Miracle-dz/UniFAR-FTUs huggingface dataset:
Early Endothelial Dysfunction in Type 1 Diabetes Is Accompanied by an Impairment of Vascular Smooth Muscle Function: A Meta-Analysis

Background: A large yet heterogeneous body of literature exists suggesting that endothelial dysfunction appears early in type 1 diabetes, due to hyperglycemia-induced oxidative stress. The latter may also affect vascular smooth muscles (VSM) function, a layer albeit less frequently considered in that pathology. This meta-analysis aims at evaluating the extent, and the contributing risk factors, of early endothelial dysfunction, and of the possible concomitant VSM dysfunction, in type 1 diabetes. Methods: PubMed, Web of Sciences, Cochrane Library databases were screened from their respective inceptions until October 2019. We included studies comparing vasodilatory capacity depending or not on endothelium (i.e., endothelial function or VSM function, respectively) in patients with uncomplicated type 1 diabetes and healthy controls. Results: Fifty-eight articles studying endothelium-dependent function, among which 21 studies also assessed VSM, were included. Global analyses revealed an impairment of standardized mean difference (SMD) (Cohen's d) of endothelial function: −0.61 (95% CI: −0.79, −0.44) but also of VSM SMD: −0.32 (95% CI: −0.57, −0.07). The type of stimuli used (i.e., exercise, occlusion-reperfusion, pharmacological substances, heat) did not influence the impairment of the vasodilatory capacity. Endothelial dysfunction appeared more pronounced within macrovascular than microvascular beds. The latter was particularly altered in cases of poor glycemic control [HbA1c > 67 mmol/mol (8.3%)]. Conclusions: This meta-analysis not only corroborates the presence of an early impairment of endothelial function, even in response to physiological stimuli like exercise, but also highlights a VSM dysfunction in children and adults with type 1 diabetes. Endothelial dysfunction seems to be more pronounced in large than small vessels, fostering the debate on their relative temporal appearance.
Deformation and Fault Propagation at the Lateral Termination of a Subduction Zone: The Alfeo Fault System in the Calabrian Arc, Southern Italy

The Calabrian Arc subduction, southern Italy, is a critical structural element in the geodynamic evolution of the central Mediterranean basin. It is a narrow, northwest-dipping slab bordered to the southwest by the Alfeo Fault System (AFS) and to the northeast by a gradual transition to a collision. We used a dense set of two-dimensional high-penetration (up to 12 s) multichannel seismic reflection profiles to build a three-dimensional model that spans the AFS for over 180 km of its length. We find that the AFS is made up of four deep-seated major blind segments that cut through the lower plate, offset the subduction interface, and only partially propagate upward across the accretionary wedge in the upper plate. These faults evolve with a scissor-like mechanism (mode III of rupture propagation). The shallow part of the accretionary wedge is affected by secondary deformation features well aligned with the AFS at depth but also mechanically decoupled from it. Despite the decoupling, the syn-tectonic Pliocene-Holocene deposits that fill in the accommodation space generated by the AFS activity at depth, constrain the age of inception of the AFS and allows us to estimate its throw and propagation rates. The maximum throw value is 6,000 m in the NW sector and decreases to the SE. Considering the age of faulting, the fault throw rate decreases accordingly from 2.31 mm/yr to 1 mm/yr. The propagation rate decreases from 62 mm/yr to 15 mm/yr during the Pliocene-Pleistocene, suggesting that also the Calabrian subduction process should have slowed down accordingly. The detailed spatial and temporal reconstruction of this type of faults can reveal necessary information about the evolution of subduction systems.
The Influence of Mental Resilience on the Positive Coping Style of Air Force Soldiers: A Moderation- Mediation Model

