Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Nanopore sequencing technology to differentiate Salmonella serotypes and serotype variants with the same or closely related antigenic formulae

Our previous study demonstrated that whole genome sequencing (WGS) data generated by Oxford Nanopore Technologies (ONT) can be used for rapid and accurate prediction of Salmnonella serotypes. However, one limitation is that established methods for WGS-based serotype prediction cannot differentiate certain serotypes and serotype variants with the same or closely related antigenic formulae. This study aimed to evaluate Nanopore sequencing and corresponding data analysis for differentiation of these serotypes and serotype variants, thus overcoming this limitation. Five workflows that combined different flow cells, library construction methods and basecaller models were evaluated and compared. The workflow that consisted of the R9 flow cell, rapid sequencing library construction kit and guppy basecaller with base modified model performed best for Single Nucleotide Polymorphism (SNP) analysis. With this workflow, as high as 99.98% matched the identity of the assembled genomes and only less than five high quality SNPs (hqSNPs) between ONT and Illumina sequencing data were achieved. SNP typing allowed differentiation of Choleraesuissensu stricto, Choleraesuis var. Kunzendorf, Choleraesuis var. Decatur, Paratyphi C, and Typhisuis that share the same antigenic formula 6,7:c:1,5. Prophage prediction further distinguished Orion var. 15+ and Orion var. 15+, 34+. Our study improves the readiness of ONT as a Salmonella subtyping and source tracking tool for food industry applications. Highlights Salmonella serotypes or serotype variants with the same antigenic formula were differentiated by SNP typing. Nanopore sequencing followed by phage prediction identified the Salmonella serotype variants caused by phage conversion. The latest ONT technology is capable of high fidelity SNP typing of Salmonella.
Structural characterization of LsrK to target quorum sensing and comparison between X-ray and homology model

Quorum sensing is being investigated as an alternative therapeutic strategy in antibacterial drug discovery to combat bacterial resistance. LsrK is an autoinducer-2 kinase, playing a key role in the phosphorylation of autoinducer-2 (AI-2) signalling molecules involved in quorum sensing. Inhibiting LsrK could result in reduced pathogenicity by interfering with the quorum sensing signalling. Previously, we have generated homology models to identify LsrK inhibitors using structure-based virtual screening and successfully found the first class of LsrK inhibitors. While conducting these studies, the crystal structure of LsrK was released providing us an opportunity to inspect the reliability and quality of our models. Structural analysis of crystal structure and homology models revealed the consistencies of constructed models with crystal structure in the structural fold and binding site. Further, binding characteristics and conformational changes are investigated using molecular dynamics. These simulations provided us insights into the protein function and flexibility that need to be considered during the structure-based drug design studies targeting LsrK.
Capture of Mouse and Human Stem Cells with Features of Formative Pluripotency

Pluripotent cells emerge via a naïve founder population in the blastocyst, acquire capacity for germline and soma formation, and then undergo lineage priming. Mouse embryonic stem (ES) cells and epiblast stem cells (EpiSCs) represent the initial naïve and final primed phases of pluripotency, respectively. Here we investigate the intermediate formative stage. Using minimal exposure to specification cues, we expand stem cells from formative mouse epiblast. Unlike ES cells or EpiSCs, formative stem (FS) cells respond directly to germ cell induction. They colonise chimaeras including the germline. Transcriptome analyses show retained pre-gastrulation epiblast identity. Gain of signal responsiveness and chromatin accessibility relative to ES cells reflect lineage capacitation. FS cells show distinct transcription factor dependencies from EpiSCs, relying critically on Otx2. Finally, FS cell culture conditions applied to human naïve cells or embryos support expansion of similar stem cells, consistent with a conserved attractor state on the trajectory of mammalian pluripotency.
The Flip Side of Distractibility—Executive Dysfunction in Functional Movement Disorders

