Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Characterization of the Arabidopsis Ammonium Transporter AtAMT1;3 With the Emphasis on Structural Determinants of Substrate Binding and Permeation Properties

AtAMT1;3 is a major contributor to high-affinity ammonium uptake in Arabidopsis roots. Using a stable electrophysiological recording strategy, we demonstrate in Xenopus laevis oocytes that AtAMT1;3 functions as a typical high-affinity NH4+ uniporter independent of protons and Ca2+. The findings that AtAMT1;3 transports methylammonium (MeA+, a chemical analog of NH4+) with extremely low affinity (Km in the range of 2.9–6.1 mM) led to investigate the mechanisms underlying substrate binding. Homologous modeling and substrate docking analyses predicted that the deduced substrate binding motif of AtAMT1;3 facilitates the binding of NH4+ ions but loosely accommodates the binding of MeA+ to a more superficial location of the permeation pathway. Amongst point mutations tested based on this analysis, P181A resulted in both significantly increased current amplitudes and substrate binding affinity, whereas F178I led to opposite effects. Thus these 2 residues, which flank W179, a major structural component of the binding site, are also important determinants of AtAMT1;3 transport capacity by being involved in substrate binding. The Q365K mutation neighboring the histidine residue H378, which confines the substrate permeation tunnel, affected only the current amplitudes but not the binding affinities, providing evidence that Q365 mainly controls the substrate diffusion rate within the permeation pathway.
Comparative Analysis of Tear Composition in Humans, Domestic Mammals, Reptiles, and Birds

Tears are an important component of the ocular surface protection mechanism and are in close contact with the corneal epithelium and the environment. Their composition is well-known in humans; however, there are few investigations on the composition and function of tears in reptiles, birds and others mammals, which would elucidate the mechanisms governing the maintenance of ocular homeostasis. In this work, electrophoretic profiles and an evaluation of total protein, albumin, urea, glucose, and cholesterol concentrations in tears of semi-aquatic, terrestrial, and marine reptiles (Caiman latirostris, Chelonia mydas, Caretta caretta, Eretmochelys imbricata, Lepidochelys olivacea, and Chelonoidis carbonaria), birds (Tyto furcata, Rupornis magnirostris and Ara ararauna), and mammals (Equus caballus and Canis lupus familiaris) were apresented. Human tear components and respective blood serum samples were used as references. The electrophoretic analysis revealed similarities whithin same Classes. The results of the tear–blood serum relationship and the comparison to human tear components showed particularities that are potentially derived from a homeostatic response to the environment. When the tear compositions of animals belonging to different ecological clusters were compared, marked differences were observed in total protein and urea concentrations. Thus, reptile, bird, and mammalian tears are complex fluids with differing concentrations of biochemical components that are potentially a result of the animals' adaptation to different environments.
Healthy Selfishness and Pathological Altruism: Measuring Two Paradoxical Forms of Selfishness

Selfishness is often regarded as an undesirable or even immoral characteristic, whereas altruism is typically considered universally desirable and virtuous. However, human history as well as the works of humanistic and psychodynamic psychologists point to a more complex picture: not all selfishness is necessarily bad, and not all altruism is necessarily good. Based on these writings, we introduce new scales for the assessment of individual differences in two paradoxical forms of selfishness that have lacked measurement in the field – healthy selfishness (HS) and pathological altruism (PA). In two studies (N1 = 370, N2 = 891), we constructed and validated the HS and PA scales. The scales showed good internal consistency and a clear two-dimensional structure across both studies. HS was related to higher levels of psychological well-being and adaptive psychological functioning as well as a genuine prosocial orientation. PA was associated with maladaptive psychological outcomes, vulnerable narcissism, and selfish motivations for helping others. These results underpin the paradoxical nature of both constructs. We discuss the implications for future research, including clinical implications.
SARS-CoV-2 Infection and the Newborn

Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) affects people at all ages and it may be encountered in pregnant women and newborns also. The information about its clinical features, laboratory findings and prognosis in children and newborns is scarce. All the reported cases in pregnant women were in the 2nd or 3rd trimester and only 1% of them developed severe disease. Miscarriages are rare. Materno-fetal transmission of the disease is controversial. Definitive diagnosis can be made by a history of contact with a proven case, fever, pneumonia and gastrointestinal disorder and a Polymerase chain reaction (PCR) test of nasopharyngeal swabs. Lymphopenia as well as liver and renal dysfunctions may be seen. Suspected or proven cases of newborns with symptoms should be quarantined in the neonatal intensive care unit for at least 14 days with standart and droplet isolation precautions. Asymptomatic infants may be quaratined at home. Transport of the neonates should be performed in a dedicated transport incubator and ambulance with isolation precautions. There is no specific treatment for the disease, but hemodynamic stabilization of the infant, respiratory management and other daily care are essential. Drugs against cytokine storm syndrome such as corticosteroids or tocilizumab are under investigation. Routine antibiotics are not recommended. No deaths have been reported so far in the neonatal population. Families and healthcare staff should receive pyschological support. Since the infection is quite new and knowledge is constantly accumulating, following developments and continuous updates are crucial.
Sparse input neural networks to differentiate 32 primary cancer types based on somatic point mutations

This paper aims to differentiate cancer types from primary tumour samples based on somatic point mutations (SPM). Primary cancer site identification is necessary to perform site-specific and potentially targeted treatment. Current methods like histopathology/lab-tests cannot accurately determine cancers origin, which results in empirical patient treatment and poor survival rates. The availability of large deoxyribonucleic-acid sequencing datasets has allowed scientists to examine the ability of SPM to classify primary cancer sites. These datasets are highly sparse since most genes will not be mutated, have low signal-to-noise ratio and are imbalanced since rare cancers have less samples. To overcome these limitations a sparse-input neural network (spinn) is suggested that projects the input data in a lower dimensional space, where the more informative genes are used for learning. To train and evaluate spinn, an extensive dataset was collected from the cancer genome atlas containing 7624 samples spanning 32 cancer types. Different sampling strategies were performed to balance the dataset but have not benefited the classifiers performance except for removing Tomek-links. This is probably due to high amount of class overlapping. Spinn consistently outperformed algorithms like extreme gradient-boosting, deep neural networks and support-vector-machines, achieving an accuracy up to 73% on independent testing data.
Non-thalamic origin of zebrafish sensory relay nucleus: convergent evolution of visual pathways in amniotes and teleosts

Ascending visual projections similar to the mammalian thalamocortical pathway are found in a wide range of vertebrate species, but their homologous relationship is debated. To get better insights into their evolutionary origin, we examined the developmental origin of a visual relay nucleus in zebrafish (a teleost fish). Similarly to the tectofugal visual thalamic nuclei in amniotes, the lateral part of the preglomerular complex (PG) in teleosts receives tectal information and projects to the pallium. However, our cell lineage study reveals that the majority of PG cells are derived from the midbrain, not from the forebrain. We also demonstrate that the PG projection neurons develop gradually until juvenile stage, unlike the thalamic projection neurons. Our data suggest that teleost PG is not homologous to the amniote thalamus and that thalamocortical-like projections can evolve from a non-forebrain cell population. Thus, sensory pathways in vertebrate brains exhibit a surprising degree of variation.
Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?

The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected over 3.8 million people, including pregnant women. To date, no consistent evidence of vertical transmission for SARS-CoV-2 exists. This new coronavirus canonically utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and the serine protease TMPRSS2 for cell entry. Herein, building upon our previous single cell study of the placenta (Pique-Regi, 2019), another study, and new single-cell/nuclei RNA-sequencing data, we investigated the expression of ACE2 and TMPRSS2 throughout pregnancy as well as in third-trimester chorioamniotic membranes. We report that co-transcription of ACE2 and TMPRSS2 is negligible, thus not a likely path of vertical transmission for SARS-CoV-2 at any stage of pregnancy. In contrast, receptors for Zika virus and cytomegalovirus which cause congenital infections are highly expressed by placental cell types. These data suggest that SARS-CoV-2 is unlikely to infect the human placenta through the canonical cell entry mediators; yet, other interacting proteins could still play a role in the viral infection.
A conceptual framework for predicting the occurrence of sediment focusing and sediment redistribution in small lakes

