Miracle-dz/UniFAR-FTUs huggingface dataset:
Protective Effects of Bisoprolol Against Cadmium-induced Myocardial Toxicity Through Inhibition of Oxidative Stress and NF-κΒ Signalling in Rats

Abstract Introduction The aim of the study was to investigate the mitigative effects of bisoprolol (BIS) in cadmium-induced myocardial toxicity on oxidative stress and its inhibitive effect on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signalling in rats. Material and Methods Male albino Wistar rats were assigned to control, Cd, BIS 2 (2 mg/kg b.w.) and BIS 8 (8 mg/kg b.w.) groups with nine rats in each. Over four weeks, the control group was administered 1% gum acacia, all other groups received 3mg/kg b.w. CdCl2 dissolved in distilled water, and the BIS groups were additionally given bisoprolol in gum acacia. Blood samples were collected for biochemical estimations. Blood pressure and serum biomarker (lactate dehydrogenase, aspirate transaminase, alanine transferase and creatine kinase-MB, enzyme (superoxide dismutase, lipid hydroxy peroxidase, catalase and malondialdehyde), and tumour necrosis factor alpha (TNF-α) concentrations were measured. Western blot analysis was conducted for NF-κB and glutathione S-transferase (GST). After sacrificing the rats, cardiac tissue samples were examined histopathologically. Results Our findings pointed to a significant decrease (P < 0.05) in the studied serum biomarkers and levels of the relevant enzymes in the BIS 8 group compared to the Cd group. A significant decrease (P < 0.05) in NF-kB p65 expression and TNF-α levels was noted in the BIS 8 group relative to the BIS 2 and Cd groups, indicating a reduction at a higher dose. In microscopy, histopathological changes in the cardiac muscles of the BIS 8 group were evident compared to those of the Cd group. Conclusion BIS seemed to have protective effects against cardiac injury induced by cadmium and could be considered a novel therapeutic drug and prognostic biomarker in the pathology of the many cardiovascular diseases caused by heavy metal intake.
Personalizing Gameful Elements in Social Exergames: An Exploratory Study

In this research, using storyboard implementation, we investigate the relationship between social game elements and the Hexad user type model for motivating exercise and play. The goal is to see if and how different gamer types are associated with interest in social features and if they can be used as the basis for player compatibility matching (similar or complementary). Participants (N = 60) rated the level of perceived persuasiveness, enjoyment, social engagement, and intention for future play on 8 social elements for step-based asynchronous exergames. Preliminary results show a significant positive relationship between social game elements and player types. Correlational analyses demonstrated that the gamification elements “Sharing Knowledge”, “Supportive Updates”, “Rotating Leadership” and “Leaderboard” were most strongly related to the “Philanthropist” player type. We conclude with recommendations for designing personalized multiplayer mobile exergames.
Squeezer - A Mixed-Initiative Tool for Designing Juice Effects

This paper presents a Mixed-Initiative version of Squeezer, a tool for designing juice effects in the Unity game engine. Drawing upon sound synthesizers and game description languages, Squeezer can synthesize common types of juice effects by combining simple building blocks into sequences. Additionally, Squeezer offers effect generation based on predefined recipes as well as an interface for interactively evolving effect sequences. We conducted a user study with five experts to verify the functionality and interest among game designers. By applying generative and evolutionary strategies to juice effect design, Squeezer allows game designers and researchers using games in their work to explore adding juice effects to their games and frameworks. Squeezer is available at: https://github.com/pyjamads/Squeezer0
Environmental variability and longevity predict the speed of the acute glucocorticoid response across birds

