Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome Wide Prediction, Mapping and Development of Genomic Resources of Mastitis Associated Genes in Water Buffalo

Water buffalo (Bubalus bubalis) are an important animal resource that contributes milk, meat, leather, dairy products, and power for plowing and transport. However, mastitis, a bacterial disease affecting milk production and reproduction efficiency, is most prevalent in populations having intensive selection for higher milk yield, especially where the inbreeding level is also high. Climate change and poor hygiene management practices further complicate the issue. The management of this disease faces major challenges, like antibiotic resistance, maximum residue level, horizontal gene transfer, and limited success in resistance breeding. Bovine mastitis genome wide association studies have had limited success due to breed differences, sample sizes, and minor allele frequency, lowering the power to detect the diseases associated with SNPs. In this work, we focused on the application of targeted gene panels (TGPs) in screening for candidate gene association analysis, and how this approach overcomes the limitation of genome wide association studies. This work will facilitate the targeted sequencing of buffalo genomic regions with high depth coverage required to mine the extremely rare variants potentially associated with buffalo mastitis. Although the whole genome assembly of water buffalo is available, neither mastitis genes are predicted nor TGP in the form of web-genomic resources are available for future variant mining and association studies. Out of the 129 mastitis associated genes of cattle, 101 were completely mapped on the buffalo genome to make TGP. This further helped in identifying rare variants in water buffalo. Eighty-five genes were validated in the buffalo gene expression atlas, with the RNA-Seq data of 50 tissues. The functions of 97 genes were predicted, revealing 225 pathways. The mastitis proteins were used for protein-protein interaction network analysis to obtain additional cross-talking proteins. A total of 1,306 SNPs and 152 indels were identified from 101 genes. Water Buffalo-MSTdb was developed with 3-tier architecture to retrieve mastitis associated genes having genomic coordinates with chromosomal details for TGP sequencing for mining of minor alleles for further association studies. Lastly, a web-genomic resource was made available to mine variants of targeted gene panels in buffalo for mastitis resistance breeding in an endeavor to ensure improved productivity and the reproductive efficiency of water buffalo.
Exploring the Mechanism Whereby Sinensetin Delays the Progression of Pulmonary Fibrosis Based on Network Pharmacology and Pulmonary Fibrosis Models

The incidence of pulmonary fibrosis (PF), a progressively fatal disease, has increased in recent years. However, there are no effective medicines available. Previous results have shown that sinensetin probably has some curative effects on PF. Therefore, this paper aims to predict the targets of sinensetin using a network pharmacology method and to confirm its effects and functional targets in PF using a mouse PF model. First, network pharmacology analysis showed that sinensetin has 105 functional targets, and 1,698 gene targets closely relate to PF. The intersection of the functional targets and gene targets produced 52 targets for the treatment of PF with sinensetin. The PPIs (protein–protein interactions) led to several potential key target genes, including MAPK1, EGFR, SRC, and PTGS2. The results of GO and KEGG analyses suggested the crucial function of apoptosis in PF and its involvement in the PI3K signaling pathway. Subsequently, we tested the molecular docking of sinensetin with the PI3K protein using the AutoDock4 software. The results showed that sinensetin could fit well into several binding sites of the PI3K protein. Furthermore, we constructed a PF mouse model through one-off intratracheal instillation of bleomycin and then intragastrically administered different concentrations of sinensetin to the model mice. Twenty-eight days later, the mice were sacrificed, and the lung tissues, serum, and bronchoalveolar lavage fluid (BALF) were collected. The in vivo tests showed that the body weight of model mice increased slightly compared with that of PF mice after intragastric sinensetin. HE and Masson staining suggested a certain extent of reduction in the pathology of lung tissues. The expression of collagens I and III, as well as hydroxyproline in the lung tissues, was reduced to a certain extent. IL-6 levels in the serum and BALF decreased markedly. The expression of vimentin and α-SMA in pulmonary tissues decreased. Cell apoptosis, as well as P-PI3K and P-AKT levels, in lung tissues also reduced. In summary, network pharmacology and in vivo test results suggest sinensetin causes an effective delay in the progression of pulmonary fibrosis, and the functional mechanism is likely related to PI3K-AKT signaling.
How a Big City Reduced the Genetic Diversity of Coyotes

