Miracle-dz/UniFAR-FTUs huggingface dataset:
MLL1 is required for maintenance of intestinal stem cells and the expression of the cell adhesion molecule JAML

Epigenetic control is crucial for lineage-specific gene expression that creates cellular identity during mammalian development and in adult organism. Histone 3 lysine 4 methylation (H3K4) is a universal epigenetic mark. Mixed lineage leukemia (MLL1) is the founding member of the mammalian family of H3K4 methyltransferases. It was originally discovered as the main gene mutated in early onset leukemias and then found to be required for hematopoietic stem cell development and maintenance. However, the roles of MLL1 in non-hematopoietic tissues remain largely unexplored. To bypass hematopoietic lethality, we used bone marrow transplantation and conditional mutagenesis to discover that the most overt phenotype in Mll1-mutant mice is intestinal failure. Loss of MLL1 is accompanied by a differentiation bias towards the secretory lineage with increased numbers of goblet cells. MLL1 is expressed in intestinal stem cells (ISCs) and transit amplifying (TA) cells but at reduced levels in Paneth cells and not in the villus. MLL1 is required for the maintenance of intestinal stem cells (ISCs) and proliferation in the crypt. Transcriptome analysis implicate MLL1-dependent expression in ISCs of several transcription factors including Pitx2, Gata4, Foxa1 and Onecut2, and also a cell adhesion molecule, Jaml. Reactive transcriptome changes in Paneth cells and organoids imply that JAML plays a key role in the crypt stem cell niche. All known postnatal functions of MLL1 relate to stem cell maintenance and lineage decisions thereby highlighting the suggestion that MLL1 is a master stem cell regulator. Author Summary The ability of adult stem cells to produce functional progenies through differentiation is critical to maintain function and integrity of organs. A fundamental challenge is to identify factors that control the transition from self-renewal to the differentiated state. Epigenetic factors amongst others can fullfill such a role. Methylation of histone 3 on lysine 4 (H3K4) is a posttranslational epigenetic modification that is associated with actively transcribed genes. In mammals, this epigenetic mark is catalyzed by one of six H3K4 methyltransferases, including the founding member of the family, MLL1. MLL1 is important for the precise functioning of the hematopoietic stem cell compartment. This raises the possibility of similar functions in other adult stem cell compartments. Due to its intense self-renewal kinetics and its simple repetitive architecture, the intestinal epithelium serves as a prime model for studying adult stem cells. We demonstrate that MLL1 controls intestinal stem cell proliferation and differentiation. Additionally, transcriptome analysis suggests a pertubation in the close interaction between intestinal stem cells and neighbouring Paneth cells through loss of junction adhesion molecule like (JAML). Our work sheds new light on the function of MLL1 for the control of intestinal stem cell identity.
mTORC1 activity is supported by spatial association with focal adhesions

The mammalian target of rapamycin complex 1 (mTORC1) integrates mitogenic and stress signals to control growth and metabolism. Activation of mTORC1 by amino acids and growth factors involves recruitment of the complex to the lysosomal membrane and is further supported by lysosome distribution to the cell periphery1–4. Here we show that translocation of lysosomes towards the cell periphery brings mTORC1 into proximity with focal adhesions (FAs). We demonstrate that FAs constitute discrete plasma membrane hubs mediating growth factor signaling and amino acid input into the cell. FAs, as well as the translocation of lysosome-bound mTORC1 to their vicinity, are necessary for both peripheral and intracellular mTORC1 activity. Conversely, lysosomal distribution to the cell periphery is dispensable for the activation of mTORC1 constitutively targeted to FAs. This study advances our understanding of spatial mTORC1 regulation by demonstrating that the localization of mTORC1 to FAs is both necessary and sufficient for its activation by growth-promoting stimuli.
Determination of a “Specific Population Who Could Benefit From Rosuvastatin”: A Secondary Analysis of a Randomized Controlled Trial to Uncover the Novel Value of Rosuvastatin for the Precise Treatment of ARDS

