Miracle-dz/UniFAR-FTUs huggingface dataset:
Positive selective sweeps of epigenetic mutations regulating specialized metabolites in plants

DNA methylation is an important factor regulating gene expression in organisms. However, whether DNA methylation plays a key role in adaptive evolution is unknown. Here, we show evidence of naturally selected DNA methylation in Arabidopsis thaliana. In comparison with single nucleotide polymorphisms, three types of methylation—methylated CGs (mCGs), mCHGs, and mCHHs—contributed highly to variable gene expression levels among an A. thaliana population. Such variably expressed genes largely affect a large variation of specialized metabolic quantities. Among the three types of methylations, only mCGs located in promoter regions of genes associated with specialized metabolites show a selective sweep signature in the A. thaliana population. Thus, naturally selected mCGs appear to be key mutations that cause the expressional diversity associated with specialized metabolites during plant evolution.
TCF7L2 regulates postmitotic differentiation programs and excitability patterns in the thalamus.

Neuronal phenotypes are controlled by terminal selector transcription factors in invertebrates, but only a few examples of such regulators have been provided in vertebrates. We hypothesised that TCF7L2 regulates different stages of postmitotic differentiation in the thalamus, and functions as a thalamic terminal selector. To investigate this hypothesis, we used complete and conditional knockouts of Tcf7l2 in mice. The connectivity and clustering of neurons were disrupted in the thalamo-habenular region in Tcf7l2-/-embryos. The expression of subregional thalamic and habenular transcription factors was lost and region-specific cell migration and axon guidance genes were downregulated. In mice with a postnatal Tcf7l2 knockout, the induction of genes that confer thalamic terminal electrophysiological features was impaired. Many of these genes proved to be direct targets of TCF7L2. The role of TCF7L2 in terminal selection was functionally confirmed by impaired firing modes in thalamic neurons in the mutant mice. These data corroborate the existence of master regulators in the vertebrate brain that control stage-specific genetic programs and regional subroutines, maintain regional transcriptional network during embryonic development, and induce terminal selection postnatally.
Diagnosis of tuberculosis: a consensus statement from the Brazilian Thoracic Association

ABSTRACT Early, accurate diagnosis of tuberculosis is one of the major pillars of the control of the disease. The purpose of this consensus statement is to provide health professionals with the most current, useful evidence for the diagnosis of tuberculosis in Brazil. To that end, the Tuberculosis Committee of the Brazilian Thoracic Association brought together 14 members of the Association with recognized expertise in tuberculosis in Brazil to compose the statement. A nonsystematic review of the following topics was carried out: clinical diagnosis, bacteriological diagnosis, radiological diagnosis, histopathological diagnosis, diagnosis of tuberculosis in children, and diagnosis of latent tuberculosis infection.
Clonal analysis of immunodominance and cross-reactivity of the CD4 T cell response to SARS-CoV-2

Probing CD4 T cell immunity to SARS-CoV-2 A better understanding of CD4+ T cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to the design of effective next-generation vaccines. Low et al. defined and estimated the CD4+ T cell repertoire of convalescent COVID-19 patients. After sorting various CD4+ T cell subsets, they generated numerous T cell clones that reacted to the SARS-CoV-2 spike protein. In around a third of all clones and almost all individuals, the T cells recognized a small conserved immunodominant region within the spike protein receptor-binding domain (RBD). The researchers isolated T cell clones that broadly reacted to the spike protein of other coronaviruses, providing evidence for the recall of preexisting cross-reactive memory T cells after SARS-CoV-2 infection. Science, abg8985, this issue p. 1336 An analysis of T helper cell clones from COVID-19 patients reveals a conserved immunodominant region in the spike protein receptor-binding domain. The identification of CD4+ T cell epitopes is instrumental for the design of subunit vaccines for broad protection against coronaviruses. Here, we demonstrate in COVID-19–recovered individuals a robust CD4+ T cell response to naturally processed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein and nucleoprotein (N), including effector, helper, and memory T cells. By characterizing 2943 S-reactive T cell clones from 34 individuals, we found that the receptor-binding domain (RBD) is highly immunogenic and that 33% of RBD-reactive clones and 94% of individuals recognized a conserved immunodominant S346–S365 region comprising nested human leukocyte antigen DR (HLA-DR)– and HLA-DP–restricted epitopes. Using pre– and post–COVID-19 samples and S proteins from endemic coronaviruses, we identified cross-reactive T cells targeting multiple S protein sites. The immunodominant and cross-reactive epitopes identified can inform vaccination strategies to counteract emerging SARS-CoV-2 variants.
Genotypic and Phenotypic Diversity among Human Isolates of Akkermansia muciniphila

