scholarly journals Differential transcript profile of inhibitors with potential anti-venom role in the liver of juvenile and adultBothrops jararacasnake

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3203 ◽  
Author(s):  
Cícera Maria Gomes ◽  
Karen de Morais-Zani ◽  
Stephen Lu ◽  
Diego de Souza Buarque ◽  
Glória Regina Cardoso Braz ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Clinical Manifestations ◽  
Fold Increase ◽  
Phospholipase A ◽  
Natural Resistance ◽  
Physiological Adaptation ◽  
Natural Immunity ◽  
Venomous Snake ◽  
Snake Bites ◽  
A Minor

BackgroundSnakes belonging to theBothropsgenus are vastly distributed in Central and South America and are responsible for most cases of reported snake bites in Latin America. The clinical manifestations of the envenomation caused by this genus are due to three major activities—proteolytic, hemorrhagic and coagulant—mediated by metalloproteinases, serine proteinases, phospholipases A2and other toxic compounds present in snake venom. Interestingly, it was observed that snakes are resistant to the toxic effects of its own and other snake’s venoms. This natural immunity may occur due the absence of toxin target or the presence of molecules in the snake plasma able to neutralize such toxins.MethodsIn order to identify anti-venom molecules, we construct a cDNA library from the liver ofB. jararacasnakes. Moreover, we analyzed the expression profile of four molecules—the already known anti-hemorrhagic factor Bj46a, one gamma-phospholipase A2inhibitor, one inter-alpha inhibitor and one C1 plasma protease inhibitor—in the liver of juvenile and adult snakes by qPCR.ResultsThe results revealed a 30-fold increase of gamma-phospholipase A2inhibitor and a minor increase of the inter-alpha inhibitor (5-fold) and of the C1 inhibitor (3-fold) in adults. However, the Bj46a factor seems to be equally transcribed in adults and juveniles.DiscussionThe results suggest the up-regulation of different inhibitors observed in the adult snakes might be a physiological adaptation to the recurrent contact with their own and even other snake’s venoms throughout its lifespan. This is the first comparative analysis of ontogenetic variation of expression profiles of plasmatic proteins with potential anti-venom activities of the venomous snakeB. jararaca. Furthermore, the present data contributes to the understanding of the natural resistance described in these snakes.

P1279INSULIN RESISTANCE IN HEMODIALYSIS PATIENS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Pavel Filinyuk ◽  
Aleksander Rumyantsev
Keyword(s):  
Insulin Resistance ◽  
Systemic Inflammation ◽  
Clinical Manifestations ◽  
Biological Response ◽  
Fold Increase ◽  
Atherogenic Dyslipidemia ◽  
Model Assessment ◽  
Peripheral Tissues ◽  
Reactive Protein ◽  
Homeostatic Model Assessment

Abstract Background and Aims insulin resistance (IR) is a decrease in the biological response of sensitive tissues to insulin. IR is known as an adverse risk factor in cardiovascular disease, which largely determines the prognosis of patients receiving hemodialysis (HD). But this issue is not well understood. For the screening of IR, special indices have been developed that characterize the sensitivity of tissues to insulin. The aim of the study was to compare the methods of screening for IR in patients receiving HD in relation to the markers of systemic inflammation and atherogenic dyslipidemia (AtD). Method 124 patients receiving HD for 75.4 ± 44.5 months were examined including 66 men and 58 women aged 57.6 ± 13.6 years. For IR screening, the Homeostatic Model Assessment-1 and 2 indices (HOMA-1 and HOMA-2), the Quantitative Insulin Sensitivity Check Index (QUICKI) and triglycerides / glucose (Tri/G) were used. Patients were examined in accordance with the recommendations of KDIGO. Data analysis was carried out using “STATISTICA 10.0”. Results fasting insulin levels were elevated in 19% of patients. But, the calculated indices were consistent with the idea that IR is much more common. So, the IR index in the HOMA -1 model was increased in 47%, in the HOMA -2 model - in 33%, in the QUICKI model - in 36%, the TriH indicator - in 91%. The sensitivity of peripheral tissues in the HOMA-1 and HOMA-2 models was equally reduced by 35-40%. The results of the correlation analysis between indicators of IR and plasma concentration of C-reactive protein and lipid profile are presented in table 1. Informativeness of IR indicators depending on the presence of obesity is presented in table 2 We were also interested in whether insulin resistance affects the development of clinical manifestations of atherosclerosis, cardiac arrhythmias, and heart failure. An analysis of this relationship did not reveal. Only the IR index in the HOMA-1 model with a value of more than 2.7 units was associated with a 4.5-fold increase in the risk of developing clinical manifestations of atherosclerotic lesions (χ2 = 4.582 p = 0.032). Statistically significant it was only in men. Given our data, perhaps IR is one of the reasons for the higher morbidity and mortality of men at HD. Conclusion a comparison of IR models allows us to distinguish HOMA-2 as the most accurate index. The highest correlation with systemic inflammation and AtD was in the HOMA-1 and HOMA-2 indices.