Four processes are important in causing either sediment focusing or overestimation of sediment accumulation rates by traps, or both. A simple model to predict the occurrence of these events was constructed from published data for monomictic and polymictic lakes which contained sufficient detail to identify the major redistribution process. Boundaries between the regions where different mechanisms dominate were calculated from the expected mode of operation of the processes. The model was tested using sediment trap and accumulation rate vs. water depth data from the literature. Other published work is in general agreement with the predictions of the model.
C-Jun N-terminal kinase (JNK) pathway activation is essential for dental papilla cells polarization

During tooth development, dental papilla cells could develop into odontoblasts with polarized morphology and cell function, c-Jun N-terminal kinase (JNK) signaling could participate in this process. Histological staining, qPCR and Western Blot shown that activation of JNK signaling in polarized mouse dental papilla tissue. In vitro cell culture and organ culture method found JNK inhibitor SP600125 postponed tooth germ development and reduced the polarization, migration and differentiation of mouse dental papilla cells (mDPCs) in vitro. The expression of polarity-related genes including Prickle3, Golga2, Golga5 and RhoA was consistent with JNK signaling activation, by screening of up-regulated polarity-related genes during the process of dental papilla development and mDPCs or A11 differentiation. Further, constitutively active RhoA mutant (RhoA Q63L) partly rescue the inhibition of SP600125 on cell differentiation and polarity formation of mDPCs. This study suggests that JNK signaling has a positive role in dental papilla cells polarization formation.
Produtividade e qualidade fisiológica de sementes de feijão em função de sistemas de manejo de solo e adubação nitrogenada

O fator climatico exerce grande influencia na producao de sementes de feijao, porem outros fatores como a acao do ambiente solo, consequencia de seu manejo, associado a nutricao adequada da planta, principalmente de nitrogenio, podem levar a resultados expressivos tanto no ganho de produtividade como na obtencao de produto de qualidade superior. O objetivo deste trabalho foi avaliar a influencia de dois sistemas de manejo de solo (preparo convencional e plantio direto) e da adubacao nitrogenada de cobertura (0, 40, 80, 120 e 160kg.ha-1 de N) sobre a produtividade e qualidade fisiologica de sementes de feijao, num delineamento experimental em blocos ao acaso em esquema de parcelas subdivididas, com quatro repeticoes. Verificou-se que a produtividade de sementes e influenciada positivamente pela adubacao nitrogenada de cobertura, tanto no sistema de preparo convencional de solo quanto no plantio direto. Nas doses de nitrogenio em cobertura utilizadas, o sistema de preparo convencional de solo apresenta maior produtividade de sementes. Aumento nas doses de nitrogenio em cobertura possibilitam acrescimos na germinacao e no vigor das sementes de feijao. O sistema de preparo convencional de solo promove sementes de maior qualidade fisiologica, expressos pelo testes de germinacao e envelhecimento acelerado.
Detection of cerebral tauopathy in P301L mice using high-resolution large-field multifocal illumination fluorescence microscopy

Current intravital microscopy techniques visualize tauopathy with high-resolution, but have a small field-of-view and depth-of-focus. Herein, we report a transcranial detection of tauopathy over the entire cortex of P301L tauopathy mice using large-field multifocal illumination (LMI) fluorescence microscopy technique and luminescent conjugated oligothiophenes. In vitro assays revealed that fluorescent ligand h-FTAA is optimal for in vivo tau imaging, which was confirmed by observing elevated probe retention in the cortex of P301L mice compared to non-transgenic littermates. Immunohistochemical staining further verified the specificity of h-FTAA to detect tauopathy in P301L mice. The new imaging platform can be leveraged in pre-clinical mechanistic studies of tau spreading and clearance as well as longitudinal monitoring of tau targeting therapeutics.
Measuring Metacognition of Direct and Indirect Parameters of Voluntary Movement