The abundance of Akkermansia muciniphila in the gastrointestinal (GI) tract is linked to multiple positive health outcomes. There are four known A. muciniphila phylogroups, yet the prevalence of these phylogroups and how they vary in their ability to influence human health is largely unknown. ABSTRACT The mucophilic anaerobic bacterium Akkermansia muciniphila is a prominent member of the gastrointestinal (GI) microbiota and the only known species of the Verrucomicrobia phylum in the mammalian gut. A high prevalence of A. muciniphila in adult humans is associated with leanness and a lower risk for the development of obesity and diabetes. Four distinct A. muciniphila phylogenetic groups have been described, but little is known about their relative abundance in humans or how they impact human metabolic health. In this study, we isolated and characterized 71 new A. muciniphila strains from a cohort of children and adolescents undergoing treatment for obesity. Based on genomic and phenotypic analysis of these strains, we found several phylogroup-specific phenotypes that may impact the colonization of the GI tract or modulate host functions, such as oxygen tolerance, adherence to epithelial cells, iron and sulfur metabolism, and bacterial aggregation. In antibiotic-treated mice, phylogroups AmIV and AmII outcompeted AmI strains. In children and adolescents, AmI strains were most prominent, but we observed high variance in A. muciniphila abundance and single phylogroup dominance, with phylogroup switching occurring in a small subset of patients. Overall, these results highlight that the ecological principles determining which A. muciniphila phylogroup predominates in humans are complex and that A. muciniphila strain genetic and phenotypic diversity may represent an important variable that should be taken into account when making inferences as to this microbe’s impact on its host’s health. IMPORTANCE The abundance of Akkermansia muciniphila in the gastrointestinal (GI) tract is linked to multiple positive health outcomes. There are four known A. muciniphila phylogroups, yet the prevalence of these phylogroups and how they vary in their ability to influence human health is largely unknown. In this study, we performed a genomic and phenotypic analysis of 71 A. muciniphila strains and identified phylogroup-specific traits such as oxygen tolerance, adherence, and sulfur acquisition that likely influence colonization of the GI tract and differentially impact metabolic and immunological health. In humans, we observed that single Akkermansia phylogroups predominate at a given time but that the phylotype can switch in an individual. This collection of strains provides the foundation for the functional characterization of A. muciniphila phylogroup-specific effects on the multitude of host outcomes associated with Akkermansia colonization, including protection from obesity, diabetes, colitis, and neurological diseases, as well as enhanced responses to cancer immunotherapies.
Detection, treatment, and course of eating disorders in Finland: A population-based study of adolescent and young adult females and males