scholarly journals Role of embB in natural and acquired resistance to ethambutol in mycobacteria.

1997 ◽  
Vol 41 (10) ◽  
pp. 2270-2273 ◽  
Author(s):  
F Alcaide ◽  
G E Pfyffer ◽  
A Telenti
Keyword(s):  
Nontuberculous Mycobacteria ◽  
Practical Implication ◽  
Acquired Resistance ◽  
Fold Increase ◽  
Drug Susceptibility ◽  
Natural Resistance ◽  
Intrinsic Resistance ◽  
Resistant Strains ◽  
High Level

The mycobacterial embCAB operon encodes arabinosyl transferases, putative targets of the antimycobacterial agent ethambutol (EMB). Mutations in embB lead to resistance to EMB in Mycobacterium tuberculosis. The basis for natural, intrinsic resistance to EMB in nontuberculous mycobacteria (NTM) is not known; neither is the practical implication of resistance to EMB in the absence of embB mutations in M. tuberculosis well understood. The conserved embB resistance-determining region (ERDR) of a collection of 13 strains of NTM and 12 EMB-resistant strains of M. tuberculosis was investigated. Genotypes were correlated with drug susceptibility phenotypes. High-level natural resistance to EMB (MIC, . or =64 microg/ml) was associated with a variant amino acid motif in the ERDR of M. abscessus, M. chelonae, and M. leprae. Transfer of the M. abscessus emb allele to M. smegmatis resulted in a 500-fold increase in the MICs. In M. tuberculosis, embB mutations were associated with MICs of > or =20 microg/ml while resistance not associated with an ERDR mutation generally resulted in MICs of < or =10 microg/ml. These data further support the notion that the emb region determines intrinsic and acquired resistance to EMB and might help in the reassessment of the current recommendations for the screening and treatment of infections with EMB-resistant M. tuberculosis and NTM.

scholarly journals Specific shifts in the endocannabinoid system in hibernating brown bears

2020 ◽  
Author(s):  
Christian Boyer ◽  
Laura Cussonneau ◽  
Charlotte Brun ◽  
Christiane Deval ◽  
Jean-Paul Pais de Barros ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Ursus Arctos ◽  
Mild Hypothermia ◽  
Endocannabinoid System ◽  
Fold Increase ◽  
Physiological Adaptation ◽  
Acid Oxidation ◽  
Brown Bears ◽  
Peripheral Tissues ◽  
Free Ranging

Abstract In small hibernators, global downregulation of the endocannabinoid system (ECS), which is involved in modulating neuronal signaling, feeding behavior, energy metabolism, and circannual rhythms, has been reported to possibly drive physiological adaptation to the hibernating state. We hypothesized that specific changes should occur in hibernating brown bears ( Ursus arctos ) due to specific features, including hibernation during half the year at only mild hypothermia while remaining physically inactive without drinking or eating, and the absence of arousal episodes although bears remain sensitive to external disturbances. We explored circulating lipids and the ECS in plasma and metabolically active tissues (muscle and adipose tissue), in free-ranging subadult Scandinavian brown bears when both active and hibernating. In winter bear serum, in addition to a 2-fold increase in total fatty acid concentration, we found significant changes in relative proportions of circulating fatty acids, such as a 2-fold increase in docosahexaenoic acid and a decrease in arachidonic acid. In adipose and muscle tissues of hibernating bears, we found lower concentrations of both two major ligands for endocannabinoid receptors, 2-arachidonoylglycerol (2-AG) and anandamide (AEA). Gene expression was reduced for enzymes that synthesize endocannabinoid compounds, whereas an increase was observed for catabolic enzymes. Reduction in ECS tone may promote mobilization of fat stores and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating of the endocannabinoid-like compound N-oleoylethanolamide (OEA) in winter could favor lipolysis and fatty acid oxidation in peripheral tissues. We also speculated on a role of OEA in the maintenance of torpor (reduction in locomotion), while promoting the capacity of bears to sense stimuli from the environment.