Background: The high heterogeneity of acute respiratory distress syndrome (ARDS) contributes to paradoxical conclusions from previous investigations of rosuvastatin for ARDS. Identification of the population (phenotype) that could benefit from rosuvastatin is a novel exploration for the precise treatment. Methods: The patient population for this analysis consisted of unique patients with ARDS enrolled in the SAILS trial (rosuvastatin vs. placebo). Phenotypes were derived using consensus k-means clustering applied to routinely available clinical variables within 6 h of hospital presentation before the patients received placebo or rosuvastatin. The Kaplan–Meier statistic was used to estimate the 90-day cumulative mortality to screen for a specific population that could benefit from rosuvastatin, with a cutoff P < 0.05. Results: The derivation cohort included 585 patients with ARDS. Of the patients with the four derived phenotypes, those with phenotype 3 were classified as the “specific population who could benefit from rosuvastatin” as rosuvastatin resulted in a significant reduction in 90-day cumulative mortality from ARDS [hazard ratio (HR), 0.29; 95% confidence interval (CI), 0.09–0.93; P = 0.027]. Additionally, rosuvastatin markedly improved the days free of cardiovascular failure (10.08 ± 3.79 in the rosuvastatin group vs. 7.31 ± 4.94 in the placebo group, P = 0.01) and coagulation abnormalities (13.65 ± 1.33 vs. 12.15 ± 3.77, P = 0.02) up to day 14 in the phenotype 3 cohort. Phenotype 3 was summarized as Platelethigh & Creatlow phenotype because these patients have a relatively higher platelet count (390.05 ± 79.43 × 109/L) and lower creatinine (1.42 ± 1.08 mg/dL) than do patients classified as other phenotypes. In addition, rosuvastatin seemed to increase 90-day mortality for patients classified as phenotype 4 (HR, 2.76; 95% CI, 0.09–9.93; P = 0.076), with an adverse effect on reducing the days free of renal failure up to day 14 (4.70 ± 4.99 vs. 10.17 ± 4.69, P = 0.01). Patients in phenotype 4 showed relatively severe illness in terms of baseline features, particularly renal failure, with high serum glucose. Therefore, phenotype 4 was defined as APACHEhigh & Serum glucosehigh phenotype. Conclusions: This secondary analysis of the SAILS trial identified that rosuvastatin seems to be harmful for patients classified as APACHEhigh & Serum glucosehigh phenotype, but benefit patients in Platelethigh & Creatlow phenotype, thus uncovering the novel value of rosuvastatin for the precise treatment of ARDS.
Type 2 Diabetes Patients' Perspectives, Experiences, and Barriers Toward Diabetes-Related Self-Care: A Qualitative Study From Pakistan

Objective: This study aimed to qualitatively explore perspectives, practices, and barriers to self-care practices (eating habits, physical activity, self-monitoring of blood glucose, and medicine intake behavior) in urban Pakistani adults with type 2 diabetes mellitus (T2DM). Methods: Pakistani adults with T2DM were recruited from the outpatient departments of two hospitals in Lahore. Semistructured interviews were conducted and audiorecorded until thematic saturation was reached. Two researchers thematically analyzed the data independently using NVivo® software with differences resolved by a third researcher. Results: Thirty-two Pakistani adults (aged 35–75 years, 62% female) participated in the study. Six themes were identified from qualitative analysis: role of family and friends, role of doctors and healthcare, patients' understanding about diabetes, complication of diabetes and other comorbidities, burden of self care, and life circumstances. A variable experience was observed with education and healthcare. Counseling by healthcare providers, family support, and fear of diabetes-associated complications are the key enablers that encourage study participants to adhere to diabetes-related self-care practices. Major barriers to self care are financial constraints, physical limitations, extreme weather conditions, social gatherings, loving food, forgetfulness, needle phobia, and a hectic job. Conclusion: Respondents identified many barriers to diabetes self care, particularly related to life situations and diabetes knowledge. Family support and education by healthcare providers were key influencers to self-care practices among Pakistani people with diabetes.
Synergistic Therapy of Celecoxib-Loaded Magnetism-Responsive Hydrogel for Tendon Tissue Injuries

