Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Triptolide on Temporal Expression of Cell Cycle Regulators During Cardiac Hypertrophy

Adult mammalian cardiomyocytes may reenter the cell cycle and cause cardiac hypertrophy. Triptolide (TP) can regulate the expressions of various cell cycle regulators in cancer cells. However, its effects on cell cycle regulators during myocardial hypertrophy and mechanism are unclear. This study was designed to explore the profile of cell cycle of cardiomyocytes and the temporal expression of their regulators during cardiac hypertrophy, as well as the effects of TP. The hypertrophy models employed were neonatal rat ventricular myocytes (NRVMs) stimulated with angiotensin II (Ang II) for scheduled times (from 5 min to 48 h) in vitro and mice treated with isoprenaline (Iso) for from 1 to 21 days, respectively. TP was used in vitro at 1 μg/L and in vivo at 10 μg/kg. NRVMs were analyzed using flow cytometry to detect the cell cycle, and the expression levels of mRNA and protein of various cell cycle regulators were determined using real-time PCR and Western blot. It was found NRVM numbers in phases S and G2 increased, while that in the G1 phase decreased significantly after Ang II stimulation. The mRNA expression levels of p21 and p27 increased soon after stimulation, and thereafter, mRNA expression levels of all cell cycle factors showed a decreasing trend and reached their lowest levels in 1–3 h, except for cyclin-dependent kinase 1 (CDK1) and CDK4 mRNA. The mRNA expression levels of CDK1, p21, and p27 increased markedly after stimulation with Ang II for 24–48 h. In myocardium tissue, CDK and cyclin expression levels peaked in 3–7 days, followed by a decreasing trend, while those of p21 and p27 mRNA remained at a high level on day 21. Expression levels of all protein were consistent with the results of mRNA in NRVMs or mice. The influence of Ang II or Iso on protein expression was more obvious than that on mRNA. TP treatment effectively prevented the imbalance in the expression of cell cycle regulators in the hypertrophy model group. In Conclusion, an imbalance in the expression of cell cycle regulators occurs during cardiac hypertrophy, and triptolide corrects these abnormal expression levels and attenuates cardiac hypertrophy.
Endothelial Dysfunction in Diabetic Retinopathy

Diabetic retinopathy (DR) is a diabetic complication which affects retinal function and results in severe loss of vision and relevant retinal diseases. Retinal vascular dysfunction caused by multifactors, such as advanced glycosylation end products and receptors, pro-inflammatory cytokines and chemokines, proliferator-activated receptor-γ disruption, growth factors, oxidative stress, and microRNA. These factors promote retinal endothelial dysfunction, which results in the development of DR. In this review, we summarize the contributors in the pathophysiology of DR for a better understanding of the molecular and cellular mechanism in the development of DR with a special emphasis on retinal endothelial dysfunction.
CD226 Deletion Reduces Type 1 Diabetes in the NOD Mouse by Impairing Thymocyte Development and Peripheral T Cell Activation

The costimulatory molecule CD226 is highly expressed on effector/memory T cells and natural killer cells. Costimulatory signals received by T cells can impact both central and peripheral tolerance mechanisms. Genetic polymorphisms in CD226 have been associated with susceptibility to type 1 diabetes and other autoimmune diseases. We hypothesized that genetic deletion of Cd226 in the non-obese diabetic (NOD) mouse would impact type 1 diabetes incidence by altering T cell activation. CD226 knockout (KO) NOD mice displayed decreased disease incidence and insulitis in comparison to wild-type (WT) controls. Although female CD226 KO mice had similar levels of sialoadenitis as WT controls, male CD226 KO mice showed protection from dacryoadenitis. Moreover, CD226 KO T cells were less capable of adoptively transferring disease compared to WT NOD T cells. Of note, CD226 KO mice demonstrated increased CD8+ single positive (SP) thymocytes, leading to increased numbers of CD8+ T cells in the spleen. Decreased percentages of memory CD8+CD44+CD62L– T cells were observed in the pancreatic lymph nodes of CD226 KO mice. Intriguingly, CD8+ T cells in CD226 KO mice showed decreased islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-tetramer and CD5 staining, suggesting reduced T cell receptor affinity for this immunodominant antigen. These data support an important role for CD226 in type 1 diabetes development by modulating thymic T cell selection as well as impacting peripheral memory/effector CD8+ T cell activation and function.
Mechanisms of M2 Macrophage-Derived Exosomal Long Non-coding RNA PVT1 in Regulating Th17 Cell Response in Experimental Autoimmune Encephalomyelitisa