Attention plays a crucial role in functional neurological disorders. Attention to the symptoms leads to their exacerbation and distraction to their improvement or even transitory disappearance. Objective: The aim was to test if the alerting, orienting and particularly the executive aspect of attention are affected in functional movement disorders. Methods: Thirty patients with a functional movement disorder, 30 patients with an organic movement disorder and 30 healthy controls performed the attention network test. Results: The alerting and orienting effects were normal, but executive control of attention under conflict was abnormal in patients with functional movement disorders, compared to patients with an organic movement disorder and healthy controls. Conclusion: Executive dysfunction seems to be an important secondary feature of functional movement disorders, due to the overutilization of attentional resources for explicit movement control. Furthermore, it provides an explanation for seemingly unrelated symptoms commonly associated with functional movement disorders, such as concentration difficulties and fatigue.
A dopamine gradient controls access to distributed working memory in monkey cortex

Dopamine is critical for working memory. However, its effects throughout the large-scale primate cortex are poorly understood. Here we report that dopamine receptor density per neuron, measured by receptor autoradiography in the macaque monkey cortex, displays a macroscopic gradient along the cortical hierarchy. We developed a connectome- and biophysically-based model for distributed working memory that incorporates multiple neuron types and a dopamine gradient. The model captures an inverted U-shaped dependence of working memory on dopamine. The spatial distribution of mnemonic persistent activity matches that observed in over 90 experimental studies. We show that dopamine filters out irrelevant stimuli by enhancing inhibition of pyramidal cell dendrites. The level of cortical dopamine can also determine whether memory encoding is through persistent activity or an internal synaptic state. Taken together, our work represents a cross-level understanding that links molecules, cell types, recurrent circuit dynamics and a core cognitive function distributed across the cortex.
Comprehensive Analysis of Respiratory Burst Oxidase Homologs (Rboh) Gene Family and Function of GbRboh5/18 on Verticillium Wilt Resistance in Gossypium barbadense

Respiratory burst oxidase homologs (Rbohs) play a predominant role in reactive oxygen species (ROS) production, which is crucial in plant growth, differentiation, as well as their responses to biotic and abiotic stresses. To date, however, there is little knowledge about the function of cotton Rboh genes. Here, we identified a total of 87 Rbohs from five sequenced Gossypium species (the diploids Gossypium arboreum, Gossypium raimondii, and Gossypium australe, and the allotetraploids Gossypium hirsutum and Gossypium barbadense) via BLAST searching their genomes. Phylogenetic analysis of the putative 87 cotton Rbohs revealed that they were divided into seven clades. All members within the same clade are generally similar to each other in terms of gene structure and conserved domain arrangement. In G. barbadense, the expression levels of GbRbohs in the CladeD were induced in response to a fungal pathogen and to hormones (i.e., jasmonic acid and abscisic acid), based upon which the main functional member in CladeD was discerned to be GbRboh5/18. Further functional and physiological analyses showed that the knock-down of GbRboh5/18 expression attenuates plant resistance to Verticillium dahliae infection. Combined with the molecular and biochemical analyses, we found less ROS accumulation in GbRboh5/18-VIGS plants than in control plants after V. dahliae infection. Overexpression of GbRboh5/18 in G. barbadense resulted in more ROS accumulation than in control plants. These results suggest that GbRboh5/18 enhances the cotton plants’ resistance against V. dahliae by elevating the levels of ROS accumulation. By integrating phylogenetic, molecular, and biochemical approaches, this comprehensive study provides a detailed overview of the number, phylogeny, and evolution of the Rboh gene family from five sequenced Gossypium species, as well as elucidating the function of GbRboh5/18 for plant resistance against V. dahliae. This study sheds fresh light on the molecular evolutionary properties and function of Rboh genes in cotton, and provides a reference for improving cotton’s responses to the pathogen V. dahliae.
Task Sensitivity in L2 English Speakers’ Syntactic Processing: Evidence for Good-Enough Processing in Self-Paced Reading

