Miracle-dz/UniFAR-FTUs huggingface dataset:
Semantic Relatedness Emerges in Deep Convolutional Neural Networks Designed for Object Recognition

Human not only can effortlessly recognize objects, but also characterize object categories into semantic concepts and construct nested hierarchical structures. Similarly, deep convolutional neural networks (DCNNs) can learn to recognize objects as perfectly as human; yet it is unclear whether they can learn semantic relatedness among objects that is not provided in the learning dataset. This is important because it may shed light on how human acquire semantic knowledge on objects without top-down conceptual guidance. To do this, we explored the relation among object categories, indexed by representational similarity, in two typical DCNNs (AlexNet and VGG11). We found that representations of object categories were organized in a hierarchical fashion, suggesting that the relatedness among objects emerged automatically when learning to recognize them. Critically, the emerged relatedness of objects in the DCNNs was highly similar to the WordNet in human, implying that top-down conceptual guidance may not be a prerequisite for human learning the relatedness among objects. Finally, the developmental trajectory of the relatedness among objects during training revealed that the hierarchical structure was constructed in a coarse-to-fine fashion, and evolved into maturity before the establishment of object recognition ability. Taken together, our study provides the first empirical evidence that semantic relatedness of objects emerged as a by-product of object recognition, implying that human may acquire semantic knowledge on objects without explicit top-down conceptual guidance. Significance Statement The origin of semantic concepts is in a long-standing debate, where top-down conceptual guidance is thought necessary to form the hierarchy structure of objects. Here we challenged this hypothesis by examining whether deep convolutional neural networks (DCNNs) for object recognition can emerge the semantic relatedness of objects with no relation information in training object datasets. We found that in the DCNNs representations of objects were organized in a hierarchical fashion, which was highly similar to WordNet in human. This finding suggests that top-down conceptual guidance may not be a prerequisite for human learning the relatedness among objects; rather, semantic relatedness of objects may emerge as a by-product of object recognition.
Global Analysis of Transcription Start Sites in the New Ovine Reference Genome (Oar rambouillet v1.0)

The overall aim of the Ovine FAANG project is to provide a comprehensive annotation of the new highly contiguous sheep reference genome sequence (Oar rambouillet v1.0). Mapping of transcription start sites (TSS) is a key first step in understanding transcript regulation and diversity. Using 56 tissue samples collected from the reference ewe Benz2616 we have performed a global analysis of TSS and TSS- Enhancer clusters using Cap Analysis Gene Expression (CAGE) sequencing. CAGE measures RNA expression by 5’ cap-trapping and has been specifically designed to allow the characterization of TSS within promoters to single-nucleotide resolution. We have adapted an analysis pipeline that uses TagDust2 for clean-up and trimming, Bowtie2 for mapping, CAGEfightR for clustering and the Integrative Genomics Viewer (IGV) for visualization. Mapping of CAGE tags indicated that the expression levels of CAGE tag clusters varied across tissues. Expression profiles across tissues were validated using corresponding polyA+ mRNA-Seq data from the same samples. After removal of CAGE tags with < 10 read counts, 39.3% of TSS overlapped with 5’ ends of 31,113 transcripts that had been previously annotated by NCBI (out of a total of 56,308 from the NCBI annotation). For 25,195 of the transcripts, previously annotated by NCBI, no TSS meeting stringent criteria were identified. A further 14.7% of TSS mapped to within 50bp of annotated promoter regions. Intersecting these predicted TSS regions with annotated promoter regions (±50bp) revealed 46% of the predicted TSS were ‘novel’ and previously un-annotated. Using whole genome bisulphite sequencing data from the same tissues we were able to determine that a proportion of these ‘novel’ TSS were hypo-methylated (32.2%) indicating that they are likely to be reproducible rather than ‘noise’. This global analysis of TSS in sheep will significantly enhance the annotation of gene models in the new ovine reference assembly. Our analyses provide one of the highest resolution annotations of transcript regulation and diversity in a livestock species to date.
Development of a growth coupled dynamic regulation network balancing malonyl-CoA node to enhance (2S)-naringenin synthesis in E. coli

