Miracle-dz/UniFAR-FTUs huggingface dataset:
Importance of endothelial Hey1 expression for thoracic great vessel development and its distal enhancer for Notch-dependent endothelial transcription.

Thoracic great vessels such as the aorta and subclavian arteries are formed through dynamic remodeling of embryonic pharyngeal arch arteries (PAAs). Previous work has shown that loss of a basic helix-loop-helix transcription factor Hey1 in mice causes abnormal 4th PAA development and lethal great vessel anomalies resembling congenital malformations in humans. However, how Hey1 mediates vascular formation remains unclear. In this study, we revealed that Hey1 in vascular endothelial cells, but not in smooth muscle cells, played essential roles for PAA development and great vessel morphogenesis in mouse embryos. Tek-Cre-mediated Hey1 deletion in endothelial cells affected endothelial tube formation and smooth muscle differentiation in embryonic 4th PAAs and resulted in interruption of the aortic arch and other great vessel malformations. Cell specificity and signal responsiveness of Hey1 expression were controlled through multiple cis-regulatory regions. We found two distal genomic regions that had enhancer activity in endothelial cells and in the pharyngeal epithelium and somites, respectively. The novel endothelial enhancer was conserved across species and was specific to large caliber arteries. Its transcriptional activity was regulated by Notch signaling in vitro and in vivo, but not by ALK1 signaling and other transcription factors implicated in endothelial cell specificity. The distal endothelial enhancer was not essential for basal Hey1 expression in mouse embryos but may likely serve for Notch-dependent transcriptional control in endothelial cells together with the proximal regulatory region. These findings help understand significance and regulation of endothelial Hey1 as a mediator of multiple signaling pathways in embryonic vascular formation.
Opportunistic and On-Demand Network Coding-Based Solutions for LPWAN Forwarding

The single-hop star-of-stars topology in low-power and wide-area networks (LPWAN) exhibits reliability and substandard coverage issues, especially in urban areas where line-of-sight (LoS) communication is difficult to achieve. Moreover, LPWAN trade-off the data rate to achieve longer coverage, preventing other end-devices from using the time resource. Locating other gateways is uneconomical as it requires infrastructure, such as the internet and a power connection. In this study, we propose a forwarding scheme with a relay to increase LPWAN coverage and reliability while not degrading the network’s capacity. A relay tends to incur unnecessary forwarding that degrades the network capacity unless proper countermeasure is prepared. Our works, namely opportunistic and on-demand network coding (OODC), minimize unnecessary forwarding and make good use of multiple-receiving relays. Network coding is also applied in the relay for better transmission efficiency and reliability simultaneously. Because network coding occurs header overhead, we perform a header compression technique to counter it. According to our simulation result, our method shows better reliability than fixed path forwarding. In an adaptive data rate settings, the OODC achieves a 92% packet delivery ratio (PDR), whereas a fixed-path forwarding only achieves an 84% PDR.
Research on the Mechanism of Action of a Citrinin and Anti-Citrinin Antibody Based on Mimotope X27

Immunoassays are developed based on antigen–antibody interactions. A mimotope is an effective recognition receptor used to study the mechanism of action of antigens and antibodies, and is used for improving the sensitivity of the antibody. In this study, we built a 3D structure of the citrinin (CIT) mimotope X27 and anti-CIT single-chain antibody fragment (ScFv) through a “homologous modeling” strategy. Then, CIT and X27 were respectively docked to anti-CIT ScFv by using the “molecular docking” program. Finally, T28, F29, N30, R31, and Y32 were confirmed as the key binding sites in X27. Furthermore, the result of the phage-ELISA showed that the mutational phage lost the binding activity to the anti-CIT ScFv when the five amino acids were mutated to “alanine”, thereby proving the correctness of the molecular docking model. Lastly, a site-directed saturation strategy was adopted for the sites (T28, F29, N30, R31, and Y32). Eighteen different amino acids were introduced to each site on average. The activities of all mutants were identified by indirect competitive ELISA. The sensitivities of mutants T28F, T28I, F29I, F29V, N30T, and N30V were 1.83-, 1.37-, 1.70-, 2.96-, 1.31-, and 2.01-fold higher than that of the wild-type, respectively. In conclusion, the binding model between the CIT and antibody was elaborated for the first time based on the mimotope method, thereby presenting another strategy for improving the sensitivity of citrinin detection in immunoassays.
Novel Eco-Friendly Tannic Acid-Enriched Hydrogels-Preparation and Characterization for Biomedical Application

