. In apomictic dandelions, exposure to various

Transgenerational Effects of Stress Exposure on Offspring Phenotypes in Apomictic Dandelion

NARCIS (Netherlands)

Verhoeven, K.J.F.; Gurp, van T.P.

2012-01-01

Heritable epigenetic modulation of gene expression is a candidate mechanism to explain parental environmental effects on offspring phenotypes, but current evidence for environment-induced epigenetic changes that persist in offspring generations is scarce. In apomictic dandelions, exposure to various

Gaucher disease types 1 and 3: Phenotypic characterization of large populations from the ICGG Gaucher Registry.

Science.gov (United States)

Grabowski, Gregory A; Zimran, Ari; Ida, Hiroyuki

2015-07-01

Study of the natural history of Gaucher disease has revealed marked phenotypic variation. Correlations to genotypes could provide insight into individual susceptibility to varying disease severity, which may impact whole-life medical care, reproductive decisions, and therapeutic choices for affected families. Importantly, pre-symptomatic or prospective interventions or the use of therapies with significant risk require accurate risk-benefit analyses based on the prognosis for individual patients. The body of international data held within the International Collaborative Gaucher Group (ICGG) Gaucher Registry provides an unprecedented opportunity to characterize the phenotypes of Gaucher disease types 1 and 3 and to appreciate demographic and ethnic factors that may influence phenotypes. The diversity of GBA gene mutations from patients with Gaucher disease represented in the ICGG Gaucher Registry database and in the literature provides the basis for initial genotype/phenotype correlations, the outcomes of which are summarized here. © 2015 Wiley Periodicals, Inc.

Comparative assessment of antibiotic susceptibility of coagulase-negative staphylococci in biofilm versus planktonic culture as assessed by bacterial enumeration or rapid XTT colorimetry.

Science.gov (United States)

Cerca, Nuno; Martins, Silvia; Cerca, Filipe; Jefferson, Kimberly K; Pier, Gerald B; Oliveira, Rosário; Azeredo, Joana

2005-08-01

To quantitatively compare the antibiotic susceptibility of biofilms formed by the coagulase-negative staphylococci (CoNS) Staphylococcus epidermidis and Staphylococcus haemolyticus with the susceptibility of planktonic cultures. Several CoNS strains were grown planktonically or as biofilms to determine the effect of the mode of growth on the level of susceptibility to antibiotics with different mechanisms of action. The utility of a new, rapid colorimetric method that is based on the reduction of a tetrazolium salt (XTT) to measure cell viability was tested by comparison with standard bacterial enumeration techniques. A 6 h kinetic study was performed using dicloxacillin, cefazolin, vancomycin, tetracycline and rifampicin at the peak serum concentration of each antibiotic. In planktonic cells, inhibitors of cell wall synthesis were highly effective over a 3 h period. Biofilms were much less susceptible than planktonic cultures to all antibiotics tested, particularly inhibitors of cell wall synthesis. The susceptibility to inhibitors of protein and RNA synthesis was affected by the biofilm phenotype to a lesser degree. Standard bacterial enumeration techniques and the XTT method produced equivalent results both in biofilms and planktonic assays. This study provides a more accurate comparison between the antibiotic susceptibilities of planktonic versus biofilm populations, because the cell densities in the two populations were similar and because we measured the concentration required to inhibit bacterial metabolism rather than to eradicate the entire bacterial population. While the biofilm phenotype is highly resistant to antibiotics that target cell wall synthesis, it is fairly susceptible to antibiotics that target RNA and protein synthesis.

Mutations and phenotype in isolated glycerol kinase deficiency

Energy Technology Data Exchange (ETDEWEB)

Walker, A.P.; Muscatelli, F.; Stafford, A.N.; Monaco, A.P. [Inst. of Molecular Medicine, Oxford (United Kingdom)] [and others

1996-06-01

We demonstrate that isolated glycerol kinase (GK) deficiency in three families results from mutation of the Xp21 GK gene. GK mutations were detected in four patients with widely differing phenotypes. Patient 1 had a splice-site mutation causing premature termination. His general health was good despite absent GK activity, indicating that isolated GK deficiency can be silent. Patient 2 had GK deficiency and a severe phenotype involving psychomotor retardation and growth delay, bone dysplasia, and seizures, similar to the severe phenotype of one of the first described cases of GK deficiency. His younger brother, patient 3, also had GK deficiency, but so far his development has been normal. GK exon 17 was deleted in both brothers, implicating additional factors in causation of the severe phenotype of patient 2. Patient 4 had both GK deficiency with mental retardation and a GK missense mutation (D440V). Possible explanations for the phenotypic variation of these four patients include ascertainment bias; metabolic or environmental stress as a precipitating factor in revealing GK-related changes, as has previously been described in juvenile GK deficiency; and interactions with functional polymorphisms in other genes that alter the effect of GK deficiency on normal development. 36 refs., 4 figs., 1 tab.

QTLs and potential candidate genes for heat stress tolerance identified from the mapping populations specifically segregating for F_v/F_m in wheat

DEFF Research Database (Denmark)

Sharma, Dew Kumari; Torp, Anna Maria; Rosenqvist, Eva

2017-01-01

Despite the fact that F-v/F-m (maximum quantum efficiency of photosystem II) is the most widely used parameter for a rapid non-destructive measure of stress detection in plants, there are barely any studies on the genetic understanding of this trait under heat stress. Our aim was to identify...... quantitative trait locus (QTL) and the potential candidate genes linked to F-v/F-m for improved photosynthesis under heat stress in wheat (Triticum aestivum L.). Three bi-parental F-2 mapping populations were generated by crossing three heat tolerant male parents (origin: Afghanistan and Pakistan) selected...... for high F-v/F-m with a common heat susceptible female parent (origin: Germany) selected for lowest F-v/F-m out of a pool of 1274 wheat cultivars of diverse geographic origin. Parents together with 140 F-2 individuals in each population were phenotyped by F-v/F-m under heat stress (40 degrees C for 3 days...

Genome-Wide Association Study among Four Horse Breeds Identifies a Common Haplotype Associated with In Vitro CD3+ T Cell Susceptibility/Resistance to Equine Arteritis Virus Infection ▿

Science.gov (United States)

Go, Yun Young; Bailey, Ernest; Cook, Deborah G.; Coleman, Stephen J.; MacLeod, James N.; Chen, Kuey-Chu; Timoney, Peter J.; Balasuriya, Udeni B. R.

2011-01-01

Previously, we have shown that horses could be divided into susceptible and resistant groups based on an in vitro assay using dual-color flow cytometric analysis of CD3+ T cells infected with equine arteritis virus (EAV). Here, we demonstrate that the differences in in vitro susceptibility of equine CD3+ T lymphocytes to EAV infection have a genetic basis. To investigate the possible hereditary basis for this trait, we conducted a genome-wide association study (GWAS) to compare susceptible and resistant phenotypes. Testing of 267 DNA samples from four horse breeds that had a susceptible or a resistant CD3+ T lymphocyte phenotype using both Illumina Equine SNP50 BeadChip and Sequenom's MassARRAY system identified a common, genetically dominant haplotype associated with the susceptible phenotype in a region of equine chromosome 11 (ECA11), positions 49572804 to 49643932. The presence of a common haplotype indicates that the trait occurred in a common ancestor of all four breeds, suggesting that it may be segregated among other modern horse breeds. Biological pathway analysis revealed several cellular genes within this region of ECA11 encoding proteins associated with virus attachment and entry, cytoskeletal organization, and NF-κB pathways that may be associated with the trait responsible for the in vitro susceptibility/resistance of CD3+ T lymphocytes to EAV infection. The data presented in this study demonstrated a strong association of genetic markers with the trait, representing de facto proof that the trait is under genetic control. To our knowledge, this is the first GWAS of an equine infectious disease and the first GWAS of equine viral arteritis. PMID:21994447

Root Traits and Phenotyping Strategies for Plant Improvement.

Science.gov (United States)

Paez-Garcia, Ana; Motes, Christy M; Scheible, Wolf-Rüdiger; Chen, Rujin; Blancaflor, Elison B; Monteros, Maria J

2015-06-15

Roots are crucial for nutrient and water acquisition and can be targeted to enhance plant productivity under a broad range of growing conditions. A current challenge for plant breeding is the limited ability to phenotype and select for desirable root characteristics due to their underground location. Plant breeding efforts aimed at modifying root traits can result in novel, more stress-tolerant crops and increased yield by enhancing the capacity of the plant for soil exploration and, thus, water and nutrient acquisition. Available approaches for root phenotyping in laboratory, greenhouse and field encompass simple agar plates to labor-intensive root digging (i.e., shovelomics) and soil boring methods, the construction of underground root observation stations and sophisticated computer-assisted root imaging. Here, we summarize root architectural traits relevant to crop productivity, survey root phenotyping strategies and describe their advantages, limitations and practical value for crop and forage breeding programs.

Root Traits and Phenotyping Strategies for Plant Improvement

Directory of Open Access Journals (Sweden)

Ana Paez-Garcia

2015-06-01

Full Text Available Roots are crucial for nutrient and water acquisition and can be targeted to enhance plant productivity under a broad range of growing conditions. A current challenge for plant breeding is the limited ability to phenotype and select for desirable root characteristics due to their underground location. Plant breeding efforts aimed at modifying root traits can result in novel, more stress-tolerant crops and increased yield by enhancing the capacity of the plant for soil exploration and, thus, water and nutrient acquisition. Available approaches for root phenotyping in laboratory, greenhouse and field encompass simple agar plates to labor-intensive root digging (i.e., shovelomics and soil boring methods, the construction of underground root observation stations and sophisticated computer-assisted root imaging. Here, we summarize root architectural traits relevant to crop productivity, survey root phenotyping strategies and describe their advantages, limitations and practical value for crop and forage breeding programs.

Genome-wide transcriptomic analysis of BR-deficient Micro-Tom reveals correlations between drought stress tolerance and brassinosteroid signaling in tomato.

Science.gov (United States)

Lee, Jinsu; Shim, Donghwan; Moon, Suyun; Kim, Hyemin; Bae, Wonsil; Kim, Kyunghwan; Kim, Yang-Hoon; Rhee, Sung-Keun; Hong, Chang Pyo; Hong, Suk-Young; Lee, Ye-Jin; Sung, Jwakyung; Ryu, Hojin

2018-06-01

Brassinosteroids (BRs) are plant steroid hormones that play crucial roles in a range of growth and developmental processes. Although BR signal transduction and biosynthetic pathways have been well characterized in model plants, their biological roles in an important crop, tomato (Solanum lycopersicum), remain unknown. Here, cultivated tomato (WT) and a BR synthesis mutant, Micro-Tom (MT), were compared using physiological and transcriptomic approaches. The cultivated tomato showed higher tolerance to drought and osmotic stresses than the MT tomato. However, BR-defective phenotypes of MT, including plant growth and stomatal closure defects, were completely recovered by application of exogenous BR or complementation with a SlDWARF gene. Using genome-wide transcriptome analysis, 619 significantly differentially expressed genes (DEGs) were identified between WT and MT plants. Several DEGs were linked to known signaling networks, including those related to biotic/abiotic stress responses, lignification, cell wall development, and hormone responses. Consistent with the higher susceptibility of MT to drought stress, several gene sets involved in responses to drought and osmotic stress were differentially regulated between the WT and MT tomato plants. Our data suggest that BR signaling pathways are involved in mediating the response to abiotic stress via fine-tuning of abiotic stress-related gene networks in tomato plants. Copyright © 2018. Published by Elsevier Masson SAS.

Loss of end-differentiated β-cell phenotype following pancreatic islet transplantation.

Science.gov (United States)

Anderson, S J; White, M G; Armour, S L; Maheshwari, R; Tiniakos, D; Muller, Y D; Berishvili, E; Berney, T; Shaw, J A M

2018-03-01

Replacement of pancreatic β-cells through deceased donor islet transplantation is a proven therapy for preventing recurrent life-threatening hypoglycemia in type 1 diabetes. Although near-normal glucose levels and insulin independence can be maintained for many years following successful islet transplantation, restoration of normal functional β-cell mass has remained elusive. It has recently been proposed that dedifferentiation/plasticity towards other endocrine phenotypes may play an important role in stress-induced β-cell dysfunction in type 2 diabetes. Here we report loss of end-differentiated β-cell phenotype in 2 intraportal islet allotransplant recipients. Despite excellent graft function and sustained insulin independence, all examined insulin-positive cells had lost expression of the end-differentiation marker, urocortin-3, or appeared to co-express the α-cell marker, glucagon. In contrast, no insulin + /urocortin-3 - cells were seen in nondiabetic deceased donor control pancreatic islets. Loss of end-differentiated phenotype may facilitate β-cell survival during the stresses associated with islet isolation and culture, in addition to sustained hypoxia following engraftment. As further refinements in islet isolation and culture are made in parallel with exploration of alternative β-cell sources, graft sites, and ultimately fully vascularized bioengineered insulin-secreting microtissues, differentiation status immunostaining provides a novel tool to assess whether fully mature β-cell phenotype has been maintained. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Amelioration of oxidative stress-induced phenotype loss of parvalbumin interneurons might contribute to the beneficial effects of environmental enrichment in a rat model of post-traumatic stress disorder.