The acute glucocorticoid response is a key mediator of the coordinated vertebrate response to unpredictable challenges. Rapid increases in glucocorticoids initiate a series of changes that can allow animals to effectively cope with or avoid stressors. It has become clear that the scope of the GC response—defined here as the absolute increase in GCs—is often associated with among-individual differences in performance and fitness and varies across species based on environment and life history. In addition to varying in scope, GC responses can differ enormously in speed; however, relatively little is known about whether speed and scope covary or how selection shapes variation in speed. We used a database of corticosterone samples collected at 5 time points from 1,750 individuals of 58 species of birds to ask i) how the speed and scope of the GC response covary among individuals and species and ii) whether variation among species in the speed of the response is predicted by environmental context or key life history traits. As predicted by a recent optimality model, faster absolute GC responses were strongly associated with a larger scope both among-individuals and among-species. Despite this covariation, the relative speed of the GC response (as a percentage of scope) varied independently of scope, suggesting that selection could operate on both features of the response independently. Species with faster relative GC responses lived in locations with more intra-season variation in temperature and had shorter lifespans. Our results suggest that rapid changes associated with the speed of the GC response, such as those occurring through non-genomic receptors, might be an important determinant of coping ability and we emphasize the need for studies explicitly designed to measure speed independently of scope.
Senataxin and RNase H2 act redundantly to suppress genome instability during class switch recombination

Class switch recombination generates antibody distinct isotypes critical to a robust adaptive immune system and defects are associated with auto-immune disorders and lymphomagenesis. Transcription is required during class switch to recruit the cytidine deaminase AID—an essential step for the formation of DNA double-strand breaks—and strongly induces the formation of R loops within the immunoglobulin heavy chain locus. However, the impact of R loops on double-strand break formation and repair during class switch recombination remains unclear. Here we report that cells lacking two enzymes involved in R loop removal— Senataxin and RNase H2—exhibit increased R loop formation and genome instability at the immunoglobulin heavy chain locus without impacting class switch recombination efficiency, transcriptional activity, or AID recruitment. Senataxin and RNase H2-deficient cells also exhibit increased insertion mutations at switch junctions, a hallmark of alternative end joining. Importantly, these phenotypes were not observed in cells lacking Senataxin or RNase H2B alone. We propose that Senataxin acts redundantly with RNase H2 to mediate timely R loop removal, promoting efficient repair while suppressing AID-dependent genome instability and insertional mutagenesis.
Comparison between radar estimated and rain gauge measured precipitation in the moldavian plateau

Heavy rainfall events have produced significant damages and casualties in the Moldavian Plateau (Romania) in the last decades. Such phenomena are characterized by large spatial and temporal variations, and the forecast of their occurrence is thus very challenging. This study aims to compare the radar estimations and the rain gauge measurements, in order to improve the quantitative precipitation estimation (QPE) in the area of interest. The research uses data from the WSR-98D (Weather Surveillance Radar 98 Doppler) S-band Doppler radar located at B rnova, and from rain gauges within weather stations run by Meteo Romania (Romanian National Meteorological Administration). Considerable spatial distinctions and areas with good radar accuracy for QPE have been emphasized during the investigations. The output validation aimed to predict the rain gauge amounts using the radar information and the resulted adjustment parameters. The validation demonstrates that the B rnova radar data are reliable within approx. 150 km radius, and the comparison with rain gauge measurements can foster consistently the QPE accuracy.
Survival of hatchery grown native oysters is associated with specific gut-associated bacteria at various locations within the Puget Sound

The Olympia oyster (Ostrea lurida) of the Puget Sound suffered a dramatic population crash, but restoration efforts hope to revive this native species. One overlooked variable in the process of assessing ecosystem health is association of bacteria with marine organisms and the environments they occupy. Oyster microbiomes are known to differ significantly between species, tissue type, and the habitat in which they are found. The goals of this study were to determine the impact of field site and habitat on the oyster microbiome and to identify core oyster-associated bacteria in the Puget Sound. Olympia oysters from one parental family were deployed at four sites in the Puget Sound both inside and outside of eelgrass (Zostera marina) beds. Using 16S rRNA gene amplicon sequencing of the oyster gut, shell, surrounding seawater and sediment, we demonstrate that gut-associated bacteria are distinct from the surrounding environment and vary by field site. Furthermore, regional differences in the gut microbiota are associated with the survival rates of oysters at each site after two months of field exposure. However, habitat type had no influence on microbiome diversity. Further work is needed to identify the specific bacterial dynamics that are associated with oyster physiology and survival rates. Importance The outcomes of this study demonstrate the need to monitor microbial ecology at potential oyster restoration sites, specifically for the native Olympia oyster in the Puget Sound. Some areas of Puget Sound may be less amenable to Olympia oyster restoration than others due to microbiome colonization trends. Furthermore, this study puts the oyster microbiome in the context of its surroundings, providing a holistic perspective on the factors that may influence oyster performance and microbial ecology.
Combinatorial transcriptional codes specify macrophage polarization destinations