Tendon tissue injury is very common and always associated with pain, tissue swelling and even malformation if not treated on time. Traditional therapeutic strategies, such as cryotherapy, electrical therapy, ultrasound therapy and anti-inflammatory drug, are still unsatisfying. In this work, a synergistic therapy, based on the combination of celecoxib drug and pulsed electromagnetic field (PEMF) regimens, was developed for the treatment of tendon injury. This celecoxib-loaded magnetism-responsive hydrogel dressing (gelatin/Fe3O4/celecoxib) showed good biocompatibility and coordinated drug release behavior under the PEMF, which could effectively reduce the inflammatory reaction of macrophage cells with the incremental proportion of M2 macrophages at the injury site. CatWalk gait analysis further verified this synergistic effect of combination therapy for achieving the outstanding recovery of the injured tendon tissue. Thus, this magnetism-responsive hydrogel may represent a promising alternative strategy in clinics for promoting tendon healing.
Discovery of a Promising Susceptibility Factor for Fusarium Head Blight in Wheat

Fusarium head blight (FHB) disease of wheat caused by Fusarium spp. deteriorates both quantity and quality of the crop. Manipulation of susceptibility factors, the genes facilitating disease development in plants, offers a novel and alternative strategy for enhancing FHB resistance in plants. In this study, a major effect susceptibility gene for FHB was identified on the short arm of chromosome 7A (7AS). Nullisomic-tetrasomic lines for homoeologous group-7 of wheat revealed dosage effect of the gene, with tetrasomic 7A being more susceptible than control Chinese Spring wheat, qualifying it as a bonafide susceptibility factor. The gene locus was conserved in six chromosome 7A inter-varietal wheat substitution lines of diverse origin and a tetraploid Triticum dicoccoides genotype. The susceptibility gene was named as SF7ASFHB and mapped on chromosome 7AS to 48.5-50.5 Mb peri-centromeric region between del7AS-3 and del7AS-8. Our results showed that deletion of SF7ASFHB imparts ~ 50-60% type 2 FHB resistance (against the spread of the fungal pathogen) and its manipulation may lead to enhanced resistance against FHB in wheat. Highlight Discovery and mapping of a conserved susceptibility factor located on the short arm of wheat chromosome 7A whose deletion makes plants resistant to Fusarium Head Blight.
Detecting flying insects using mega-nets and meta-barcoding

Insect diversity and abundance are increasingly reported as being under pressure. However, monitoring insects across space and time is challenging, due to their vast taxonomic and functional diversity. This study demonstrates how nets mounted on rooftops of cars (car nets) and DNA metabarcoding can be applied to sample flying insect diversity across a large spatial scale within a limited time period. During June 2018, 365 car net samples were collected by 151 volunteers during two daily time intervals on 218 routes in Denmark. Insect bulk samples were processed with a DNA metabarcoding protocol to estimate taxonomic composition, and the results were compared to known flying insect diversity and occurrence data. We detected 15 out of 19 flying insect orders present in Denmark. Diptera. Psocoptera and Thysanoptera were overrepresented, while Hymenoptera, Coleoptera, Lepidoptera, Trichoptera, Odonata, Neuroptera and Plecoptera were underrepresented, compared to Danish estimates. We detected 319 species not known for Denmark. Our results indicate that this method can assess the flying insect fauna to a wide extent, but may be, like other methods, biased towards certain insect orders. Furthermore, car net sampling and DNA metabarcoding can update species records for Denmark while preserving specimens for natural history collections.
Expression of Proteinase-Activated Receptor 2 During Colon Volvulus in the Horse