Science.gov (United States)

Sun, Xiao R; Zhang, Hui; Zhao, Hong T; Ji, Mu H; Li, Hui H; Wu, Jing; Li, Kuan Y; Yang, Jian J

2016-10-01

Post-traumatic stress disorder (PTSD) is a common psychiatric disease following exposure to a severe traumatic event or physiological stress, which is characterized by anxiety- and depression-like behaviors and cognitive impairment. However, the underlying mechanisms remain elusive. Parvalbumin (PV) interneurons that are susceptible to oxidative stress are a subset of inhibitory GABAergic neurons regulating the excitability of pyramidal neurons, while dysfunction of PV interneurons is casually linked to many mental disorders including PTSD. We therefore hypothesized that environmental enrichment (EE), a method of enhanced cognitive, sensory and motor stimulation, can reverse the behavioral impairments by normalizing PV interneurons in a rat model of PTSD induced by inescapable foot shocks (IFS). Behavioral changes were determined by the open field, elevated plus maze, fear conditioning, and Morris water maze tests. The levels of nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), NOX4, PV, glutamic acid decarboxylase 67 (GAD-67), and 8-hydroxy-2-deoxyguanosine (8-OH-dG) in the hippocampus and prefrontal cortex were determined. Our results showed that in this PTSD model, rats displayed the anxiety-like behavior, enhanced fear learning behavior, and hippocampus- dependent spatial memory deficit, which were accompanied by the up-regulation of NOX2, 8-OH-dG, and down-regulation of PV and GAD-67. Notably, EE reversed all these abnormalities. These results suggest that restoration of PV interneurons by inhibiting oxidative stress in the hippocampus and prefrontal cortex might represent a mechanism through which EE reverses the behavioral impairments in a rat model of PTSD induced by IFS. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessment of Susceptibility to Liquefaction of Saturated Road Embankment Subjected to Dynamic Loads

Science.gov (United States)

Borowiec, Anna; Maciejewski, Krzysztof

2014-03-01

Liquefaction has always been intensely studied in parts of the world where earthquakes occur. However, the seismic activity is not the only possible cause of this phenomenon. It may in fact be triggered by some human activities, such as constructing and mining or by rail and road transport. In the paper a road embankment built across a shallow water reservoir is analyzed in terms of susceptibility to liquefaction. Two types of dynamic loadings are considered: first corresponding to an operation of a vibratory roller and second to an earthquake. In order to evaluate a susceptibility of soil to liquefaction, a factor of safety against triggering of liquefaction is used (FSTriggering). It is defined as a ratio of vertical effective stresses to the shear stresses both varying with time. For the structure considered both stresses are obtained using finite element method program, here Plaxis 2D. The plastic behavior of the cohesionless soils is modeled by means of Hardening Soil (HS) constitutive relationship, implemented in Plaxis software. As the stress tensor varies with time during dynamic excitation, the FSTriggering has to be calculated for some particular moment of time when liquefaction is most likely to occur. For the purposes of this paper it is named a critical time and established for reference point at which the pore pressures were traced in time. As a result a factor of safety distribution throughout embankment is generated. For the modeled structure, cyclic point loads (i.e., vibrating roller) present higher risk than earthquake of magnitude 5.4. Explanation why considered structure is less susceptible to earthquake than typical dam could lay in stabilizing and damping influence of water, acting here on both sides of the slope. Analogical procedure is applied to assess liquefaction susceptibility of the road embankment considered but under earthquake excitation. Only the higher water table is considered as it is the most unfavorable. Additionally the

Early Life Stress, Nicotinic Acetylcholine Receptors and Alcohol Use Disorders

Directory of Open Access Journals (Sweden)

Joan Y. Holgate

2015-06-01

Full Text Available Stress is a major driving force in alcohol use disorders (AUDs. It influences how much one consumes, craving intensity and whether an abstinent individual will return to harmful alcohol consumption. We are most vulnerable to the effects of stress during early development, and exposure to multiple traumatic early life events dramatically increases the risk for AUDs. However, not everyone exposed to early life stress will develop an AUD. The mechanisms determining whether an individual’s brain adapts and becomes resilient to the effects of stress or succumbs and is unable to cope with stress remain elusive. Emerging evidence suggests that neuroplastic changes in the nucleus accumbens (NAc following early life stress underlie the development of AUDs. This review discusses the impact of early life stress on NAc structure and function, how these changes affect cholinergic signaling within the mesolimbic reward pathway and the role nicotinic acetylcholine receptors (nAChRs play in this process. Understanding the neural pathways and mechanism determining stress resilience or susceptibility will improve our ability to identify individuals susceptible to developing AUDs, formulate cognitive interventions to prevent AUDs in susceptible individuals and to elucidate and enhance potential therapeutic targets, such as the nAChRs, for those struggling to overcome an AUD.

Systematic genotype-phenotype analysis of autism susceptibility loci implicates additional symptoms to co-occur with autism

NARCIS (Netherlands)

Buizer-Voskamp, Jacobine E.; Franke, Lude; Staal, Wouter G.; van Daalen, Emma; Kemner, Chantal; Ophoff, Roel A.; Vorstman, Jacob A. S.; van Engeland, Herman; Wijmenga, Cisca

2010-01-01

Many genetic studies in autism have been performed, resulting in the identification of multiple linkage regions and cytogenetic aberrations, but little unequivocal evidence for the involvement of specific genes exists. By identifying novel symptoms in these patients, enhanced phenotyping of autistic

Candida Species From Eye Infections: Drug Susceptibility, Virulence Factors, and Molecular Characterization.

Science.gov (United States)

Ranjith, Konduri; Sontam, Bhavani; Sharma, Savitri; Joseph, Joveeta; Chathoth, Kanchana N; Sama, Kalyana C; Murthy, Somasheila I; Shivaji, Sisinthy

2017-08-01

To determine the type of Candida species in ocular infections and to investigate the relationship of antifungal susceptibility profile to virulence factors. Fifty isolates of yeast-like fungi from patients with keratitis, endophthalmitis, and orbital cellulitis were identified by Vitek-2 compact system and DNA sequencing of ITS1-5.8S-ITS2 regions of the rRNA gene, followed by phylogenetic analysis for phenotypic and genotypic identification, respectively. Minimum inhibitory concentration of six antifungal drugs was determined by E test/microbroth dilution methods. Phenotypic and genotypic methods were used to determine the virulence factors. Phylogenetic analysis showed the clustering of all isolates into eight distinct groups with a major cluster formed Candida parapsilosis (n = 21), which was the most common species by both Vitek 2 and DNA sequencing. Using χ2 test no significant difference was noted between the techniques except that Vitek 2 did not identify C. viswanathii, C. orthopsilosis, and two non-Candida genera. Of 43 tested Candida isolates high susceptibility to amphotericin B (39/43, 90.6%) and natamycin (43/43, 100%) was noted. While none of the isolates produced coagulase, all produced esterase and catalase. The potential to form biofilm was detected in 23/43 (53.4%) isolates. Distribution of virulence factors by heat map analysis showed difference in metabolic activity of biofilm producers from nonbiofilm producers. Identified by Vitek 2 and DNA sequencing methods C. parapsilosis was the most common species associated with eye infections. Irrespective of the virulence factors elaborated, the Candida isolates were susceptible to commonly used antifungal drugs such as amphotericin B and natamycin.

Phenotypic low-level isoniazid resistance as a marker to predict ethionamide resistance in Mycobacterium tuberculosis

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Salima Qamar

2017-01-01

Full Text Available Background: Tuberculosis is one of the most prevalent diseases in Pakistan. Pakistan has the highest burden of MDR-TB in the Eastern Mediterranean region. Ethionamide is an anti-tuberculous drug frequently used to treat MDR-TB. Its drug susceptibility testing is not easily available in resource limited settings. Since it acts on the same target protein as isoniazid (inhA protein encoded by inhA gene, we sought to find out if phenotypic isoniazid resistance can be a marker of ethionamide resistance. Materials and Methods: This was a retrospective observational study conducted at the Aga Khan University hospital section of microbiology. Data was retrieved between 2011 to 2014 for all culture positive MTB strains. All culture positive MTB isolates with susceptibilities to isoniazid and ethionamide recorded were included in the study. Isoniazid and ethionamide susceptibilities were performed using agar proportion method on Middlebrook 7H10 agar. Rate of Ethionamide resistance between low-level isoniazid resistant, high level isoniazid resistant and isoniazid sensitive MTB was compared. Results: A total of 11,274 isolates were included in the study. A statistically significant association (P < 0.001 was found between Ethionamide resistance and low-level isoniazid resistance (26.6% as compared to high-level isoniazid resistance (8.85% and isoniazid sensitivity (0.71% in MTB strains. However this association was not seen in XDR-TB strains. Conclusion: Low level isoniazid resistance may be used as marker for phenotypic ethionamide resistance and hence guide clinicians' choice of antituberculous agent for MDR-TB in Pakistan. Further studies involving detection of genotypic association of isoniazid and ethionamide susceptibilities are needed before a final conclusion can be derived.

Association of STAT4 polymorphisms with susceptibility to type-1 autoimmune hepatitis in the Japanese population.

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Migita, Kiyoshi; Nakamura, Minoru; Abiru, Seigo; Jiuchi, Yuka; Nagaoka, Shinya; Komori, Atsumasa; Hashimoto, Satoru; Bekki, Shigemune; Yamasaki, Kazumi; Komatsu, Tatsuji; Shimada, Masaaki; Kouno, Hiroshi; Hijioka, Taizo; Kohjima, Motoyuki; Nakamuta, Makoto; Kato, Michio; Yoshizawa, Kaname; Ohta, Hajime; Nakamura, Yoko; Takezaki, Eiichi; Nishimura, Hideo; Sato, Takeaki; Ario, Keisuke; Hirashima, Noboru; Oohara, Yukio; Naganuma, Atsushi; Muro, Toyokichi; Sakai, Hironori; Mita, Eiji; Sugi, Kazuhiro; Yamashita, Haruhiro; Makita, Fujio; Yatsuhashi, Hiroshi; Ishibashi, Hiromi; Yasunami, Michio

2013-01-01

Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study. Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694). The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23-2.11; P = 0.001), and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13-1.99; P = 0.005). Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44) or without liver cirrhosis (n = 186) demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies). This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.

Antimicrobial susceptibility profiles of Staphylococcus spp. from domestic and wild animals

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Isabela de Godoy

Full Text Available ABSTRACT: The aim of this study was to determine the prevalence and diversity of veterinary clinical isolates of Staphylococcus and analyze their antimicrobial susceptibility. One hundred Staphylococcus spp. clinical isolates from domestic and wild animals were subjected to partial sequencing of the 16S rRNA gene to species determination. Antimicrobial susceptibility was obtained by a disk diffusion test against six antibiotics: amoxicillin (AMX, cephalexin (LEX, ciprofloxacin (CIP, erythromycin (ERY, gentamicin (GEN and trimethoprim-sulfamethoxazole (SXT. The most common specie was S. pseudintermedius (61%, 61/100 and resistance to ERY (57%, 57/100, SXT (50%, 50/100 and AMX (46%, 46/100 was detected most frequently. In total, 40% (40/100 of Staphylococcus spp. exhibited a multidrug-resistant (MDR phenotype. Results of this study emphasize that animals are reservoir of MDR Staphylococcus spp.

Phenotypic and genetic characterization of Piscirickettsia salmonis from Chilean and Canadian salmonids.

Science.gov (United States)

Otterlei, Alexander; Brevik, Øyvind J; Jensen, Daniel; Duesund, Henrik; Sommerset, Ingunn; Frost, Petter; Mendoza, Julio; McKenzie, Peter; Nylund, Are; Apablaza, Patricia

2016-03-15

The study presents the phenotypic and genetic characterization of selected P. salmonis isolates from Atlantic salmon and rainbow trout suffering from SRS (salmonid rickettsial septicemia) in Chile and in Canada. The phenotypic characterization of the P. salmonis isolates were based on growth on different agar media (including a newly developed medium), different growth temperatures, antibiotics susceptibility and biochemical tests. This is the first study differentiating Chilean P. salmonis isolates into two separate genetic groups. Genotyping, based on 16S rRNA-ITS and concatenated housekeeping genes grouped the selected isolates into two clades, constituted by the Chilean strains, while the Canadian isolates form a branch in the phylogenetic tree. The latter consisted of two isolates that were different in both genetic and phenotypic characteristics. The phylogenies and the MLST do not reflect the origin of the isolates with respect to host species. The isolates included were heterogeneous in phenotypic tests. The genotyping methods developed in this study provided a tool for separation of P. salmonis isolates into distinct clades. The SRS outbreaks in Chile are caused by minimum two different genetic groups of P. salmonis. This heterogeneity should be considered in future development of vaccines against this bacterium in Chile. Two different strains of P. salmonis, in regards to genetic and phenotypic characteristics, can occur in the same contemporary outbreak of SRS.

Residual Stresses in SAVY 4000 and Hagan Container Bodies

Energy Technology Data Exchange (ETDEWEB)

Stroud, Mary Ann [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hill, Mary Ann [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Tokash, Justin Charles [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Forsyth, Robert Thomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hyer, Holden Christopher [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-11-02

Chloride-induced stress corrosion cracking (SCC) has been investigated as a potential failure mechanism for the SAVY 4000 and the Hagan containers used to store plutonium-bearing materials at Los Alamos National Laboratory. This report discusses the regions of the container bodies most susceptible to SCC and the magnitude of the residual stresses in those regions. Boiling MgCl2 testing indicated that for both containers the region near the top weld was most susceptible to SCC. The Hagan showed through wall cracking after 22-24 hours of exposure both parallel (axial stresses) and perpendicular (hoop stresses) to the weld. The SAVY 4000 container showed significant cracking above and below the weld after 47 hours of exposure but there was no visual evidence of a through wall crack and the cracks did not leak water. Two through wall holes formed in the bottom of the SAVY 4000 container after 44-46 hours of exposure. For both containers, average “through wall” residual stresses were determined from hole drilling data 4 mm below the weld. In the Hagan body, average tensile hoop stresses were 194 MPa and average compressive axial stresses were -120 MPa. In the SAVY 4000 body, average compressive hoop stresses were 11 MPa and average tensile axial stresses were 25 MPa. Results suggest that because the Hagan container exhibited through wall cracking in a shorter time in boiling MgCl2 and had the higher average tensile stress, 194 MPa hoop stress, it is more susceptible to SCC than the SAVY 4000 container.

Colorectal Adenomatous Polyposis: Heterogeneity of Susceptibility Gene Mutations and Phenotypes in a Cohort of Italian Patients.

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Marabelli, Monica; Molinaro, Valeria; Abou Khouzam, Raefa; Berrino, Enrico; Panero, Mara; Balsamo, Antonella; Venesio, Tiziana; Ranzani, Guglielmina Nadia

2016-12-01

Colorectal adenomatous polyposis entailing cancer predisposition is caused by constitutional mutations in different genes. APC is associated with the familial adenomatous polyposis (FAP/AFAP) and MUTYH with the MUTYH-associated polyposis (MAP), while POLE and POLD1 mutations cause the polymerase proofreading-associated polyposis (PPAP). We screened for mutations in patients with multiple adenomas/FAP: 121 patients were analyzed for APC and MUTYH mutations, and 36 patients were also evaluated for POLE and POLD1 gene mutations. We found 20 FAP/AFAP, 15 MAP, and no PPAP subjects: pathogenic mutations proved to be heterogeneous, and included 5 APC and 1 MUTYH novel mutations. The mutation detection rate was significantly different between patients with 5-100 polyps and those with >100 polyps (p = 8.154 × 10 -7 ), with APC mutations being associated with an aggressive phenotype (p = 1.279 × 10 -9 ). Mean age at diagnosis was lower in FAP/AFAP compared to MAP (p = 3.055 × 10 -4 ). Mutation-negative probands showed a mean age at diagnosis that was significantly higher than FAP/AFAP (p = 3.46986 × 10 -7 ) and included 45.3% of patients with <30 polyps and 70.9% of patients with no family history. This study enlarges the APC and MUTYH mutational spectra, and also evaluated variants of uncertain significance, including the MUTYH p.Gln338His mutation. Moreover this study underscores the phenotypic heterogeneity and genotype-phenotype correlations in a cohort of Italian patients.

Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

International Nuclear Information System (INIS)

Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

2009-01-01

Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

HLA associations reveal genetic heterogeneity in psoriatic arthritis and in the psoriasis phenotype.

LENUS (Irish Health Repository)

Winchester, Robert

2012-04-01

Rigorously ascertained cases of psoriatic arthritis in subjects presenting to a rheumatology unit were compared with cases of psoriasis in subjects presenting to a dermatology unit, where subjects with musculoskeletal features were excluded, to address 1) the extent to which the contribution of the major histocompatibility complex (MHC) to psoriatic arthritis susceptibility resembles that in psoriasis, and 2) whether MHC genes determine quantitative traits within the psoriatic arthritis phenotype.

