Miracle-dz/UniFAR-FTUs huggingface dataset:
Temperature-dependent effects of house fly proto-Y chromosomes on gene expression act independently of the sex determination pathway

Sex determination, the developmental process by which sexually dimorphic phenotypes are established, evolves fast. Species with polygenic sex determination, in which master regulatory genes are found on multiple different proto-sex chromosomes, are informative models to study the evolution of sex determination. House flies are such a model system, with male determining loci possible on all six chromosomes and a female-determiner on one of the chromosomes as well. The distributions of the two most common male-determining proto-Y chromosomes across natural populations suggests that temperature variation is an important selection pressure responsible for maintaining polygenic sex determination in this species. To test that hypothesis, we used RNA-seq to identify temperature-dependent effects of the proto-Y chromosomes on gene expression. We find no evidence for ecologically meaningful temperature-dependent expression of sex determining genes between male genotypes, but we identified hundreds of other genes whose expression depends on the interaction between proto-Y chromosome genotype and temperature. Notably, genes with genotype-by-temperature interactions on expression are not enriched on the proto-sex chromosomes. Moreover, there is no evidence that temperature-dependent expression is driven by chromosome-wide expression divergence between the proto-Y and proto-X alleles. Therefore, if temperature-dependent gene expression is responsible for differences in phenotypes and fitness of proto-Y genotypes across house fly populations, these effects are driven by a small number of temperature-dependent alleles on the proto-Y chromosomes.
H3 K27M and EZHIP impede H3K27-methylation spreading by inhibiting allosterically stimulated PRC2

Diffuse midline gliomas and posterior fossa type-A ependymomas contain the highly recurrent histone H3 K27M mutation and the H3 K27M-mimic EZHIP, respectively. In vitro, H3 K27M and EZHIP are competitive inhibitors of Polycomb Repressive Complex 2 (PRC2) lysine methyltransferase activity. In vivo, these proteins reduce overall H3K27me3 levels, however residual peaks of H3K27me3 remain at CpG islands through an unknown mechanism. Here, we report that EZHIP and H3 K27M preferentially interact with an allosterically activated form of PRC2 in vivo. The formation of H3 K27M- and EZHIP-PRC2 complexes occurs at CpG islands containing H3K27me3 and impedes PRC2 and H3K27me3 spreading. While EZHIP is not found outside of placental mammals, we find that expression of human EZHIP reduces H3K27me3 in Drosophila melanogaster through a conserved molecular mechanism. Our results highlight the mechanistic similarities between EZHIP and H3 K27M in vivo and provide mechanistic insight for the retention of residual H3K27me3 in tumors driven by these oncogenes.
BrumiR: A toolkit for de novo discovery of microRNAs from sRNA-seq data

MicroRNAs (miRNAs) are small non-coding RNAs that are key players in the regulation of gene expression. In the last decade, with the increasing accessibility of high-throughput sequencing technologies, different methods have been developed to identify miRNAs, most of which rely on pre-existing reference genomes. However, when a reference genome is absent or is not of high quality, such identification becomes more difficult. In this context, we developed BrumiR, an algorithm that is able to discover miRNAs directly and exclusively from sRNA-seq data. We benchmarked BrumiR with datasets encompassing animal and plant species using real and simulated sRNA-seq experiments. The results demonstrate that BrumiR reaches the highest recall for miRNA discovery, while at the same time being much faster and more efficient than the state-of-the-art tools evaluated. The latter allows BrumiR to analyze a large number of sRNA-seq experiments, from plants or animals species. Moreover, BrumiR detects additional information regarding other expressed sequences (sRNAs, isomiRs, etc.), thus maximizing the biological insight gained from sRNA-seq experiments. Finally, when a reference genome is available, BrumiR provides a new mapping tool (BrumiR2ref) that performs an a posteriori exhaustive search to identify the precursor sequences. The code of BrumiR is freely available at https://github.com/camoragaq/BrumiR.
Targeted Achilles Tendon Training and Rehabilitation Using Personalized and Real-Time Multiscale Models of the Neuromusculoskeletal System