Native (L1) and second-language (L2) sentence processing can sometimes be shallow. A Good-Enough approach suggests that speakers may engage in shallow processing if the task permits. This study tests English native speakers and native Chinese L2 learners of English to explore whether different task demands affect their sentence processing. In a self-paced reading task, participants read globally or temporarily ambiguous sentences with relative clauses preceded by a matrix clause containing two noun phrases (NPs). Comprehension questions modulated task difficulty: Half the participants received comprehension questions that probed their interpretation of the relative clauses whereas the remaining half received superficial questions unrelated to the relative clauses. Task difficulty affected reading times at the point of disambiguation for both L1 and L2 participants. Additionally, participants’ attachment choices for globally ambiguous sentences were consistent with reading times of the disambiguating region in both L1 and L2 readers. The results suggest that both L1 and L2 syntactic processing is modulated by the task at hand. We argue for a similar treatment of shallowness for L1 and L2 speakers in models of sentence processing, along the lines of the Good-Enough approach to language processing.
Progesterone Receptor Signaling Selectively Modulates Cytokine-Induced Global Gene Expression in Human Cervical Stromal Cells

Preterm birth (PTB) is the leading cause of morbidity and mortality in infants <1 year of age. Intrauterine inflammation is a hallmark of preterm and term parturition; however, this alone cannot fully explain the pathobiology of PTB. For example, the cervix undergoes a prolonged series of biochemical and biomechanical events, including extracellular matrix (ECM) remodeling and mechanochemical changes, culminating in ripening. Vaginal progesterone (P4) prophylaxis demonstrates great promise in preventing PTB in women with a short cervix (<25 mm). We used a primary culture model of human cervical stromal fibroblasts to investigate gene expression signatures in cells treated with interleukin-1β (IL-1β) in the presence or absence of P4 following 17β-estradiol (17β-E2) priming for 7–10 days. Microarrays were used to measure global gene expression in cells treated with cytokine or P4 alone or in combination, followed by validation of select transcripts by semiquantitative polymerase chain reactions (qRT-PCR). Primary/precursor (MIR) and mature microRNAs (miR) were quantified by microarray and NanoString® platforms, respectively, and validated by qRT-PCR. Differential gene expression was computed after data normalization followed by pathway analysis using Kyoto Encyclopedia Genes and Genomes (KEGG), Panther, Gene Ontology (GO), and Ingenuity Pathway Analysis (IPA) upstream regulator algorithm tools. Treatment of fibroblasts with IL-1β alone resulted in the differential expression of 1432 transcripts (protein coding and non-coding), while P4 alone led to the expression of only 43 transcripts compared to untreated controls. Cytokines, chemokines, and their cognate receptors and prostaglandin endoperoxide synthase-2 (PTGS-2) were among the most highly upregulated transcripts following either IL-1β or IL-1β + P4. Other prominent differentially expressed transcripts were those encoding ECM proteins, ECM-degrading enzymes, and enzymes involved in glycosaminoglycan (GAG) biosynthesis. We also detected differential expression of bradykinin receptor-1 and -2 transcripts, suggesting (prominent in tissue injury/remodeling) a role for the kallikrein–kinin system in cervical responses to cytokine and/or P4 challenge. Collectively, this global gene expression study provides a rich database to interrogate stromal fibroblasts in the setting of a proinflammatory and endocrine milieu that is relevant to cervical remodeling/ripening during preparation for parturition.
Neonatal End-of-Life Symptom Management

Purpose of review: Despite advances in technology and treatment options, over 15,000 neonates die each year in the United States. The majority of the deaths, with some estimates as high as 80%, are the result of a planned redirection of care or comfort measures only approach to care. When curative or life-prolonging interventions are not available or have been exhausted, parents focus on preserving quality of life and eliminating needless suffering. Parents hope their child will have a peaceful death and will not feel pain. A significant component of end-of-life care is high quality symptom evaluation and management. It is important that neonatal providers are knowledgeable in symptom management to address common sources of suffering and distress for babies and their families at the end-of-life (EOL). Recent findings: Medically complex neonates with life-threatening conditions are a unique patient population and there is little research on end-of-life symptom assessment and management. While there are tools available to assess symptoms for adolescents and adults, there is not a recognized set of tools for the neonatal population. Nonetheless, it is widely accepted that neonates experience significant symptoms at end-of-life. Most commonly acknowledged manifestations are pain, dyspnea, agitation, and secretions. In the absence of data and established guidelines, there is variability in their clinical management. This contributes to provider discomfort and inadequate symptom control. Summary: End-of-life symptom assessment and management is an important component of neonatal end-of-life care. While there remains a paucity of studies and data, it is prudent that providers adequately manage symptoms. Likewise, it is important that providers are educated so that they can effectively guide families through the dying process by discussing disease progression, physical changes, and providing empathetic support. In this review, the authors make recommendations for non-pharmacological and pharmacological management of end-of-life symptoms in neonates.
Effectiveness of using a hybrid rye cultivar in feeding broiler chickens