We can make exquisitely precise movements without the apparent need for conscious monitoring. But can we monitor the low-level movement parameters when prompted? And what are the mechanisms that allow us to monitor our movements? To answer these questions, we designed a semi-virtual ball throwing task. On each trial, participants first threw a virtual ball by moving their arm (with or without visual feedback, or replayed from a previous trial) and then made a two-alternative forced choice on the resulting ball trajectory. They then rated their confidence in their decision. We measured metacognitive efficiency using meta-d’/d’ and compared it between different informational domains of the first-order task (motor, visuomotor or visual information alone), as well as between two different versions of the task based on different parameters of the movement: proximal (position of the arm) or distal (resulting trajectory of the ball thrown). We found that participants were able to monitor their performance based on distal motor information as well as when proximal information was available. Their metacognitive efficiency was also equally high in conditions with different sources of information available. The analysis of correlations across participants revealed an unexpected result: while metacognitive efficiency correlated between informational domains (which would indicate domain-generality of metacognition), it did not correlate across the different parameters of movement. We discuss possible sources of this discrepancy and argue that specific first-order task demands may play a crucial role in our metacognitive ability and should be considered when making inferences about domain-generality based on correlations.
PhylSim: A New Phylogenetic Tool for Modeling Trait Evolution and Speciation

We present a new software tool in R, the PhylSim package, which allows the user to simulate trait evolution on a phylogeny, while varying the speciation rate and evolutionary model over the course of the simulation. In particular, the user can specify any number of regimes, with a different speciation rate for each regime, or set the speciation rate to vary when the value of a trait exceeds a certain threshold. The evolutionary model can also be varied as many times as necessary over the course of the simulation, to account for traits tending toward different optima at different periods in evolutionary history. We illustrate the use of the package with an example, a simulation of the adaptive radiation of Antarctic notothenioids in the Southern Ocean.
Variation in Hull Composition and Digestibility Among Oat Genotypes 1

Little attention has been given to the study of genotypic variation in the composition and digestibility of oat (Arena sativa L.) hulls. The aim of this study was to examine the variability in levels of acid detergent fiber (ADF), its components—cellulose, acid detergent lignin (ADL), and insoluble ash (mainly silica)— and pepsin cellulase digestibility (PCD) in hulls separated from current Western Australian genotypes. Analyses were conducted on six genotypes grown in trials at up to seven locations in Western Australia in 1981. In 1983, the same genotypes, and one other, were tested at five locations. In both years, considerable genotypic variance was observed in levels of PCD, ADF, and ADL. Location affected all traits, particularly insoluble ash, in both years. Genotype ✕ location interaction was not measured in 1981, but in 1983 was found to be significant for all traits. Interaction effects were of sufficient magnitude to mask the small genotypic variations in cellulose, but clear differentiation between genotypes with high or low PCD, ADF, and ADL was observed at each location. While PCD was highly correlated with ADF (r = −0.97** (significant at the 0.01 probability level), based on means for each of seven genotypes over five locations), differences between genotypes in both PCD and ADF were associated mainly with ADL (r = −0.98** and 0.95**, respectively). Among the genotypes tested, Swan (PCD, 293 g kg−1 ; ADL, 8 g kg⁻¹) and ‘Mortlock’ (PCD, 108 g kg⁻¹; ADL, 76 g kg⁻¹) had the highest and lowest quality hulls, respectively. This study has shown considerable variation to exist in the highly correlated factors PCD and ADL among current Western Australian genotypes, and indicates potential for improvement in the feeding quality of oat grain through plant breeding.
Architecture and self-assembly of the SARS-CoV-2 nucleocapsid protein