The world’s cities are expanding at a very fast rate, taking over natural land inhabited by many different animals. It is very important that we monitor the impact this expansion is having on animals in and around our cities. Coyotes are the perfect species to study the effects of urbanization on wildlife, because they are found in both urban and natural environments. We examined how urbanization affects coyotes throughout the Los Angeles area in the United States. We discovered that urbanization influences where different groups of coyotes choose to live and that it also reduces the genetic diversity of coyotes. We should be concerned for the well-being of coyotes because low genetic diversity decreases the ability of any species to fight diseases and deal with other threats. We conclude that the coyote, a species formerly thought to be resistant to human disturbance, is in fact impacted by urbanization.
The Release of Nitric Oxide Is Involved in the β-Arrestin1-Induced Antihypertensive Effect in the Rostral Ventrolateral Medulla

β-Arrestin1 is a multifunctional scaffold protein with the ability to interact with diverse signaling molecules independent of G protein-coupled receptors. We previously reported that overexpression of β-arrestin1 in the rostral ventrolateral medulla (RVLM) decreased blood pressure (BP) and renal sympathetic nerve activity (RSNA) in spontaneously hypertensive rats (SHRs). Nitric oxide (NO) is widely reported to be involved in central cardiovascular regulation. The goal of this study was to investigate whether NO signaling contributes to the β-arrestin1-mediated antihypertensive effect in the RVLM. It was found that bilateral injection of adeno-associated virus containing Arrb1 gene (AAV-Arrb1) into the RVLM of SHRs significantly increased NO production and NO synthase (NOS) activity. Microinjection of the non-selective NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME; 10 nmol) into the RVLM prevented the β-arrestin1-induced cardiovascular inhibitory effect. Furthermore, β-arrestin1 overexpression in the RVLM significantly upregulated the expression of phosphorylated neuronal NOS (nNOS) by 3.8-fold and extracellular regulated kinase 1/2 (ERK1/2) by 5.6-fold in SHRs. The β-arrestin1-induced decrease in BP and RSNA was significantly abolished by treatment with ERK1/2 small interfering RNA (ERK1/2 siRNA). Moreover, ERK1/2 siRNA attenuated the β-arrestin1-induced NO production, NOS activity, and nNOS phosphorylation in the RVLM. Taken together, these data demonstrate that the antihypertensive effect of β-arrestin1 in the RVLM is mediated by nNOS-derived NO release, which is associated with ERK1/2 activation.
Highly Efficient CRISPR-Mediated Base Editing in Sinorhizobium meliloti

Rhizobia are widespread gram-negative soil bacteria and indispensable symbiotic partners of leguminous plants that facilitate the most highly efficient biological nitrogen fixation in nature. Although genetic studies in Sinorhizobium meliloti have advanced our understanding of symbiotic nitrogen fixation (SNF), the current methods used for genetic manipulations in Sinorhizobium meliloti are time-consuming and labor-intensive. In this study, we report the development of a few precise gene modification tools that utilize the CRISPR/Cas9 system and various deaminases. By fusing the Cas9 nickase to an adenine deaminase, we developed an adenine base editor (ABE) system that facilitated adenine-to-guanine transitions at one-nucleotide resolution without forming double-strand breaks (DSB). We also engineered a cytidine base editor (CBE) and a guanine base editor (GBE) that catalyze cytidine-to-thymine substitutions and cytidine-to-guanine transversions, respectively, by replacing adenine deaminase with cytidine deaminase and other auxiliary enzymes. All of these base editors are amenable to the assembly of multiple synthetic guide RNA (sgRNA) cassettes using Golden Gate Assembly to simultaneously achieve multigene mutations or disruptions. These CRISPR-mediated base editing tools will accelerate the functional genomics study and genome manipulation of rhizobia.
Case Report: A Clinical and Genetic Analysis of Childhood Growth Hormone Deficiency With Familial Hypercholesterolemia