Evaluation of the effect of gamma rays on the venom of Vipera lebetina by biochemical study

2003 ◽  
Vol 81 (12) ◽  
pp. 1110-1117 ◽  
Author(s):  
Nouara Bennacef-Heffar ◽  
Fatima Laraba-Djebari
Keyword(s):  
Gamma Radiation ◽  
Gamma Rays ◽  
Biochemical Characterization ◽  
Biochemical Study ◽  
Gel Filtration ◽  
Public Health Problem ◽  
Phospholipase A ◽  
Snake Bites ◽  
Vipera Lebetina

Snake bites represent a serious public health problem in many areas of the world. In Algeria, two widespread snakes are Vipera lebetina and Cerastes cerastes. Vipera lebetina venom causes local hemorrhage and necrosis, and it may lead to permanent limb loss. The principal causes of mortality after snakebites are acute renal failure and hemorrhage, which occur not only locally, at the site of the bite, but also systemically, contributing to the cardiovascular shock characteristic of severe envenomation. Gamma radiation has been shown to be effective for attenuating venom toxicity. Vipera lebetina venom was irradiated with two doses of gamma rays (1 and 2 kGy) from a 60Co source, and the venom's toxic, enzymatic, and structural properties were analyzed. Intraperitoneal injection of the irradiated venoms (100–500 µg/20 g mouse body mass) revealed a significant decrease of the toxicity. Irradiated venoms with 1 and 2 kGy doses were four and nine times less toxic, respectively, than the native venom. A biochemical characterization of in vitro enzymatic activities was performed. Vipera lebetina displayed in vitro caseinolytic, amidolytic, esterasic, coagulant, and phospholipase A2 activities. Caseinolytic, amidolytic, esterasic, and coagulative activities were reduced for the irradiated venoms; only phospholipase A2 activity was abolished in the irradiated venom with a dose of 2 kGy. The native and irradiated venoms were separated by gel filtration and electrophoresis. Chromatographic and electrophoretic profiles were drastically changed as compared with the native venom. Vipera lebetina venom detoxified by gamma rays was used for active immunization, and the presence of antibody in the immune sera was detected by ELISA. The immunogenic properties were preserved and the antisera obtained with the irradiated venoms could cross-react. Antisera were able to neutralize the toxic effect of V. lebetina native venom. These results indicate that irradiation of V. lebetina venom with a dose of 2 kGy can promote a significant detoxification, keeping the immunological properties intact.Key words: Vipera lebetina venom, gamma radiation, enzymes, detoxification, immune sera, immunoreactivity.

scholarly journals Two pulses of morphological diversification in Pacific pelagic fishes following the Cretaceous–Palaeogene mass extinction

2018 ◽  
Vol 285 (1888) ◽  
pp. 20181194 ◽  
Author(s):  
Elizabeth Sibert ◽  
Matt Friedman ◽  
Pincelli Hull ◽  
Gene Hunt ◽  
Richard Norris
Keyword(s):  
Sediment Core ◽  
Mass Extinction ◽  
Middle Eocene ◽  
South Pacific ◽  
Fold Increase ◽  
Fish Diversity ◽  
Evolutionary Patterns ◽  
Morphological Diversification ◽  
Pelagic Fishes ◽  
A Minor