Objective: We assessed the detection, treatment and outcomes of DSM-5 eating disorders in a nationwide community setting. Method: The FinnTwin12 cohort comprises twins born in 1983–1987 in Finland (n = 5,600), with follow-up starting at age 12. We outline treatment and outcomes of the 127 females and 15 males diagnosed with a lifetime DSM-5 eating disorder in interviews conducted for a subsample (n = 1,347) in their early 20s. Results: Only 45 (32%) of those diagnosed with eating disorder in the interviews had their condition detected in healthcare, and even fewer received treatment (30% of females, 13% of males). Anorexia nervosa (AN), bulimia nervosa, and atypical AN were detected and treated more often than other eating disorders. Five years after disease onset, 41% of those diagnosed had recovered. There were no statistically significant differences in the course of different eating disorders (log-rank p = 0.66) but the outcome was more favourable among males (log-rank p = 0.008). The likelihood of 5-year recovery did not differ between those who had and who had not received treatment (41.1% vs. 40.5%, log-rank p = 0.66). Conclusion: Although eating disorders are common and symptoms are persistent for many, they remain under-diagnosed and under-treated. In real-world settings, effectiveness of provided treatments may be limited.
Darcy Scale Modeling of Smoldering: Impact of Heat Loss

ABSTRACT Modeling the propagation of smoldering fronts with forced air feeding in a porous medium remains a challenge to science. One of the main difficulties is to describe the carbon oxidation reaction that supports this self-sustained process. Pore scale approaches are required to tackle this complex coupled heat and mass transfer problem with chemistry. They, nevertheless, require high computation effort and still miss experimental validation. Furthermore, the heat loss at the walls of the cells inherent to every laboratory scale system adds another level of complexity in the understanding of the coupling between the phenomena at stake. Indeed, it induces a nonhomogeneous temperature field throughout the system. In this article, a 2D Darcy scale model is developed and validated by confrontation with experimental results from the literature, covering wide ranges of carbon content of the medium and forced air velocity. A reasonable description of the front temperature, velocity, and non-consumption oxygen amount is reached. The model finally enables understanding of the impact of heat loss, which controls the front shape and stability near the system walls.
Disruption of disulfides within RBD of SARS‐CoV‐2 spike protein prevents fusion and represents a target for viral entry inhibition by registered drugs

The SARS‐CoV‐2 pandemic imposed a large burden on health and society. Therapeutics targeting different components and processes of the viral infection replication cycle are being investigated, particularly to repurpose already approved drugs. Spike protein is an important target for both vaccines and therapeutics. Insights into the mechanisms of spike‐ACE2 binding and cell fusion could support the identification of compounds with inhibitory effects. Here, we demonstrate that the integrity of disulfide bonds within the receptor‐binding domain (RBD) plays an important role in the membrane fusion process although their disruption does not prevent binding of spike protein to ACE2. Several reducing agents and thiol‐reactive compounds are able to inhibit viral entry. N‐acetyl cysteine amide, L‐ascorbic acid, JTT‐705, and auranofin prevented syncytia formation, viral entry into cells, and infection in a mouse model, supporting disulfides of the RBD as a therapeutically relevant target.
Preexisting Depression and Daytime Sleepiness in Women and Men

ABSTRACT Background Sleep problems can persist following the treatment of depression and remission of symptoms. The extent to which having a previous history of depression may be associated with current daytime sleepiness is largely unknown. Methods Data were obtained from the spring 2017 American College Health Association-National College Health Assessment (ACHA-NCHA) survey (92 institutions) which assessed self-reported health in U.S. college students (n = 41,670). Among the sample, 93.5% were 18–24 year of age, and 69.6% women. Logistic regression estimated the association between reported prior lifetime diagnosis of depression and daytime sleepiness from the past 7 days, while adjusting for depressive symptoms and antidepressant use from the past year. Unadjusted and adjusted logistic regression models stratified by gender were performed. Results Among those who reported problems with sleepiness, 31.6% women and 19.4% men had a preexisting depression diagnosis. Individuals with preexisting depression were more likely than those without this diagnosis to report sleepiness problems (women: OR = 1.4, CI = 1.3–1.6, p < .001; men: OR = 1.2, CI = 1.0–1.4, p < .01). However, this association differed significantly by gender, with women with a preexisting depression diagnosis having a 13.0% greater likelihood of sleepiness compared to men. Conclusions Those with a preexisting depression diagnosis, and specifically women, may be at risk for daytime sleepiness even in the absence of current depressive mood-related symptoms. Given that many individuals are at risk for daytime sleepiness, mental health initiatives, including those on college campuses, should incorporate sleep hygiene within their programming.
Mindfulness and equanimity moderate approach/avoidance motor responses