In this study, 697 air force soldiers from China were investigated with the Chinese Resilience Scale, Military Emotional Regulation Scale, Simple Coping Scale, and Social Support Rating Scale. Structural equation modeling revealed the following: (1) resilience had a positive predictive effect on active coping style; (2) the emotion regulation strategy of self-comfort mediated the relationship between resilience and positive coping style; and (3) social support moderated the latter half of the intermediary process, in which resilience influenced the active coping style of soldiers through self-comfort. The influence of resilience on air force soldiers was a mediating effect, in which resilience could not only directly predict the coping style of soldiers but also influence their coping style through self-comfort. Social support enhanced the influence of self-comfort on coping style. The study has great theoretical and empirical value for promoting the mental health of soldiers and using positive coping strategies.
Genetic Diversity of Bovine Pestiviruses Detected in Backyard Cattle Farms Between 2014 and 2019 in Henan Province, China

Bovine pestiviruses include Pestivirus A (BVDV-1), Pestivirus B (BVDV-2), and Pestivirus H, which was originally called HoBi-like pestivirus. We conducted an epidemiological investigation for pestiviruses circulating in backyard cattle farms in central China. RT-PCR assays and sequences analysis were conducted on 54 nasal swabs, 26 serum samples, and three lung samples from cattle with respiratory infections and identified 29 pestivirus strains, including 24 Pestivirus A and five Pestivirus H strains. Phylogenetic analysis based on partial 5′-UTR and Npro sequences showed that the genotypes of 24 Pestivirus A strains included Pestivirus A 1b (six isolates), Pestivirus A 1m (six isolates), Pestivirus A 1q (two isolates), Pestivirus A 1u (one isolates), and Pestivirus A 1o (nine isolates, a putative new sub-genotype). In addition, a single Pestivirus H agenotype included all five Pestivirus H strains. This study revealed extensive genetic variations within bovine pestivirus isolates derived from cattle in backyard farms in Central China, and this epidemiological information improves our understanding of the epidemics of bovine Pestiviruses, as well as will be useful in designing and evaluating diagnostic methods and developing more effective vaccines.
Photosynthetic Conversion of Carbon Dioxide to Oleochemicals by Cyanobacteria: Recent Advances and Future Perspectives

Sustainable production of biofuels and biochemicals has been broadly accepted as a solution to lower carbon dioxide emissions. Besides being used as lubricants or detergents, oleochemicals are also attractive biofuels as they are compatible with existing transport infrastructures. Cyanobacteria are autotrophic prokaryotes possessing photosynthetic abilities with mature genetic manipulation systems. Through the introduction of exogenous or the modification of intrinsic metabolic pathways, cyanobacteria have been engineered to produce various bio-chemicals and biofuels over the past decade. In this review, we specifically summarize recent progress on photosynthetic production of fatty acids, fatty alcohols, fatty alk(a/e)nes, and fatty acid esters by genetically engineered cyanobacteria. We also summarize recent reports on fatty acid and lipid metabolisms of cyanobacteria and provide perspectives for economic cyanobacterial oleochemical production in the future.
The Relationship Between Parental Play Beliefs, Preschoolers’ Home Experience, and Executive Functions: An Exploratory Study in Ethiopia

Although research has highlighted the importance of home experience and especially of play in early brain development, the value of this factor for executive function (EF) development has not received the attention it deserves. The purpose of the present study was to investigate the link between parental play beliefs and preschoolers’ play frequency at home on the one hand and their EF skills on the other. Additionally, other types of home activities were also assessed. A total of 102 preschoolers (45 girls; mean age = 62.08 months; SD = 7.66 months; range, 50–74 months) with their parents (mean age = 35.21 years; SD = 6.96 years) representing low to middle socioeconomic status (SES) families in Ethiopia participated in the study. Results revealed that children’s home activities (frequency of breakfast at home, spending mealtime together with family, participation in peer play, participation in pretend play, and participation in arts and crafts) and parental play support were significantly positively correlated with their performance on EF tasks. Hierarchical regression analyses controlling for age and SES showed that parental play support and frequency of breakfast at home were medium-sized predictors (β = 0.36, p < 0.001 and β = 0.31, p = 0.001, respectively) explaining a significant level of variance in inhibitory control, while participation in arts and crafts at home was a significant predictor (β = 0.22, p = 0.03) of children’s performance on a visual–spatial working memory (VSWM) task. In conclusion, parental play support and preschoolers’ home activities are important factors linked with EF development in early childhood.
What Is the Best Regimen for Ovarian Stimulation of Poor Responders in ART/IVF?