Large colon volvulus in horses is associated with a poor prognosis, especially when ischemic-reperfusion injury of the affected intestinal tract develops. Proteinase-activated receptor 2 (PAR2) plays an important role in the pathogenesis of inflammation in the gastrointestinal tract. The aim of this study was to evaluate the distribution and expression of PAR2 in colonic pelvic flexure of horses spontaneously affected by large colon volvulus (CVH group). Eight horses admitted for severe abdominal colon volvolus and which underwent surgery were included. Colon samples were collected after enterotomy. Data previously obtained from healthy horses were used as a control group. Histologic evaluation was carried out to grade the severity of the colon lesions. Immunofluorescence, western blot and quantitative polymerase chain reaction (RT-qPCR) were carried out on colon samples to evaluate PAR2 expression. In addition, the transcriptional profile of cytokines and chemokines was evaluated using RT2 Profiler™ PCR Array Horse Cytokines & Chemokines. Three out of the eight patients were euthanised due to clinical deterioration. Immunostaining for PAR2 was observed in the enterocytes, intestinal glands and neurons of the submucosal and myenteric plexi. In the CVH horses, the expression of PAR2 mesenger RNA (mRNA) did not differ significantly from that of the healthy animals; western blots of the mucosa of the colon tracts showed a clear band of the expected molecular weight for PAR2 (~44 kDa) and a band smaller than the expected molecular weight for PAR2 (25kDa), suggesting its activation. The gene expressions for C-X-C motif ligand 1 (CXCL1); interleukin 8 (IL8), macrophage inflammatory protein 2 beta (MIP-2BETA) were upregulated in the colic horses as compared with the colons of the healthy horses. Therefore, in the present study, the expression and activation of PAR2 in the colons of horses in the presence of an inflammatory reaction like that occurring in those with spontaneous colon volvulus was confirmed.
QTL Analysis and Fine Mapping of a Major QTL Conferring Kernel Size in Maize (Zea mays)

Kernel size is an important agronomic trait for grain yield in maize. The purpose of this study is to map QTLs and predict candidate genes for kernel size in maize. A total of 199 F2 and its F2:3 lines from the cross between SG5/SG7 were developed. A composite interval mapping (CIM) method was used to detect QTLs in three environments of F2 and F2:3 populations. The result showed that a total of 10 QTLs for kernel size were detected, among which were five QTLs for kernel length (KL) and five QTLs for kernel width (KW). Two stable QTLs, qKW-1, and qKL-2, were mapped in all three environments. Three QTLs, qKL-1, qKW-1, and qKW-2, were overlapped with the QTLs identified from previous studies. In order to validate and fine map qKL-2, near-isogenic lines (NILs) were developed by continuous backcrossing between SG5 as the donor parent and SG7 as the recurrent parent. Marker-assisted selection was conducted from BC2F1 generation with molecular markers near qKL-2. A secondary linkage map with six markers around the qKL-2 region was developed and used for fine mapping of qKL-2. Finally, qKL-2 was confirmed in a 1.95 Mb physical interval with selected overlapping recombinant chromosomes on maize chromosome 9 by blasting with the Zea_Mays_B73 v4 genome. Transcriptome analysis showed that a total of 11 out of 40 protein-coding genes differently expressed between the two parents were detected in the identified qKL-2 interval. GRMZM2G006080 encoding a receptor-like protein kinase FERONIA, was predicted as a candidate gene to control kernel size. The work will not only help to understand the genetic mechanisms of kernel size of maize but also lay a foundation for further fine mapping and even cloning of the promising loci.
Fine-scale population structure reveals high genetic heterogeneity of the Kuwaiti population in the Arabian Peninsula

Recent studies have showed the diverse genetic architecture of the highly consanguineous populations inhabiting the Arabian Peninsula. Consanguinity coupled with heterogeneity is complex and makes it difficult to understand the bases of population-specific genetic diseases in the region. Therefore, comprehensive genetic characterization of the populations at the finest scale is warranted. Here, we revisit the genetic structure of the Kuwait population by analyzing genome-wide single nucleotide polymorphisms data from 583 Kuwaiti individuals sorted into three subgroups. We envisage a diverse demographic genetic history among the three subgroups based on drift and allelic sharing with modern and ancient individuals. Furthermore, our comprehensive haplotype-based analyses disclose a high genetic heterogeneity among the Kuwaiti populations. We infer the major sources of ancestry within the newly defined groups; one with an obvious predominance of sub-Saharan/Western Africa mostly comprising Kuwait-B individuals, and other with West Eurasia including Kuwait-P and Kuwait-S individuals. Overall, our results recapitulate the historical population movements and reaffirm the genetic imprints of the legacy of continental trading in the region. Such deciphering of fine-scale population structure and their regional genetic heterogeneity would provide clues to the uncharted areas of disease-gene discovery and related associations in populations inhabiting the Arabian Peninsula.
EmotionSense