Background Growth hormone deficiency (GHD) is a developmental disorder in children characterized by low growth hormone (GH), short stature and unfavorable lipid profiles. Familial hypercholesteremia (FH) is an inborn disorder of low-density lipoprotein cholesterol (LDL-C) metabolism which results in premature cardiovascular events. The co-occurrence of GHD and FH, which may aggravate the hypercholesteremic condition in the affected individuals, had rarely been discussed in previous publication. Methods This work reports two cases of GHD with FH, and explores the lipid profiles of GHD children and their therapeutic response to recombinant human growth hormone (rhGH). The diagnosis of GHD is based on low peak GH level (<7 ng/mL) in GH provocation test. FH is diagnosed by high LDL-C level (≥ 4 mmol/L) and confirmed genetic mutations in the LDL-C metabolic pathway. We also searched all previously published metabolic studies on GHD children as of December 31, 2020. Information on their LDL-C, duration and dose of rhGH treatment were retrieved and summarized. Results The first case was a 5.3 year-old boy. His height was 103.6 cm (SDS = -2.29) and his peak GH in provocative test was 6.37 ng/mL. Additionally, his LDL-C was 4.80 mmol/L and he harbored a heterozygous mutation for the apolipoprotein B (APOB) gene (c.10579 C > T). The second case was a 9-year-old girl at the height of 117.3 cm (SDS = -2.91). Her GH peaked at 4.99 ng/mL in insulin-induced hypoglycemic test and 2.80 ng/mL in L-dopa test. Her LDL-C was 6.16 mmol/L, and she carried a mutated copy of the low-density lipoprotein receptor (LDLR) gene (c.809 G > A). Literature review indicated that GHD children suffered from higher baseline LDL-C, but it was significantly reduced after rhGH treatment. Conclusions FH should be considered if a GHD child has remarkably elevated LDL-C that cannot be attributed to low GH level alone. Genetic mutations in the LDL-C metabolic pathway prevent the body from effectively metabolizing lipids, thereby resulting in early-onset hypercholesteremia and probably playing a negative role in children’s growth.
. Cortical Thickness Adaptive Response to Mechanical Loading Depends on Periosteal Position and Varies Linearly With Loading Magnitude. Frontiers in Bioengineering and

The aim of the current study was to quantify the local effect of mechanical loading on cortical bone formation response at the periosteal surface using previously obtained µ CT data from a mouse tibia mechanical loading study. A novel image analysis algorithm was developed to quantify local cortical thickness changes ( (cid:49) Ct.Th) along the periosteal surface due to different peak loads (0N ≤ F ≤ 12N) applied to right-neurectomised mature female C57BL
Comparative Secretome Analyses of Mycoplasma bovis Virulent and Attenuated Strains Revealed MbovP0145 as a Promising Diagnostic Biomarker

Mycoplasmas are successful pathogens both in humans as well as in animals. In cattle, Mycoplasma bovis (M. bovis) is known to be responsible for serious health complications, including pneumonia, mastitis, and arthritis. However, M. bovis pathogenesis remains unclear. Secreted proteins of M. bovis could influence infection and modify host defense signaling pathways after they enter their extracellular space in the host micro-environment. Therefore, this study was aimed to compare the secretomes of M. bovis HB0801 virulent (P1) and attenuated (P150) strains and identify potential pathogenesis-related secreted proteins and biomarkers. The cells of P1 and P150 strains were grown in pleuropneumonia-like organism medium to log phase and then transferred to phosphate-buffered saline for 2 h. Then, the supernatant was analyzed by using label-free quantitative proteomics, and 477 potential secreted proteins were identified. Combined with the bioinformatics prediction, we found that 178 proteins were commonly secreted by the P1 and P150 strains, and 49 of them were encoded by mycoplasmal core genes. Additionally, 79 proteins were found to have a different abundance between the P1 and P150 strains. Among these proteins, 34 were more abundant and uniquely expressed in P1, indicating a possible association with the virulence of M. bovis. Three differentially secreted proteins, MbovP0145, MbovP0725, and MbovP0174, as well as one equally secreted protein, MbovP0481, as positive control and one protein of inner membrane, MbovP0310, as negative control were, respectively, cloned, expressed, and evaluated for antigenicity, subcellular location, and the secretion nature with their mouse antisera by western blotting and colony immunoblotting assay. Among them, MbovP0145 was confirmed to be more secreted by P1 than P150 strain, highly reactive with the antisera from naturally infected and P1 experimentally infected cattle but not with the P150 vaccinated calves, indicating its potential as a diagnostic antigen. In conclusion, these findings may represent the most extensive compilation of potentially secreted proteins in mycoplasma species and the largest number of differentially secreted proteins between the virulent and attenuated M. bovis strains to date and provide new insights into M. bovis pathogenesis and diagnosis.
Quantifying the Speed of Chromatophore Activity at the Single-Organ Level in Response to a Visual Startle Stimulus in Living, Intact Squid