Long non-coding RNA (lncRNA) is pivotal for multiple sclerosis (MS), but the potential mechanism of lncRNA PVT1 in MS animal model, experimental autoimmune encephalomyelitis (EAE) still remains unclear. In this study, macrophages were firstly isolated and induced to polarize into M2 macrophages. M2 macrophage-derived exosomes (M2-exos) were extracted and identified, and EAE mouse model was established and treated with M2-exos. The effect of M2-exos on EAE mice was evaluated by clinical scores. The proportion of Treg and Th17 cells in spinal cord cells and splenocytes, and levels of inflammatory factors were measured. The targeting relationships among PVT1, miR-21-5p, and SOCS5 were verified. The expression of JAKs/STAT3 pathway-related proteins was measured. After M2-exo treatment, the clinical score of EAE mice decreased, and demyelination and inflammatory infiltration improved; Th17 cells decreased, Treg cells increased, and the levels of inflammatory factors decreased significantly. SOCS5 and PVT1 were downregulated and miR-21-5p was upregulated in EAE mice. PVT1 could sponge miR-21-5p to regulate SOCS5. SOCS5 alleviated EAE symptoms by repressing the JAKs/STAT3 pathway. Together, M2-exos-carried lncRNA PVT1 sponged miR-21-5p to upregulate SOCS5 and inactivate the JAKs/STAT3 pathway, thus reducing inflammation and protecting EAE mice. This study may offer novel treatments for MS.
Understanding LrgAB Regulation of Streptococcus mutans Metabolism

Lack of LrgAB renders cariogenic Streptococcus mutans more sensitive to oxidative stress, as well as limits the capacity of this organism to re-uptake pyruvate upon starvation. This study was aimed at investigating the ecological and metabolic contribution of LrgAB to competitive fitness, using S. mutans strains, that either lack or overexpress lrgAB. These experiments revealed that impaired aerobic growth of the ΔlrgAB mutant can be effectively restored by supplementation of pyruvate, and that perturbated expression of lrgAB significantly affects pyruvate flux and the conversion of pyruvate to acetyl-CoA by the Pdh pathway, verifying that LrgAB is closely linked to pyruvate catabolism. In vitro competition assays revealed that LrgAB plays an important role in S. mutans competition with H2O2-producing S. gordonii, an interaction which can also be modulated by external pyruvate. However, no obvious competitive disadvantage was observed against S. gordonii by either the S. mutans lrgAB mutant or lrgAB overexpression strain in vivo using a mouse caries model. Organic acid analysis of mouse dental biofilms revealed that metabolites produced by the host and/or dental plaque microbiota could complement the deficiency of a lrgAB mutant, and favored S. mutans establishment compared to S. gordonii. Collectively, these results reinforce the importance of the oral microbiota and the metabolic environment in the oral cavity battleground, and highlight that pyruvate uptake through LrgAB may be crucial for interspecies competition that drives niche occupancy.
MicroRNA-140-5p Mediates Renal Fibrosis Through TGF-β1/Smad Signaling Pathway by Directly Targeting TGFBR1