Musculoskeletal tissues, including tendons, are sensitive to their mechanical environment, with both excessive and insufficient loading resulting in reduced tissue strength. Tendons appear to be particularly sensitive to mechanical strain magnitude, and there appears to be an optimal range of tendon strain that results in the greatest positive tendon adaptation. At present, there are no tools that allow localized tendon strain to be measured or estimated in training or a clinical environment. In this paper, we first review the current literature regarding Achilles tendon adaptation, providing an overview of the individual technologies that so far have been used in isolation to understand in vivo Achilles tendon mechanics, including 3D tendon imaging, motion capture, personalized neuromusculoskeletal rigid body models, and finite element models. We then describe how these technologies can be integrated in a novel framework to provide real-time feedback of localized Achilles tendon strain during dynamic motor tasks. In a proof of concept application, Achilles tendon localized strains were calculated in real-time for a single subject during walking, single leg hopping, and eccentric heel drop. Data was processed at 250 Hz and streamed on a smartphone for visualization. Achilles tendon peak localized strains ranged from ∼3 to ∼11% for walking, ∼5 to ∼15% during single leg hop, and ∼2 to ∼9% during single eccentric leg heel drop, overall showing large strain variation within the tendon. Our integrated framework connects, across size scales, knowledge from isolated tendons and whole-body biomechanics, and offers a new approach to Achilles tendon rehabilitation and training. A key feature is personalization of model components, such as tendon geometry, material properties, muscle geometry, muscle-tendon paths, moment arms, muscle activation, and movement patterns, all of which have the potential to affect tendon strain estimates. Model personalization is important because tendon strain can differ substantially between individuals performing the same exercise due to inter-individual differences in these model components.
Host metabolic reprogramming in response to SARS-Cov-2 infection

Understanding the pathogenesis of SARS-CoV-2 is important for developing effective treatment strategies. Viruses hijack the host metabolism to redirect the resources for their replication and survival. How SARS-CoV-2 influences the host metabolism is still unclear. In this study, we analyzed transcriptomic data obtained from different human respiratory cell lines and patient samples (Swab, PBMC, lung biopsy, BALF) to understand the metabolic alterations in response to SARS-CoV-2 infection. For this purpose, the expression pattern of metabolic genes in the human genome-scale metabolic network model Recon3D was explored. We identified metabolic genes and pathways and reporter metabolites under each SARS-CoV-2-infected condition and compared them to identify common and unique changes in the metabolism. Our analysis revealed host-dependent dysregulation of glycolysis, mitochondrial metabolism, amino acid metabolism, glutathione metabolism, polyamine synthesis, and lipid metabolism. We observed different metabolic changes that are pro- and antiviral in nature. We generated hypotheses on how antiviral metabolism can be targeted/enhanced for reducing viral titers. These warrant further exploration with more samples and in vitro studies to test predictions.
Assessment of Knowledge Levels Following an Education Program for Parents of Children With Inflammatory Bowel Disease

Children with inflammatory bowel disease (IBD) and their parents have increasing roles in disease management and require sufficient, appropriate information for communication with their clinical team. Formal education is effective at improving disease knowledge, disease outcomes, and mental health, yet few interventions have been targeted for parents of children with IBD. A two day parent education program was held at the annual residential camp for children with IBD in New Zealand with knowledge levels tested pre and post intervention using a validated assessment tool: IBD-KID2. Thirty parents consented, 25 completed the study, 70% were female and 83% had a child with Crohn's disease. The pre-intervention mean score (maximum fifteen) was 10.6 (SD 2.9), with no associations with independent variables. Knowledge levels increased significantly following the education program to a mean 12.6 (SD 2.0) (p < 0.005). Disease specific knowledge may improve outcomes and should, therefore, be reinforced during clinic encounters, and regarded as an ongoing endeavor.
Changes in a Cone Opsin Repertoire Affect Color-Dependent Social Behavior in Medaka but Not Behavioral Photosensitivity