The speed of adaptive body patterning in coleoid cephalopods is unmatched in the natural world. While the literature frequently reports their remarkable ability to change coloration significantly faster than other species, there is limited research on the temporal dynamics of rapid chromatophore coordination underlying body patterning in living, intact animals. In this exploratory pilot study, we aimed to measure chromatophore activity in response to a light flash stimulus in seven squid, Doryteuthis pealeii. We video-recorded the head/arms, mantle, and fin when squid were presented with a light flash startle stimulus. Individual chromatophores were detected and tracked over time using image analysis. We assessed baseline and response chromatophore surface area parameters before and after flash stimulation, respectively. Using change-point analysis, we identified 4,065 chromatophores from 185 trials with significant surface area changes elicited by the flash stimulus. We defined the temporal dynamics of chromatophore activity to flash stimulation as the latency, duration, and magnitude of surface area changes (expansion or retraction) following the flash presentation. Post stimulation, the response’s mean latency was at 50 ms (± 16.67 ms), for expansion and retraction, across all body regions. The response duration ranged from 217 ms (fin, retraction) to 384 ms (heads/arms, expansion). While chromatophore expansions had a mean surface area increase of 155.06%, the retractions only caused a mean reduction of 40.46%. Collectively, the methods and results described contribute to our understanding of how cephalopods can employ thousands of chromatophore organs in milliseconds to achieve rapid, dynamic body patterning.
Pathological Features of Enterovirus 71-Associated Brain and Lung Damage in Mice Based on Quantitative Proteomic Analysis

The outbreaks of enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) have emerged as an emergency of global health due to its association with fatal encephalitis and subsequent neurogenic pulmonary edema; however, the molecular characteristics and pathological features underlying EV71-associated encephalitis and pulmonary edema remain largely unknown. In this study, we performed a proteomic analysis of fresh brain and lung tissues from EV71-infected mice at 7 days post infection. We detected a perturbed expression of 148 proteins in the brain and 78 proteins in the lung after EV71 expression. Further analysis showed that the dysregulated proteins in the brain are involved in a variety of fundamental biological pathways, including complement and coagulation cascades, innate and adaptive immune responses, platelet activation, and nitrogen metabolism, and those proteins in the lung participate in innate and adaptive immune responses, phagosome, arginine biosynthesis, and hypoxia-inducible factor 1 signaling pathway. Our results suggested that immune activation, complement and coagulation dysfunction, platelet activation, imbalance of nitrogen metabolism, and hypoxia could be involved in the pathogenesis of EV71, which explains the major clinical manifestation of hyperinflammatory status of severe HFMD cases. Our study provides further understanding of the molecular basis of EV71 pathogenesis.
Heat Adaptation Induced Cross Protection Against Ethanol Stress in Tetragenococcus halophilus: Physiological Characteristics and Proteomic Analysis