The infertile patients with aging ovaries—also sometimes referred to as impending premature ovarian insufficiency (POI), impending premature ovarian failure (POF), or poor ovarian responders (POR), constitute a significant and increasing bulk of the patients appealing to IVF/ART. Different causes have been cited in the literature, among the identified etiologies, including chromosomal and genetic etiology, metabolic, enzymatic, iatrogenic, toxic, autoimmune, and infectious causes. Although the most successful and ultimate treatment of POI/POF/POR patients is egg donation (ED), many, if not most, of these infertile women are reluctant to consent to ED upon the initial diagnostic interview, requesting alternative solutions despite the low odds for success. Despite anecdotal case reports, no unequivocal treatment proved to be successful for these patients in prospective randomized controlled trials. Nevertheless, the addition of growth hormone (GH) to ovarian stimulation in POR with GH deficiency may improve the results of controlled ovarian hyperstimulation (COH) and the IVF success. In patients with autoimmune etiology for POR/POI, the combination of glucocorticosteroids, pituitary-ovarian suppression, and COH may be successful in achieving the desired conception.
Learning and Consolidation of Declarative Memory in Good and Poor Readers of English as a Second Language

Declarative memory abilities may be important for children who are learning to read in a second language. In the present study, we investigated declarative memory in a recognition memory task in 7-to-13-year-old, Kannada native-speaking, good (n = 22) and poor (n = 22) readers of English, in Karnataka, India. Recognition memory was tested shortly (∼10 min) after encoding (day 1) and again on the next (day 2). Analyses revealed that the two groups did not differ in recognition memory performance on day 1. On day 2, the good readers improved from day 1, whereas poor readers did not. A partial correlation analysis suggests that consolidation – the change in performance in recognition memory between the 2 days – is associated with reading skills in good readers, but not in poor readers. Taken together, these results suggest that children who struggle to read in a second language may have deficits in declarative memory consolidation.
Prolonged exposure to constant environmental conditions prompts nonrandom genetic variation

Long-term environmental exposure under selection-free conditions has no consequences for fitness under the neo-Darwinian paradigm but it may provoke adaptive developmental buffering if environmental pressures foster directional organismal changes. To test this hypothesis, we revisited a Mutation Accumulation (MA) experiment where isogenic lines of the ciliate Paramecium were propagated for >40 sexual cycles (∼4 years) in a nearly selection-free and nutrient-rich environment. We find that these MA lines’ somatic genome is enriched with intervening segments of DNA (IESs), which are normally eliminated during germline-soma differentiation. Across independent replicate MA lines, an excess of these somatic IESs fall into a class of epigenetically controlled sequences, map to the same genomic locations, and preferentially disrupt loci that regulate nutrient metabolism. Although further work is needed to assess the phenotypic consequences of somatic IESs, these findings support a model where environmentally induced developmental variants may restore an adaptive fit between phenotype and environment. In this model, positive selection is surprisingly dispensable for adaptation.
DDR2 induces linear invadosome to promote angiogenesis in a fibrillar type I collagen context

To generate new vessels, endothelial cells (ECs) form invadosomes, which are actin-based microdomains with a proteolytic activity that degrade the basement membrane. We previously demonstrated that ECs form linear invadosomes in fibrillar type I collagen context. In this study, we aim to investigate the molecular mechanisms by which ECs guides angiogenesis in a fibrillar type I collagen context. We found that Discoidin Domain Receptor 2 (DDR2) is the collagen receptor tyrosine kinase required to form linear invadosomes in ECs. We further demonstrated that it acts in synergy with VEGF to promote extracellular matrix degradation. We highlighted the involvement of an interaction between DDR2 and the matrix metalloproteinase MMP14 in this process. Finally, using in vitro and ex-vivo angiogenesis assays, we demonstrated a pro-angiogenic function of DDR2 in a collagen-rich microenvironment. This study allows us to propose DDR2-dependent linear invadosomes as targets to modulate angiogenesis.
Triclosan depletes the membrane potential in Pseudomonas aeruginosa biofilms inhibiting aminoglycoside induced adaptive resistance