Sodium alginate and tannic acid are natural compounds that can be mixed with each other. In this study, we propose novel eco-friendly hydrogels for biomedical applications. Thus, we conducted the following assessments including (i) observation of the structure of hydrogels by scanning electron microscope; (ii) bioerosion and the concentration of released tannic acid from subjected material; (iii) dehydrogenase activity assay to determine antibacterial activity of prepared hydrogels; and (iv) blood and cell compatibility. The results showed that hydrogels based on sodium alginate/tannic acid exert a porous structure. The immersion in simulated body fluid (SBF) results in the biomineralization process occurring on their surface while the bioerosion studies revealed that the addition of tannic acid improves hydrogels’ stability proportional to its concentration. Besides, tannic acid release concentration depends on the type of hydrogels and the highest amount was noticed for those based on sodium alginate with the content of 30% tannic acid. Antibacterial activity of hydrogels was proven for both Gram-negative and Gram-positive bacteria, the hemolysis rate was below 5% and the viability of the cells was elevated with an increasing amount of tannic acid in hydrogels. Collectively, we assume that obtained materials make the imperative to consider them for biomedical applications.
Immunomodulatory and Anti-Inflammatory Effects of Fucoidan: A Review

Inflammation is the initial response of the immune system to potentially harmful stimuli (e.g., injury, stress, and infections). The process involves activation of macrophages and neutrophils, which produce mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), pro-inflammatory and anti-inflammatory cytokines. The pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) are considered as biomarkers of inflammation. Even though it occurs as a physiological defense mechanism, its involvement in the pathogenesis of various diseases is reported. Rheumatoid arthritis, inflammatory bowel disease, Alzheimer’s disease, and cardiovascular diseases are only a part of the diseases, in which pathogenesis the chronic inflammation is involved. Fucoidans are complex polysaccharides from brown seaweeds and some marine invertebrates, composed mainly of l-fucose and sulfate ester groups and minor amounts of neutral monosaccharides and uronic acids. Algae-derived fucoidans are studied intensively during the last years regarding their multiple biological activities and possible therapeutic potential. However, the source, species, molecular weight, composition, and structure of the polysaccharides, as well as the route of administration of fucoidans, could be crucial for their effects. Fucoidan is reported to act on different stages of the inflammatory process: (i) blocking of lymphocyte adhesion and invasion, (ii) inhibition of multiple enzymes, and (iii) induction of apoptosis. In this review, we focused on the immunemodulating and anti-inflammatory effects of fucoidans derived from macroalgae and the models used for their evaluation. Additional insights on the molecular structure of the compound are included.
Keeping It Together: Structures, Functions, and Applications of Viral Decoration Proteins

Decoration proteins are viral accessory gene products that adorn the surfaces of some phages and viral capsids, particularly tailed dsDNA phages. These proteins often play a “cementing” role, reinforcing capsids against accumulating internal pressure due to genome packaging, or environmental insults such as extremes of temperature or pH. Many decoration proteins serve alternative functions, including target cell recognition, participation in viral assembly, capsid size determination, or modulation of host gene expression. Examples that currently have structures characterized to high-resolution fall into five main folding motifs: β-tulip, β-tadpole, OB-fold, Ig-like, and a rare knotted α-helical fold. Most of these folding motifs have structure homologs in virus and target cell proteins, suggesting horizontal gene transfer was important in their evolution. Oligomerization states of decoration proteins range from monomers to trimers, with the latter most typical. Decoration proteins bind to a variety of loci on capsids that include icosahedral 2-, 3-, and 5-fold symmetry axes, as well as pseudo-symmetry sites. These binding sites often correspond to “weak points” on the capsid lattice. Because of their unique abilities to bind virus surfaces noncovalently, decoration proteins are increasingly exploited for technology, with uses including phage display, viral functionalization, vaccination, and improved nanoparticle design for imaging and drug delivery. These applications will undoubtedly benefit from further advances in our understanding of these versatile augmenters of viral functions.
Does the COVID-19 pandemic impact parents’ and adolescents’ well-being? An EMA-study on daily affect and parenting