Ethanol is a toxic factor that damages membranes, disturbs metabolism, and may kill the cell. Tetragenococcus halophilus, considered as the cell factory during the manufacture of traditional fermented foods, encounters ethanol stress, which may affect the viability and fermentative performance of cells. In order to improve the ethanol tolerance of T. halophilus, a strategy based on cross protection was proposed in the current study. The results indicated that cross protection induced by heat preadaptation (45°C for 1.5 h) could significantly improve the stress tolerance (7.24-fold increase in survival) of T. halophilus upon exposure to ethanol (10% for 2.5 h). Based on this result, a combined analysis of physiological approaches and TMT-labeled proteomic technology was employed to investigate the protective mechanism of cross protection in T. halophilus. Physiological analysis showed that the heat preadapted cells exhibited a better surface phenotype, higher membrane integrity, and higher amounts of unsaturated fatty acids compared to unadapted cells. Proteomic analysis showed that a total of 163 proteins were differentially expressed in response to heat preadaptation. KEGG enrichment analysis showed that energy metabolism, membrane transport, peptidoglycan biosynthesis, and genetic information processing were the most abundant metabolic pathways after heat preadaptation. Three proteins (GpmA, AtpB, and TpiA) involved in energy metabolism and four proteins (ManM, OpuC, YidC, and HPr) related to membrane transport were up-regulated after heat preadaptation. In all, the results of this study may help understand the protective mechanisms of preadaptation and contribute to the improvement of the stress resistance of T. halophilus during industrial processes.
Insights Into Chemical Reactions at the Beginning of the Universe: From HeH+ to H3 +

At the dawn of the Universe, the ions of the light elements produced in the Big Bang nucleosynthesis recombined with each other. In our present study, we have tried to mimic the conditions in the early Universe to show how the recombination process would have led to the formation of the first ever formed diatomic species of the Universe: HeH+, as well as the subsequent processes that would have led to the formation of the simplest triatomic species: H3 +. We have also studied some special cases: higher positive charge with fewer number of hydrogen atoms in a dense atmosphere, and the formation of unusual and interesting linear, dicationic He chains beginning from light elements He and H in a positively charged atmosphere. For all the simulations, the ab initio nanoreactor (AINR) dynamics method has been employed.
Simultaneous Assessment of Electroencephalography Microstates and Resting State Intrinsic Networks in Alzheimer's Disease and Healthy Aging

Electroencephalography (EEG) microstate topologies may serve as building blocks of functional brain activity in humans. Here, we studied the spatial and temporal correspondences between simultaneously acquired EEG microstate topologies and resting state functional MRI (rs-fMRI) intrinsic networks in 14 patients with Alzheimer's disease (AD) and 14 healthy age and sex matched controls. We found an anteriorisation of EEG microstates' topologies in AD patients compared with controls; this corresponded with reduced spatial expression of default mode and increased expression of frontal lobe networks in rs-fMRI. In a hierarchical cluster analysis the time courses of the EEG microstates were associated with the time courses of spatially corresponding rs-fMRI networks. We found prevalent negative correlations of time courses between anterior microstate topologies and posterior rs-fMRI components as well as between posterior microstate topology and anterior rs-fMRI components. These negative correlations were significantly more expressed in controls than in AD patients. In conclusion, our data support the notion that the time courses of EEG microstates underlie the temporal expression of rs-fMRI networks. Furthermore, our findings indicate that the anterior-to-posterior connectivity of microstates and rs-fMRI components may be reduced in AD, indicative of a break-down of long-reaching intrahemispheric connections.
Mindsets and Self-Concepts About Self-Regulated Learning: Their Relationships With Emotions, Strategy Knowledge, and Academic Achievement

Being a self-regulated learner and believing that deliberate strategy use might be an effective way of overcoming learning challenges is important for achieving academic success. Learners' self-theories about their abilities might explain why some students are more inclined to engage in self-regulated learning (SRL) than others. This study aims to investigate the relationships between students' mindsets and self-concepts about SRL and their correlation with enjoyment, boredom, strategy knowledge, and academic achievements. As covariates, we included gender, age, and academic track. We surveyed 244 students (46.3% female) from the lower secondary school level with a mean age of 14.57 years. The results revealed that mindsets about SRL support more adaptive learning emotions (i.e., higher enjoyment and lower boredom) and positively relate to students' strategy knowledge. The students' self-concepts about SRL are positively related to their enjoyment and academic achievements. Gender-specific differences between the students revealed a disadvantage for the boys, who had lower self-concepts about SRL, lower strategy knowledge, and lower academic achievements in comparison to the girls. Furthermore, the study also revealed that students in the lower academic track adhered more to a fixed mindset about SRL and had lower strategy knowledge than their peers in the higher academic track. Finally, we found an indirect relationship between mindset about SRL and academic achievement via self-concepts about SRL. Overall, our results emphasize the importance of students' mindsets and self-concepts about SRL for their learning and academic achievements.