Phenotypic detection of beta-lactamases production in enterobacteriaceae

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Ćirković Ivana

2014-01-01

Full Text Available Introduction. Beta-lactam antibiotics are the most commonly used antibacterial drugs. However, many bacteria have developed resistance to these antibiotics, and the most common form of resistance is the production of beta-lactamase enzymes. Many members of the Enterobacteriaceae family produce different types of these enzymes. Objective. The aim of this study was to perform phenotypic detection of production and identification of beta-lactamase type in Enterobacteriaceae isolated from different clinical specimens from patients hospitalized in the Clinical Center of Serbia. Methods. The strains of Enterobacteriaceae were collected between November 2011 and January 2012 in the laboratory of the Clinical Center of Serbia. The isolates were identified according to the standard microbiology procedures and confirmed by the Vitek2 automated system. Antimicrobial susceptibility testing was performed by the disk diffusion method, and the phenotypic detection of production and identification of betalactamases was performed according to previously described methodologies. Results. In this study, a total of 172 Enterobacteriaceae strains were isolated. Further testing was performed on 54/145 (37.2% strains showing decreased susceptibility to beta-lactam antibiotics: 13/85 (15.3% Escherichia coli, 31/46 (67.4% Klebsiella pneumoniae and 10/14 (71.4% Proteus mirabilis. Among them, 40/145 (27.6% strains produced extended spectrum betalactamases (ESBLs, 9/145 (6.2% - AmpC, 1/145 (0.7% - K1 beta-lactamase and 4/145 (2.8% - carbapenemases. Carbapenemases were predominantly detected in K. pneumoniae (75%. Conclusion. Enterobacteriaceae produce different types of betalactamases, and the most common type in our study was ESBLs. Production of carbapenemases detected in Enterobacteriaceae is also an associated problem. [Projekat Ministarstva nauke Republike Srbije, br. ON 175039

Detection of the tetM resistance determinant among phenotypically sensitive Ureaplasma species by a novel real-time PCR method.

Science.gov (United States)

Kotrotsiou, Tzimoula; Tzimoula, Kotrotsiou; Exindari, Maria; Maria, Exindari; Diza, Eudoxia; Eudoxia, Diza; Gioula, Georgia; Georgia, Gioula; Melidou, Angeliki; Angeliki, Melidou; Malisiovas, Nikolaos; Nikolaos, Malisiovas

2015-02-01

The study aimed to identify the proportion of tetM-positive Ureaplasma spp. isolates phenotypically susceptible to tetracycline by real-time PCR. Ureaplasma spp. strains of urogenital origin were isolated from 100 female or male adults on A7 agar plates. The presence of Ureaplasma was confirmed by the presence of urease gene by a novel real-time PCR method. Genotyping and sensitivity to tetracyclines were examined using commercial methods. The tetM gene was detected by a novel real-time PCR method especially designed for this study. Ureaplasma parvum was isolated from 87 of the specimens; Ureaplasma urealyticum, from 12; and both species were isolated from a single specimen. All isolates were phenotypically susceptible to tetracyclines. Thirty-five strains were tetM carriers; 29 (82.9%), U. parvum; 5 (14.3%), U. urealyticum; and 1 (2.9%), U. parvum/U. urealyticum. No statistically significant difference was observed between the 3 groups. Four (40%) tetM carriers were isolated from 10 symptomatic men; 11 (32.4%), from 34 symptomatic women; and 20 (35.7%), from 56 asymptomatic women. No statistically significant difference was observed between the 3 groups. The tetM determinant is detected in 35% of phenotypically susceptible to tetracycline Ureaplasma spp. Greek isolates. The use of a real-time PCR technique is particularly helpful, as it makes its detection easy; cost-effective; rapid; and, therefore, more convenient for the surveillance of the dissemination of the tetM resistance gene. Copyright © 2015 Elsevier Inc. All rights reserved.

Estimation of psychological stress in humans: a combination of theory and practice.

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Parul Sood

Full Text Available Stress has long been known to increase susceptibility to health disorders. In 2009, American Psychological Association further established association of stress to serious health problems. However, a quantitative and accurate way to evaluate and estimate stress status of individuals is still a big challenge. It has been shown, in large animal models using cattle, that psychological stress can be quantified as well as disease susceptibility could be predicted through biomarker discovery. Taking cue from those studies, we have evaluated and estimated psychological stress level of individuals theoretically and validated experimentally. Various biomarkers have also been identified which can be associated to psychological stress to predict stress status of unknown individuals.

Phenotypic and Genotypic Features of a Salmonella Heidelberg Strain Isolated in Broilers in Brazil and Their Possible Association to Antibiotics and Short-Chain Organic Acids Resistance and Susceptibility.

Science.gov (United States)

Santin, Elizabeth; Hayashi, Ricardo Mitsuo; Wammes, Jessica Caroline; Gonzalez-Esquerra, Ricardo; Carazzolle, Marcelo Falsarella; Freire, Caio César de Melo; Monzani, Paulo Sérgio; da Cunha, Anderson Ferreira

2017-01-01

Salmonella enterica serovar Heidelberg is a human pathogen also found in broilers. A strain (UFPR1) has been associated with field reports of resistance to short-chain organic acids (SCOA) in broilers in the South of Brazil, but was susceptible to a Bacillus subtilis -based probiotic added in feed in a related study. This work aimed to (i) report clinical symptoms caused by SH UFPR1 in broilers, (ii) study its susceptibility to some antibiotics in vitro , and (iii) SCOA in vivo ; and (iv) relate these phenotypic observations with its genome characteristics. Two in vivo trials used 1-day-old chicks housed for 21 days in 8 sterilized isolated negative pressure rooms with 4 battery cages of 12 birds each. Birds were challenged or not with 10 7  CFU/bird of SH UFPR1 orally and exposed or not to SCOA in a 2 × 2 factorial design. Zootechnical parameters were unaffected ( P  > 0.05), no clinical signs were observed, and few cecal and hepatic histologic and immune-related alterations were seen, in birds challenged with SH. Formic and propionic acids added together in drinking water, fumaric and benzoic acid in feed (Trial 1), and coated calcium butyrate in feed (Trial 2) did not reduce the SH isolation frequencies seen in cecum and liver in broilers after SH challenge ( P  > 0.05). SH UFPR1 was susceptible to amikacin, amoxicillin + clavulanate, ceftiofur, cephalexin, doxycycline and oxytetracycline; and mildly susceptible to ampicillin + sulbactam, cephalothin, ciprofloxacin, enrofloxacin, and gentamycin in an in vitro minimum inhibitory concentration model using Mueller-Hinton agar. The whole genome of SH UFPR1 was sequenced and consisted of a circular chromosome, spanning 4,760,321 bp with 52.18% of GC-content encoding 84 tRNA, 22 rRNA, and 4,427 protein-coding genes. The comparison between SH UFPR1 genome and a multidrug-resistant SL476 strain revealed 11 missing genomic fragments and 5 insertions related to bgt, bgr , and rpoS genes. The

Phenotypic and Genotypic Features of a Salmonella Heidelberg Strain Isolated in Broilers in Brazil and Their Possible Association to Antibiotics and Short-Chain Organic Acids Resistance and Susceptibility

Directory of Open Access Journals (Sweden)

Elizabeth Santin

2017-11-01

Full Text Available Salmonella enterica serovar Heidelberg is a human pathogen also found in broilers. A strain (UFPR1 has been associated with field reports of resistance to short-chain organic acids (SCOA in broilers in the South of Brazil, but was susceptible to a Bacillus subtilis-based probiotic added in feed in a related study. This work aimed to (i report clinical symptoms caused by SH UFPR1 in broilers, (ii study its susceptibility to some antibiotics in vitro, and (iii SCOA in vivo; and (iv relate these phenotypic observations with its genome characteristics. Two in vivo trials used 1-day-old chicks housed for 21 days in 8 sterilized isolated negative pressure rooms with 4 battery cages of 12 birds each. Birds were challenged or not with 107 CFU/bird of SH UFPR1 orally and exposed or not to SCOA in a 2 × 2 factorial design. Zootechnical parameters were unaffected (P > 0.05, no clinical signs were observed, and few cecal and hepatic histologic and immune-related alterations were seen, in birds challenged with SH. Formic and propionic acids added together in drinking water, fumaric and benzoic acid in feed (Trial 1, and coated calcium butyrate in feed (Trial 2 did not reduce the SH isolation frequencies seen in cecum and liver in broilers after SH challenge (P > 0.05. SH UFPR1 was susceptible to amikacin, amoxicillin + clavulanate, ceftiofur, cephalexin, doxycycline and oxytetracycline; and mildly susceptible to ampicillin + sulbactam, cephalothin, ciprofloxacin, enrofloxacin, and gentamycin in an in vitro minimum inhibitory concentration model using Mueller–Hinton agar. The whole genome of SH UFPR1 was sequenced and consisted of a circular chromosome, spanning 4,760,321 bp with 52.18% of GC-content encoding 84 tRNA, 22 rRNA, and 4,427 protein-coding genes. The comparison between SH UFPR1 genome and a multidrug-resistant SL476 strain revealed 11 missing genomic fragments and 5 insertions related to bgt, bgr, and rpoS genes. The

Functional analysis of atfA gene to stress response in pathogenic thermal dimorphic fungus Penicillium marneffei.

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Panjaphorn Nimmanee

Full Text Available Penicillium marneffei, the pathogenic thermal dimorphic fungus is a causative agent of a fatal systemic disease, penicilliosis marneffei, in immunocompromised patients especially HIV patients. For growth and survival, this fungus has to adapt to environmental stresses outside and inside host cells and this adaptation requires stress signaling pathways and regulation of gene expression under various kinds of stresses. In this report, P. marneffei activating transcription factor (atfA gene encoding bZip-type transcription factor was characterized. To determine functions of this gene, atfA isogenic mutant strain was constructed using the modified split marker recombination method. The phenotypes and susceptibility to varieties of stresses including osmotic, oxidative, heat, UV, cell wall and cell membrane stresses of the mutant strain were compared with the wild type and the atfA complemented strains. Results demonstrated that the mRNA expression level of P. marneffei atfA gene increased under heat stress at 42°C. The atfA mutant was more sensitive to sodium dodecyl sulphate, amphotericin B and tert-butyl hydroperoxide than the wild type and complemented strains but not hydrogen peroxide, menadione, NaCl, sorbitol, calcofluor white, itraconazole, UV stresses and heat stress at 39°C. In addition, recovery of atfA mutant conidia after mouse and human macrophage infections was significantly decreased compared to those of wild type and complemented strains. These results indicated that the atfA gene was required by P. marneffei under specific stress conditions and might be necessary for fighting against host immune cells during the initiation of infection.

High-throughput phenotyping to detect drought tolerance QTL in wild barley introgression lines

KAUST Repository

Honsdorf, Nora

2014-05-13

Drought is one of the most severe stresses, endangering crop yields worldwide. In order to select drought tolerant genotypes, access to exotic germplasm and efficient phenotyping protocols are needed. In this study the high-throughput phenotyping platform "The Plant Accelerator", Adelaide, Australia, was used to screen a set of 47 juvenile (six week old) wild barley introgression lines (S42ILs) for drought stress responses. The kinetics of growth development was evaluated under early drought stress and well watered treatments. High correlation (r = 0.98) between image based biomass estimates and actual biomass was demonstrated, and the suitability of the system to accurately and non-destructively estimate biomass was validated. Subsequently, quantitative trait loci (QTL) were located, which contributed to the genetic control of growth under drought stress. In total, 44 QTL for eleven out of 14 investigated traits were mapped, which for example controlled growth rate and water use efficiency. The correspondence of those QTL with QTL previously identified in field trials is shown. For instance, six out of eight QTL controlling plant height were also found in previous field and glasshouse studies with the same introgression lines. This indicates that phenotyping juvenile plants may assist in predicting adult plant performance. In addition, favorable wild barley alleles for growth and biomass parameters were detected, for instance, a QTL that increased biomass by approximately 36%. In particular, introgression line S42IL-121 revealed improved growth under drought stress compared to the control Scarlett. The introgression line showed a similar behavior in previous field experiments, indicating that S42IL-121 may be an attractive donor for breeding of drought tolerant barley cultivars. © 2014 Honsdorf et al.

High-throughput phenotyping to detect drought tolerance QTL in wild barley introgression lines.

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Nora Honsdorf

Full Text Available Drought is one of the most severe stresses, endangering crop yields worldwide. In order to select drought tolerant genotypes, access to exotic germplasm and efficient phenotyping protocols are needed. In this study the high-throughput phenotyping platform "The Plant Accelerator", Adelaide, Australia, was used to screen a set of 47 juvenile (six week old wild barley introgression lines (S42ILs for drought stress responses. The kinetics of growth development was evaluated under early drought stress and well watered treatments. High correlation (r=0.98 between image based biomass estimates and actual biomass was demonstrated, and the suitability of the system to accurately and non-destructively estimate biomass was validated. Subsequently, quantitative trait loci (QTL were located, which contributed to the genetic control of growth under drought stress. In total, 44 QTL for eleven out of 14 investigated traits were mapped, which for example controlled growth rate and water use efficiency. The correspondence of those QTL with QTL previously identified in field trials is shown. For instance, six out of eight QTL controlling plant height were also found in previous field and glasshouse studies with the same introgression lines. This indicates that phenotyping juvenile plants may assist in predicting adult plant performance. In addition, favorable wild barley alleles for growth and biomass parameters were detected, for instance, a QTL that increased biomass by approximately 36%. In particular, introgression line S42IL-121 revealed improved growth under drought stress compared to the control Scarlett. The introgression line showed a similar behavior in previous field experiments, indicating that S42IL-121 may be an attractive donor for breeding of drought tolerant barley cultivars.

NASAs VESGEN: Systems Analysis of Vascular Phenotypes from Stress and Other Signaling Pathways Using GeneLab.

Science.gov (United States)

Parsons-Wingerter, Patricia A.; Weitzel, Alexander; Vyas, Ruchi J.; Murray, Matthew C.; Wyatt, Sarah E.

2016-01-01

One fundamental requirement shared by humans with all higher terrestrial life forms, including insect wings, higher land plants and other vertebrates, is a complex, fractally branching vascular system. NASA's VESsel GENeration Analysis (VESGEN) software maps and quantifies vascular trees, networks, and tree-network composites according to weighted physiological rules such as vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport requires a complex distributed system of highly regulated laminar flow. Microvascular branching rules within vertebrates, dicot leaves and the other organisms therefore display many similarities. One unifying perspective is that vascular patterning offers a useful readout that necessarily integrates complex molecular signaling pathways. VESGEN has elucidated changes in vascular pattern resulting from inflammatory, stress response, developmental and other signaling within numerous tissues and major model organisms studied for Space Biology. For a new VESGEN systems approach, we analyzed differential gene expression in leaves of Arabidopsis thaliana reported by GeneLab (GLDS-7) for spaceflight. Vascular-related changes in leaf gene expression were identified that can potentially be phenocopied by mutants in ground-based experiments. To link transcriptional, protein and other molecular change with phenotype, alterations in the Euclidean and dynamic dimensions (x,y,t) of vascular patterns for Arabidopsis leaves and other model species are being co-localized with signaling patterns of single molecular expression analyzed as information dimensions (i,j,k,...). Previously, Drosophila microarray data returned from space suggested significant changes in genes related to wing venation development that include EGF, Notch, Hedghog, Wingless and Dpp signaling. Phenotypes of increasingly abnormal ectopic wing venation in the (non-spaceflight) Drosophila wing generated by overexpression of a

Developmental post-natal stress can alter the effects of pre-natal stress on the adult redox balance.