ABSTRACT A person’s tendency to approach pleasant stimuli and to avoid unpleasant stimuli reflects a basic psychological phenomenon. The present research aimed to investigate the extent to which mindfulness practices and trait equanimity can attenuate this motivational process. In two studies, participants were asked to perform an Approach/Avoidance Task (AAT). In Study 1 (N = 84), prior to completing the AAT, participants were randomly assigned to one of two guided mindfulness-based meditation conditions (breathing or body-scan) or to an active control condition. In Study 2 (N = 71), which controlled for mindfulness practice, motor responses to the AAT were compared by level of equanimity of the participants (low vs. high). The results revealed that breathing meditation practice and trait equanimity significantly moderated participants’ motor responses to the AAT, and that the body-scan meditation did not moderate these responses. Bayesian analyses showed that participants in the breathing meditation group (Study 1) and those with higher equanimity (Study 2) showed a reduction of bias in their motor responses to the AAT. These results suggest that meditation practice and trait equanimity may promote a decrease in automatic motivational approach and avoidance tendencies evoked by positive and negative stimuli.
Prenatal Maternal Infections and Children’s Neurodevelopment in the UK Millennium Cohort Study: A Focus on ASD and ADHD

Objective: No clear answer has yet been attained as to the influence of prenatal exposure to infection on autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), either alone or as co-occurring issues. The current study examined links between hospital-recorded and maternal-reported prenatal infections and ASD, ADHD, and co-occurring ASD and ADHD. Methods: Participants were n = 15,462 children and mother pairs from the Millennium Cohort Study (MCS), a population-representative UK sample. Results: Findings show associations between maternal-reported infections and ASD, and some evidence of links with ADHD and co-occurring ASD and ADHD. Hospital-recorded infections were not found to be associated with ASD, ADHD, or their co-occurrence. Agreement between hospital-recorded and maternal-reported infections was low, which may explain the discrepant findings. Conclusion: Prenatal maternal infections may be associated with increased odds of ASD and ADHD. Findings point to the importance of drawing on multiple sources of information when ascertaining prenatal infection status.
Bimodal molecular mass distribution upon polymerization in the presence of dilithium initiators : A two-phase process model

A mathematical model describing polymerization of hydrocarbon monomers under the action of dilithium catalysts in a hydrocarbon medium is proposed. The model takes into account a two-phase character of the process and the possible growth of living chains in both solution and precipitate. It is assumed that predominantly monofunctional macromolecules are present in solution, while the precipitate for the most part contains bifunctional macromolecules forming a gel as a result of polyfunctional association of chain ends. The model is capable of explaining some experimental features such as the bimodal molecular mass distribution, the pattern of variation of the mass ratio of the high- and low-molecular-mass fractions during polymerization and as a function of the initial reaction conditions, and the S-shaped character of the kinetic curves at low (but not at high) initiator concentrations.
On-line field measurements of monoterpene emissions from Scots pine by proton-transfer-reaction mass spectrometry