Generally, high- and low-performance nongenetic variants and young and aged cells co-existed in culture at all growth phases. In this regard, individually and dynamically regulating the metabolic flux of single cells based on their cellular state is highly useful for improving the performance of populations. However, balancing the trade-offs between biomass formation and compound over-production requires sophisticated dynamic regulation networks (DRNs) which can be challenging. Here, we developed a growth coupled NCOMB (Naringenin-Coumaric acid-Malonyl-CoA-Balanced) DRN with systematic optimization of (2S)-naringenin and p-coumaric acid-responsive regulation pathways for real-time control of intracellular supply of malonyl-CoA. In doing so, the acyl carrier protein was used as a new critical node for fine-tuning malonyl-CoA consumption instead of fatty acid synthase. Following directed evolution of the NCOMB DRN, we obtained a strain with cumulative 8.4-fold improvement in (2S)-naringenin production with balanced cell growth, demonstrating the high efficiency of this system for improving pathway production.
RED-BACKED VOLE (CLETHRIONOMYS GAPPERI) RESPONSE TO DISTURBANCE IN SUBALPINE FORESTS: USE OF REGENERATING PATCHES

Abstract We investigated scale-dependent habitat selection by the southern red-backed vole (Clethrionomys gapperi) in subalpine forests and 20- to 30-year-old regenerating timber harvests of the central Rocky Mountains. At the macrohabitat level, C. gapperi preferred forest stands, which had more overstory canopy cover, more uniformly distributed coarse woody debris (CWD), and more dwarf huckleberry (Vaccinium scoparium) than regenerating harvested stands. Further, C. gapperi was captured in forest stands up to harvest boundaries but crossed them significantly less than expected by chance. Analysis of microhabitat selection indicated that, in forest stands, C. gapperi showed selection at a fine spatial scale, strongly favoring CWD microhabitats and avoiding those dominated by V. scoparium. Our results suggest that older, regenerating clear-cuts in the Rocky Mountains can have clearly defined impacts on C. gapperi similar to those immediately after timber harvests, but that regenerating clear-cuts do support some use by C. gapperi. The results support the association of C. gapperi with CWD and forest overstory in western montane habitats and indicate a noticeable response to forest boundaries but no direct edge effect.
A Small interfering RNA lead targeting RNA-dependent RNA-polymerase effectively inhibit the SARS-CoV-2 infection in Golden Syrian hamster and Rhesus macaque

A small interfering RNA (siRNA) inhibitors have demonstrated the novel modality for suppressing infectious diseases. Sixty-one siRNA molecules, predicted by the bioinformatics programs, were screened for the possibility of treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using an in vitro plaque assay. Among six siRNA leads with the efficacy of reducing plaque number, the siRNA targeting RNA-dependent RNA polymerase (RdRp) showed a reduction in SARS-CoV-2 infection-induced fever and virus titer in the Golden Syrian hamster and rhesus macaque. These results suggest the potential for RdRp targeting siRNA as a new treatment for the coronavirus disease 2019 (COVID-19).
A Trypanosoma cruzi Zinc Finger protein that controls expression of epimastigote specific genes and affects metacyclogenesis