Science.gov (United States)

Marasco, Valeria; Spencer, Karen A; Robinson, Jane; Herzyk, Pawel; Costantini, David

2013-09-15

Across diverse vertebrate taxa, stressful environmental conditions during development can shape phenotypic trajectories of developing individuals, which, while adaptive in the short-term, may impair health and survival in adulthood. Regardless, the long-lasting benefits or costs of early life stress are likely to depend on the conditions experienced across differing stages of development. Here, we used the Japanese quail (Coturnix coturnix japonica) to experimentally manipulate exposure to stress hormones in developing individuals. We tested the hypothesis that interactions occurring between pre- and post-natal developmental periods can induce long-term shifts on the adult oxidant phenotype in non-breeding sexually mature individuals. We showed that early life stress can induce long-term alterations in the basal antioxidant defences. The magnitude of these effects depended upon the timing of glucocorticoid exposure and upon interactions between the pre- and post-natal stressful stimuli. We also found differences among tissues with stronger effects in the erythrocytes than in the brain in which the long-term effects of glucocorticoids on antioxidant biomarkers appeared to be region-specific. Recent experimental work has demonstrated that early life exposure to stress hormones can markedly reduce adult survival (Monaghan et al., 2012). Our results suggest that long-term shifts in basal antioxidant defences might be one of the potential mechanisms driving such accelerated ageing processes and that post-natal interventions during development may be a potential tool to shape the effects induced by pre-natally glucococorticoid-exposed phenotypes. Copyright © 2013 Elsevier Inc. All rights reserved.

Phenotypic and genetic characteristics of fluoroquinolone- and methicillin-resistant Staphylococcus aureus.

Science.gov (United States)

Moreno-Flores, Antonio; Potel-Alvarellos, Carmen; Otero-Fernández, Susana; Álvarez-Fernández, Maximiliano

2017-07-20

Fluoroquinolone resistance in methicillin-resistant Staphylococcus aureus (MRSA) has increased in recent years. The objective of this study was to characterise two MRSA populations, one susceptible to fluoroquinolones and other resistant identifying the clonal types and the differential characteristics of both MRSA populations. Molecular typing using PFGE, MLST, spa and SSCmec was performed on 192 MRSA strains isolated from 2009 to 2011, 49 only oxacillin-resistant (OX-R) and 143 oxacillin and levofloxacin-resistant (OX-R-LEV-R). Mutations that conferred resistance to fluoroquinolones, hypermutable phenotypes and the presence of eight microbial surface components recognising adhesive matrix molecules (MSCRAMMs) were also studied. A statistically significant increase in the OX-R-LEV-R phenotype was observed (p<0.05). The most common clone of the OX-R isolates was sequence type (ST) 8 (32.6%), followed by ST72 (26.5%) and ST5 (26.5%). In the OX-R-LEV-R phenotype, the ST5 clone was the most common (65.7%), followed by ST72 (15.4%), and ST125 (12.6%). All isolates except the ST398 clone carried the SCCmecIVc. Clones ST5, ST72, ST125, and ST30 had hypermutable phenotypes. The ST72 clone and the ST30 clone in the OX-R phenotype harboured the highest number of MSCRAMMs. ST5 and ST72 clones were the most frequent clones identified in OX-R-LEV-R phenotype. Both clones showed a hypermutable phenotype that favours their selection as the fluoroquinolone resistant clones. The genetic relationships identified indicate that OX-R-LEV-R clones have evolved from OX-R MRSA clones. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Comprehensive phenotypic analysis of rice (Oryza sativa) response to salinity stress

KAUST Repository

Pires, Inê s S.; Negrã o, Só nia; Oliveira, M. Margarida; Purugganan, Michael D.

2015-01-01

affected by salt stress in rice, which puts in question the importance of K+/Na+ when analyzing rice salt stress response. Not only do our results contribute to improve our global understanding of salt stress response in an important crop, but we also use

Feasibility study of determining axial stress in ferromagnetic bars using reciprocal amplitude of initial differential susceptibility obtained from static magnetization by permanent magnets

Science.gov (United States)

Deng, Dongge; Wu, Xinjun

2018-03-01

An electromagnetic method for determining axial stress in ferromagnetic bars is proposed. In this method, the tested bar is under the static magnetization provided by permanent magnets. The tested bar do not have to be magnetized up to the technical saturation because reciprocal amplitude of initial differential susceptibility (RAIDS) is adopted as the feature parameter. RAIDS is calculated from the radial magnetic flux density Br Lo = 0.5 at the Lift-off Lo = 0.5 mm, radial magnetic flux density Br Lo = 1 at the Lift-off Lo = 1 mm and axial magnetic flux density Bz Lo = 1 at the Lift-off Lo = 1 mm from the surface of the tested bar. Firstly, the theoretical derivation of RAIDS is carried out according to Gauss' law for magnetism, Ampere's Law and the Rayleigh relation in Rayleigh region. Secondly, the experimental system is set up for a 2-meter length and 20 mm diameter steel bar. Thirdly, an experiment is carried out on the steel bar to analyze the relationship between the obtained RAIDS and the axial stress. Experimental results show that the obtained RAIDS decreases almost linearly with the increment of the axial stress inside the steel bar in the initial elastic region. The proposed method has the potential to determine tensile axial stress in the slender cylindrical ferromagnetic bar.

Maternal influence on susceptibility of offspring to Brugia malayi infection in a murine model of filariasis.

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Rajan, T V; Bailis, J M; Yates, J A; Shultz, L D; Greiner, D L; Nelson, F K

1994-12-01

We have used the severe combined immunodeficient C.B-17-scid/scid mouse to investigate the influences of maternal immune status and parasite burden on the susceptibility (or resistance) of offspring to infection with the human filarial parasite, Brugia malayi. C.B-17-scid/scid mice are permissive for infection while immunocompetent C.B-17(-)+/+ mice are uniformly resistant. Reciprocal matings of C.B-17-scid/scid and C.B-17(-)+/+ mice were performed. The C.B-17-scid/scid females were either naive or infected with Brugia malayi. The resulting immunocompetent C.B-17-scid/+ and C.B-17(-)+/scid progeny were challenged at weaning with an intraperitoneal injection of Brugia malayi third stage larvae known to produce patent infection in > 95% of C.B-17-scid/scid mice. We observed that 40.0%l (34/85) of the immunocompetent offspring of C.B-17-scid/scid females x C.B-17(-)+/+ males were permissive for the growth and development of Brugia malayi larvae to adults. No difference was observed in susceptibility to infection between the progeny of infected or uninfected C.B-17-scid/scid mothers mated with C.B-17(-)+/+ fathers, arguing against acquired immunological tolerance to the parasite in the former. In marked contrast, only 4.8% (2/42) of the heterozygous progeny of wild type C.B-17(-)+/+ females mated with C.B-17-scid/scid males were permissive. These observations document conversion of a 'resistant' phenotype to a 'susceptible' phenotype by manipulation of maternal immune status and provide clear evidence of maternal influence on offspring susceptibility to infection with Brugia malayi.

Residual stresses in zircaloy welds

International Nuclear Information System (INIS)

Santisteban, J. R.; Fernandez, L; Vizcaino, P.; Banchik, A.D.; Samper, R; Martinez, R. L; Almer, J; Motta, A.T.; Colas, K.B; Kerr, M.; Daymond, M.R

2009-01-01

Welds in Zirconium-based alloys are susceptible to hydrogen embrittlement, as H enters the material due to dissociation of water. The yield strain for hydride cracking has a complex dependence on H concentration, stress state and texture. The large thermal gradients produced by the applied heat; drastically changes the texture of the material in the heat affected zone, enhancing the susceptibility to delayed hydride cracking. Normally hydrides tend to form as platelets that are parallel to the normal direction, but when welding plates, hydride platelets may form on cooling with their planes parallel to the weld and through the thickness of the plates. If, in addition to this there are significant tensile stresses, the susceptibility of the heat affected zone to delayed hydride cracking will be increased. Here we have measured the macroscopic and microscopic residual stressed that appear after PLASMA welding of two 6mm thick Zircaloy-4 plates. The measurements were based on neutron and synchrotron diffraction experiments performed at the Isis Facility, UK, and at Advanced Photon Source, USA, respectively. The experiments allowed assessing the effect of a post-weld heat treatment consisting of a steady increase in temperature from room temperature to 450oC over a period of 4.5 hours; followed by cooling with an equivalent cooling rate. Peak tensile stresses of (175± 10) MPa along the longitudinal direction were found in the as-welded specimen, which were moderately reduced to (150±10) MPa after the heat-treatment. The parent material showed intergranular stresses of (56±4) MPa, which disappeared on entering the heat-affected zone. In-situ experiments during themal cyclong of the material showed that these intergranular stresses result from the anisotropy of the thermal expansion coefficient of the hexagonal crystal lattice. [es

The genetic diversity and phenotypic characterisation of Streptococcus agalactiae isolates from Rio de Janeiro, Brazil

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Ana Beatriz de Almeida Corrêa

2011-12-01

Full Text Available Streptococcus agalactiae isolates are more common among pregnant women, neonates and nonpregnant adults with underlying diseases compared to other demographic groups. In this study, we evaluate the genetic and phenotypic diversity in S. agalactiae strains from Rio de Janeiro (RJ that were isolated from asymptomatic carriers. We analysed these S. agalactiae strains using pulsed-field gel electrophoresis (PFGE, serotyping and antimicrobial susceptibility testing, as well as by determining the macrolide resistance phenotype, and detecting the presence of the ermA/B, mefA/E and lnuB genes. The serotypes Ia, II, III and V were the most prevalent serotypes observed. The 60 strains analysed were susceptible to penicillin, vancomycin and levofloxacin. Resistance to clindamycin, chloramphenicol, erythromycin, rifampin and tetracycline was observed. Among the erythromycin and/or clindamycin resistant strains, the ermA, ermB and mefA/E genes were detected and the constitutive macrolides, lincosamides and streptogramin B-type resistance was the most prevalent phenotype observed. The lnuB gene was not detected in any of the strains studied. We found 56 PFGE electrophoretic profiles and only 22 of them were allocated in polymorphism patterns. This work presents data on the genetic diversity and prevalent capsular serotypes among RJ isolates. Approximately 85% of these strains came from pregnant women; therefore, these data may be helpful in developing future prophylaxis and treatment strategies for neonatal syndromes in RJ.

Stress tolerances of nullmutants of function-unknown genes encoding menadione stress-responsive proteins in Aspergillus nidulans.

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Leiter, Éva; Bálint, Mihály; Miskei, Márton; Orosz, Erzsébet; Szabó, Zsuzsa; Pócsi, István

2016-07-01

A group of menadione stress-responsive function-unkown genes of Aspergillus nidulans (Locus IDs ANID_03987.1, ANID_06058.1, ANID_10219.1, and ANID_10260.1) was deleted and phenotypically characterized. Importantly, comparative and phylogenetic analyses of the tested A. nidulans genes and their orthologs shed light only on the presence of a TANGO2 domain with NRDE protein motif in the translated ANID_06058.1 gene but did not reveal any recognizable protein-encoding domains in other protein sequences. The gene deletion strains were subjected to oxidative, osmotic, and metal ion stress and, surprisingly, only the ΔANID_10219.1 mutant showed an increased sensitivity to 0.12 mmol l(-1) menadione sodium bisulfite. The gene deletions affected the stress sensitivities (tolerances) irregularly, for example, some strains grew more slowly when exposed to various oxidants and/or osmotic stress generating agents, meanwhile the ΔANID_10260.1 mutant possessed a wild-type tolerance to all stressors tested. Our results are in line with earlier studies demonstrating that the deletions of stress-responsive genes do not confer necessarily any stress-sensitivity phenotypes, which can be attributed to compensatory mechanisms based on other elements of the stress response system with overlapping functions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Resistome: A Comprehensive Database of Escherichia coli Resistance Phenotypes.

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Winkler, James D; Halweg-Edwards, Andrea L; Erickson, Keesha E; Choudhury, Alaksh; Pines, Gur; Gill, Ryan T

2016-12-16

The microbial ability to resist stressful environmental conditions and chemical inhibitors is of great industrial and medical interest. Much of the data related to mutation-based stress resistance, however, is scattered through the academic literature, making it difficult to apply systematic analyses to this wealth of information. To address this issue, we introduce the Resistome database: a literature-curated collection of Escherichia coli genotypes-phenotypes containing over 5,000 mutants that resist hundreds of compounds and environmental conditions. We use the Resistome to understand our current state of knowledge regarding resistance and to detect potential synergy or antagonism between resistance phenotypes. Our data set represents one of the most comprehensive collections of genomic data related to resistance currently available. Future development will focus on the construction of a combined genomic-transcriptomic-proteomic framework for understanding E. coli's resistance biology. The Resistome can be downloaded at https://bitbucket.org/jdwinkler/resistome_release/overview .

Residual stresses and stress corrosion cracking in pipe fittings

International Nuclear Information System (INIS)

Parrington, R.J.; Scott, J.J.; Torres, F.

1994-06-01

Residual stresses can play a key role in the SCC performance of susceptible materials in PWR primary water applications. Residual stresses are stresses stored within the metal that develop during deformation and persist in the absence of external forces or temperature gradients. Sources of residual stresses in pipe fittings include fabrication processes, installation and welding. There are a number of methods to characterize the magnitude and orientation of residual stresses. These include numerical analysis, chemical cracking tests, and measurement (e.g., X-ray diffraction, neutron diffraction, strain gage/hole drilling, strain gage/trepanning, strain gage/section and layer removal, and acoustics). This paper presents 400 C steam SCC test results demonstrating that residual stresses in as-fabricated Alloy 600 pipe fittings are sufficient to induce SCC. Residual stresses present in as-fabricated pipe fittings are characterized by chemical cracking tests (stainless steel fittings tested in boiling magnesium chloride solution) and by the sectioning and layer removal (SLR) technique

Lysosomal Disorders Drive Susceptibility to Tuberculosis by Compromising Macrophage Migration

Science.gov (United States)

Berg, Russell D.; Levitte, Steven; O’Sullivan, Mary P.; O’Leary, Seónadh M.; Cambier, C.J.; Cameron, James; Takaki, Kevin K.; Moens, Cecilia B.; Tobin, David M.; Keane, Joseph; Ramakrishnan, Lalita

2016-01-01

Summary A zebrafish genetic screen for determinants of susceptibility to Mycobacterium marinum identified a hypersusceptible mutant deficient in lysosomal cysteine cathepsins that manifests hallmarks of human lysosomal storage diseases. Under homeostatic conditions, mutant macrophages accumulate undigested lysosomal material, which disrupts endocytic recycling and impairs their migration to, and thus engulfment of, dying cells. This causes a buildup of unengulfed cell debris. During mycobacterial infection, macrophages with lysosomal storage cannot migrate toward infected macrophages undergoing apoptosis in the tuberculous granuloma. The unengulfed apoptotic macrophages undergo secondary necrosis, causing granuloma breakdown and increased mycobacterial growth. Macrophage lysosomal storage similarly impairs migration to newly infecting mycobacteria. This phenotype is recapitulated in human smokers, who are at increased risk for tuberculosis. A majority of their alveolar macrophages exhibit lysosomal accumulations of tobacco smoke particulates and do not migrate to Mycobacterium tuberculosis. The incapacitation of highly microbicidal first-responding macrophages may contribute to smokers’ susceptibility to tuberculosis. PMID:27015311

Neuroprotection via Reduction in Stress: Altered Menstrual Patterns as a Marker for Stress and Implications for Long-Term Neurologic Health in Women

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David Prokai

2016-12-01

Full Text Available Individuals under chronic psychological stress can be difficult to identify clinically. There is often no outwardly visible phenotype. Chronic stress of sufficient magnitude not only impacts reproductive function, but also concomitantly elicits a constellation of neuroendocrine changes that may accelerate aging in general and brain aging in particular. Functional hypothalamic amenorrhea, a phenotypically recognizable form of stress, is due to stress-induced suppression of endogenous gonadotropin-releasing hormone secretion. Reversal of functional hypothalamic amenorrhea includes restoration of ovulatory ovarian function and fertility and amelioration of hypercortisolism and hypothyroidism. Taken together, recovery from functional hypothalamic amenorrhea putatively offers neuroprotection and ameliorates stress-induced premature brain aging and possibly syndromic Alzheimer’s disease. Amenorrhea may be viewed as a sentinel indicator of stress. Hypothalamic hypogonadism is less clinically evident in men and the diagnosis is difficult to establish. Whether there are other sex differences in the impact of stress on brain aging remains to be better investigated, but it is likely that both low estradiol from stress-induced anovulation and low testosterone from stress-induced hypogonadism compromise brain health.