Common ancestors of vertebrates had four types of cone opsins: short-wavelength sensitive 1 (SWS1), SWS2, rhodopsin 2 (RH2), and long-wavelength sensitive (LWS) types. Whereas fish and birds retain all the types, mammals have lost two of them (SWS2 and RH2) possibly because of their nocturnal lifestyle during the Mesozoic Era. Considering that the loss of cone opsin types causes so-called color blindness in humans (e.g., protanopia), the ability to discriminate color by trichromatic humans could be lower than that in potentially tetrachromatic birds and fish. Behavioral studies using color-blind (cone opsin-knockout) animals would be helpful to address such questions, but it is only recently that the genome-editing technologies have opened up this pathway. Using medaka as a model, we introduced frameshift mutations in SWS2 (SWS2a and/or SWS2b) after detailed characterization of the loci in silico, which unveiled the existence of a GC–AG intron and non-optic expressed-sequence-tags (ESTs) that include SWS2a in part. Transcripts from the mutated SWS2 loci are commonly reduced, suggesting that the SWS2a/b-double mutants could produce, if any, severely truncated (likely dysfunctional) SWS2s in small amounts. The mutants exhibited weakened body color preferences during mate choice. However, the optomotor response (OMR) test under monochromatic light revealed that the mutants had no defect in spectral sensitivity, even at the absorbance maxima (λmax) of SWS2s. Evolutionary diversification of cone opsins has often been discussed in relation to adaptation to dominating light in habitats (i.e., changes in the repertoire or λmax are for increasing sensitivity to the dominating light). However, the present results seem to provide empirical evidence showing that acquiring or losing a type of cone opsin (or changes in λmax) need not substantially affect photopic or mesopic sensitivity. Other points of view, such as color discrimination of species-specific mates/preys/predators against habitat-specific backgrounds, may be necessary to understand why cone opsin repertories are so various among animals.
STAG2 loss-of-function affects short-range genomic contacts and modulates urothelial differentiation in bladder cancer cells

Cohesin exists in two variants, containing either STAG1 or STAG2. STAG2 is one of the most commonly mutated genes in human cancer, and a major bladder cancer tumor suppressor. Little is known about how its inactivation contributes to tumor development. Here, we analyze the genomic distribution of STAG1 and STAG2 and perform STAG2 loss-of-function experiments using RT112 bladder cancer cells; we then analyze the resulting genomic effects by integrating gene expression and chromatin interaction data. Cohesin-STAG2 is required for DNA contacts within topological domains, but not for compartment maintenance of domain boundary integrity. Cohesin-STAG2-mediated interactions are short-ranged and engage promoters and gene bodies with higher frequency than those mediated by cohesin-STAG1. STAG2 knockdown resulted in a modest but consistent down-regulation of the luminal urothelial differentiation signature, mirroring differences between STAG2-high and STAG2-low bladder tumors. Both lost and gained contacts were enriched among STAG1/STAG2 common sites as well as STAG2-enriched sites. Contacts lost upon depletion of STAG2 were significantly assortative, indicating their proximity at the 3D level, and were associated with changes in gene expression. Overall, our findings indicate that, in urothelial cells, STAG2 is required for the establishment and/or maintenance of DNA looping that, in turn, sustains the luminal differentiation program. This mechanism may contribute to the tumor suppressor function of STAG2 in bladder cancer.
CAR T Cell Therapy for Pediatric Brain Tumors