Trypanosoma cruzi has three biochemically and morphologically distinct developmental stages that are programed to rapidly respond to environmental changes the parasite faces during its life cycle. Unlike other eukaryotes, Trypanosomatid genomes contain protein coding genes that are transcribed into polycistronic pre-mRNAs and control of gene expression relies on mechanisms acting at the post-transcriptional level. Transcriptome analyses comparing epimastigote, trypomastigote and intracellular amastigote stages revealed changes in gene expression that reflect the parasite adaptation to distinct environments. Several genes encoding RNA binding proteins (RBP), known to act as key post-transcriptional regulatory factors, were also differentially expressed. We characterized one T. cruzi RBP (TcZH3H12) that contains a zinc finger domain, and whose transcripts are upregulated in epimastigotes compared to trypomastigotes and amastigotes. TcZC3H12 knockout epimastigotes showed decreased growth rates and increased capacity to differentiate into metacyclic trypomastigotes. Comparative transcriptome analysis revealed a TcZC3H12-dependent expression of epimastigote specific genes encoding amino acid transporters and proteins associated with differentiation (PAD), among others. RNA immunoprecipitation assays showed that transcripts from the PAD family interact with TcZC3H12. Taken together, these findings suggest that TcZC3H12 positively regulates the expression of genes involved in epimastigote proliferation and also acts as a negative regulator of metacyclogenesis.
Crash landing of Vibrio cholerae by MSHA pili-assisted braking and anchoring in a viscous environment

Mannose-sensitive hemagglutinin (MSHA) pili and flagellum are critical for the surface attachment of Vibrio cholerae. However, the cell landing mechanism remains largely unknown. Here, combining the cysteine-substitution-based labelling method with single-cell tracking techniques, we quantitatively characterized the landing of V. cholerae by directly observing both pili and flagellum of cells in viscous solutions. MSHA pili are evenly distributed along the cell length and can stick to surfaces at any point along the filament. With such properties, MSHA pili are observed to act as a brake and anchor during cell landing which include three phases: running, lingering, and attaching. Resistive-force-theory based models are proposed to describe near-surface motion. Importantly, the role of MSHA pili during cell landing is more apparent in viscous solutions. Our work provides a detailed picture of the landing dynamics of V. cholerae under viscous conditions, which can provide insights into ways to better control V. cholerae infections.
A model of traumatic brain injury using human iPSC-derived cortical brain organoids

Traumatic brain injury confers a significant and growing public health burden and represents a major environmental risk factor for dementia. Previous efforts to model traumatic brain injury and elucidate pathologic mechanisms have been hindered by complex interactions between multiple cell types, biophysical, and degenerative properties of the human brain. Here, we use high-intensity focused ultrasound to induce mechanical injury in 3D human pluripotent stem cell-derived cortical organoids to mimic traumatic brain injury in vitro. Our results show that mechanically injured organoids recapitulate key hallmarks of traumatic brain injury, phosphorylation of tau and TDP-43, neurodegeneration, and transcriptional programs indicative of energy deficits. We present high-intensity focused ultrasound as a novel, reproducible model of traumatic brain injury in cortical organoids with potential for scalable and temporally-defined mechanistic studies.
Neurofeedback Training of Auditory Selective Attention Enhances Speech-In-Noise Perception

Selective attention enhances cortical responses to attended sensory inputs while suppressing others, which can be an effective strategy for speech-in-noise (SiN) understanding. Here, we introduce a training paradigm designed to reinforce attentional modulation of auditory evoked responses. Subjects attended one of two speech streams while our EEG-based attention decoder provided online feedback. After four weeks of this neurofeedback training, subjects exhibited enhanced cortical response to target speech and improved performance during a SiN task. Such training effects were not found in the Placebo group that underwent attention training without neurofeedback. These results suggest an effective rehabilitation for SiN deficits.
Calumenin contributes to epithelial-mesenchymal transition and predicts poor survival in glioma

Abstract Background Calumenin (CALU) has been reported to be associated with invasiveness and metastasis in some malignancies. However, in glioma, the role of CALU remains unclear. Methods Clinical and transcriptome data of 998 glioma patients, including 301 from CGGA and 697 from TCGA dataset, were included. R language was used to perform statistical analyses. Results CALU expression was significantly upregulated in more malignant gliomas, including higher grade, IDH wildtype, mesenchymal, and classical subtype. Gene Ontology analysis revealed that CALU-correlated genes were mainly enriched in cell/biological adhesion, response to wounding, and extracellular matrix/structure organization, all of which were strongly correlated with the epithelial-mesenchymal transition (EMT) phenotype. GSEA further validated the profound involvement of CALU in EMT. Subsequent GSVA suggested that CALU was particularly correlated with three EMT signaling pathways, including TGFβ, PI3K/AKT, and hypoxia pathway. Furthermore, CALU played synergistically with EMT key markers, including N-cadherin, vimentin, snail, slug, and TWIST1. Survival and Cox regression analysis showed that higher CALU predicted worse survival, and the prognostic value was independent of WHO grade and age. Conclusions CALU was correlated with more malignant phenotypes in glioma. Moreover, CALU seemed to serve as a pro-EMT molecular target and could contribute to predict prognosis independently in glioma.
NCBP3 is a productive mRNP component