Macrophages are driven to form distinct functional phenotypes in response to different immunological stimuli, in a process widely referred to as macrophage polarization. Transcriptional regulators that guide macrophage polarization in response to a given trigger remain largely unknown. In this study, we interrogate the programmable landscape in macrophages to find regulatory panels that determine the precise polarization state that a macrophage is driven to. Towards this, we configure an integrative network analysis pipeline that utilizes macrophage transcriptomes in response to 28 different stimuli and reconstructs contextualized human gene regulatory networks, and identifies epicentres of perturbations in each case. We find that these contextualized regulatory networks form a spectrum of thirteen distinct clusters with M1 and M2 at the two ends. Using our computational pipeline, we identify combinatorial panels of epicentric transcription factors (TFs) for each polarization state. We demonstrate that a set of three TFs i.e., NFE2L2, BCL3 and CEBPB, is sufficient to change the polarization destination from M1 to M2. siRNA-mediated knockdown of the 3-TF set in THP1 derived M0 cells, despite exposure to an M1 stimulant, significantly attenuated the shift to M1 phenotype, and instead switched to an M2-like phenotype. Further, the siRNA-mediated knockdown of the 3-TF set rendered the macrophages hyper-susceptible to S. aureus infection, clearly showing the effect of the knockdown.
Identification of Bacterial Drug-Resistant Cells by the Convolutional Neural Network in Transmission Electron Microscope Images

The emergence of bacteria that are resistant to antibiotics is common in areas where antibiotics are used widely. The current standard procedure for detecting bacterial drug resistance is based on bacterial growth under antibiotic treatments. Here we describe the morphological changes in enoxacin-resistant Escherichia coli cells and the computational method used to identify these resistant cells in transmission electron microscopy (TEM) images without using antibiotics. Our approach was to create patches from TEM images of enoxacin-sensitive and enoxacin-resistant E. coli strains, use a convolutional neural network for patch classification, and identify the strains on the basis of the classification results. The proposed method was highly accurate in classifying cells, achieving an accuracy rate of 0.94. Using a gradient-weighted class activation mapping to visualize the region of interest, enoxacin-resistant and enoxacin-sensitive cells were characterized by comparing differences in the envelope. Moreover, Pearson’s correlation coefficients suggested that four genes, including lpp, the gene encoding the major outer membrane lipoprotein, were strongly associated with the image features of enoxacin-resistant cells.
Microbial community dispersal in sourdough

Understanding how microbes disperse in ecosystems is critical to understand the dynamics and evolution of microbial communities. However, microbial dispersal is difficult to study because of uncertainty about the vectors that may contribute to their migration. This applies to both microbial communities in natural and human-associated environments. Here, we studied microbial dispersal among French sourdoughs and flours used to make bread. Sourdough is a naturally fermented mixture of flour and water. It hosts a community of bacteria and yeasts whose origins are only partially known. We analyzed whether flour is a carrier of sourdough yeast and bacteria and studied whether microbial migration occurs between sourdoughs. The microbial community of a collection of 46 sourdough samples, as well as that of the flour from which each was made, was studied by 16S rDNA and ITS1 metabarcoding. No sourdough yeast species were detected in the flours. Sourdough lactic acid bacteria (LAB) were found in only five flour samples, and they did not have the same amplicon sequence variant (ASV) as found in the corresponding sourdough. The species shared between the sourdough and flour samples are commonly found on plants and are not known to be alive in sourdough. Thus, the flour microorganisms did not appear to grow in the sourdough microbial community. Dispersal between sourdoughs was also studied. Sourdoughs shared no yeast ASV, except in few cases where groups of three to five bakers shared some. These results suggest that there is little migration between sourdoughs, except in a few situations where bakers may exchange sourdough or be vectors of yeast dispersal themselves.
Human placental bed transcriptomic profiling reveals inflammatory activation of endothelial cells in preeclampsia