Due to the COVID- 19 outbreak in the Netherlands (March 2020) and the associated social distancing measures, families were enforced to stay at home as much as possible. Adolescents and their families may be particularly affected by this enforced proximity, as adolescents strive to become more independent. Yet, whether these measures impact emotional well-being in families with adolescents has not been examined. In this ecological momentary assessment study, we investigated if the COVID-19 pandemic affected positive and negative affect of parents and adolescents and parenting behaviors (warmth and criticism). Additionally, we examined possible explanations for the hypothesized changes in affect and parenting. To do so, we compared daily reports on affect and parenting that were gathered during two periods of 14 consecutive days, once before the COVID-19 pandemic (2018–2019) and once during the COVID-19 pandemic. Multilevel analyses showed that only parents’ negative affect increased as compared to the period before the pandemic, whereas this was not the case for adolescents’ negative affect, positive affect and parenting behaviors (from both the adolescent and parent perspective). In general, intolerance of uncertainty was linked to adolescents’ and parents’ negative affect and adolescents’ positive affect. However, Intolerance of uncertainty, nor any pandemic related characteristics (i.e. living surface, income, relatives with COVID-19, hours of working at home, helping children with school and contact with COVID-19 patients at work) were linked to the increase of parents’ negative affect during COVID-19. It can be concluded that on average, our sample (consisting of relatively healthy parents and adolescents) seems to deal fairly well with the circumstances. The substantial heterogeneity in the data however, also suggest that whether or not parents and adolescents experience (emotional) problems can vary from household to household. Implications for researchers, mental health care professionals and policy makers are discussed.
Polymorphism of the Melanocortin 1 Receptor (MC1R) Gene and its Role in Determining the Coat Colour of Central European Cattle Breeds

Simple Summary Animal coat colour has been the subject of numerous studies for many years. While most phenotypic features of animals result from the interaction of genetic and environmental factors, coat colour is considered to be almost exclusively genetically determined. Differences in coat colour underscore the distinct character of a given breed or group of animals, testify to its uniqueness, and sometimes serve as selection criteria. Observations of changes in cattle coat colour are an important source of information used to track domestication processes and discover how animals were selected for breeding. One of the genes responsible for variation in coat colour is the melanocortin receptor (MC1R) gene locus, which controls the production of black and red pigments that determine basic colours. Other interacting genes also influence cattle phenotypes. In view of the complexity of the genetic factors influencing cattle coat colour, this study investigated the genetic basis of different coat colours of Central European cattle breeds. Abstract There are many genes responsible for the appearance of different coat colours, among which the melanocortin 1 receptor gene (MC1R) plays an important role. The aim of the study was to characterize genetic variation in Central European cattle breeds based on polymorphism of the MC1R gene and factors determining their coat colour. The study was conducted on 290 individuals of the following breeds: Polish White-Backed (PW), Lithuanian White-Backed (LW), Polish Red (PR), Lithuanian Red (LR), Carpathian Brown (CB), Ukrainian Grey (UG), and Slovak Pinzgau (SP). Polymorphism at the MC1R gene locus was analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using two restriction enzymes: Cfr10I and SsiI. The proportions of alleles and genotypes in the MC1R locus indicates a strong relationship between polymorphism and the coat colour of cattle: The ED allele proved to be characteristic for the breeds with a white-backed coat (PW and LW), while the dominant allele in the red breeds (PR and LR) was E+. It is noteworthy that coat colour in the SP population was determined only by the recessive e allele, which resulted in the formation of a separate clade in the phylogenetic tree.
Bovine Oviduct Epithelial Cell-Derived Culture Media and Exosomes Improve Mitochondrial Health by Restoring Metabolic Flux during Pre-Implantation Development