The nuclear Cap Binding Complex (CBC), consisting of Nuclear Cap Binding Protein 1 (NCBP1) and 2 (NCBP2), associates with the nascent 5’cap of RNA polymerase II transcripts and impacts RNA fate decisions. Recently, the C17orf85 protein, also called NCBP3, was suggested to form an alternative CBC by replacing NCBP2. However, applying protein-protein interaction screening of NCBP1, 2 and 3, we find that the interaction profile of NCBP3 is distinct. Whereas NCBP1 and 2 identify known CBC interactors, NCBP3 primarily interacts with components of the Exon Junction Complex (EJC) and the TRanscription and EXport (TREX) complex. NCBP3-EJC association in vitro and in vivo requires EJC core integrity and the in vivo RNA binding profiles of EJC and NCBP3 overlap. We further show that NCBP3 competes with the RNA degradation factor ZC3H18 for binding CBC-bound transcripts, and that NCBP3 positively impacts the nuclear export of polyadenylated RNAs and the expression of large multi-exonic transcripts. Collectively, our results place NCBP3 with the EJC and TREX complexes in supporting the productive fate of mRNA.
Systematic Analysis of the Eocene Primate Family Omomyidae Using Gnathic and Postcranial Data

Abstract Relationships within the primate order Omomyidae are assessed with dental and postcranial data, using cladistic techniques. Quantitative and qualitative characters of the dentition, mandible, maxilla and, where known, calcaneus and astragalus were evaluated for 28 omomyid species. Characters were subjected to a series of parsimony analyses including dental only, and combined dental and postcranial data, as well as evaluations with limited and expanded numbers of taxa. Trees were rooted through the use of a hypothetical outgroup taxon consisting of closely related primate and nonprimate taxa. Tarsal elements showed variability within the Omomyidae and this variability contained phylogenetic signal. When all dental and postcranial data were evaluated cladistically, omomyids prove to consist of three subfamilies: Omomyinae, Anaptomorphinae, and Microchoerinae. The omomyines consist of the tribes Washakiini, Uintaniini, Omomyini and Macrotarsiini, whereas the anaptomorphines consist of a paraphyletic Trogolemurini and Anaptomorphini. The European subfamily Microchoerinae seems more closely related to Anaptomorphinae. Species traditionally allocated to the genus Teilhardina are paraphyletic and may warrant generic distinction. Taxonomic actions include the descriptions of Arapahoviina Tornow new subtribe and Bazius Tornow new genus, and transfer of Loveinia wapitiensis Gunnell, Bartels, Gingerich and Torres, 1992 to the new genus as Bazius wapitiensis new combination.
Genomic Estimation Of Heritability Under Different Gene Action Scenarios

Different versions of genomic models are proposed to predict breeding values for animals using dense markers. However, so far little attention has been payed to estimating the genomic explained variance from the data, or to compare ”genomic” heritability estimates with pedigree-based heritability estimates. One group of genomic models is based on mixed models, using markers to build genomic relationship matrices (e.g., Garrick (2007), VanRaden (2008)). These models could be straightforwardly applied to estimate genomic (co)variances and heritabilities by REML, but have limited possibilities for extensions. For instance, extensions to multi-trait estimation, to add interaction variances, or to estimate genomic (co)variances by chromosome would result in an unmanageably large number of relationship matrices and (co)variance components to deal with. Also, these genomic relationship matrices may be singular, requiring bending which effectively reduces the off-diagonals, and then could be expected to lead to biases in genomic variance estimates.
Bidirectional Regulation of Cognitive and Anxiety-like Behaviors by Dentate Gyrus Mossy Cells in Male and Female Mice