The COVID-2019 pandemic is the most severe acute public health threat of the twenty-first century. To properly address this crisis with both robust testing and novel treatments, we require a deep understanding of the life cycle of the causative agent, the SARS-CoV-2 coronavirus. Here, we examine the architecture and self-assembly properties of the SARS-CoV-2 nucleocapsid (N) protein, which binds viral RNA and assembles into a filament that is packaged into new virions. We determined a 1.4 Å resolution crystal structure of this protein’s N2b domain, revealing a compact, intertwined dimer very similar to that of related coronaviruses SARS-CoV and MERS-CoV. Using size exclusion chromatography and multi-angle light scattering, we find that this domain forms a dimer in solution, and that addition of the C-terminal spacer B/N3 domain mediates tetramer formation. Using hydrogen-deuterium exchange mass spectrometry, we find evidence that at least part of this putatively disordered domain is structured, potentially forming an α-helix that either self-associates or docks against the N2b domain to mediate tetramer formation. Finally, we map the locations of over 4,400 individual amino acid substitutions in the N protein from ~17,000 SARS-CoV-2 genome sequences, and find that they are strongly clustered in the protein’s N2a linker domain. The nearly 300 substitutions identified within the N1b and N2b domains cluster away from their functional RNA binding and dimerization interfaces. Overall, this work reveals the architecture and self-assembly properties of a key protein in the SARS-CoV-2 life cycle. As the N protein is a common target of patient antibodies, this work will also benefit ongoing efforts to develop robust and specific serological tests, and could also benefit the analysis of patient-derived antibodies. Significance Statement After infecting a cell, the SARS-CoV-2 coronavirus replicates its genome and packages it into new virus particles. The virus’s nucleocapsid (N) protein is critical for this process, binding the genomic RNA and assembling into large filaments before being packaged into new virions. Here, we sought to understand the structure of the SARS-CoV-2 N protein and how it forms large assemblies. We combined x-ray crystallography and two biochemical methods to show that the protein’s N2b and N3 domains mediate self-association into dimers and tetramers, respectively. We have therefore outlined the first two steps of a probable three-step self-assembly mechanism of the SARS-CoV-2 nucleocapsid. This work will benefit ongoing efforts to develop robust viral tests and to develop new drugs targeting key steps in the viral life cycle.
Performance assessment of Respiratory Viral ELITe MGB® assay for the quantitative detection of influenza A/B and respiratory syncytial viruses

Influenza (Flu) and respiratory syncytial virus (RSV) are responsible for lower respiratory tract infections (LRTIs) associated with significant hospitalization among young children. In the present study, the performances of a triplex PCR assay detecting Flu A/B and RSV were compared with our in-house single-plex assays using 160 stored respiratory specimens previously tested using a panel of laboratory-developed real-time RT-PCR. Of them, 61 were positive for FluA, 41 for FluB, and 58 for RSV. All samples were retrospectively quantified with Respiratory Viral (RV) ELITe MGB® Panel (ELITechGroup Molecular Diagnostics, Puteaux, France) processed using ELITe InGenius® system. Overall, the total percentage agreement observed was 93.4% (57/61) for FluA, 92.7% (38/41) for FluB, and 86.2% (50/58) for RSV. A significant correlation of VL values was observed between the two methods for FluA and RSV (ρ= 0.91 and 0.84). This finding was supported by the strength of agreement between the two methods, as showed by the linear regression analysis (R2 =0.84 and 0.80). FluB viral load values measured by RV Panel were less significantly correlated (ρ= 0.77 and R2 =0.56). The bland-Altman analysis showed how 84.2% (48/57) of FluA and 86.0% of RSV (43/50) samples fell within ±1.0 Log10 variation from our laboratory results, while only 21.1% (8/38) of FluB results fell within this range. The great majority of FluB samples (29/30) outside range had values higher than +1.0 Log10 (median +2.1 Log10 range +1.0 to +3.5 Log10). In conclusion, RV ELITe MGB® Panel constitutes a valid and robust system for simultaneous detection and quantification of Flu A/B and RSV.