Linkage analysis using co-phenotypes in the BRIGHT study reveals novel potential susceptibility loci for hypertension.

Science.gov (United States)

Wallace, Chris; Xue, Ming-Zhan; Newhouse, Stephen J; Marcano, Ana Carolina B; Onipinla, Abiodun K; Burke, Beverley; Gungadoo, Johannie; Dobson, Richard J; Brown, Morris; Connell, John M; Dominiczak, Anna; Lathrop, G Mark; Webster, John; Farrall, Martin; Mein, Charles; Samani, Nilesh J; Caulfield, Mark J; Clayton, David G; Munroe, Patricia B

2006-08-01

Identification of the genetic influences on human essential hypertension and other complex diseases has proved difficult, partly because of genetic heterogeneity. In many complex-trait resources, additional phenotypic data have been collected, allowing comorbid intermediary phenotypes to be used to characterize more genetically homogeneous subsets. The traditional approach to analyzing covariate-defined subsets has typically depended on researchers' previous expectations for definition of a comorbid subset and leads to smaller data sets, with a concomitant attrition in power. An alternative is to test for dependence between genetic sharing and covariates across the entire data set. This approach offers the advantage of exploiting the full data set and could be widely applied to complex-trait genome scans. However, existing maximum-likelihood methods can be prohibitively computationally expensive, especially since permutation is often required to determine significance. We developed a less computationally intensive score test and applied it to biometric and biochemical covariate data, from 2,044 sibling pairs with severe hypertension, collected by the British Genetics of Hypertension (BRIGHT) study. We found genomewide-significant evidence for linkage with hypertension and several related covariates. The strongest signals were with leaner-body-mass measures on chromosome 20q (maximum LOD = 4.24) and with parameters of renal function on chromosome 5p (maximum LOD = 3.71). After correction for the multiple traits and genetic locations studied, our global genomewide P value was .046. This is the first identity-by-descent regression analysis of hypertension to our knowledge, and it demonstrates the value of this approach for the incorporation of additional phenotypic information in genetic studies of complex traits.

Feedlot cattle susceptibility to heat stress: an animal specific model

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The extreme effects of heat stress in a feedlot situation can cause losses exceeding 5% of all the cattle on feed in a single feedlot. These losses can be very devastating to a localized area of feedlot producers. Animal stress is a result of the combination of three different components: environm...

Trajectories of the healthy ageing phenotype among middle-aged and older Britons, 2004-2013.

Science.gov (United States)

Tampubolon, Gindo

2016-06-01

Since the ageing population demands a response to ensure older people remain healthy and active, we studied the dynamics of a recently proposed healthy ageing phenotype. We drew the phenotype's trajectories and tested whether their levels and rates of change are influenced by health behaviours, comorbidities and socioeconomic positions earlier in the life course. The English Longitudinal Ageing Study, a prospective, nationally representative sample of people aged ≥50 years, measured a set of eight biomarkers which make up the outcome of the healthy ageing phenotype three times over nearly a decade (N2004=5009, N2008=5301, N2013=4455). A cluster of health behaviours, comorbidities and socioeconomic positions were also measured repeatedly. We assessed the phenotype's distribution non-parametrically, then fitted linear mixed models to phenotypic change and further examined time interactions with gender and socioeconomic position. We ran additional analyses to test robustness. Women had a wider distribution of the healthy ageing phenotype than men had. The phenotype declined annually by -0.242 (95% confidence interval [CI]: -0.352, -0.131). However, there was considerable heterogeneity in the levels and rates of phenotypic change. Women started at higher levels, then declined more steeply by -0.293 (CI: -0.403, -0.183) annually, leading to crossover in the trajectories. Smoking and physical activity assessed on the Allied Dunbar scale were strongly associated with the trajectories. Though marked by secular decline, the trajectories of the healthy ageing phenotype showed distinct socioeconomic gradients. The trajectories were also susceptible to variations in health behaviours, strengthening the case for serial interventions to attain healthy and active ageing. Copyright © 2016 The Author. Published by Elsevier Ireland Ltd.. All rights reserved.

Heritability of Susceptibility to Ionizing Radiation-Induced Apoptosis of Human Lymphocyte Subpopulations

International Nuclear Information System (INIS)

Schmitz, Annette; Bayer, Jan; Dechamps, Nathalie; Goldin, Lynn; Thomas, Gilles

2007-01-01

Purpose: To evaluate the heritability of intrinsic radiosensitivity, the induction of apoptosis in lymphocyte subpopulations was determined on samples from related individuals belonging to large kindred families. Methods and Materials: Quiescent lymphocytes from 334 healthy individuals were gamma-irradiated in vitro. Apoptosis was determined 18 h after irradiation by eight-color flow cytometry. Radiosensitivity was quantified from dose-effect curves. Intrafamilial correlations and heritability were computed for 199 father-mother-offspring trios using the programs SOLAR (Sequential Oligogenic Linkage Analysis Routines) and SAGE (Statistical Analysis for Genetic Epidemiology). Segregation analyses were conducted using SAGE. Results: Marked differential susceptibility of naive and memory T lymphocytes was demonstrated. Also, although age and gender were significant covariates, their effects only accounted for a minor part of the inter-individual variation. Parent-offspring and sib-sib correlations were significant for the radiosensitivity of B cells, T4, and T8 and of effector memory T4 and T8 subpopulations. In the T4-effector memory subpopulation, the phenotype showed correlations most consistent with dominant or additive genetic effects, and the results of the segregation analysis were consistent with the contribution of a bi-allelic dominant locus. Conclusions: Heritability was demonstrated for the susceptibility to ionizing radiation-induced apoptosis of lymphocyte populations, and the segregation of the T4-effector memory radiosensitivity phenotype was consistent with a simple mendelian transmission model involving one major gene

The Composition and Metabolic Phenotype of Neisseria gonorrhoeae Biofilms

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Michael A Apicella

2011-04-01

Full Text Available N. gonorrhoeae has been shown to form biofilms during cervical infection. Thus, biofilm formation may play an important role in the infection of women. The ability of N. gonorrhoeae to form membrane blebs is crucial to biofilm formation. Blebs contain DNA and outer membrane structures, which have been shown to be major constituents of the biofilm matrix. The organism expresses a DNA thermonuclease that is involved in remodeling of the biofilm matrix. Comparison of the transcriptional profiles of gonococcal biofilms and planktonic runoff indicate that genes involved in anaerobic metabolism and oxidative stress tolerance are more highly expressed in biofilm. The expression of aniA, ccp, and norB, which encode nitrite reductase, cytochrome c peroxidase, and nitric oxide reductase respectively, is required for mature biofilm formation over glass and human cervical cells. In addition, anaerobic respiration occurs in the substratum of gonococcal biofilms and disruption of the norB gene required for anaerobic respiration, results in a severe biofilm attenuation phenotype. It has been demonstrated that accumulation of nitric oxide (NO contributes to the phenotype of a norB mutant and can retard biofilm formation. However, NO can also enhance biofilm formation, and this is largely dependent on the concentration and donation rate or steady state kinetics of NO. The majority of the genes involved in gonococcal oxidative stress tolerance are also required for normal biofilm formation, as mutations in the following genes result in attenuated biofilm formation over cervical cells and/or glass: oxyR, gor, prx, mntABC, trxB, and estD. Overall, biofilm formation appears to be an adaptation for coping with the environmental stresses present in the female genitourinary tract. Therefore, this review will discuss the studies, which describe the composition and metabolic phenotype of gonococcal biofilms.

Effect of nitrogen in austenitic stainless steel on deformation behavior and stress corrosion cracking susceptibility in BWR simulated environment

International Nuclear Information System (INIS)

Roychowdhury, S.; Kain, V.; Dey, G.K.

2012-01-01

Intergranular stress corrosion cracking (IGSCC) of austenitic stainless steel (SS) components in boiling water reactor (BWR has been a serious issue and is generic in nature. Initial cracking incidences were attributed to weld induced sensitisation and low temperature sensitisation which was mitigated by the use of low carbon grade of SS and molybdenum and nitrogen containing nuclear grade SS. However, IGSCC has occurred in these SS in the non-sensitised condition which was attributed to residual weld induced strain. Strain hardening in SS has been identified as a major cause for enhanced IGSCC susceptibility in BWR environment. Nitrogen in SS has a significant effect on the strain hardening characteristics and has potential to affect the IGSCC susceptibility in BWR environment. Type 304LN stainless steel is a candidate material for use in future reactors with long design life like the Advanced Heavy Water Reactor (AHWR), in which the operating conditions are similar to BWR. This study reports the effect of nitrogen in type 304LN stainless steel on the strain hardening behaviour and deformation characteristics and its effect on the IGSCC susceptibility in BWR/AHWR environment. Two heats of type 304LN stainless steel were used containing different levels of nitrogen, 0.08 and 0.16 wt % (SS alloys A and B, respectively). Both the SS was strain hardened by cross rolling at 200℃ to simulate the strain hardened regions having higher IGSCC susceptibility in BWRs. Tensile testing was done at both room temperature and 288℃(temperature simulating operating BWR conditions) and the effect of nitrogen on the tensile properties were established. Tensile testing was done at strain rates similar to the crack tip strain rates associated with a growing IGSCC in SS. Detailed transmission electron microscopic (TEM) studies were done to establish the effect of nitrogen on the deformation modes. Results indicated twinning was the major mode of deformation during cross rolling while

Cortisol responsiveness to stress in channel catfish influences susceptibility to Edwardsiella ictaluri

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Stress is unavoidable in aquaculture and hence strains of fish that are resilient and adaptable to stress need to be developed. Past studies have demonstrated that fish subjected to handling stress or poor water quality had reduced ability to resist pathogens. Cortisol is the primary stress hormone...

In Vitro Assays for Mouse Müller Cell Phenotyping Through microRNA Profiling in the Damaged Retina.

Science.gov (United States)

Reyes-Aguirre, Luis I; Quintero, Heberto; Estrada-Leyva, Brenda; Lamas, Mónica

2018-01-01

microRNA profiling has identified cell-specific expression patterns that could represent molecular signatures triggering the acquisition of a specific phenotype; in other words, of cellular identity and its associated function. Several groups have hypothesized that retinal cell phenotyping could be achieved through the determination of the global pattern of miRNA expression across specific cell types in the adult retina. This is especially relevant for Müller glia in the context of retinal damage, as these cells undergo dramatic changes of gene expression in response to injury, that render them susceptible to acquire a progenitor-like phenotype and be a source of new neurons.We describe a method that combines an experimental protocol for excitotoxic-induced retinal damage through N-methyl-D-aspartate subretinal injection with magnetic-activated cell sorting (MACS) of Müller cells and RNA isolation for microRNA profiling. Comparison of microRNA patterns of expression should allow Müller cell phenotyping under different experimental conditions.

Prediction of Phenotypic Antimicrobial Resistance Profiles From Whole Genome Sequences of Non-typhoidal Salmonella enterica.

Science.gov (United States)

Neuert, Saskia; Nair, Satheesh; Day, Martin R; Doumith, Michel; Ashton, Philip M; Mellor, Kate C; Jenkins, Claire; Hopkins, Katie L; Woodford, Neil; de Pinna, Elizabeth; Godbole, Gauri; Dallman, Timothy J

2018-01-01

Surveillance of antimicrobial resistance (AMR) in non-typhoidal Salmonella enterica (NTS), is essential for monitoring transmission of resistance from the food chain to humans, and for establishing effective treatment protocols. We evaluated the prediction of phenotypic resistance in NTS from genotypic profiles derived from whole genome sequencing (WGS). Genes and chromosomal mutations responsible for phenotypic resistance were sought in WGS data from 3,491 NTS isolates received by Public Health England's Gastrointestinal Bacteria Reference Unit between April 2014 and March 2015. Inferred genotypic AMR profiles were compared with phenotypic susceptibilities determined for fifteen antimicrobials using EUCAST guidelines. Discrepancies between phenotypic and genotypic profiles for one or more antimicrobials were detected for 76 isolates (2.18%) although only 88/52,365 (0.17%) isolate/antimicrobial combinations were discordant. Of the discrepant results, the largest number were associated with streptomycin (67.05%, n = 59). Pan-susceptibility was observed in 2,190 isolates (62.73%). Overall, resistance to tetracyclines was most common (26.27% of isolates, n = 917) followed by sulphonamides (23.72%, n = 828) and ampicillin (21.43%, n = 748). Multidrug resistance (MDR), i.e., resistance to three or more antimicrobial classes, was detected in 848 isolates (24.29%) with resistance to ampicillin, streptomycin, sulphonamides and tetracyclines being the most common MDR profile ( n = 231; 27.24%). For isolates with this profile, all but one were S . Typhimurium and 94.81% ( n = 219) had the resistance determinants bla TEM-1, strA-strB, sul2 and tet (A). Extended-spectrum β-lactamase genes were identified in 41 isolates (1.17%) and multiple mutations in chromosomal genes associated with ciprofloxacin resistance in 82 isolates (2.35%). This study showed that WGS is suitable as a rapid means of determining AMR patterns of NTS for public health surveillance.

Genetic modification of glaucoma associated phenotypes between AKXD-28/Ty and DBA/2J mice

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Zabaleta Adriana

2001-01-01

Full Text Available Abstract Background Glaucoma is a common disease but its molecular etiology is poorly understood. It involves retinal ganglion cell death and optic nerve damage that is often associated with elevated intraocular pressure. Identifying genes that modify glaucoma associated phenotypes is likely to provide insights to mechanisms of glaucoma. We previously reported glaucoma in DBA/2J mice caused by recessive alleles at two loci, isa and ipd, that cause iris stromal atrophy and iris pigment dispersion, respectively. A approach for identifying modifier genes is to study the effects of specific mutations in different mouse strains. When the phenotypic effect of a mutation is modified upon its introduction into a new strain, crosses between the parental strains can be used to identify modifier genes. The purpose of this study was to determine if the effects of the DBA/2J derived isa and ipd loci are modified in strain AKXD-28/Ty. Results AKXD-28/Ty mice develop glaucoma characterized by intraocular pressure elevation, retinal ganglion loss, and optic nerve excavation. In AKXD-28/Ty, isa causes an iris stromal atrophy phenotype as in DBA/2J. However, the iris pigment dispersion phenotype associated with ipd in DBA/2J does not occur in AKXD-28/Ty. Additionally, a greater severity and speed of retinal and optic nerve damage following intraocular pressure elevation in AKXD-28/Ty compared to DBA/2J mice suggests that AKXD-28/Ty is more susceptible to pressure-induced cell death. Conclusions The consequences of the ipd and isa mutations are modified in the AKXD-28/Ty background. These strains provide a resource for the identification of modifier genes that modulate pigment dispersion and susceptibility to pressure-induced cell death.

