177 research outputs found
Endothelial Dysfunction and Diabetes: Effects on Angiogenesis, Vascular Remodeling, and Wound Healing
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia due to lack of or resistance to insulin. Patients with DM are frequently afflicted with ischemic vascular disease or wound healing defect. It is well known that type 2 DM causes amplification of the atherosclerotic process, endothelial cell dysfunction, glycosylation of extracellular matrix proteins, and vascular denervation. These complications ultimately lead to impairment of neovascularization and diabetic wound healing. Therapeutic angiogenesis remains an attractive treatment modality for chronic ischemic disorders including PAD and/or diabetic wound healing. Many experimental studies have identified better approaches for diabetic cardiovascular complications, however, successful clinical translation has been limited possibly due to the narrow therapeutic targets of these agents or the lack of rigorous evaluation of pathology and therapeutic mechanisms in experimental models of disease. This paper discusses the current body of evidence identifying endothelial dysfunction and impaired angiogenesis during diabetes
Caudal regression syndrome: a rare case report
Caudal regression syndrome is a rare disorder characterised by abnormal development of structures in the caudal region of the embryo like lower lumbar and sacral vertebrae, urogenital and lower gastrointestinal system. It is secondary to abnormal development of mesoderm. Multiple hypotheses like genetic, metabolic and vascular hypoperfusion have been proposed as etiologies. It can be picked up in early second trimester by ultrasound. It has a higher incidence in diabetic pregnancies
From Molecules to Materials: Pre-training Large Generalizable Models for Atomic Property Prediction
Foundation models have been transformational in machine learning fields such
as natural language processing and computer vision. Similar success in atomic
property prediction has been limited due to the challenges of training
effective models across multiple chemical domains. To address this, we
introduce Joint Multi-domain Pre-training (JMP), a supervised pre-training
strategy that simultaneously trains on multiple datasets from different
chemical domains, treating each dataset as a unique pre-training task within a
multi-task framework. Our combined training dataset consists of 120M
systems from OC20, OC22, ANI-1x, and Transition-1x. We evaluate performance and
generalization by fine-tuning over a diverse set of downstream tasks and
datasets including: QM9, rMD17, MatBench, QMOF, SPICE, and MD22. JMP
demonstrates an average improvement of 59% over training from scratch, and
matches or sets state-of-the-art on 34 out of 40 tasks. Our work highlights the
potential of pre-training strategies that utilize diverse data to advance
property prediction across chemical domains, especially for low-data tasks
Sex-Specific Differences in Shoaling Affect Parasite Transmission in Guppies
Background: Individuals have to trade-off the costs and benefits of group membership during shoaling behaviour. Shoaling can increase the risk of parasite transmission, but this cost has rarely been quantified experimentally. Guppies (Poecilia reticulata) are a model system for behavioural studies, and they are commonly infected by gyrodactylid parasites, notorious fish pathogens that are directly transmitted between guppy hosts.
Methodology/Principal Findings:Parasite transmission in single sex shoals of male and female guppies were observed using an experimental infection of Gyrodactylus turnbulli. Parasite transmission was affected by sex-specific differences in host behaviour, and significantly more parasites were transmitted when fish had more frequent and more prolonged contact with each other. Females shoaled significantly more than males and had a four times higher risk to contract an infection.
Conclusions/Significance: Intersexual differences in host behaviours such as shoaling are driven by differences in natural and sexual selection experienced by both sexes. Here we show that the potential benefits of an increased shoaling tendency are traded off against increased risks of contracting an infectious parasite in a group-living species
Precautionary Regulation in Europe and the United States: A Quantitative Comparison
Much attention has been addressed to the question of whether Europe or the United States adopts a more precautionary stance to the regulation of potential environmental, health, and safety risks. Some commentators suggest that Europe is more risk-averse and precautionary, whereas the US is seen as more risk-taking and optimistic about the prospects for new technology. Others suggest that the US is more precautionary because its regulatory process is more legalistic and adversarial, while Europe is more lax and corporatist in its regulations. The flip-flop hypothesis claims that the US was more precautionary than Europe in the 1970s and early 1980s, and that Europe has become more precautionary since then. We examine the levels and trends in regulation of environmental, health, and safety risks since 1970. Unlike previous research, which has studied only a small set of prominent cases selected non-randomly, we develop a comprehensive list of almost 3,000 risks and code the relative stringency of regulation in Europe and the US for each of 100 risks randomly selected from that list for each year from 1970 through 2004. Our results suggest that: (a) averaging over risks, there is no significant difference in relative precaution over the period, (b) weakly consistent with the flip-flop hypothesis, there is some evidence of a modest shift toward greater relative precaution of European regulation since about 1990, although (c) there is a diversity of trends across risks, of which the most common is no change in relative precaution (including cases where Europe and the US are equally precautionary and where Europe or the US has been consistently more precautionary). The overall finding is of a mixed and diverse pattern of relative transatlantic precaution over the period
Cystathionine γ-lyase regulates arteriogenesis through NO-dependent monocyte recruitment