Oviduct flushing is enriched by a wide variety of nutrients that guide the 3–4 days journey of pre-implantation embryo through the oviduct as it develops into a competent blastocyst (BL). However, little is known about the specific requirement and role of these nutrients that orchestrate the early stages of embryonic development. In this study, we aimed to characterize the effect of in vitro-derived bovine oviduct epithelial cell (BOECs) secretion that mimics the in vivo oviduct micro-fluid like environment, which allows successful embryonic development. In this study, the addition of an in vitro derived BOECs-condition media (CM) and its isolated exosomes (Exo) significantly enhances the quality and development of BL, while the hatching ability of BLs was found to be high (48.8%) in the BOECs-Exo supplemented group. Surprisingly, BOECs-Exo have a dynamic effect on modulating the embryonic metabolism by restoring the pyruvate flux into TCA-cycle. Our analysis reveals that Exo treatment significantly upregulates the pyruvate dehydrogenase (PDH) and glutamate dehydrogenase (GLUD1) expression, required for metabolic fine-tuning of the TCA-cycle in the developing embryos. Exo treatment increases the influx into TCA-cycle by strongly suppressing the PDH and GLUD1 upstream inhibitors, i.e., PDK4 and SIRT4. Improvement of TCA-cycle function was further accompanied by higher metabolic activity of mitochondria in BOECs-CM and Exo in vitro embryos. Our study uncovered, for the first time, the possible mechanism of BOECs-derived secretion in re-establishing the TCA-cycle flux by the utilization of available nutrients and highlighted the importance of pyruvate in supporting bovine in vitro embryonic development.
Sexual dimorphism in the nociceptive effects of hyaluronan.

Intradermal administration of low molecular weight hyaluronan (LMWH) in the hindpaw induced dose-dependent (0.1, 1, or 10 µg) mechanical hyperalgesia, of similar magnitude in male and female rats. However, the duration of LMWH hyperalgesia was greater in females. This sexual dimorphism was eliminated by bilateral ovariectomy, and by intrathecal administration of an oligodeoxynucleotide (ODN) antisense to the G-protein-coupled estrogen receptor (GPR30) mRNA, in females, indicating estrogen dependence. To assess the receptors at which LMWH acts to induce hyperalgesia, LMWH was administered to groups of male and female rats that had been pretreated with ODN antisense (or mismatch) to the mRNA for one of three hyaluronan receptors, cluster of differentiation 44 (CD44), toll-like receptor 4 (TLR4) or receptor for HA-mediated motility (RHAMM). While LMWH-induced hyperalgesia was attenuated in both male and female rats pretreated with ODN antisense for CD44 and TLR4 mRNA, RHAMM antisense pretreatment only attenuated LMWH-induced hyperalgesia in males. ODN antisense for RHAMM, however, attenuated LMWH-induced hyperalgesia in female rats treated with ODN antisense to GPR30, as well as in ovariectomized females. LMWH-induced hyperalgesia was significantly attenuated by pretreatment with high molecular weight hyaluronan (HMWH) in male, but not in female rats. Following gonadectomy or treatment with ODN antisense to GPR30 expression in females, HMWH produced similar attenuation of LMWH-induced hyperalgesia to that seen in males. These experiments identify nociceptors at which LMWH acts to produce mechanical hyperalgesia, establishes estrogen dependence in the role of RHAMM in female rats, and establishes estrogen-dependence in the inhibition of LMWH-induced hyperalgesia by HMWH.
Estimating the Statistical Significance of Hominin Encephalization