Chimeric Antigen Receptor (CAR) T cell therapy has recently begun to be used for solid tumors such as glioblastoma multiforme. Many children with pediatric malignant brain tumors develop extensive long-term morbidity of intensive multimodal curative treatment. Others with certain diagnoses and relapsed disease continue to have limited therapies and a dismal prognosis. Novel treatments such as CAR T cells could potentially improve outcomes and ameliorate the toxicity of current treatment. In this review, we discuss the potential of using CAR therapy for pediatric brain tumors. The emerging insights on the molecular subtypes and tumor microenvironment of these tumors provide avenues to devise strategies for CAR T cell therapy. Unique characteristics of these brain tumors, such as location and associated morbid treatment induced neuro-inflammation, are novel challenges not commonly encountered in adult brain tumors. Despite these considerations, CAR T cell therapy has the potential to be integrated into treatment schema for aggressive pediatric malignant brain tumors in the future.
Optimal Operational Decision Making of Manufacturers and Authorized Remanufacturers with Patent Licensing under Carbon Cap-and-Trade Regulations

Constrained by production capacity and the pressure to reduce emissions, many original equipment manufacturers (OEMs) authorize third-party remanufacturers (TPRs) to remanufacture patented products. We investigate the operational decisions of OEMs and authorized TPRs under carbon cap-and-trade regulations in a two-echelon supply chain. We first formulate an operational decision model for OEMs before a TPR enters. Then, for the cases of centralized and decentralized decision making, we formulate an operational decision-making model for the TPR and, subsequently, establish one for the OEM after the TPR enters. We further analyze the effects of carbon emissions cap, trading price of carbon permits, yield rate, and consumer willingness to pay (WTP) on optimal decisions. Our results indicate: whether TPRs accept authorization remanufacturing depending on the ratio of carbon emissions cap to carbon emissions for producing per remanufactured product; royalty rate is negatively affected by trading price of carbon permits and per remanufactured product’ carbon emissions other than that for per new product, and can offset the threat caused by TPRs; the implementation of carbon cap-and-trade regulations causes OEMs to charge TPRs lower royalty rate; centralized decision making increases the total profit of the supply chain and delivers superior environmental benefits. As yield rate and WTP increase, the total profit increases, increasingly sensitive to WTP.
Polyp detection using CNNs in colonoscopy video

Polyps are a group of cells growing on the inner surface of the colon. Over time, some polyps can lead to colon cancer, which is often fatal if found in its later stages. Colon cancer can be prevented if the polyps are identified and removed in their early stages. Colonoscopy is a very effective screening method to remove polyps and it largely prevents colon cancer. However, some polyps may not be detected during a colonoscopy due to human error. Over the past two decades, many studies have been conducted on computer-aided detection to reduce the miss rate of polyps. This study consists of two distinct parts, the detection of frames containing polyps and polyp segmentation. In the first section, a new convolutional neural network based on the VGG network is proposed. The proposed network has an accuracy of 86% on a newly collected dataset. In the polyp segmentation section, a fully convolutional network and an effective post-processing algorithm are presented. An evaluation of the proposed polyp segmentation system on the ETIS-LARIB database achieves an overall 82.00% F2 score, which outperforms the methods that participated in the sub-challenge of MICCAI.
Multiomics analysis reveals extensive epigenome remodeling during cortical development

Despite huge advances in stem-cell, single-cell and epigenetic technologies, the precise molecular mechanisms that determine lineage specification remain largely unknown. Applying an integrative multiomics approach, e.g. combining single-cell RNA-seq, single-cell ATAC-seq together with cell-type-specific DNA methylation and 3D genome measurements, we systematically map the regulatory landscape in the mouse neocortex in vivo. Our analysis identifies thousands of novel enhancer-gene pairs associated with dynamic changes in chromatin accessibility and gene expression along the differentiation trajectory. Crucially, we provide evidence that epigenetic remodeling generally precedes transcriptional activation, yet true priming appears limited to a subset of lineage-determining enhancers. Notably, we reveal considerable heterogeneity in both contact strength and dynamics of the generally cell-type-specific enhancer-promoter contacts. Finally, our work suggests a so far unrecognized function of several key transcription factors which act as putative “molecular bridges” and facilitate the dynamic reorganization of the chromatin landscape accompanying lineage specification in the brain.
Songbirds can learn flexible contextual control over syllable sequencing