Biofilm-based infections are difficult to treat due to their inherent resistance to antibiotic treatment. Discovering new approaches to enhance antibiotic efficacy in biofilms would be highly significant in treating many chronic infections. Exposure to aminoglycosides induces adaptive resistance in Pseudomonas aeruginosa biofilms. Adaptive resistance is primarily the result of active antibiotic export by RND-type efflux pumps, which use the proton motive force as an energy source. We show that the protonophore uncoupler triclosan depletes the membrane potential of biofilm growing P. aeruginosa, leading to decreased activity of RND-type efflux pumps. This disruption results in increased intracellular accumulation of tobramycin and enhanced antimicrobial activity in vitro. In addition, we show that triclosan enhances tobramycin effectiveness in vivo using a mouse wound model. Combining triclosan with tobramycin is a new anti-biofilm strategy that targets bacterial energetics, increasing the susceptibility of P. aeruginosa biofilms to aminoglycosides. Author summary Adaptive resistance is a phenotypic response that allows P. aeruginosa to transiently survive aminoglycosides such as tobramycin. To date, few compounds have been identified that target adaptive resistance. Here, we show the protonophore uncoupler triclosan disrupts the membrane potential of P. aeruginosa. The depletion of the membrane potential reduces efflux pump activity, which is essential for adaptive resistance, leading to increased tobramycin accumulation and a shorter onset of action. Our results demonstrate that in addition to its canonical mechanism inhibiting membrane biosynthesis, triclosan can exert antibacterial properties by functioning as a protonophore that targets P. aeruginosa energetics.
Changes to the resistome of Pseudomonas aeruginosa clone ST308 associated with corneal infection over time

Objectives This study compared the resistomes of isolates of Pseudomonas aeruginosa clone ST308 from 2018 and 1997 from India. Methods Two ocular clonal type ST308 isolates of Pseudomonas aeruginosa (198 and 219) isolated in 2018 and five historical isolates (31, 32, 33, 35 and 37) isolated in 1997 at the LV Prasad Eye Institute in India were analysed for their susceptibilities to ciprofloxacin, levofloxacin, gentamicin, tobramycin, piperacillin, imipenem, ceftazidime and polymyxin B. DNA was extracted using the DNeasy® Blood and Tissue. Paired-end library was prepared using Nextera XT DNA library preparation kit. Libraries were sequenced on Illumina® MiSeq bench top sequencer generating 300 bp paired-end reads. Spades v3.12. 0 was used for assembly, Resfinder v3.1. for acquired resistance genes and Snippy V2 for variants calling. Integron finder v1.5. 1 was used to identify the integrons present in the genomes. Results The recent isolate 219 was resistant to all tested antibiotics except polymyxin while isolate 198 was resistant to ciprofloxacin, levofloxacin, gentamicin and tobramycin. Among historical isolates five were resistant to gentamicin, tobramycin and ciprofloxacin, four were resistant to levofloxacin while two were resistant to polymyxin. Twenty-four acquired resistance genes were present in the 2018 isolates compared to 11 in the historical isolates. All isolates contained the following genes encoding for aminoglycoside aph(6)-Id, aph(3′)-lIb, aph(3″)-Ib), beta-lactam (blaPAO), tetracycline (tet(G)), fosfomycin (fosA), chloramphenicol (catB7), sulphonamide (sul1), quaternary ammonium (qacEdelta1) and fluoroquinolone (crpP) resistance. Isolate 198 possessed aph(3′)-VI, rmtD2, qnrVC1, blaOXA-488, blaPME-1, while 219 possessed aadA1, rmtB, aac(6′)-Ib-cr, blaTEM-1B, blaVIM-2, mph(E), mph(A), msr(E). In the isolate 219 genes blaTEM-1b, blaVIM-2, sul1, qnrvc1, rmtB and aadA1 were carried on class 1 integron. While an incomplete class 1 integron was also found in isolate 198 which was located on the genome where gene rmtB, blaPME-1, qnrVC1 and sul1 genes were positioned. There were no notable differences in the number of single nucleotide polymorphisms, but recent isolates carried more insertions and deletions in their genes. Conclusion P. aeruginosa ocular clonal isolates have changed over time, with strains acquiring genes and having more insertions and deletions in their chromosomal genes that confirm resistance to antibiotics. Highlights Recent clonal ocular isolates of Pseudomonas aeruginosa from India have acquired a number of resistance genes compared to historical clones Consequently, resistance to antibiotics particularly fluoroquinolones in recent clones of P. aeruginosa appears to have increased. The acquired resistance genes found in the recent P. aeruginosa isolates were related to mobile genetic elements.
Communicability distance reveals hidden patterns of Alzheimer’s disease