The dentate gyrus (DG) of the hippocampus is important for cognition and behavior. However, the circuits underlying these functions are unclear. DG mossy cells (MCs) are potentially important because of their excitatory synapses on the primary cell type, granule cells (GCs). However, MCs also activate GABAergic neurons, which inhibit GCs. The dentate gyrus (DG) of the hippocampus is important for cognition and behavior. However, the circuits underlying these functions are unclear. DG mossy cells (MCs) are potentially important because of their excitatory synapses on the primary cell type, granule cells (GCs). However, MCs also activate GABAergic neurons, which inhibit GCs. We used viral delivery of designer receptors exclusively activated by designer drugs (DREADDs) in mice to implement a gain- and loss-of-function study of MCs in diverse behaviors. Using this approach, manipulations of MCs could bidirectionally regulate behavior. The results suggest that inhibiting MCs can reduce anxiety-like behavior and improve cognitive performance. However, not all cognitive or anxiety-related behaviors were influenced, suggesting specific roles of MCs in some, but not all, types of cognition and anxiety. Notably, several behaviors showed sex-specific effects, with females often showing more pronounced effects than the males. We also used the immediate early gene c-Fos to address whether DREADDs bidirectionally regulated MC or GC activity. We confirmed excitatory DREADDs increased MC c-Fos. However, there was no change in GC c-Fos, consistent with MC activation leading to GABAergic inhibition of GCs. In contrast, inhibitory DREADDs led to a large increase in GC c-Fos, consistent with a reduction in MC excitation of GABAergic neurons, and reduced inhibition of GCs. Together, these results suggest that MCs regulate anxiety and cognition in specific ways. We also raise the possibility that cognitive performance may be improved by reducing anxiety. SIGNIFICANCE STATEMENT The dentate gyrus (DG) has many important cognitive roles as well as being associated with affective behavior. This study addressed how a glutamatergic DG cell type called mossy cells (MCs) contributes to diverse behaviors, which is timely because it is known that MCs regulate the activity of the primary DG cell type, granule cells (GCs), but how MC activity influences behavior is unclear. We show, surprisingly, that activating MCs can lead to adverse behavioral outcomes, and inhibiting MCs have an opposite effect. Importantly, the results appeared to be task-dependent and showed that testing both sexes was important. Additional experiments indicated what MC and GC circuitry was involved. Together, the results suggest how MCs influence behaviors that involve the DG.
Differential expression of abscisic acid metabolism and signalling genes induced by seed-covering structures or hypoxia in barley (Hordeum vulgare L.) grains

Abstract Dormant barley grains cannot germinate at 30°C and this inability to germinate is imposed mostly by the glumellae which have been suggested to limit oxygen supply to the embryo. Hypoxia imposed either artificially or by the glumellae to embryos from dormant grains, increases embryo sensitivity to abscisic acid (ABA) and promotes the accumulation of ABA during the first hours after imbibition. Expression of candidate genes involved in ABA synthesis (HvNCED), catabolism (HvABA8OH1) and signalling (HvABI5, HvVP1 and HvPKABA) was analysed in embryos isolated from dormant whole or de-hulled grains incubated in air or in hypoxia (5% oxygen). The presence of the glumellae enhanced the expression of genes involved in ABA metabolism and signalling with respect to that observed in de-hulled grains incubated in air. These results suggest that at least part of the observed physiological responses to the presence of the glumellae are regulated at the level of gene expression. However, hypoxia imposed on dormant de-hulled grains did not mimic the presence of the glumellae in terms of expression of candidate genes. Hypoxia mimics the presence of the glumellae in terms of dormancy maintenance and ABA accumulation and sensitivity, but its effects appear to operate through different mechanisms.