factor x
Recently Published Documents


TOTAL DOCUMENTS

2223
(FIVE YEARS 228)

H-INDEX

83
(FIVE YEARS 6)

2022 ◽  
Author(s):  
Jean-Philippe Corre ◽  
Dorian Obino ◽  
Pierre Nivoit ◽  
Aline Yatim ◽  
Taliah Schmitt ◽  
...  

Meningococcal infections remain particularly difficult to treat. Despite antibiotic therapy, the state of the patients often rapidly deteriorates. Early clinical studies suggest that meningococci acquire a form of resistance to antibiotic treatments during infections. Taking advantage of a humanized animal model of infection, we confirm that adherent bacteria become highly resistant to antibiotic treatments as early as 3-6 hours post infection, although fully sensitive in vitro. Within this time frame, meningococci adhere to the endothelium via their type IV pili, proliferate and eventually fill the vessel lumen. Using intravital imaging, we show that rapidly upon infection blood flow is dramatically decreased, thus limiting antibiotic access to infected vessels. Concomitantly, fibrin is deposited inside infected vessels in proximity to bacterial aggregates. Pharmacologically impairing thrombin generation by inhibiting Factor X activity not only improves blood flow in infected vessels, but also enhances the efficacy of the antibiotic treatment. Our results indicate that the combined administration of anticoagulants together with antibiotics might represent a therapeutic approach to treat meningococcal sepsis more efficiently.


Symmetry ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 115
Author(s):  
Sakhi Zaman ◽  
Latif Ullah Khan ◽  
Irshad Hussain ◽  
Lucian Mihet-Popa

The paper demonstrates symmetric integral operator and interpolation based numerical approximations for linear and nonlinear ordinary differential equations (ODEs) with oscillatory factor x′=ψ(x)+χω(t), where the function χω(t) is an oscillatory forcing term. These equations appear in a variety of computational problems occurring in Fourier analysis, computational harmonic analysis, fluid dynamics, electromagnetics, and quantum mechanics. Classical methods such as Runge–Kutta methods etc. fail to approximate the oscillatory ODEs due the existence of oscillatory term χω(t). Two types of methods are presented to approximate highly oscillatory ODEs. The first method uses radial basis function interpolation, and then quadrature rules are used to evaluate the integral part of the solution equation. The second approach is more generic and can approximate highly oscillatory and nonoscillatory initial value problems. Accordingly, the first-order initial value problem with oscillatory forcing term is transformed into highly oscillatory integral equation. The transformed symmetric oscillatory integral equation is then evaluated numerically by the Levin collocation method. Finally, the nonlinear form of the initial value problems with an oscillatory forcing term is converted into a linear form using Bernoulli’s transformation. The resulting linear oscillatory problem is then computed by the Levin method. Results of the proposed methods are more reliable and accurate than some state-of-the-art methods such as asymptotic method, etc. The improved results are shown in the numerical section.


BMC Biology ◽  
2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Bing Xie ◽  
Daniel Dashevsky ◽  
Darin Rokyta ◽  
Parviz Ghezellou ◽  
Behzad Fathinia ◽  
...  

Abstract Background The explosive radiation and diversification of the advanced snakes (superfamily Colubroidea) was associated with changes in all aspects of the shared venom system. Morphological changes included the partitioning of the mixed ancestral glands into two discrete glands devoted for production of venom or mucous respectively, as well as changes in the location, size and structural elements of the venom-delivering teeth. Evidence also exists for homology among venom gland toxins expressed across the advanced snakes. However, despite the evolutionary novelty of snake venoms, in-depth toxin molecular evolutionary history reconstructions have been mostly limited to those types present in only two front-fanged snake families, Elapidae and Viperidae. To have a broader understanding of toxins shared among extant snakes, here we first sequenced the transcriptomes of eight taxonomically diverse rear-fanged species and four key viperid species and analysed major toxin types shared across the advanced snakes. Results Transcriptomes were constructed for the following families and species: Colubridae - Helicops leopardinus, Heterodon nasicus, Rhabdophis subminiatus; Homalopsidae – Homalopsis buccata; Lamprophiidae - Malpolon monspessulanus, Psammophis schokari, Psammophis subtaeniatus, Rhamphiophis oxyrhynchus; and Viperidae – Bitis atropos, Pseudocerastes urarachnoides, Tropidolaeumus subannulatus, Vipera transcaucasiana. These sequences were combined with those from available databases of other species in order to facilitate a robust reconstruction of the molecular evolutionary history of the key toxin classes present in the venom of the last common ancestor of the advanced snakes, and thus present across the full diversity of colubroid snake venoms. In addition to differential rates of evolution in toxin classes between the snake lineages, these analyses revealed multiple instances of previously unknown instances of structural and functional convergences. Structural convergences included: the evolution of new cysteines to form heteromeric complexes, such as within kunitz peptides (the beta-bungarotoxin trait evolving on at least two occasions) and within SVMP enzymes (the P-IIId trait evolving on at least three occasions); and the C-terminal tail evolving on two separate occasions within the C-type natriuretic peptides, to create structural and functional analogues of the ANP/BNP tailed condition. Also shown was that the de novo evolution of new post-translationally liberated toxin families within the natriuretic peptide gene propeptide region occurred on at least five occasions, with novel functions ranging from induction of hypotension to post-synaptic neurotoxicity. Functional convergences included the following: multiple occasions of SVMP neofunctionalised in procoagulant venoms into activators of the clotting factors prothrombin and Factor X; multiple instances in procoagulant venoms where kunitz peptides were neofunctionalised into inhibitors of the clot destroying enzyme plasmin, thereby prolonging the half-life of the clots formed by the clotting activating enzymatic toxins; and multiple occasions of kunitz peptides neofunctionalised into neurotoxins acting on presynaptic targets, including twice just within Bungarus venoms. Conclusions We found novel convergences in both structural and functional evolution of snake toxins. These results provide a detailed roadmap for future work to elucidate predator–prey evolutionary arms races, ascertain differential clinical pathologies, as well as documenting rich biodiscovery resources for lead compounds in the drug design and discovery pipeline.


PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0260897
Author(s):  
Marissa J. M. Traets ◽  
Roel H. T. Nijhuis ◽  
Servaas A. Morré ◽  
Sander Ouburg ◽  
Jasper A. Remijn ◽  
...  

Background Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest with varying disease severity and mortality. Genetic predisposition influences the clinical course of infectious diseases. We investigated whether genetic polymorphisms in candidate genes ACE2, TIRAP, and factor X are associated with clinical outcomes in COVID-19. Methods We conducted a single-centre retrospective cohort study. All patients who visited the emergency department with SARS-CoV-2 infection proven by polymerase chain reaction were included. Single nucleotide polymorphisms in ACE2 (rs2285666), TIRAP (rs8177374) and factor X (rs3211783) were assessed. The outcomes were mortality, respiratory failure and venous thromboembolism. Respiratory failure was defined as the necessity of >5 litres/minute oxygen, high flow nasal oxygen suppletion or mechanical ventilation. Results Between March and April 2020, 116 patients (35% female, median age 65 [inter quartile range 55–75] years) were included and treated according to the then applicable guidelines. Sixteen patients (14%) died, 44 patients (38%) had respiratory failure of whom 23 required endotracheal intubation for mechanical ventilation, and 20 patients (17%) developed venous thromboembolism. The percentage of TIRAP polymorphism carriers in the survivor group was 28% as compared to 0% in the non-survivor group (p = 0.01, Bonferroni corrected p = 0.02). Genotype distribution of ACE2 and factor X did not differ between survivors and non-survivors. Conclusion This study shows that carriage of TIRAP polymorphism rs8177374 could be associated with a significantly lower mortality in COVID-19. This TIRAP polymorphism may be an important predictor in the outcome of COVID-19.


Author(s):  
V.G. Griguletsky ◽  

The article provides a brief analysis of the results of plot and field experiments to study the productivity (yield) of sunflower, depending on the area of plant nutrition, performed at VNIIMK. Based on the analysis of the experimental dependencies that determine the change in yield, the following statement is applied: yield (y) and its increase rise with an increase in the amount of growth factor (x) and are proportional to the amount of yield (A - y) that does not reach the maximum the limiting value (A), and the possible yield value (B + y), is higher than a certain minimum (initial) value (B) of the yield. The analytic formulas for the quantitative determination of yield value (у), maximum limiting yield (A), amount of nutrients in soil, a rate of action of growth factors, etc. are present for the first time. These formulas allow studying many problems of soil management in certain hydro-temperature conditions and landscape. The samples of accounts due to the new methodology which showed good correspondence between test and theme data are presented.