With the recent surge of smart wearable devices, it is possible to obtain the physiological and behavioral data of human beings in a more convenient and non-invasive manner. Based on such data, researchers have developed a variety of systems or applications to recognize and understand human behaviors, including both physical activities (e.g., gestures) and mental states (e.g., emotions). Specifically, it has been proved that different emotions can cause different changes in physiological parameters. However, other factors, such as activities, may also impact one’s physiological parameters. To accurately recognize emotions, we need not only explore the physiological data but also the behavioral data. To this end, we propose an adaptive emotion recognition system by exploring a sensor-enriched wearable smart watch. First, an activity identification method is developed to distinguish different activity scenes (e.g., sitting, walking, and running) by using the accelerometer sensor. Based on the identified activity scenes, an adaptive emotion recognition method is proposed by leveraging multi-mode sensory data (including blood volume pulse, electrodermal activity, and skin temperature). Specifically, we extract fine-grained features to characterize different emotions. Finally, the adaptive user emotion recognition model is constructed and verified by experiments. An accuracy of 74.3% for 30 participants demonstrates that the proposed system can recognize human emotions effectively.
Is male dimorphism under sexual selection in humans? A meta-analysis

Humans are sexually dimorphic: men and women differ in body build and composition, craniofacial structure, and voice pitch, likely mediated in part by developmental testosterone. Sexual selection hypotheses posit that, ancestrally, more ‘masculine’ men may have acquired more mates and/or sired more viable offspring. Thus far, however, evidence for either association is unclear. Here, we meta-analyze the relationship between six masculine traits and mating/reproductive outcomes (96 studies, 474 effects, N = 177,044). Voice pitch, height, digit ratios, and testosterone all predicted mating; however, strength/muscularity was the strongest and only consistent predictor of both mating and reproduction. Facial masculinity did not significantly predict either. There was insufficient evidence for any effects of masculinity on offspring viability. Our findings support arguments that strength/muscularity can be considered sexually selected in humans, but raise concerns over other forms of masculinity and highlight the need to increase tests of evolutionary hypotheses outside of industrialized populations.
Prediction error signaling explains neuronal mismatch responses in the medial prefrontal cortex

The mismatch negativity (MMN) is a key biomarker of automatic deviance detection thought to emerge from two cortical sources. First, the auditory cortex (AC) encodes spectral regularities and reports frequency-specific deviances. Then, more abstract representations in the prefrontal cortex (PFC) allow to detect contextual changes of potential behavioral relevance. However, the precise location and time asynchronies between neuronal correlates underlying this fronto-temporal network remain unclear and elusive. Our study presented auditory oddball paradigms along with ‘no-repetition’ controls to record mismatch responses in neuronal spiking activity and local field potentials at the rat medial PFC. Whereas mismatch responses in the auditory system are mainly induced by stimulus-dependent effects, we found that auditory responsiveness in the PFC was driven by unpredictability, yielding context-dependent, comparatively delayed, more robust and longer-lasting mismatch responses mostly comprised of prediction error signaling activity. This characteristically different composition discarded that mismatch responses in the PFC could be simply inherited or amplified downstream from the auditory system. Conversely, it is more plausible for the PFC to exert top-down influences on the AC, since the PFC exhibited flexible and potent predictive processing, capable of suppressing redundant input more efficiently than the AC. Remarkably, the time course of the mismatch responses we observed in the spiking activity and local field potentials of the AC and the PFC combined coincided with the time course of the large-scale MMN-like signals reported in the rat brain, thereby linking the microscopic, mesoscopic and macroscopic levels of automatic deviance detection.