The communicability distance between pairs of regions in human brain is used as a quantitative proxy for studying Alzheimer disease. Using this distance we obtain the shortest communicability path lengths between different regions of brain networks from Alzheimer diseased (AD) patients and healthy cohorts (HC). We show that the shortest communicability path length is significantly better than the shortest topological path length in distinguishing AD patients from HC. Based on this approach we identify 399 pairs of brain regions for which there are very significant changes in the shortest communicability path length after AD appears. We find that 42% of these regions interconnect both brain hemispheres, 28% connect regions inside the left hemisphere only and 20% affects vermis connection with brain hemispheres. These findings clearly agree with the disconnection syndrome hypothesis of Alzheimer disease. Finally, we show that in 76.9% damaged brain regions the shortest communicability path length drops in AD in relation to HC. This counterintuitive finding indicates that AD transforms the brain network into a more efficient system from the perspective of the transmission of the disease, because it drops the circulability of the disease factor around the brain regions in relation to its transmissibility to other regions.
Testing the ‘caves as islands’ model in two cave-obligate invertebrates with a genomic approach

Caves offer selective pressures that are distinct from the surface. Organisms that have evolved to exist under these pressures typically exhibit a suite of convergent characteristics, including a loss or reduction of eyes and pigmentation. As a result, cave-obligate taxa, termed troglobionts, are no longer viable on the surface. This circumstance has led to a “caves as islands” model of troglobiont evolution that predicts extreme genetic divergence between cave populations even across relatively small areas. An effective test of this model would involve (1) common troglobionts from (2) nearby caves in a cave-dense region, (3) good sample sizes per cave, (4) multiple taxa, and (5) genome-wide characterization. With these criteria in mind, we used RAD-seq to genotype an average of ten individuals of the troglobiotic spider Nesticus barri and the troglobiotic beetle Ptomaphagus hatchi, each from four closely located caves (ranging from 3-13 km apart) in the cave-rich southern Cumberland Plateau of Tennessee, USA. Consistent with the caves as islands model, we find that populations from separate caves are indeed highly genetically isolated. In addition, nucleotide diversity was correlated to cave length, suggesting that cave size is a dominant force shaping troglobiont population size and genetic diversity. Our results support the idea of caves as natural laboratories for the study of parallel evolutionary processes.
NUDT21 links mitochondrial IPS-1 to RLR-containing stress granules and activates host antiviral defense

Viral RNA in the cytoplasm of mammalian host cells is recognized by retinoic acid– inducible protein–I (RIG-I)–like receptors (RLRs), which localize to cytoplasmic stress granules (SGs). Activated RLRs associate with the mitochondrial adaptor protein IPS-1, which activates antiviral host defense mechanisms including type I interferon (IFN) induction. It has remained unclear, however, how RLRs in SGs and IPS-1 in the mitochondrial outer membrane associate physically and engage in information transfer. Here we show that NUDT21, an RNA binding protein that regulates alternative transcript polyadenylation, physically associates with IPS-1 and mediates its localization to SGs in response to transfection with poly(I:C), a mimic of viral double-stranded RNA. We found that, despite its well-established function in the nucleus, a fraction of NUDT21 localizes to mitochondria in resting cells and becomes localized to SGs in response to poly(I:C) transfection. NUDT21 was also found to be required for efficient type I IFN induction in response to viral infection. Our results together indicate that NUDT21 links RLRs in SGs to mitochondrial IPS-1 and thereby activates host defense responses to viral infection.