The flexible control of sequential behavior is a fundamental aspect of speech, enabling endless reordering of a limited set of learned vocal elements (i.e. syllables or words). Songbirds are phylogenetically distant from humans, but share the capacity for vocal learning as well as neural circuitry for vocal control that includes direct cortical-brainstem projections. Based on these similarities, we hypothesized that songbirds might likewise be able to learn flexible, moment-by-moment control over vocal production. Here, we demonstrate that Bengalese finches, which sing variable syllable sequences, can learn to rapidly modify the probability of specific sequences (e.g. ‘ab-c’ versus ‘ab-d’) in response to arbitrary visual cues. Moreover, once learned, this modulation of sequencing occurs immediately following changes in contextual cues and persists in the absence of external reinforcement. Our findings reveal a capacity in songbirds for learned contextual control over syllable sequencing that parallels aspects of human cognitive control over speech.
Interpretation of exercise-induced changes in human skeletal muscle mRNA expression depends on the timing of the post-exercise biopsies

Aim Exercise elicits a range of adaptive responses in skeletal muscle that include changes in mRNA expression. To better understand the health benefits of exercise training, it is essential to investigate the underlying molecular mechanisms of skeletal muscle adaptations to exercise. However, most studies have assessed the molecular events at a few convenient time points within a short time frame post exercise, and the variations of gene expression kinetics have not been addressed systematically. Method Muscle biopsies were collected from nine participants at baseline and six time points (0, 3, 9, 24, 48, and 72 h) following a session of high-intensity interval exercise. We assessed the mRNA content of 23 gene isoforms from the muscle samples. Result The temporal patterns of target gene expression were highly variable and the mRNA contents detected were largely dependent on the muscle sample timing. The maximal levels of mRNA content of all tested target genes were observed between 3 to 48 h post exercise. Conclusion Our findings highlight a critical gap in knowledge regarding the molecular response to exercise, where the use of a few time points within a short period after exercise has led to an incomplete understanding of the molecular responses to exercise. The timing of muscle sampling for individual studies needs to be carefully chosen based on existing literature and preliminary analysis of the molecular targets of interest. We propose that a comprehensive time-course analysis on the exercise-induced transcriptional response in humans will significantly benefit the field of exercise molecular biology.
In vitro Antibacterial Activity of Manilkara hexandra (Sapotaceae) Seed Extracts and Violacein against Multidrug Resistant Streptococcus mutans

Extracts of the Pongamia pinnata, Manilkara hexandra, and Pyrus pyrifolia seeds prepared by microwave assisted extraction method, and the violet pigment- violacein extracted from Chromobacterium violaceoum were screened for their antibacterial activity against Streptococcus mutans.M. hexandra extracts were able to inhibit both the test strains of S. mutans used in this study with minimum inhibitory concentration (MIC) ranging from 600-800 µg/mL. These extracts exerted bactericidal action against S. mutans with minimum bactericidal concentration (MBC) of 600-900 µg/mL. Acetone extract of M. hexandra seeds registered highest average total activity of 231.20 mL/g. Extraction efficiency was found to have a moderately good correlation with antibacterial activity. Violacein exerted bactericidal action with MIC and MBC of less than 2 µg/mL against both the strains.
A Polling-Based Dynamic Order-Picking System considering Priority Orders

Nowadays, how to offer extremely fast response to customer orders has become a major challenge for warehouse management, especially in e-commerce. Due to the time urgency aspect of some “VIP” orders that need priority processing, one of the most important issues for logistics distribution centres is how to improve the VIP order-picking priority without reducing the common order-picking efficiency. With this consideration, this article put forward a new priority polling model to describe and analyse this problem. We divide orders into priority and common categories according to their time urgency. A mathematical model is established for such a system by applying polling theory, a probability generating function, and an embedded Markov chain. Numerical analysis shows that this priority polling-based picking system can improve the picking efficiency and is well suited to practical operations.