Renal tubulointerstitial fibrosis is usually the final outcome of various end-stage renal diseases. Recent studies have reported that microRNAs (miRNAs) play an important role in renal fibrosis. However, the biological function of microRNAs in renal fibrosis is complicated and remains unclear. In this study, our results show that miR-140-5p expression is significantly down-regulated in mice with unilateral ureteral obstruction and human proximal tubule epithelial cells (HK2) treated with TGF-β1. The knockdown of miR-140-5p upregulates the expression levels of collagen I, collagen IV, and α-SMA, decreases E-cadherin expression, and increases Smad-2/3 phosphorylation. In contrast, the overexpression of miR-140-5p decreases the expression levels of collagen I, collagen IV, and α-SMA, enhances E-cadherin expression, and inhibits the phosphorylation of Smad-2/3 in HK2 cells treated with TGF-β1. The dual-luciferase reporter assay revealed that TGFBR1 is a direct target gene of miR-140-5p. The enforced expression of miR-140-5p significantly inhibited the expression of TGFBR1 in HK2 cells. Furthermore, the knockdown of TGFBR1 has a similar effect of miR-140-5p overexpression on blocking the TGF-β1/smad signal pathway activation. In contrast, the overexpression of TGFBR1 reverses the effect of miR-140-5p inhibition on the activation of the TGF-β1/smad signal pathway. This study demonstrates that miR-140-5p regulates the TGF-β1/smad signaling pathway by suppressing the expression of TGFBR1. Therefore, miR-140-5p may have a therapeutic potential for preventing fibrotic kidney diseases through inhibiting the TGF-β1/Smad signaling pathway by directly targeting TGFBR1.
Systematic Review of the Diagnostic Validity of Brief Cognitive Screenings for Early Dementia Detection in Spanish-Speaking Adults in Latin America

Objectives: The aim of this study was to evaluate the validity of brief cognitive screening (BCS) tools designed to diagnose mild cognitive impairment (MCI) or dementia in Spanish-speaking individuals over the age of 50 years from Latin America (LA). Methods: A systematic search of titles and abstracts in Medline, Biomed Central, Embase, Scopus, Scirus, PsycINFO, LILACS, and SciELO was conducted. Inclusion criteria were papers written in English or Spanish involving samples from Spanish-speaking Latin American individuals published until 2018. Standard procedures were applied for reviewing the literature. The data related to the study sample, methodology, and procedures applied, as well as the performance obtained with the corresponding BCS, were collected and systematized. Results: Thirteen of 211 articles met the inclusion criteria. The studies primarily involved memory clinic-based samples, with the exception of two studies from an adult day-care center, one from a primary care clinic, and one from a community-based sample. All the studies originated from five of the 20 countries of LA and all used standardized diagnostic criteria for the diagnosis of dementia and MCI; however, the diagnostic protocols applied differed. Most studies reported samples with an average of 10 years of education and only one reported a sample with an average of <5 years of education. No publication to date has included an illiterate population. Although the Montreal cognitive assessment (MoCA) is the most widely-used BCS tool in LA, it is significantly influenced by education level. Conclusions: Although evidence is still limited, the findings from studies on LA populations suggest that MoCA requires cultural adaptations and different cutoff points according to education level. Moreover, the diagnostic validity of the INECO frontal screening (IFS) test should be evaluated in populations with a low level of education. Given the heterogeneity that exists in the levels of education in LA, more studies involving illiterate and indigenous populations are required.
In Search of Effective Treatments Targeting α-Synuclein Toxicity in Synucleinopathies: Pros and Cons

Parkinson’s disease (PD), multiple system atrophy (MSA) and Dementia with Lewy bodies (DLB) represent pathologically similar, progressive neurodegenerative disorders characterized by the pathological aggregation of the neuronal protein α-synuclein. PD and DLB are characterized by the abnormal accumulation and aggregation of α-synuclein in proteinaceous inclusions within neurons named Lewy bodies (LBs) and Lewy neurites (LNs), whereas in MSA α-synuclein inclusions are mainly detected within oligodendrocytes named glial cytoplasmic inclusions (GCIs). The presence of pathologically aggregated α-synuclein along with components of the protein degradation machinery, such as ubiquitin and p62, in LBs and GCIs is considered to underlie the pathogenic cascade that eventually leads to the severe neurodegeneration and neuroinflammation that characterizes these diseases. Importantly, α-synuclein is proposed to undergo pathogenic misfolding and oligomerization into higher-order structures, revealing self-templating conformations, and to exert the ability of “prion-like” spreading between cells. Therefore, the manner in which the protein is produced, is modified within neural cells and is degraded, represents a major focus of current research efforts in the field. Given that α-synuclein protein load is critical to disease pathogenesis, the identification of means to limit intracellular protein burden and halt α-synuclein propagation represents an obvious therapeutic approach in synucleinopathies. However, up to date the development of effective therapeutic strategies to prevent degeneration in synucleinopathies is limited, due to the lack of knowledge regarding the precise mechanisms underlying the observed pathology. This review critically summarizes the recent developed strategies to counteract α-synuclein toxicity, including those aimed to increase protein degradation, to prevent protein aggregation and cell-to-cell propagation, or to engage antibodies against α-synuclein and discuss open questions and unknowns for future therapeutic approaches.
Getting Big Cows by Feeding Their Tiny Microbes