Abstract: The aim of this research was to evaluate the effectiveness of the use of hybrid rye in rations for broiler chickens. The study covered 160 chickens split into four equal groups [I (control), II, III, IV] and kept for 42 d. Rye was introduced into the above-mentioned diets as a partial substitute for maize in the following quantities: (I), no rye; (II), 5% rye in starter feed and 10% rye in grower and finisher feed; (III), 10% rye in starter feed and 20% rye in grower and finisher feed; (IV), 15% rye in starter feed and 30% rye in grower and finisher feed. During the 42 d rearing period, the most favourable body weight gain (P ≤ 0.05) and feed conversion ratio (P ≤ 0.01) were observed in chickens fed with rations containing the highest share of hybrid rye (group IV). The rye did not affect the dressing percentage and muscularity but diversified the fatness of birds. The muscles of chickens from group IV showed higher (P ≤ 0.01) red saturation and lower (P ≤ 0.01) yellow saturation and hue compared with the muscle of birds receiving diets with the lowest rye content (group I). The results of the study show that the inclusion of hybrid rye can be recommended in broiler chicken diets at a share of 15% in starter feed and 30% in grower and finisher feed, respectively.
Substituting Far-Red for Traditionally Defined Photosynthetic Photons Results in Equal Canopy Quantum Yield for CO2 Fixation and Increased Photon Capture During Long-Term Studies: Implications for Re-Defining PAR

Far-red photons regulate shade avoidance responses and can have powerful effects on plant morphology and radiation capture. Recent studies have shown that far-red photons (700 to 750 nm) efficiently drive photosynthesis when added to traditionally defined photosynthetic photons (400–700 nm). But the long-term effects of far-red photons on canopy quantum yield have not yet been determined. We grew lettuce in a four-chamber, steady-state canopy gas-exchange system to separately quantify canopy photon capture, quantum yield for CO2 fixation, and carbon use efficiency. These measurements facilitate a mechanistic understanding of the effect of far-red photons on the components of plant growth. Day-time photosynthesis and night-time respiration of lettuce canopies were continuously monitored from seedling to harvest in five replicate studies. Plants were grown under a background of either red/blue or white light, each background with or without 15% (50 μmol m−2 s−1) of far-red photons substituting for photons between 400 and 700 nm. All four treatments contained 31.5% blue photons, and an equal total photon flux from 400 to 750 nm of 350 μmol m−2 s−1. Both treatments with far-red photons had higher canopy photon capture, increased daily carbon gain (net photosynthesis minus respiration at night), and 29 to 31% more biomass than control treatments. Canopy quantum yield was similar among treatments (0.057 ± 0.002 mol of CO2 fixed in gross photosynthesis per mole of absorbed photons integrated over 400 to 750 nm). Carbon use efficiency (daily carbon gain/gross photosynthesis) was also similar for mature plants (0.61 ± 0.02). Photosynthesis increased linearly with increasing photon capture and had a common slope among all four treatments, which demonstrates that the faster growth with far-red photon substitution was caused by enhanced photon capture through increased leaf expansion. The equivalent canopy quantum yield among treatments indicates that the absorbed far-red photons were equally efficient for photosynthesis when acting synergistically with the 400–700 nm photons.
TWIST1 and chromatin regulatory proteins interact to guide neural crest cell differentiation