Encephalization, the increase in endocranial volume through the Pleistocene, is examined from a creationist perspective. By correcting for body size using a linear regression model based on extant primates, the residual can be used to estimate the significance of the encephalization of fossil taxa. Using this method, significant encephalization is seen only in Homo and two australopiths, A. africanus and A. sediba . Since Wood (2010, 2016b) classifies all of Homo and A. sediba as human, these results indicate that all humans except H. naledi and only one nonhuman ( A. africanus ) are significantly encephalized. Based on these results, creationist neuroscientists ought to consider the possible causes of the encephalization trend in humans.
Changes in proteolytic activities in glucose-starved maize root tips. Regulation by sugars

Excised maize (Zea mays L.) root tips were used to monitor the changes in different proteolytic activities during a four-day period of glucose starvation. Starvation-induced protein degradation was correlated with a transient increase (up to 48 h) of free amino acids and a rise in global autoproteolytic activities (up to 96 h). This rise in autolytic activities was linked with an increase in acidic endopeptidase and carboxypeptidase activities, whereas aminopeptidase activities continuously decreased during starvation. The endopeptidase activities involved in the response to starvation appear to be different from those present in non-starved root tips: (a) the sensitivity to protease inhibitors and the change of optimum pH show the involvement of a new set of serine and cysteine protease activities in the course of starvation
Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential

Multiple sclerosis (MS) is an inflammatory autoimmune disorder affecting the central nervous system (CNS), with unresolved aetiology. Previous studies have implicated N-glycosylation, a highly regulated enzymatic attachment of complex sugars to targeted proteins, in MS pathogenesis. We investigated individual variation in N-glycosylation of the total plasma proteome and of IgG in MS. Both plasma protein and IgG N-glycans were chromatographically profiled and quantified in 83 MS cases and 88 age- and sex-matched controls. Comparing levels of glycosylation features between MS cases and controls revealed that core fucosylation (p = 6.96 × 10−3) and abundance of high-mannose structures (p = 1.48 × 10−2) were the most prominently altered IgG glycosylation traits. Significant changes in plasma protein N-glycome composition were observed for antennary fucosylated, tri- and tetrasialylated, tri- and tetragalactosylated, high-branched N-glycans (p-value range 1.66 × 10−2–4.28 × 10−2). Classification performance of N-glycans was examined by ROC curve analysis, resulting in an AUC of 0.852 for the total plasma N-glycome and 0.798 for IgG N-glycome prediction models. Our results indicate that multiple aspects of protein glycosylation are altered in MS, showing increased proinflammatory potential. N-glycan alterations showed substantial value in classification of the disease status, nonetheless, additional studies are warranted to explore their exact role in MS development and utility as biomarkers.
Theta and gamma activity is linked with affective and cognitive symptoms in Parkinson's disease

Background The progression of Parkinsons disease (PD) can often exacerbate symptoms of depression, anxiety, and/or cognitive impairment. In this study, we explore the possibility that multiple brain network responses are associated with symptoms of depression, anxiety and cognitive impairment in PD. This association is likely to provide insights into a single multivariate relationship, where common affective symptoms occurring in PD cohorts are related with alterations to electrophysiological response. Methods 70 PD patients and 21 healthy age-matched controls (HC) participated in a high-density electroencephalography (EEG) study. Functional connectivity differences between PD and HC groups of oscillatory activity at rest and during completion of an emotion-cognition task were examined to identify key brain oscillatory activities. A canonical correlation analysis (CCA) was applied to identify a putative multivariate relationship between connectivity patterns and affective symptoms in PD groups. Results A CCA analysis identified a single mode of co-variation linking theta and gamma connectivity with affective symptoms in PD groups. Increases in frontotemporal gamma, frontal and parietal theta connectivity were related with increased anxiety and cognitive impairment. Decreases in temporal region theta and frontoparietal gamma connectivity were associated with higher depression ratings and PD patient age. Limitations This study only reports on optimal dosage of dopaminergic treatment (on state) in PD and did not investigate at off medication. Conclusions Theta and gamma connectivity during rest and task-states are linked to affective and cognitive symptoms within fronto-temporo-parietal networks, suggesting a potential assessment avenue for understanding brain-behavior associations in PD with electrophysiological task paradigms.