Molecular phylogenies suggest some major radiations of open-ocean fish clades occurred roughly coincident with the Cretaceous–Palaeogene (K/Pg) boundary, however the timing and nature of this diversification is poorly constrained. Here, we investigate evolutionary patterns in ray-finned fishes across the K/Pg mass extinction 66 million years ago (Ma), using microfossils (isolated teeth) preserved in a South Pacific sediment core spanning 72–43 Ma. Our record does not show significant turnover of fish tooth morphotypes at the K/Pg boundary: only two of 48 Cretaceous tooth morphotypes disappear at the event in the South Pacific, a rate no different from background extinction. Capture–mark–recapture analysis finds two pulses of origination in fish tooth morphotypes following the mass extinction. The first pulse, at approximately 64 Ma, included short-lived teeth, as well as forms that contribute to an expansion into novel morphospace. A second pulse, centred at approximately 58 Ma, produced morphotype novelty in a different region of morphospace from the first pulse, and contributed significantly to Eocene tooth morphospace occupation. There was no significant increase in origination rates or expansion into novel morphospace during the early or middle Eocene, despite a near 10-fold increase in tooth abundance during that interval. Our results suggest that while the K/Pg event had a minor impact on fish diversity in terms of extinction, the removal of the few dominant Cretaceous morphotypes triggered a sequence of origination events allowing fishes to rapidly diversify morphologically, setting the stage for exceptional levels of ray-finned fish diversity in the Cenozoic.

scholarly journals A XRCC4 mutant mouse, a model for human X4 syndrome, reveals interplays with Xlf, PAXX, and ATM in lymphoid development

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Benoit Roch ◽  
Vincent Abramowski ◽  
Olivier Etienne ◽  
Stefania Musilli ◽  
Pierre David ◽  
...  
Keyword(s):  
Dna Repair ◽  
Clinical Manifestations ◽  
Adaptive Immune System ◽  
Embryonic Lethality ◽  
Dna Ligase ◽  
Mouse Development ◽  
Dna Ligase Iv ◽  
Ligase Iv ◽  
A Minor

We developed a Xrcc4M61R separation of function mouse line to overcome the embryonic lethality of Xrcc4 deficient mice. XRCC4M61R protein does not interact with Xlf, thus obliterating XRCC4-Xlf filament formation while preserving the ability to stabilize DNA Ligase IV. X4M61R mice, which are DNA repair deficient, phenocopy the Nhej1-/- (known as Xlf -/-) setting with a minor impact on the development of the adaptive immune system. The core NHEJ DNA repair factor XRCC4 is therefore not mandatory for V(D)J recombination aside from its role in stabilizing DNA ligase IV. In contrast, Xrcc4M61R mice crossed on Paxx-/-, Nhej1-/-, or Atm-/- backgrounds are severely immunocompromised, owing to aborted V(D)J recombination as in Xlf-Paxx and Xlf-Atm double KO settings. Furthermore, massive apoptosis of post-mitotic neurons causes embryonic lethality of Xrcc4M61R -Nhej1-/- double mutants. These in vivo results reveal new functional interplays between XRCC4 and PAXX, ATM and Xlf in mouse development and provide new insights in the understanding of the clinical manifestations of human XRCC4 deficient condition, in particular its absence of immune deficiency.

scholarly journals Conservation and Divergence in Duplicated Fiber Coexpression Networks Accompanying Domestication of the Polyploid Gossypium hirsutum L

2020 ◽  
Vol 10 (8) ◽  
pp. 2879-2892 ◽  
Author(s):  
Joseph P. Gallagher ◽  
Corrinne E. Grover ◽  
Guanjing Hu ◽  
Josef J. Jareczek ◽  
Jonathan F. Wendel
Keyword(s):  
Gossypium Hirsutum ◽  
Cotton Fiber ◽  
Expression Profiles ◽  
Fold Increase ◽  
Genome Wide ◽  
Expression Bias ◽  
Gene Usage ◽  
Coexpression Networks ◽  
Developmental Dynamics ◽  
Modular Structures

Gossypium hirsutum L. (Upland cotton) has an evolutionary history involving inter-genomic hybridization, polyploidization, and subsequent domestication. We analyzed the developmental dynamics of the cotton fiber transcriptome accompanying domestication using gene coexpression networks for both joint and homoeologous networks. Remarkably, most genes exhibited expression for at least one homoeolog, confirming previous reports of widespread gene usage in cotton fibers. Most coexpression modules comprising the joint network are preserved in each subgenomic network and are enriched for similar biological processes, showing a general preservation of network modular structure for the two co-resident genomes in the polyploid. Interestingly, only one fifth of homoeologs co-occur in the same module when separated, despite similar modular structures between the joint and homoeologous networks. These results suggest that the genome-wide divergence between homoeologous genes is sufficient to separate their co-expression profiles at the intermodular level, despite conservation of intramodular relationships within each subgenome. Most modules exhibit D-homoeolog expression bias, although specific modules do exhibit A-homoeolog bias. Comparisons between wild and domesticated coexpression networks revealed a much tighter and denser network structure in domesticated fiber, as evidenced by its fewer modules, 13-fold increase in the number of development-related module member genes, and the poor preservation of the wild network topology. These results demonstrate the amazing complexity that underlies the domestication of cotton fiber.