Stress corrosion cracking evaluation of precipitation-hardening stainless steel

Science.gov (United States)

Humphries, T. S.; Nelson, E. E.

1970-01-01

Accelerated test program results show which precipitation hardening stainless steels are resistant to stress corrosion cracking. In certain cases stress corrosion susceptibility was found to be associated with the process procedure.

Colonisation of a phage susceptible Campylobacter jejuni population in two phage positive broiler flocks.

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Sophie Kittler

Full Text Available The pathogens Campylobacter jejuni and Campylobacter coli are commensals in the poultry intestine and campylobacteriosis is one of the most frequent foodborne diseases in developed and developing countries. Phages were identified to be effective in reducing intestinal Campylobacter load and this was evaluated, in the first field trials which were recently carried out. The aim of this study was to further investigate Campylobacter population dynamics during phage application on a commercial broiler farm. This study determines the superiority in colonisation of a Campylobacter type found in a field trial that was susceptible to phages in in vitro tests. The colonisation factors, i.e. motility and gamma glutamyl transferase activity, were increased in this type. The clustering in phylogenetic comparisons of MALDI-TOF spectra did not match the ST, biochemical phenotype and phage susceptibility. Occurrence of Campylobacter jejuni strains and phage susceptibility types with different colonisation potential seem to play a very important role in the success of phage therapy in commercial broiler houses. Thus, mechanisms of both, phage susceptibility and Campylobacter colonisation should be further investigated and considered when composing phage cocktails.

Machine learning modelling for predicting soil liquefaction susceptibility

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P. Samui

2011-01-01

Full Text Available This study describes two machine learning techniques applied to predict liquefaction susceptibility of soil based on the standard penetration test (SPT data from the 1999 Chi-Chi, Taiwan earthquake. The first machine learning technique which uses Artificial Neural Network (ANN based on multi-layer perceptions (MLP that are trained with Levenberg-Marquardt backpropagation algorithm. The second machine learning technique uses the Support Vector machine (SVM that is firmly based on the theory of statistical learning theory, uses classification technique. ANN and SVM have been developed to predict liquefaction susceptibility using corrected SPT [(N₁₆₀] and cyclic stress ratio (CSR. Further, an attempt has been made to simplify the models, requiring only the two parameters [(N₁₆₀ and peck ground acceleration (a_max/g], for the prediction of liquefaction susceptibility. The developed ANN and SVM models have also been applied to different case histories available globally. The paper also highlights the capability of the SVM over the ANN models.

Phenotypic Approaches to Drought in Cassava: Review

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Emmanuel eOkogbenin

2013-05-01

Full Text Available Cassava is an important crop in Africa, Asia, Latin America and the Caribbean. Cassava can be produced adequately in drought conditions making it the ideal food security crop in marginal environments. Although cassava can tolerate drought stress, it can be genetically improved to enhance productivity in such environments. Drought adaptation studies in over three decades in cassava have identified relevant mechanisms which have been explored in conventional breeding. Drought is a quantitative trait and its multigenic nature makes it very challenging to effectively manipulate and combine genes in breeding for rapid genetic gain and selection process. Cassava has a long growth cycle of 12 - 18 months which invariably contributes to a long breeding scheme for the crop. Modern breeding using advances in genomics and improved genotyping, is facilitating the dissection and genetic analysis of complex traits including drought tolerance, thus helping to better elucidate and understand the genetic basis of such traits. A beneficial goal of new innovative breeding strategies is to shorten the breeding cycle using minimized, efficient or fast phenotyping protocols. While high throughput genotyping have been achieved, this is rarely the case for phenotyping for drought adaptation. Some of the storage root phenotyping in cassava are often done very late in the evaluation cycle making selection process very slow. This paper highlights some modified traits suitable for early-growth phase phenotyping that may be used to reduce drought phenotyping cycle in cassava. Such modified traits can significantly complement the high throughput genotyping procedures to fast track breeding of improved drought tolerant varieties. The need for metabolite profiling, improved phenomics to take advantage of next generation sequencing technologies and high throughput phenotyping are basic steps for future direction to improve genetic gain and maximize speed for drought tolerance

Sublethal effects of a metal contamination due to uranium mine tailings in the three-spined stickleback (Gasterosteus aculeatus L.). Implication in the susceptibility to a biological stress

International Nuclear Information System (INIS)

Le Guernic, Antoine

2015-01-01

Uranium extraction has resulted in a remobilization of this actinide into mine surrounding ecosystems. Uses of metal salts during mining site rehabilitation, and the natural presence of metals have increased the metal contamination in hydro systems submitted to mine tailings. In situ experiments were conducted in two former French uranium mining sites. Three-spined stickleback caging was used to determine the sublethal effects of this metal mixture on this freshwater fish, as well as its effects on fish susceptibility to a sudden biological stress. This pollution, characterised by higher metal concentrations (especially for uranium), has led to an oxidative stress in sticklebacks visible through several bio-markers, and other effects dependent on the study site. The polymetallic contamination has modified the stickleback responses to the biological stress, by preventing their phagocytic and antioxidant responses. This work has reinforced the interest of the caging technique during environmental studies and that of immuno-markers in a multi-bio-marker approach. (author)

A three-tier phenotyping approach for hunting QTLs related to heat tolerance in bread wheat

DEFF Research Database (Denmark)

Sharma, Dew Kumari; Rosenqvist, Eva; Ottosen, Carl-Otto

2014-01-01

In the global climate change scenario, heatstress together with other abiotic stresses will remain an importantdeterminant of future food security. Wheat (Triticum aestivum L.) is the third most important crop, feeding about one third of the world population. Being a crop of temperate climate......, wheat is sensitive to heat stress, particularly at the reproductive phase. Heat tolerance is a complex trait. In the present study, a combined approach of physiological phenotyping and quantitative genetics was used to dissect the complex nature of heat tolerance into photosynthesis related traits......- with a top-to-bottom (forward) approach: Tier 1: Phenotyping: As a starting point,the quantification of heat tolerance was done by the chlorophyll fluorescence parameter, Fv/Fm, as a measure of maximum quantum efficiency of PSII photochemistry after heat stress treatment (40°C for 72h). This way...

Identification of genus Acinetobacter: Standardization of in-house PCR and its comparison with conventional phenotypic methods.

Science.gov (United States)

Kulkarni, Sughosh S; Madalgi, Radhika; Ajantha, Ganavalli S; Kulkarni, Raghavendra D

2017-01-01

Acinetobacter is grouped under nonfermenting Gram-negative bacilli. It is increasingly isolated from pathological samples. The ability of this genus to acquire drug resistance and spread in the hospital settings is posing a grave problem in healthcare. Specific treatment protocols are advocated for Acinetobacter infections. Hence, rapid identification and drug susceptibility profiling are critical in the management of these infections. To standardize an in-house polymerase chain reaction (PCR) for identification of genus Acinetobacter and to compare PCR with two protocols for its phenotypic identification. A total of 96 clinical isolates of Acinetobacter were included in the study. An in-house PCR for genus level identification of Acinetobacter was standardized. All the isolates were phenotypically identified by two protocols. The results of PCR and phenotypic identification protocols were compared. The in-house PCR standardized was highly sensitive and specific for the genus Acinetobacter . There was 100% agreement between the phenotypic and molecular identification of the genus. The preliminary identification tests routinely used in clinical laboratories were also in complete agreement with phenotypic and molecular identification. The in-house PCR for genus level identification is specific and sensitive. However, it may not be essential for routine identification as the preliminary phenotypic identification tests used in the clinical laboratory reliably identify the genus Acinetobacter .

Hyperinducibility of Ia antigen on astrocytes correlates with strain-specific susceptibility to experimental autoimmune encephalomyelitis

International Nuclear Information System (INIS)

Massa, P.T.; ter Meulen, V.; Fontana, A.

1987-01-01

In search of a phenotypic marker determining genetically controlled susceptibility to delayed-type hypersensitivity (DTH) reactions in the brain-in particular, experimental autoimmune encephalomyelitis (EAE)- the authors have compared the γ-interferon (IFN-γ) induction of Ia molecules on astrocytes and macrophages from rat and mouse strains that are susceptible or resistant to this disease. They focused on Ia expression because DTH reactions to self or foreign antigens are largely mediated by lymphocytes restricted by class II (Ia) antigens of the major histocompatibility complex (MHC). The data demonstrate that Lewis (fully susceptible) and Brown Norway (BN) (fully resistant) rats are very different in that Lewis astrocytes express much higher levels of Ia than BN astrocytes. Similar data were obtained from an analysis of EAE-susceptible and -resistant mouse strains (SJL and BALB/c, respectively), which suggest that this phenomenon may be universal and not limited to only one mammalian species. At least one gene responsible for Ia hyperinduction is located outside the rat RT-1 or the mouse MHC locus. Animals congenic at the RT-1 or MHC locus of the resistant strain but with background genes of the susceptible strain exhibit intermediate levels of Ia compared to fully resistant and susceptible rodents, which fits well with the reduced EAE susceptibility of these congenic animals. Furthermore, hyperinduction of Ia is astrocyte specific, since peritoneal macrophages of susceptible and resistant strains exhibit identical profiles of Ia induction. Thus, astrocyte Ia hyperinducibility may be a major strain- and tissue-specific factor that contributes to Ia-restricted DTH reactions in the brain

Exploring the Genome and Phenotype of Multi-Drug Resistant Klebsiella pneumoniae of Clinical Origin

OpenAIRE

João Anes; Daniel Hurley; Marta Martins; Séamus Fanning; Séamus Fanning

2017-01-01

Klebsiella pneumoniae is an important nosocomial pathogen with an extraordinary resistant phenotype due to a combination of acquired resistant-elements and efflux mechanisms. In this study a detailed molecular characterization of 11 K. pneumoniae isolates of clinical origin was carried out. Eleven clinical isolates were tested for their susceptibilities, by disk diffusion and broth microdilution and interpreted according to CLSI guidelines. Efflux activity was determined by measuring the extr...

Stress, cortisol, and obesity: a role for cortisol responsiveness in identifying individuals prone to obesity.

Science.gov (United States)

Hewagalamulage, S D; Lee, T K; Clarke, I J; Henry, B A

2016-07-01

There is a strong inter-relationship between activation of the hypothalamo-pituitary-adrenal axis and energy homeostasis. Patients with abdominal obesity have elevated cortisol levels. Furthermore, stress and glucocorticoids act to control both food intake and energy expenditure. In particular, glucocorticoids are known to increase the consumption of foods enriched in fat and sugar. It is well-known that, in all species, the cortisol response to stress or adrenocorticotropin is highly variable. It has now emerged that cortisol responsiveness is an important determinant in the metabolic sequelae to stress. Sheep that are characterized as high-cortisol responders (HRs) have greater propensity to weight gain and obesity than low-cortisol responders (LRs). This difference in susceptibility to become obese is associated with a distinct metabolic, neuroendocrine, and behavioral phenotype. In women and ewes, HR individuals eat more in response to stress than LR. Furthermore, HR sheep have impaired melanocortin signaling and reduced skeletal muscle thermogenesis. High-cortisol responder sheep exhibit reactive coping strategies, whereas LRs exhibit proactive coping strategies. This complex set of traits leads to increased food intake and reduced energy expenditure in HR and thus, predisposition to obesity. We predict that cortisol responsiveness may be used as a marker to identify individuals who are at risk of weight gain and subsequent obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of STAT4 polymorphisms with susceptibility to type-1 autoimmune hepatitis in the Japanese population.

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Kiyoshi Migita

Full Text Available BACKGROUND/AIMS: Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO AIH multicenter cohort study. METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694. The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23-2.11; P = 0.001, and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13-1.99; P = 0.005. Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44 or without liver cirrhosis (n = 186 demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies. CONCLUSIONS/SIGNIFICANCE: This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.

Advanced transgenic approaches to understand alcohol-related phenotypes in animals.

Science.gov (United States)

Bilbao, Ainhoa

2013-01-01

During the past two decades, the use of genetically manipulated animal models in alcohol research has greatly improved the understanding of the mechanisms underlying alcohol addiction. In this chapter, we present an overview of the progress made in this field by summarizing findings obtained from studies of mice harboring global and conditional mutations in genes that influence alcohol-related phenotypes. The first part reviews behavioral paradigms for modeling the different phases of the alcohol addiction cycle and other alcohol-induced behavioral phenotypes in mice. The second part reviews the current data available using genetic models targeting the main neurotransmitter and neuropeptide systems involved in the reinforcement and stress pathways, focusing on the phenotypes modeling the alcohol addiction cycle. Finally, the third part will discuss the current findings and future directions, and proposes advanced transgenic mouse models for their potential use in alcohol research.

The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype.

Science.gov (United States)

Rueda, B; Broen, J; Simeon, C; Hesselstrand, R; Diaz, B; Suárez, H; Ortego-Centeno, N; Riemekasten, G; Fonollosa, V; Vonk, M C; van den Hoogen, F H J; Sanchez-Román, J; Aguirre-Zamorano, M A; García-Portales, R; Pros, A; Camps, M T; Gonzalez-Gay, M A; Coenen, M J H; Airo, P; Beretta, L; Scorza, R; van Laar, J; Gonzalez-Escribano, M F; Nelson, J L; Radstake, T R D J; Martin, J

2009-06-01

The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy controls, from an initial case-control set of Spanish Caucasian ancestry and five independent cohorts of European ancestry (The Netherlands, Germany, Sweden, Italy and USA), were included in the study. The rs7574865 polymorphism was selected as STAT4 genetic marker. We observed that the rs7574865 T allele was significantly associated with susceptibility to lcSSc in the Spanish population [P = 1.9 x 10(-5) odds ratio (OR) 1.61 95% confidence intervals (CI) 1.29-1.99], but not with dcSSc (P = 0.41 OR 0.84 95% CI 0.59-1.21). Additionally, a dosage effect was observed showing individuals with rs7574865 TT genotype higher risk for lcSSc (OR 3.34, P = 1.02 x 10(-7) 95% CI 2.11-5.31). The association of the rs7574865 T allele with lcSSc was confirmed in all the replication cohorts with different effect sizes (OR ranging between 1.15 and 1.86), as well as the lack of association of STAT4 with dcSSc. A meta-analysis to test the overall effect of the rs7574865 polymorphism showed a strong risk effect of the T allele for lcSSc susceptibility (pooled OR 1.54 95% CI 1.36-1.74; P < 0.0001). Our data show a strong and reproducible association of the STAT4 gene with the genetic predisposition to lcSSc suggesting that this gene seems to be one of the genetic markers influencing SSc phenotype.

High-Resolution Phenotypic Landscape of the RNA Polymerase II Trigger Loop.

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Chenxi Qiu

2016-11-01

Full Text Available The active sites of multisubunit RNA polymerases have a "trigger loop" (TL that multitasks in substrate selection, catalysis, and translocation. To dissect the Saccharomyces cerevisiae RNA polymerase II TL at individual-residue resolution, we quantitatively phenotyped nearly all TL single variants en masse. Three mutant classes, revealed by phenotypes linked to transcription defects or various stresses, have distinct distributions among TL residues. We find that mutations disrupting an intra-TL hydrophobic pocket, proposed to provide a mechanism for substrate-triggered TL folding through destabilization of a catalytically inactive TL state, confer phenotypes consistent with pocket disruption and increased catalysis. Furthermore, allele-specific genetic interactions among TL and TL-proximal domain residues support the contribution of the funnel and bridge helices (BH to TL dynamics. Our structural genetics approach incorporates structural and phenotypic data for high-resolution dissection of transcription mechanisms and their evolution, and is readily applicable to other essential yeast proteins.