Protein interaction is critical molecular regulatory activity underlining cellular functions and precise cell fate choices. Using TWIST1 BioID-proximity-labelling and network propagation analyses, we discovered and characterized a TWIST-chromatin regulatory module (TWIST1-CRM) in the neural crest cell (NCC). Combinatorial perturbation of core members of TWIST1-CRM: TWIST1, CHD7, CHD8, and WHSC1 in cell models and mouse embryos revealed that loss of the function of the regulatory module resulted in abnormal specification of NCCs and compromised craniofacial tissue patterning. Our results showed that in the course of cranial neural crest differentiation, phasic activity of TWIST1 and the interacting chromatin regulators promote the choice of NCC fate while suppressing neural stem cell fates, and subsequently enhance ectomesenchyme potential and cell motility. We have revealed the connections between TWIST1 and potential neurocristopathy factors which are functionally interdependent in NCC specification. Moreover, the NCC module participate in the genetic circuit delineating dorsal-ventral patterning of neural progenitors in the neuroepithelium.
QSIPrep: An integrative platform for preprocessing and reconstructing diffusion MRI

Diffusion-weighted magnetic resonance imaging (dMRI) has become the primary method for non-invasively studying the organization of white matter in the human brain. While many dMRI acquisition sequences have been developed, they all sample q-space in order to characterize water diffusion. Numerous software platforms have been developed for processing dMRI data, but most work on only a subset of sampling schemes or implement only parts of the processing workflow. Reproducible research and comparisons across dMRI methods are hindered by incompatible software, diverse file formats, and inconsistent naming conventions. Here we introduce QSIPrep, an integrative software platform for the processing of diffusion images that is compatible with nearly all dMRI sampling schemes. Drawing upon a diverse set of software suites to capitalize upon their complementary strengths, QSIPrep automatically applies best practices for dMRI preprocessing, including denoising, distortion correction, head motion correction, coregistration, and spatial normalization. Throughout, QSIPrep provides both visual and quantitative measures of data quality as well as “glass-box” methods reporting. Taken together, these features facilitate easy implementation of best practices for processing of diffusion images while simultaneously ensuring reproducibility.
Loss of Fgf-responsive Pea3 transcription factors results in ciliopathy-associated phenotypes during early zebrafish development

FGF signaling is used reiteratively during development and elicits several different responses, such as cell proliferation, differentiation, or migration. We parsed the complex FGF intracellular response by creating triple homozygous mutants in the Pea3 subgroup of ETS transcription factors, designated 3etv mutants. The Pea3 proteins Etv4 and Etv5 are expressed in areas of FGF activity; however, their role in FGF signal transduction as either positive or negative modulators of FGF activity was unclear. Using 3etv mutants, we found these genes act redundantly and have phenotypes consistent with known FGF defects in inner ear, pectoral fin, and posterior mesoderm development. Additionally, we uncovered a novel role for the FGF/Pea3 pathway during body axis straightening. 3etv larvae develop a curly-tail up (CTU) phenotype that we linked to mis-regulation of the polycystin and urotensin pathways, which have opposing actions to ensure a straight body orientation along the dorsal-ventral axis. We find that the Etv4/5 transcription factors act as positive regulators of FGF signaling and propose a model where Etv4/5 are required for cilia function downstream of Fgf8a. Summary Statement Pea3 transcription factor triple mutants reveal a role for FGF signaling in balancing polycystin and urotensin signaling to achieve a straight body axis.
Histone tails cooperate to control the breathing of genomic nucleosomes

Genomic DNA is packaged in chromatin, a dynamic fiber variable in size and compaction. In chromatin, repeating nucleosome units wrap 146 DNA basepairs around histone proteins. Genetic and epigenetic regulation of genes relies on structural transitions in chromatin which are driven by intra- and internucleosome dynamics and modulated by chemical modifications of the unstructured terminal tails of histones. Here we demonstrate how the interplay between histone H3 and H2A tails control ample nucleosome breathing motions. We monitored large openings of two genomic nucleosomes, and only moderate breathing of an engineered nucleosome in atomistic molecular simulations amounting to 18μs. Transitions between open and closed nucleosome conformations were driven by the displacement and changes in compaction of the two histone tails. These motions involved changes in the DNA interaction profiles of clusters of epigenetic regulatory aminoacids in the tails. Histone tail modulated nucleosome breathing is a key mechanism of chromatin dynamics.