AIMS: Hydrogen sulfide (H2S) is a vasoactive gasotransmitter that is endogenously produced in the vasculature by the enzyme cystathionine γ-lyase (CSE). However, the importance of CSE activity and local H2S generation for ischaemic vascular remodelling remains completely unknown. In this study, we examine the hypothesis that CSE critically regulates ischaemic vascular remodelling involving H2S-dependent mononuclear cell regulation of arteriogenesis. METHODS AND RESULTS: Arteriogenesis including mature vessel density, collateral formation, blood flow, and SPY angiographic blush rate were determined in wild-type (WT) and CSE knockout (KO) mice at different time points following femoral artery ligation (FAL). The role of endogenous H2S in regulation of IL-16 expression and subsequent recruitment of monocytes, and expression of VEGF and bFGF in ischaemic tissues, were determined along with endothelial progenitor cell (CD34/Flk1) formation and function. FAL of WT mice significantly increased CSE activity, expression and endogenous H2S generation in ischaemic tissues, and monocyte infiltration, which was absent in CSE-deficient mice. Treatment of CSE KO mice with the polysulfide donor diallyl trisulfide restored ischaemic vascular remodelling, monocyte infiltration, and cytokine expression. Importantly, exogenous H2S therapy restored nitric oxide (NO) bioavailability in CSE KO mice that was responsible for monocyte recruitment and arteriogenesis. CONCLUSION: Endogenous CSE/H2S regulates ischaemic vascular remodelling mediated during hind limb ischaemia through NO-dependent monocyte recruitment and cytokine induction revealing a previously unknown mechanism of arteriogenesis
Getting into hot water:sick guppies frequent warmer thermal conditions
Ectotherms depend on the environmental temperature for thermoregulation and exploit thermal regimes that optimise physiological functioning. They may also frequent warmer conditions to up-regulate their immune response against parasite infection and/or impede parasite development. This adaptive response, known as ‘behavioural fever’, has been documented in various taxa including insects, reptiles and fish, but only in response to endoparasite infections. Here, a choice chamber experiment was used to investigate the thermal preferences of a tropical freshwater fish, the Trinidadian guppy (Poecilia reticulata), when infected with a common helminth ectoparasite Gyrodactylus turnbulli, in female-only and mixed-sex shoals. The temperature tolerance of G. turnbulli was also investigated by monitoring parasite population trajectories on guppies maintained at a continuous 18, 24 or 32 °C. Regardless of shoal composition, infected fish frequented the 32 °C choice chamber more often than when uninfected, significantly increasing their mean temperature preference. Parasites maintained continuously at 32 °C decreased to extinction within 3 days, whereas mean parasite abundance increased on hosts incubated at 18 and 24 °C. We show for the first time that gyrodactylid-infected fish have a preference for warmer waters and speculate that sick fish exploit the upper thermal tolerances of their parasites to self medicate
AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia
Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia through the so-called oxygen-dependent metabolic regulation, which involves the competitive binding of deoxyhemoglobin and glycolytic enzymes to the N-terminal cytosolic domain of band 3. This mechanism promotes the accumulation of 2,3-DPG, stabilizing the deoxygenated state of hemoglobin, and cytosol acidification, triggering oxygen off-loading through the Bohr effect. Despite in vitro studies, in vivo adaptations to hypoxia have not yet been completely elucidated. Within the framework of the AltitudeOmics study, erythrocytes were collected from 21 healthy volunteers at sea level, after exposure to high altitude (5260m) for 1, 7 and 16days, and following reascent after 7days at 1525m. UHPLC-MS metabolomics results were correlated to physiological and athletic performance parameters. Immediate metabolic adaptations were noted as early as a few hours from ascending to >5000m, and maintained for 16 days at high altitude. Consistent with the mechanisms elucidated in vitro, hypoxia promoted glycolysis and deregulated the pentose phosphate pathway, as well purine catabolism, glutathione homeostasis, arginine/nitric oxide and sulphur/H2S metabolism. Metabolic adaptations were preserved one week after descent, consistently with improved physical performances in comparison to the first ascendance, suggesting a mechanism of metabolic memory
Using Workflows to Explore and Optimise Named Entity Recognition for Chemistry
Chemistry text mining tools should be interoperable and adaptable regardless of
system-level implementation, installation or even programming issues. We aim to
abstract the functionality of these tools from the underlying implementation via
reconfigurable workflows for automatically identifying chemical names. To
achieve this, we refactored an established named entity recogniser (in the
chemistry domain), OSCAR and studied the impact of each component on the net
performance. We developed two reconfigurable workflows from OSCAR using an
interoperable text mining framework, U-Compare. These workflows can be altered
using the drag-&-drop mechanism of the graphical user
interface of U-Compare. These workflows also provide a platform to study the
relationship between text mining components such as tokenisation and named
entity recognition (using maximum entropy Markov model (MEMM) and pattern
recognition based classifiers). Results indicate that, for chemistry in
particular, eliminating noise generated by tokenisation techniques lead to a
slightly better performance than others, in terms of named entity recognition
(NER) accuracy. Poor tokenisation translates into poorer input to the classifier
components which in turn leads to an increase in Type I or Type II errors, thus,
lowering the overall performance. On the Sciborg corpus, the workflow based
system, which uses a new tokeniser whilst retaining the same MEMM component,
increases the F-score from 82.35% to 84.44%. On the PubMed corpus,
it recorded an F-score of 84.84% as against 84.23% by OSCAR
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