Cattle are used for many purposes, but today beef cattle are mainly raised to provide people with meat and many other useful products. Did you know that leather, soap, gelatin, and even medicines come from beef animals? Besides, cattle can thrive on low-quality land not suitable for building houses or growing plants for people to eat. More importantly, they eat foods that other animals cannot use up. Cows rely on plants as their main source of food and they can digest tough plant parts because they have a team of microbes in their gut. The microbes in this tiny team (called the microbiome) provide cattle with about 70% of the energy they need. As the microbe team is very important for cattle to grow and get nutrients from food, scientists are working on strategies to get bigger, healthier cows while, at the same time, caring for our planet.
Algorithmic Speedup and Final Evaluation

: This report describes the efforts on algorithmic speedup as well as the ﬁnal evaluation of the outcome of WP3. The algorithmic speedup, mainly done by University of Groningen (RUG), focused on the DUGMA algorithm which is used for point cloud alignment. We also investigated using faster local feature extractors in the visual SLAM as well as using pre-computations for accelerating the motion planning for the robotic arm. Since most of the individual parts of WP3 have have been evaluated in previous deliverables (see D3.2 and D3.5), we focus on evaluating the ﬁnal pipeline that was used for the ﬁnal demonstrator.
Genetic diversity of symbiodinium in selected corals in the Western Indian Ocean.

Coastal communities along the east African coastline rely on coral reefs and their associated resources for food security and income. However, increases in the frequency and severity of episodes of coral bleaching have resulted in mass coral moralities in many locations around the world including the western Indian Ocean (WIO). Reef corals obligately host dinoflagellate algal symbionts of the genus Symbiodinium. Coral bleaching is caused by the loss of these symbionts from the host, resulting from a variety of stresses, the major ones being increased seawater temperature and irradiance. The Symbiodinum genus is diverse and the distribution of symbionts is influenced by the host biology, external light environment and geographic location. Ten distinct clades of Symbiodinium have been identified. Although the Caribbean and Great Barrier Reef have been studied intensively with respect to Symbiodinium diversity in many locations in the WIO Symbiodinium diversity is unknown. The aim of this study was to determine diversity, distribution and prevalence of Symbiodinium types in corals along the east African coastline. The Symbiodinium ssrDNA region was analysed using restriction fragment length polymorphism (RFLP) in order to assess the cladal diversity of Symbiodinium. The results showed all samples analysed to belong to clade C. To gain more insight into Symbiodinium genetic diversity, the ITS region was employed to assess Symbiodinium diversity at the subcladal level. Twenty ITS types were identified. The most prevalent type was found to be subclade C1. No phylogeographic structuring was found amongst the symbiont types, however, specificity of symbiont types to coral hosts was demonstrated indicating potential susceptibility to perturbations such as increased seawater temperature.
Domestication and nutrition in fish

The aim of this paper is to evaluate to what extent, the study of feeding regimes of fish could be valuable to indicate the possibilities and the constraints of their domestication. Though the natural feeding regime of fish seems to be disadvantageous for their domestication, as protein requirement is high, different species could be considered as domesticated. These species are herbivorous, detritivorous, omnivorous as well as carnivorous. In the same way, there are large differences in gut anatomy, but domestication concerns species with or without stomach, and species with short or very long intestine. Nutritional requirements do not allow predicting species that could be domesticated. Some species seem to be able to use vegetable protein in substitution to fish meal, and it appears that even the most carnivorous species can be fed in large part with a mixture of vegetable protein. Some species can tolerate high dietary lipid levels, others can utilize carbohydrates. These physiological trends must be taken into consideration in their domestication process. But domestication would certainly affect nutritional metabolism and consequently fish biochemical composition as well.
Gene conservation in European beech (Fagus sylvatica L.)