Tackling venomous snake bites worldwide

The Lancet ◽  
2001 ◽  
Vol 357 (9269) ◽  
pp. 1680 ◽  
Author(s):  
David McNamee
Keyword(s):  
Venomous Snake ◽  
Snake Bites

scholarly journals Diversity, Epidemiology, and Genetics of Class D β-Lactamases

2009 ◽  
Vol 54 (1) ◽  
pp. 24-38 ◽  
Author(s):  
Laurent Poirel ◽  
Thierry Naas ◽  
Patrice Nordmann
Keyword(s):  
Natural Resistance ◽  
Minor Role ◽  
Insertion Sequences ◽  
Class 1 Integron ◽  
Gram Negative ◽  
Class D ◽  
Class 1 ◽  
Great Heterogeneity ◽  
Genes Encoding ◽  
A Minor

ABSTRACT Class D β-lactamase-mediated resistance to β-lactams has been increasingly reported during the last decade. Those enzymes also known as oxacillinases or OXAs are widely distributed among Gram negatives. Genes encoding class D β-lactamases are known to be intrinsic in many Gram-negative rods, including Acinetobacter baumannii and Pseudomonas aeruginosa, but play a minor role in natural resistance phenotypes. The OXAs (ca. 150 variants reported so far) are characterized by an important genetic diversity and a great heterogeneity in terms of β-lactam hydrolysis spectrum. The acquired OXAs possess either a narrow spectrum or an expanded spectrum of hydrolysis, including carbapenems in several instances. Acquired class D β-lactamase genes are mostly associated to class 1 integron or to insertion sequences.

Expression profiles of metamorphosis-related genes during natural transformations in tadpoles of wild Wood Frogs (Lithobates sylvaticus)

2012 ◽  
Vol 90 (9) ◽  
pp. 1059-1071 ◽  
Author(s):  
Laia Navarro-Martín ◽  
Chantal Lanctôt ◽  
Christopher Edge ◽  
Jeff Houlahan ◽  
Vance L. Trudeau
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Rana Sylvatica ◽  
Fold Increase ◽  
Gonadal Development ◽  
Specific Expression ◽  
Wood Frogs ◽  
Lithobates Sylvaticus ◽  
Expression Levels ◽  
Gene Expression Levels

Numerous studies using laboratory-reared tadpoles have shown the importance of thyroid hormones (TH), thyroid receptors (TR), and deiodinase (Dio) enzymes during anuran metamorphosis. Our study focuses on the analysis of thyroid-related genes in tadpoles of wild Wood Frogs ( Lithobates sylvaticus (LeConte, 1825); also known as Rana sylvatica (Cope, 1889)) during metamorphosis. Results showed that, in concordance with laboratory-reared studies, thyroid receptor beta (trb) gene expression profiles presented the most marked changes. At climax and compared with premetamorphic stages, brains, tails, and gonad–mesonephros complex (GMC) tissues increased trb expression levels 5-, 21-, and 41-fold, respectively (p < 0.05). In addition, gene expression levels of brain deiodinase type II and III showed opposite trends, where 3-fold decrease and 10-fold increase were, respectively, found. This finding supports the idea that thyroid hormone, as it has been demonstrated in laboratory-reared tadpoles, is also involved in natural metamorphosis in wild tadpoles. Interestingly, and contrary to our predictions, we observed that whole brain corticotropin-releasing factor (crf) and crf receptor 1 (crfr1) gene expression levels significantly decrease through metamorphosis in wild L. sylvaticus tadpoles. Further analyses are required to determine if a role of TH in the timing of anuran gonadal development exists, as well as the importance of cell-specific and tissue-specific expression of crf and crfr1 to metamorphosis.

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