Phenotypic and genetic diversity in Sinorhizobium meliloti and S. medicae from drought and salt affected regions of Morocco

Directory of Open Access Journals (Sweden)

Udupa Sripada M

2010-01-01

Full Text Available Abstract Background Sinorhizobium meliloti and S. medicae are symbiotic nitrogen fixing bacteria in root nodules of forage legume alfalfa (Medicago sativa L.. In Morocco, alfalfa is usually grown in marginal soils of arid and semi-arid regions frequently affected by drought, extremes of temperature and soil pH, soil salinity and heavy metals, which affect biological nitrogen fixing ability of rhizobia and productivity of the host. This study examines phenotypic diversity for tolerance to the above stresses and genotypic diversity at Repetitive Extragenic Pallindromic DNA regions of Sinorhizobium nodulating alfalfa, sampled from marginal soils of arid and semi-arid regions of Morocco. Results RsaI digestion of PCR amplified 16S rDNA of the 157 sampled isolates, assigned 136 isolates as S. meliloti and the rest as S. medicae. Further phenotyping of these alfalfa rhizobia for tolerance to the environmental stresses revealed a large degree of variation: 55.41%, 82.16%, 57.96% and 3.18% of the total isolates were tolerant to NaCl (>513 mM, water stress (-1.5 MPa, high temperature (40°C and low pH (3.5, respectively. Sixty-seven isolates of S. meliloti and thirteen isolates of S. medicae that were tolerant to salinity were also tolerant to water stress. Most of the isolates of the two species showed tolerance to heavy metals (Cd, Mn and Zn and antibiotics (chloramphenicol, spectinomycin, streptomycin and tetracycline. The phenotypic clusters observed by the cluster analysis clearly showed adaptations of the S. meliloti and S. medicae strains to the multiple stresses. Genotyping with rep-PCR revealed higher genetic diversity within these phenotypic clusters and classified all the 157 isolates into 148 genotypes. No relationship between genotypic profiles and the phenotypes was observed. The Analysis of Molecular Variance revealed that largest proportion of significant (P Conclusion High degree of phenotypic and genotypic diversity is present in S

Mitochondrial Genetic Background Modulates Bioenergetics and Susceptibility to Acute Cardiac Volume – Overload

Science.gov (United States)

Fetterman, Jessica L.; Zelickson, Blake R.; Johnson, Larry W.; Moellering, Douglas R.; Westbrook, David G.; Pompilius, Melissa; Sammy, Melissa J.; Johnson, Michelle; Dunham-Snary, Kimberly J.; Cao, Xuemei; Bradley, Wayne E.; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G.; Kesterson, Robert A.; Dell’Italia, Louis J.; Darley-Usmar, Victor M.; Welch, Danny R.; Ballinger, Scott W.

2013-01-01

Synopsis Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mitochondrial DNA (mtDNA) sequence variation contributes to disease susceptibility. In this study we present a novel animal model of mtDNA polymorphisms, the mitochondrial nuclear exchange mouse (MNX), in which the mtDNA from C3H/HeN mouse has been inserted onto the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harboring the C57/BL6J mtDNA generate more reactive oxygen species (ROS) and have a higher mitochondrial membrane potential relative to those having the C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the “mitochondrial paradigm” for the development of disease susceptibility, and show that the mtDNA modulates, cellular bioenergetics, mitochondrial reactive oxygen species generation and susceptibility to cardiac stress. PMID:23924350

Mitigation of stress corrosion cracking in pressurized water reactor (PWR) piping systems using the mechanical stress improvement process (MSIPR) or underwater laser beam welding

International Nuclear Information System (INIS)

Rick, Grendys; Marc, Piccolino; Cunthia, Pezze; Badlani, Manu

2009-01-01

A current issue facing pressurized water reactors (PWRs) is primary water stress corrosion cracking (PWSCC) of bi metallic welds. PWSCC in a PWR requires the presence of a susceptible material, an aggressive environment and a tensile stress of significant magnitude. Reducing the potential for SCC can be accomplished by eliminating any of these three elements. In the U.S., mitigation of susceptible material in the pressurizer nozzle locations has largely been completed via the structural weld overlay (SWOL) process or NuVision Engineering's Mechanical Stress Improvement Process (MSIP R) , depending on inspectability. The next most susceptible locations in Westinghouse designed power plants are the Reactor Vessel (RV) hot leg nozzle welds. However, a full SWOL Process for RV nozzles is time consuming and has a high likelihood of in process weld repairs. Therefore, Westinghouse provides two distinctive methods to mitigate susceptible material for the RV nozzle locations depending on nozzle access and utility preference. These methods are the MSIP and the Underwater Laser Beam Welding (ULBW) process. MSIP applies a load to the outside diameter of the pipe adjacent to the weld, imposing plastic strains during compression that are not reversed after unloading, thus eliminating the tensile stress component of SCC. Recently, Westinghouse and NuVision successfully applied MSIP on all eight RV nozzles at the Salem Unit 1 power plant. Another option to mitigate SCC in RV nozzles is to place a barrier between the susceptible material and the aggressive environment. The ULBW process applies a weld inlay onto the inside pipe diameter. The deposited weld metal (Alloy 52M) is resistant to PWSCC and acts as a barrier to prevent primary water from contacting the susceptible material. This paper provides information on the approval and acceptance bases for MSIP, its recent application on RV nozzles and an update on ULBW development

Close-range hyperspectral image analysis for the early detection of stress responses in individual plants in a high-throughput phenotyping platform

Science.gov (United States)

Mohd Asaari, Mohd Shahrimie; Mishra, Puneet; Mertens, Stien; Dhondt, Stijn; Inzé, Dirk; Wuyts, Nathalie; Scheunders, Paul

2018-04-01

The potential of close-range hyperspectral imaging (HSI) as a tool for detecting early drought stress responses in plants grown in a high-throughput plant phenotyping platform (HTPPP) was explored. Reflectance spectra from leaves in close-range imaging are highly influenced by plant geometry and its specific alignment towards the imaging system. This induces high uninformative variability in the recorded signals, whereas the spectral signature informing on plant biological traits remains undisclosed. A linear reflectance model that describes the effect of the distance and orientation of each pixel of a plant with respect to the imaging system was applied. By solving this model for the linear coefficients, the spectra were corrected for the uninformative illumination effects. This approach, however, was constrained by the requirement of a reference spectrum, which was difficult to obtain. As an alternative, the standard normal variate (SNV) normalisation method was applied to reduce this uninformative variability. Once the envisioned illumination effects were eliminated, the remaining differences in plant spectra were assumed to be related to changes in plant traits. To distinguish the stress-related phenomena from regular growth dynamics, a spectral analysis procedure was developed based on clustering, a supervised band selection, and a direct calculation of a spectral similarity measure against a reference. To test the significance of the discrimination between healthy and stressed plants, a statistical test was conducted using a one-way analysis of variance (ANOVA) technique. The proposed analysis techniques was validated with HSI data of maize plants (Zea mays L.) acquired in a HTPPP for early detection of drought stress in maize plant. Results showed that the pre-processing of reflectance spectra with the SNV effectively reduces the variability due to the expected illumination effects. The proposed spectral analysis method on the normalized spectra successfully

Investigating the effects of different physical and chemical stress ...

African Journals Online (AJOL)

2018-04-09

Apr 9, 2018 ... bacteria from extreme physical and chemical stress conditions. Additionally .... by inducing stress response genes, become more tolerant phenotypes ..... biofilm, monochloramine is more effective than free chlorine over long ...

Phenotypic characteristics of early Wolfram syndrome.

Science.gov (United States)

Marshall, Bess A; Permutt, M Alan; Paciorkowski, Alexander R; Hoekel, James; Karzon, Roanne; Wasson, Jon; Viehover, Amy; White, Neil H; Shimony, Joshua S; Manwaring, Linda; Austin, Paul; Hullar, Timothy E; Hershey, Tamara

2013-04-27

Wolfram Syndrome (WFS:OMIM 222300) is an autosomal recessive, progressive, neurologic and endocrinologic degenerative disorder caused by mutations in the WFS1 gene, encoding the endoplasmic reticulum (ER) protein wolframin, thought to be involved in the regulation of ER stress. This paper reports a cross section of data from the Washington University WFS Research Clinic, a longitudinal study to collect detailed phenotypic data on a group of young subjects in preparation for studies of therapeutic interventions. Eighteen subjects (ages 5.9-25.8, mean 14.2 years) with genetically confirmed WFS were identified through the Washington University International Wolfram Registry. Examinations included: general medical, neurologic, ophthalmologic, audiologic, vestibular, and urologic exams, cognitive testing and neuroimaging. Seventeen (94%) had diabetes mellitus with the average age of diabetes onset of 6.3 ± 3.5 years. Diabetes insipidus was diagnosed in 13 (72%) at an average age of 10.6 ± 3.3 years. Seventeen (94%) had optic disc pallor and defects in color vision, 14 (78%) had hearing loss and 13 (72%) had olfactory defects, eight (44%) had impaired vibration sensation. Enuresis was reported by four (22%) and nocturia by three (17%). Of the 11 tested for bladder emptying, five (45%) had elevated post-void residual bladder volume. WFS causes multiple endocrine and neurologic deficits detectable on exam, even early in the course of the disease. Defects in olfaction have been underappreciated. The proposed mechanism of these deficits in WFS is ER stress-induced damage to neuronal and hormone-producing cells. This group of subjects with detailed clinical phenotyping provides a pool for testing proposed treatments for ER stress. Longitudinal follow-up is necessary for establishing the natural history and identifying potential biomarkers of progression.

Starvation induces phenotypic diversification and convergent evolution in Vibrio vulnificus.

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Hwajiun Chen

Full Text Available Starvation is a common stress experienced by bacteria living in natural environments and the ability to adapt to and survive intense stress is of paramount importance for any bacterial population. A series of starvation experiments were conducted using V. vulnificus 93U204 in phosphate-buffered saline and seawater. The starved population entered the death phase during the first week and approximately 1% of cells survived. After that the population entered a long-term stationary phase, and could survive for years. Starvation-induced diversification (SID of phenotypes was observed in starved populations and phenotypic variants (PVs appeared in less than 8 days. The cell density, rather than the population size, had a major effect on the extent of SID. SID was also observed in strain YJ016, where it evolved at a faster pace. PVs appeared to emerge in a fixed order: PV with reduced motility, PV with reduced proteolytic activity, and PV with reduced hemolytic activity. All of the tested PVs had growth advantages in the stationary phase phenotypes and increased fitness compared with 93U204 cells in co-culture competition experiments, which indicates that they had adapted to starvation. We also found that SID occurred in natural seawater with a salinity of 1%-3%, so this mechanism may facilitate bacterial adaptation in natural environments.

Neuroepigenetics of stress.

Science.gov (United States)

Griffiths, B B; Hunter, R G

2014-09-05

Stress, a common if unpredictable life event, can have pronounced effects on physiology and behavior. Individuals show wide variation in stress susceptibility and resilience, which are only partially explained by variations in coding genes. Developmental programing of the hypothalamic-pituitary-adrenal stress axis provides part of the explanation for this variance. Epigenetic approaches have successfully helped fill the explanatory gaps between the influences of gene and environment on stress responsiveness, and differences in the sequelae of stress across individuals and generations. Stress and the stress axis interacts bi-directionally with epigenetic marks within the brain. It is now clear that exposure to stress, particularly in early life, has both acute and lasting effects on these marks. They in turn influence cognitive function and behavior, as well as the risk for suicide and psychiatric disorders across the lifespan and, in some cases, unto future generations. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Adaptation of the Biolog Phenotype MicroArrayTM Technology to Profile the Obligate Anaerobe Geobacter metallireducens

Energy Technology Data Exchange (ETDEWEB)

Joyner, Dominique; Fortney, Julian; Chakraborty, Romy; Hazen, Terry

2010-05-17

The Biolog OmniLog? Phenotype MicroArray (PM) plate technology was successfully adapted to generate a select phenotypic profile of the strict anaerobe Geobacter metallireducens (G.m.). The profile generated for G.m. provides insight into the chemical sensitivity of the organism as well as some of its metabolic capabilities when grown with a basal medium containing acetate and Fe(III). The PM technology was developed for aerobic organisms. The reduction of a tetrazolium dye by the test organism represents metabolic activity on the array which is detected and measured by the OmniLog(R) system. We have previously adapted the technology for the anaerobic sulfate reducing bacterium Desulfovibrio vulgaris. In this work, we have taken the technology a step further by adapting it for the iron reducing obligate anaerobe Geobacter metallireducens. In an osmotic stress microarray it was determined that the organism has higher sensitivity to impermeable solutes 3-6percent KCl and 2-5percent NaNO3 that result in osmotic stress by osmosis to the cell than to permeable non-ionic solutes represented by 5-20percent ethylene glycol and 2-3percent urea. The osmotic stress microarray also includes an array of osmoprotectants and precursor molecules that were screened to identify substrates that would provide osmotic protection to NaCl stress. None of the substrates tested conferred resistance to elevated concentrations of salt. Verification studies in which G.m. was grown in defined medium amended with 100mM NaCl (MIC) and the common osmoprotectants betaine, glycine and proline supported the PM findings. Further verification was done by analysis of transcriptomic profiles of G.m. grown under 100mM NaCl stress that revealed up-regulation of genes related to degradation rather than accumulation of the above-mentioned osmoprotectants. The phenotypic profile, supported by additional analysis indicates that the accumulation of these osmoprotectants as a response to salt stress does not

Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection.

Science.gov (United States)

MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

2015-01-20

Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies.

Clonal relationships among penicillin-susceptible, multiresistant serotype 6B Streptococcus pneumoniae isolates recovered in Greece and France.

Science.gov (United States)

Syrogiannopoulos, G A; Doit, C; Grivea, I N; Geslin, P; Bingen, E

2001-01-01

In January 1996 the emergence of penicillin-susceptible, multiresistant serotype 6B Streptococcus pneumoniae isolates resistant to chloramphenicol, tetracycline, erythromycin, clindamycin and trimethoprim-sulfamethoxazole was observed in young carriers in the city of Patras, located in the southwestern region of Greece. Later, a significant spread of pneumococci with this unusual phenotype was noted in carriers living in various other areas of the country. Using restriction fragment length polymorphism of the ribosomal RNA genes, clonal relationships were found between these Greek strains and serotype 6B penicillin-susceptible, multiresistant pneumococci isolated in France between January 1992 and September 1996. The French and Greek isolates appear to have a common ancestry.