We measured the daily patterns of monoterpene emissions from Scots pine (Pinus sylvestris) trees in a boreal coniferous forest in August and September 2004, using an on-line chamber method combined with a proton-transfer-reaction mass spectrometry (PTR-MS) analyzer. The on-line measurements were made in two chambers with a one-year old shoot inside. Simultaneous measurements were performed for carbon dioxide (CO 2 ) exchange, transpiration (H 2 O), exchange of trace gases (NO x , O 3 ), photosynthetic.photon flux density (PPFD), air temperature and relative humidity (RH). The composition of the monoterpene emission did not change during the measurement period, with Δ 3 -carene and α-pinene being the dominant species. The total monoterpene emission rate (per needle area) was on average 0.5 ng m2 s -1 , varied from non detectable to 2.1 ng m2 s -1 , and showed a typical diurnal pattern with afternoon maximum and nighttime minimum. The emission rates determined with this on-line chamber method were in agreement with results from a simultaneously used established adsorbent sampling technique with offline GC-MS analysis. The monoterpene emissions from the chamber walls were correlated with the chamber temperature and this measurement artifact was dominating at night. Emission rates normalized to 30 °C, using temperature regression coefficient of 0.09 °C -1 , ranged from 2.1 μg g(dw) -1 h -1 to 4.4 μg g(dw) -1 h -1 Measurements of emission dynamics of biogenic volatile organic compounds (BVOCs) together with plant physiological activity are urgently needed for the development of mechanistic BVOC emission models in order to assess their regional and global influence.
Application of deep learning to understand resilience to Alzheimer's disease pathology

People who have Alzheimer's disease neuropathologic change (ADNC) typically associated with dementia but not the associated cognitive decline can be considered to be “resilient” to the effects of ADNC. We have previously reported lower neocortical levels of hyperphosphorylated tau (pTau) and less limbic‐predominant age‐related TDP‐43 encephalopathy neuropathologic change (LATE‐NC) in the resilient participants compared to those with dementia and similar ADNC as determined by current NIA‐AA recommendations using traditional semi‐quantitative assessments of amyloid β and pathological tau burden. To better understand differences between AD‐dementia and resilient participants, we developed and applied a deep learning approach to analyze the neuropathology of 14 brain donors from the Adult Changes in Thought study, including seven stringently defined resilient participants and seven age‐matched AD‐dementia controls. We created two novel, fully automated deep learning algorithms to quantify the level of phosphorylated TDP‐43 (pTDP‐43) and pTau in whole slide imaging. The models performed better than traditional techniques for quantifying pTDP‐43 and pTau. The second model was able to segment lesions staining for pTau into neurofibrillary tangles (NFTs) and tau neurites (neuronal processes positive for pTau). Both groups had similar quantities of pTau localizing to neurites, but the pTau burden associated with NFTs in the resilient group was significantly lower compared to the group with dementia. These results validate use of deep learning approaches to quantify clinically relevant microscopic characteristics from neuropathology workups. These results also suggest that the burden of NFTs is more strongly associated with cognitive impairment than the more diffuse neuritic tau commonly seen with tangle pathology and suggest that additional factors may underlie resilience mechanisms defined by traditional means.
Age and sex influence the activation‐dependent stiffness of the pectoralis major

The pectoralis major fiber regions contribute uniquely to the mobility and the stability of the shoulder complex. It is unknown how age and sex influence the stiffness of these regions during volitional contractions, but this knowledge is critical to inform clinical interventions targeting the pectoralis major. The aim of the present study was to determine if the activation‐dependent stiffness of the pectoralis major fiber regions differs between the sexes and if it is altered with age. Ultrasound shear wave elastography was used to acquire shear wave velocity from the clavicular and the sternocostal fiber regions of 48 healthy participants, including 24 younger (12 males, 12 females, mean ± SD age 25 ± 4.1 years) and 24 older adults (12 males, 12 females, 55 ± 3.6 years). Participants performed vertical adduction and horizontal flexion torques in neutral and 90° externally rotated shoulder positions, and one of the two shoulder abduction positions (60° and 90°) at varying torque magnitudes (passive, 15% and 30% of maximal voluntary contraction). Separate linear mixed‐effects models were run for each fiber region and shoulder position to determine if the activation‐dependent stiffness differed between the sexes and was altered in older adults. Age‐related alterations in stiffness during volitional contractions were observed in both fiber regions and were dependent on the task. Alterations in activation‐dependent stiffness due to age were more pronounced in females than males. Additionally, females had greater stiffness than males during volitional contractions in both fiber regions. The present findings provide the first line of evidence that the activation‐dependent stiffness of the pectoralis major fiber regions is influenced by sex and changes with age.