Rationale Functional characteristics of endothelial cells (ECs) within the human placental bed are unknown and may provide insight into the adaptive biology of ECs in disorders of vascular remodelling like preeclampsia. Objective To determine transcriptional profiles of human placental bed ECs and systemic biomarker profiles in women with normal pregnancy, and women with preeclampsia, a condition characterized by extensive EC dysfunction, poor development of spiral arteries underlying the placenta and long-term susceptibility to atherosclerosis and hypertension. Methods & results We obtained biopsy samples from the uterine placental bed, of five women with preeclampsia with fetal growth restriction (FGR) due to impaired spiral artery development and four controls undergoing Caesarean section. CD31+CD146+ ECs were isolated and sorted by flow cytometry for RNA-sequencing using CEL-Seq2 protocol. Data were analyzed by unsupervised clustering, gene set enrichment (GSEA) and pathway analysis. 67 circulating biomarkers of EC function and inflammation were measured in 20 women with preeclampsia with FGR and 20 controls by multiplex immunoassay. Transcriptional profiling showed various differentially expressed genes (FDR<0.05) in placental bed ECs of preeclampsia patients, with enhanced activity of pathways associated with vasoconstriction, platelet activation and innate immunity. GSEA was suggestive of a VEGF- and PlGF deprived state of preeclampsia-derived ECs. Moreover, the transcriptomic profile was similar to that of human umbilical vein endothelial cells (HUVECs) treated with plasma from preeclampsia patients, pointing towards a central role for circulating factors in EC dysfunction. Unsupervised clustering of subjects by EC-related circulating factors identified distinct profiles for healthy pregnancy and preeclampsia, in particular for those women with low platelets and elevated liver enzymes, which was predominantly driven by sFLT-1, endoglin, PlGF, leptin, SAA-1 and sICAM-1. Conclusions We revealed inflammatory activation of EC and a key role for systemic factors in EC dysfunction in women with preeclampsia associated with impaired spiral artery development.
Genetic mouse models of autism spectrum disorder present subtle heterogenous cardiac abnormalities

Background Autism Spectrum Disorder (ASD) and Congenital Heart Disease (CHD) are strongly linked on a functional and genetic level. Most work has been focused on neurodevelopmental abnormalities in CHD. Conversely, cardiac abnormalities in ASD have been less studied. In this work we investigate the prevalence of cardiac comorbidities relative to genetic contributors of ASD. Methods Using high frequency ultrasound imaging, we screened 9 mouse models with ASD-related genetic alterations (Arid1b(+/-), Chd8(+/-), 16p11.2 (deletion), Sgsh(+/-), Sgsh(-/-), Shank3 Δexon 4-9(+/-), Shank3 Δexon 4-9(-/-), Fmr1(-/-), Vps13b(+/-)), and pooled wild-type littermates (WT). Using a standardised imaging protocol, we measured heart rate (HR), aorta diameter (AoD), thickness and thickening of the left-ventricular (LV) anterior and posterior walls, LV chamber diameter, fractional shortening, stroke volume and cardiac output, Peak E and A velocity ratio of mitral inflow, Velocity Time Integral (VTI) through the ascending aorta. Results Mutant groups presented small-scale alterations in cardiac structure and function compared to WTs. A greater number of significant differences was observed among mutant groups than between mutant groups and WTs. Mutant groups differed primarily in measures of structure (LV chamber diameter and anterior wall thickness, HR, AoD). When compared to WTs, they differed in both structure and function (LV anterior wall thickness and thickening, chamber diameter and fractional shortening, HR). The mutant groups with most differences to WTs were 16p11.2 (deletion), Fmrl(-/-), Arid1b(+/-). Among mutant groups, the groups differing most from others were 16p11.2 (deletion), Sgsh(+/-), Fmrl(-/-). Our results broadly recapitulate the associated clinical findings. Limitations Various genetically driven cardiac abnormalities occur early in life, so repeating this work in non-adult mice may be valuable. To identify possible sex differences, we must extend this work to female mice. The downsampling procedure used (total correlation calculation) must be verified. Only indirect comparison between our results and clinical literature is possible due to differing study designs. Conclusions The characteristic heterogeneity of ASD was recapitulated in the observed cardiac phenotype. The type of measures (morphological, functional) mutant groups differ in can highlight common underlying mechanisms. Clinically, knowledge of cardiac abnormalities in ASD can be essential as even non-lethal cardiac abnormalities can impact normal development.
MIR822 modulates monosporic female gametogenesis through an ARGONAUTE9-dependent pathway in Arabidopsis thaliana