Image-based phenotyping for non-destructive screening of different salinity tolerance traits in rice

KAUST Repository

Hairmansis, Aris

2014-08-14

Background Soil salinity is an abiotic stress wide spread in rice producing areas, limiting both plant growth and yield. The development of salt-tolerant rice requires efficient and high-throughput screening techniques to identify promising lines for salt affected areas. Advances made in image-based phenotyping techniques provide an opportunity to use non-destructive imaging to screen for salinity tolerance traits in a wide range of germplasm in a reliable, quantitative and efficient way. However, the application of image-based phenotyping in the development of salt-tolerant rice remains limited. Results A non-destructive image-based phenotyping protocol to assess salinity tolerance traits of two rice cultivars (IR64 and Fatmawati) has been established in this study. The response of rice to different levels of salt stress was quantified over time based on total shoot area and senescent shoot area, calculated from visible red-green-blue (RGB) and fluorescence images. The response of rice to salt stress (50, 75 and 100 mM NaCl) could be clearly distinguished from the control as indicated by the reduced increase of shoot area. The salt concentrations used had only a small effect on the growth of rice during the initial phase of stress, the shoot Na+ accumulation independent phase termed the ‘osmotic stress’ phase. However, after 20 d of treatment, the shoot area of salt stressed plants was reduced compared with non-stressed plants. This was accompanied by a significant increase in the concentration of Na+ in the shoot. Variation in the senescent area of the cultivars IR64 and Fatmawati in response to a high concentration of Na+ in the shoot indicates variation in tissue tolerance mechanisms between the cultivars. Conclusions Image analysis has the potential to be used for high-throughput screening procedures in the development of salt-tolerant rice. The ability of image analysis to discriminate between the different aspects of salt stress (shoot ion

Corrosion under stress of AISI 304 steel in thiocyanate solutions

International Nuclear Information System (INIS)

Perillo, P.M.; Duffo, G.S.

1989-01-01

Corrosion susceptibility under stress of AISI 304 steel sensitized in a sodium thiocyanate solution has been studied and results were compared with those obtained with solutions of thiosulfate and tetrathionate. Sensitized steel type 304 is highly susceptible to corrosion when under intergranular stress (IGSCC) in thiocyanate solutions but the aggressiveness of this anion is less than that of the other sulphur anions studied (thiosulfate and tetrathionate). This work has been partly carried out in the Chemistry Department. (Author) [es

FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory.

Science.gov (United States)

Zoladz, Phillip R; Dailey, Alison M; Nagle, Hannah E; Fiely, Miranda K; Mosley, Brianne E; Brown, Callie M; Duffy, Tessa J; Scharf, Amanda R; Earley, McKenna B; Rorabaugh, Boyd R

2017-03-01

FK506 binding protein 51 (FKBP5) is a co-chaperone of heat shock protein 90 and significantly influences glucocorticoid receptor sensitivity. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene are associated with altered hypothalamus-pituitary-adrenal (HPA) axis function, changes in the structure and function of several cognitive brain areas, and increased susceptibility to post-traumatic stress disorder, major depression, bipolar disorder and suicidal events. The mechanisms underlying these associations are largely unknown, but it has been speculated that the influence of these SNPs on emotional memory systems may play a role. In the present study, 112 participants were exposed to the socially evaluated cold pressor test (stress) or control (no stress) conditions immediately prior to learning a list of 42 words. Participant memory was assessed immediately after learning (free recall) and 24 h later (free recall and recognition). Participants provided a saliva sample that enabled the genotyping of three FKBP5 polymorphisms: rs1360780, rs3800373 and rs9296158. Results showed that stress impaired immediate recall in risk allele carriers. More importantly, stress enhanced long-term recall and recognition memory in non-carriers of the risk alleles, effects that were completely absent in risk allele carriers. Follow-up analyses revealed that memory performance was correlated with salivary cortisol levels in non-carriers, but not in carriers. These findings suggest that FKBP5 risk allele carriers may possess a sensitized stress response system, perhaps specifically for stress-induced changes in corticosteroid levels, which might aid our understanding of how SNPs in the FKBP5 gene confer increased risk for stress-related psychological disorders and their related phenotypes. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Colitis susceptibility in p47(phox-/-) mice is mediated by the microbiome.

Science.gov (United States)

Falcone, E Liana; Abusleme, Loreto; Swamydas, Muthulekha; Lionakis, Michail S; Ding, Li; Hsu, Amy P; Zelazny, Adrian M; Moutsopoulos, Niki M; Kuhns, Douglas B; Deming, Clay; Quiñones, Mariam; Segre, Julia A; Bryant, Clare E; Holland, Steven M

2016-04-05

Chronic granulomatous disease (CGD) is caused by defects in nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) complex subunits (gp91(phox) (a.k.a. Nox2), p47(phox), p67(phox), p22(phox), p40(phox)) leading to reduced phagocyte-derived reactive oxygen species production. Almost half of patients with CGD develop inflammatory bowel disease, and the involvement of the intestinal microbiome in relation to this predisposing immunodeficiency has not been explored. Although CGD mice do not spontaneously develop colitis, we demonstrate that p47(phox-/-) mice have increased susceptibility to dextran sodium sulfate colitis in association with a distinct colonic transcript and microbiome signature. Neither restoring NOX2 reactive oxygen species production nor normalizing the microbiome using cohoused adult p47(phox-/-) with B6Tac (wild type) mice reversed this phenotype. However, breeding p47(phox+/-) mice and standardizing the microflora between littermate p47(phox-/-) and B6Tac mice from birth significantly reduced dextran sodium sulfate colitis susceptibility in p47(phox-/-) mice. We found similarly decreased colitis susceptibility in littermate p47(phox-/-) and B6Tac mice treated with Citrobacter rodentium. Our findings suggest that the microbiome signature established at birth may play a bigger role than phagocyte-derived reactive oxygen species in mediating colitis susceptibility in CGD mice. These data further support bacteria-related disease in CGD colitis.

In-vitro characterization of stress corrosion cracking of aluminium-free magnesium alloys for temporary bio-implant applications.

Science.gov (United States)

Choudhary, Lokesh; Singh Raman, R K; Hofstetter, Joelle; Uggowitzer, Peter J

2014-09-01

The complex interaction between physiological stresses and corrosive human body fluid may cause premature failure of metallic biomaterials due to the phenomenon of stress corrosion cracking. In this study, the susceptibility to stress corrosion cracking of biodegradable and aluminium-free magnesium alloys ZX50, WZ21 and WE43 was investigated by slow strain rate tensile testing in a simulated human body fluid. Slow strain rate tensile testing results indicated that each alloy was susceptible to stress corrosion cracking, and this was confirmed by fractographic features of transgranular and/or intergranular cracking. However, the variation in alloy susceptibility to stress corrosion cracking is explained on the basis of their electrochemical and microstructural characteristics. Copyright © 2014 Elsevier B.V. All rights reserved.

Iodine stress-corrosion cracking in irradiated Zircaloy cladding

International Nuclear Information System (INIS)

Mattas, R.F.; Yaggee, F.L.; Neimark, L.A.

1979-01-01

Irradiated Zircaloy cladding specimens, which had experienced fluences from 0.1 to 6 x 10 21 n/cm 2 (E>0.1 MeV), were gas-pressure tested in an iodine environment to investigate their stress-corrosion cracking (SCC) susceptibility. The test temperatures and hoop stresses ranged from 320 to 360 0 C and 150 to 500 MPa, respectively. The results indicate that irradiation, in general, increases the susceptibility of Zircaloy to iodine SCC. For specimens that experienced fluences >2 x 10 21 n/cm 2 (E>0.1 MeV), the 24-h failure stress was 177+-18 MPa, regardless of the preirradiation metallurgical condition. An analytical model for iodine SCC has been developed which agrees reasonably well with the test results

Rapid antimicrobial susceptibility testing of clinical isolates by digital time-lapse microscopy

DEFF Research Database (Denmark)

Fredborg, M; Rosenvinge, F S; Spillum, E

2015-01-01

(168 antimicrobial agent-organism combinations) demonstrated 3.6 % minor, no major and 1.2 % very major errors of the oCelloScope system compared to conventional susceptibility testing, as well as a rapid and correct phenotypic detection of strains with methicillin-resistant Staphylococcus aureus (MRSA......-to-result, enabling same-day targeted antimicrobial therapy, facilitating antibiotic stewardship and better patient management. A full-scale validation of the oCelloScope system including more isolates is necessary to assess the impact of using it for AST....

Pre-disposition and epigenetics govern variation in bacterial survival upon stress.

Directory of Open Access Journals (Sweden)

Ming Ni

Full Text Available Bacteria suffer various stresses in their unpredictable environment. In response, clonal populations may exhibit cell-to-cell variation, hypothetically to maximize their survival. The origins, propagation, and consequences of this variability remain poorly understood. Variability persists through cell division events, yet detailed lineage information for individual stress-response phenotypes is scarce. This work combines time-lapse microscopy and microfluidics to uniformly manipulate the environmental changes experienced by clonal bacteria. We quantify the growth rates and RpoH-driven heat-shock responses of individual Escherichia coli within their lineage context, stressed by low streptomycin concentrations. We observe an increased variation in phenotypes, as different as survival from death, that can be traced to asymmetric division events occurring prior to stress induction. Epigenetic inheritance contributes to the propagation of the observed phenotypic variation, resulting in three-fold increase of the RpoH-driven expression autocorrelation time following stress induction. We propose that the increased permeability of streptomycin-stressed cells serves as a positive feedback loop underlying this epigenetic effect. Our results suggest that stochasticity, pre-disposition, and epigenetic effects are at the source of stress-induced variability. Unlike in a bet-hedging strategy, we observe that cells with a higher investment in maintenance, measured as the basal RpoH transcriptional activity prior to antibiotic treatment, are more likely to give rise to stressed, frail progeny.

Stress corrosion cracking of Zircaloy-4 in non-aqueous iodine solutions

International Nuclear Information System (INIS)

Gomez Sanchez, Andrea V.

2006-01-01

In the present work the susceptibility to intergranular attack and stress corrosion cracking of Zircaloy-4 in different iodine alcoholic solutions was studied. The influence of different variables such as the molecular weight of the alcohols, the water content of the solutions, the alcohol type (primary, secondary or tertiary) and the temperature was evaluated. To determine the susceptibility to stress corrosion cracking the slow strain rate technique was used. Specimens of Zircaloy-4 were also exposed between 0.5 and 300 hours to the solutions without applied stress to evaluate the susceptibility to intergranular attack. The electrochemical behavior of the material in the corrosive media was studied by potentiodynamic polarization tests. It was determined that the active species responsible for the stress corrosion cracking of Zircaloy-4 in iodine alcoholic solutions is a molecular complex between the alcohol and iodine. The intergranular attack precedes the 'true' stress corrosion cracking phenomenon (which is associated to the transgranular propagation of the crack) and it is controlled by the diffusion of the active specie to the tip of the crack. Water acts as inhibitor to intergranular attack. Except for methanolic solutions, the minimum water content necessary to inhibit stress corrosion cracking was determined. This critical water content decreases when increasing the molecular weight of the alcohol. An explanation for this behavior is proposed. The susceptibility to stress corrosion cracking also depends on the type of the alcohol used as solvent. The temperature dependence of the crack propagation rate is in agreement with a thermal activated process, and the activation energy is consistent with a process controlled by the volume diffusion of the active species. (author) [es

Identification of a herpes simplex labialis susceptibility region on human chromosome 21.

Science.gov (United States)

Hobbs, Maurine R; Jones, Brandt B; Otterud, Brith E; Leppert, Mark; Kriesel, John D

2008-02-01

Most of the United States population is infected with either herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2, or both. Reactivations of HSV-1 infection cause herpes simplex labialis (HSL; cold sores or fever blisters), which is the most common recurring viral infection in humans. To investigate the possibility of a human genetic component conferring resistance or susceptibility to cold sores (i.e., a HSL susceptibility gene), we conducted a genetic linkage analysis that included serotyping and phenotyping 421 individuals from 39 families enrolled in the Utah Genetic Reference Project. Linkage analysis identified a 2.5-Mb nonrecombinant region of interest on the long arm of human chromosome 21, with a multipoint logarithm of odds score of 3.9 noted near marker abmc65 (D21S409). Nonparametric linkage analysis of the data also provided strong evidence for linkage (P = .0005). This region of human chromosome 21 contains 6 candidate genes for herpes susceptibility. The development of frequent cold sores is associated with a region on the long arm of human chromosome 21. This region contains several candidate genes that could influence the frequency of outbreaks of HSL.

Lethal mutagenesis: targeting the mutator phenotype in cancer.

Science.gov (United States)

Fox, Edward J; Loeb, Lawrence A

2010-10-01

The evolution of cancer and RNA viruses share many similarities. Both exploit high levels of genotypic diversity to enable extensive phenotypic plasticity and thereby facilitate rapid adaptation. In order to accumulate large numbers of mutations, we have proposed that cancers express a mutator phenotype. Similar to cancer cells, many viral populations, by replicating their genomes with low fidelity, carry a substantial mutational load. As high levels of mutation are potentially deleterious, the viral mutation frequency is thresholded at a level below which viral populations equilibrate in a traditional mutation-selection balance, and above which the population is no longer viable, i.e., the population undergoes an error catastrophe. Because their mutation frequencies are fine-tuned just below this error threshold, viral populations are susceptible to further increases in mutational load and, recently this phenomenon has been exploited therapeutically by a concept that has been termed lethal mutagenesis. Here we review the application of lethal mutagenesis to the treatment of HIV and discuss how lethal mutagenesis may represent a novel therapeutic approach for the treatment of solid cancers. Copyright © 2010 Elsevier Ltd. All rights reserved.

Gracob: a novel graph-based constant-column biclustering method for mining growth phenotype data

KAUST Repository

Alzahrani, Majed A.

2017-04-05

Growth phenotype profiling of genome-wide genedeletion strains over stress conditions can offer a clear picture that the essentiality of genes depends on environmental conditions. Systematically identifying groups of genes from such high-throughput data that share similar patterns of conditional essentiality and dispensability under various environmental conditions can elucidate how genetic interactions of the growth phenotype are regulated in response to the environment.We first demonstrate that detecting such\\\\co-fit

Gracob: a novel graph-based constant-column biclustering method for mining growth phenotype data

KAUST Repository

Alzahrani, Majed A.; Kuwahara, Hiroyuki; Wang, Wei; Gao, Xin

2017-01-01

Growth phenotype profiling of genome-wide genedeletion strains over stress conditions can offer a clear picture that the essentiality of genes depends on environmental conditions. Systematically identifying groups of genes from such high-throughput data that share similar patterns of conditional essentiality and dispensability under various environmental conditions can elucidate how genetic interactions of the growth phenotype are regulated in response to the environment.We first demonstrate that detecting such\\co-fit

The effect of early life stress on the cognitive phenotype of children with an extra X chromosome (47,XXY/47,XXX).

Science.gov (United States)

van Rijn, Sophie; Barneveld, Petra; Descheemaeker, Mie-Jef; Giltay, Jacques; Swaab, Hanna

2018-02-01

Studies on gene-environment interactions suggest that some individuals may be more susceptible to life adversities than others due to their genetic profile. This study assesses whether or not children with an extra X chromosome are more vulnerable to the negative impact of early life stress on cognitive functioning than typically-developing children. A total of 50 children with an extra X chromosome and 103 non-clinical controls aged 9 to 18 years participated in the study. Cognitive functioning in domains of language, social cognition and executive functioning were assessed. Early life stress was measured with the Questionnaire of Life Events. High levels of early life stress were found to be associated with compromised executive functioning in the areas of mental flexibility and inhibitory control, irrespective of group membership. In contrast, the children with an extra X chromosome were found to be disproportionally vulnerable to deficits in social cognition on top of executive dysfunction, as compared to typically-developing children. Within the extra X group the number of negative life events is significantly correlated with more problems in inhibition, mental flexibility and social cognition. It is concluded that children with an extra X chromosome are vulnerable to adverse life events, with social cognition being particularly impacted in addition to the negative effects on executive functioning. The findings that developmental outcome is codependent on early environmental factors in genetically vulnerable children also underscores opportunities for training and support to positively influence the course of development.