Author(s):  
Akitada Ichinose ◽  
Tsukasa Osaki ◽  
Masayoshi Souri

AbstractCoagulation factor V (or FV for the purpose of medical safety) is an essential cofactor of coagulation factor X in the common pathway of coagulation; severe FV deficiency leads to a bleeding tendency. Although both congenital and acquired FV deficiencies are widely recognized, FV deficiency also presents as an autoimmune disorder. A nationwide survey on autoimmune coagulation factor deficiencies (AiCFDs) conducted in Japan by our Japanese Collaborative Research Group identified 24 new patients with autoimmune FV deficiency (AiFVD) in the past 5 years. Furthermore, our extensive literature search confirmed that 177 AiFVD cases have been reported in previous articles published from Japan. Patients with AiFVD in Japan were predominantly men, with age similar to those with other AiCFDs. AiFVD was confirmed as a relatively mild type of bleeding diathesis, associated with lower mortality rate than that for AiFVD and other AiCFDs reported in previous studies. Patients with AiFVD had variable FV inhibitor titers and both neutralizing anti-FV autoantibodies and nonneutralizing counterparts. Although spontaneous resolution occurs in some patients, timely initiation of hemostatic and immunosuppressive therapies helps arrest the bleeding and eliminate anti-FV antibodies, resulting in a high cumulative recovery rate. Immunological anti-FV antibody detection is recommended to avoid missing AiFVD cases for the presence of nonneutralizing anti-FV autoantibodies. Further investigation is necessary to clarify the long-term prognosis and optimal management of AiFVD.


Author(s):  
Amalie Carnbring Bonde ◽  
Jacob Lund ◽  
Jens Jacob Hansen ◽  
Jakob Rahr Winther ◽  
Per Franklin Nielsen ◽  
...  
Keyword(s):  

2021 ◽  
Vol 22 (24) ◽  
pp. 13486
Author(s):  
Bianca op den Brouw ◽  
Francisco C. P. Coimbra ◽  
Nicholas R. Casewell ◽  
Syed Abid Ali ◽  
Freek J. Vonk ◽  
...  

The snake genus Daboia (Viperidae: Viperinae; Oppel, 1811) contains five species: D. deserti, D. mauritanica, and D. palaestinae, found in Afro-Arabia, and the Russell’s vipers D. russelii and D. siamensis, found in Asia. Russell’s vipers are responsible for a major proportion of the medically important snakebites that occur in the regions they inhabit, and their venoms are notorious for their coagulopathic effects. While widely documented, the extent of venom variation within the Russell’s vipers is poorly characterised, as is the venom activity of other species within the genus. In this study we investigated variation in the haemotoxic activity of Daboia using twelve venoms from all five species, including multiple variants of D. russelii, D. siamensis, and D. palaestinae. We tested the venoms on human plasma using thromboelastography, dose-response coagulometry analyses, and calibrated automated thrombography, and on human fibrinogen by thromboelastography and fibrinogen gels. We assessed activation of blood factors X and prothrombin by the venoms using fluorometry. Variation in venom activity was evident in all experiments. The Asian species D. russelii and D. siamensis and the African species D. mauritanica possessed procoagulant venom, while D. deserti and D. palaestinae were net-anticoagulant. Of the Russell’s vipers, the venom of D. siamensis from Myanmar was most toxic and D. russelli of Sri Lanka the least. Activation of both factor X and prothrombin was evident by all venoms, though at differential levels. Fibrinogenolytic activity varied extensively throughout the genus and followed no phylogenetic trends. This venom variability underpins one of the many challenges facing treatment of Daboia snakebite envenoming. Comprehensive analyses of available antivenoms in neutralising these variable venom activities are therefore of utmost importance.


Oncogene ◽  
2021 ◽  
Author(s):  
Luis Coronel ◽  
David Häckes ◽  
Katjana Schwab ◽  
Konstantin Riege ◽  
Steve Hoffmann ◽  
...  

AbstractIn recent years the tumor suppressor p53 has been increasingly recognized as a potent regulator of the cell metabolism and for its ability to inhibit the critical pro-survival kinases AKT and mTOR. The mechanisms through which p53 controls AKT and mTOR, however, are largely unclear. Here, we demonstrate that p53 activates the metabolic regulator DDIT4 indirectly through the regulatory factor X 7 (RFX7). We provide evidence that DDIT4 is required for p53 to inhibit mTOR complex 2 (mTORC2)-dependent AKT activation. Most strikingly, we also find that the DDIT4 regulator RFX7 is required for p53-mediated inhibition of mTORC1 and AKT. Our results suggest that AMPK activation plays no role and p53-mediated AKT inhibition is not critical for p53-mediated mTORC1 inhibition. Moreover, using recently developed physiological cell culture media we uncover that basal p53 and RFX7 activity can play a critical role in restricting mTORC1 activity under physiological nutrient conditions, and we propose a nutrient-dependent model for p53-RFX7-mediated mTORC1 inhibition. These results establish RFX7 and its downstream target DDIT4 as essential effectors in metabolic control elicited by p53.


Sign in / Sign up

Export Citation Format

Share Document