The European beech belongs to the most important broadleaved tree species in Europe occurring in various ecological conditions. After establishment of numerous provenance experiments (the last one containing 188 provenances and 23 trials), extensive genetic inventories in most part of Europe has been carried out. In situ and ex situ gene conservation in European beech is outlined.
Top-Down Performance Analysis of Workflow Applications

Scientific simulation frameworks are common to use on HPC systems. They contain parallelized algorithms and provide various solvers for a specific application domain. Usually, engineers execute multiple steps to solve a particular problem which are often distributed over multiple jobs. Finding performance bottlenecks and the causing step in such a complex system is very difficult. Therefore in this work, we present a top-down approach that provides summarized performance metrics for the workflow, jobs, and job steps. These summaries guide the user to identify inefficiencies and determine the responsible job step. Finally, Vampir can be used for a detailed analysis of the regarding execution in order to resolve the issue.
Describing the Diet of Juvenile White Sturgeon in the Upper Columbia River Canada with Lethal and Nonlethal Methods

AbstractWe describe the overall composition and prey selectivity in the diet of hatchery-reared juvenile White Sturgeon Acipenser transmontanus in the upper Columbia River, Canada. The efficacy of two sampling methods, nonlethal gastric lavage and lethal sampling to remove stomach contents, were evaluated across different ages, size-classes, and river sections. Gastric lavage samples were collected from 108 fish angled in October 2012 and 2013. In 2012 only, a subsample of 48 individuals were euthanized following gastric lavage, and stomach contents were collected. To describe food availability, 45 benthic grabs were collected from areas of juvenile capture. Identifiable prey taxa were recovered from 60.3% of lavage and 98% of lethal stomachs sampled. While the diet of juvenile White Sturgeon was composed of 16 diverse prey taxa, most were selected less than their availability in the river. Prey diversity in lethal samples was influenced by river section, not by fish size or age; fish in deeper, slower wa.
Type 2 Diabetes: A Risk Factor for Hospital Readmissions and Mortality in Australian Patients With Cirrhosis

Although there is evidence that type 2 diabetes mellitus (T2D) impacts adversely on liver‐related mortality, its influence on hospital readmissions and development of complications in patients with cirrhosis, particularly in alcohol‐related cirrhosis (the most common etiological factor among Australian hospital admissions for cirrhosis) has not been well studied. This study aimed to investigate the association between T2D and liver cirrhosis in a population‐based cohort of patients admitted for cirrhosis in the state of Queensland, Australia. A retrospective cohort analysis was conducted using data from the Queensland Hospital Admitted Patient Data Collection, which contains information on all hospital episodes of care for patients with liver cirrhosis, and the Death Registry during 2008‐2017. We used demographic, clinical data, and socioeconomic characteristics. A total of 8,631 patients were analyzed. A higher proportion of patients with T2D had cryptogenic cirrhosis (42.4% vs. 27.3%, respectively; P < 0.001) or nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (13.8% vs. 3.4%, respectively; P < 0.001) and an admission for hepatocellular carcinoma (18.0% vs. 12.2%, respectively; P < 0.001) compared to patients without T2D. Patients with liver cirrhosis with T2D compared to those without T2D had a significantly increased median length of hospital stay (6 [range, 1‐11] vs. 5 [range, 1‐11] days, respectively; P < 0.001), double the rate of noncirrhosis‐related admissions (incidence rate ratios [IRR], 2.03; 95% confidence interval [CI], 1.98‐2.07), a 1.35‐fold increased rate of cirrhosis‐related admissions (IRR, 1.35; 95% CI, 1.30‐1.41), and significantly lower survival (P < 0.001). Conclusion: Among hospitalized patients with cirrhosis, the cohort with T2D is at higher risk and may benefit from attention to comorbidities and additional support to reduce readmissions.