In the ovule of flowering plants, the establishment of the haploid generation occurs when a somatic subepidermal cell specified as the gametophytic precursor differentiates into a Megaspore Mother Cell (MMC) and initiates meiosis. As most flowering plants, Arabidopsis thaliana (Arabidopsis) undergoes a monosporic type of gametogenesis as three meiotically derived cells degenerate without further division, and a single one – the functional megaspore (FM) - divides mitotically to form the female gametophyte. The genetic basis and molecular mechanisms that control monosporic gametogenesis remain largely unknown. In Arabidopsis, ARGONAUTE proteins are involved the control of megasporogenesis. In particular, mutations in ARGONAUTE9 (AGO9) lead to the ectopic differentiation of gametic precursors that can give rise to apomeiotically derived female gametophytes. Here, we show that Arabidopsis plants carrying loss-of-function mutations in the AGO9-interacting microRNA miR822a give rise to extranumerary surviving megaspores that acquire a FM identity and divide without giving rise to differentiated female gametophytes. The overexpression of three miR822a target genes encoding Cysteine/Histidine-Rich C1 domain proteins (At5g02350, At5g02330 and At2g13900) results in defects equivalent to those found in mir822 plants. All three miR822a targets are overexpressed in ago9 mutant ovules, confirming that miR822a acts through an AGO9-dependent pathway to negatively regulate Cysteine/Histidine-Rich C1 domain proteins and restricts the survival of meiotically derived cells to a single megaspore. Our results identify a microRNA-dependent mechanism that is involved in the control of megaspore degeneration and the most prevalent form of female gametogenesis in flowering plants.
High survival following bleaching highlights the resilience of a highly disturbed region of the Great Barrier Reef

Natural bleaching events provide an opportunity to examine how local scale environmental variation influences bleaching severity and recovery. During the 2020 marine heatwave, we documented widespread and severe coral bleaching (75 – 98% of coral cover) throughout the Keppel Islands in the Southern inshore Great Barrier Reef. Acropora, Pocillopora and Porites were the most severely affected genera, while Montipora was comparatively less susceptible. Site-specific heat-exposure metrics were not correlated with Acropora bleaching severity, but recovery was faster at sites that experienced lower heat exposure. Despite severe bleaching and exposure to accumulated heat that often results in coral mortality (degree heating weeks ∼ 4 – 8), cover remained stable. Approximately 94% of fate-tracked Acropora millepora colonies survived, perhaps owing to reduced irradiance stress from high turbidity, heterotrophic feeding, and large tidal flows that can increase mass transfer. Severe bleaching followed by rapid recovery, and the continuing dominance of Acropora populations in the Keppel Islands is indicative of high resilience. These coral communities have survived an 0.8 °C increase in average temperatures over the last 150 years. However, recovery following the 2020 bleaching was driven by the easing of thermal stress, which may challenge their recovery potential under further warming. Open Research Statement Data are not yet provided but are being compiled. Upon acceptance data will be archived on GitHub.
A Novel Niederreiter-like cryptosystem based on the (u|u + υ)-construction codes

In this paper, we present a new variant of the Niederreiter Public Key Encryption (PKE) scheme which is resistant against recent attacks. The security is based on the hardness of the Rank Syndrome Decoding (RSD) problem and it presents a (u|u + υ)-construction code using two different types of codes: Ideal Low Rank Parity Check (ILRPC) codes and λ-Gabidulin codes. The proposed encryption scheme benefits are a larger minimum distance, a new efficient decoding algorithm and a smaller ciphertext and public key size compared to the Loidreau’s variants and to its IND-CCA secure version.