Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental infection of domestic geese (Anser anser var. domesticus) with H5N8 Gs/GD and H7N1 highly pathogenic avian influenza viruses

ABSTRACT Prior to the emergence of the Asian-origin H5 Goose/Guangdong/1/96 (Gs/GD) lineage, highly pathogenic avian influenza viruses (HPAIV) had rarely caused high mortalities in domestic geese. In 2016/2017 European epidemics, H5N8 Gs/GD clade 2.3. 4.4 Group B produced an unprecedented number of outbreaks in waterfowl holdings. In this study, the pathogenesis of H5N8 HPAIV in comparison with H7N1 HPAIV, and the role of domestic geese in the epidemiology of these viruses, were evaluated. Local and commercial geese (Anser anser var. domesticus) were intranasally inoculated with 105 ELD50 of A/goose/Spain/IA17CR02699/2017 (H5N8) or A/Chicken/Italy/5093/1999 (H7N1) and monitored daily during 15 days. H5N8 was highly virulent to domestic geese, reaching 100% mortality by 10 days post-infection. Systemic microscopic necrotizing lesions associated with widespread AIV-antigen were detected by IHC techniques, the central nervous system being the most severely affected. High viral loads, measured by qRT-PCR, were present in all samples collected: oral and cloacal swabs, plasma tissues, and moderate levels in pool water. Domestic geese were also susceptible to H7N1 infection, as demonstrated by seroconversion and detection of viral RNA in tissues and plasma in some geese, but all lacked clinical signs. Viral shedding was confirmed in only some geese and was restricted to the oral route, but levels were high and still detected at the end of the study. Overall, H7N1 presents a lower lethality and shedding than H5N8 in geese; however, the viral shedding indicates that these species could play a role in the epidemiology of Gs/GD and other lineages of HPAIVs. RESEARCH HIGHLIGHTS H5N8 Gs/GD clade 2.3. 4.4 Group B is highly virulent to domestic geese. The severity of H5N8 is associated with multisystemic replication. H7N1 can infect domestic geese but is avirulent to this species. Domestic geese could play a role in the epidemiology of Gs/GD HPAIVs.
Mitochondrial DNA Copy Number is Associated with Attention Deficit Hyperactivity Disorder.

BACKGROUND Attention deficit hyperactivity disorder (ADHD) is the most common psychiatric disorder in children. Several hypotheses have been proposed to explain its etiology. Mitochondrial dysfunction (MD) is suggested to be one of the causes of Attention Deficit Hyperactivity Disorder. The objective of the study was to evaluate the relationship between MD and ADHD by investigating mitochondrial DNA (mtDNA) levels from peripheral blood leukocytes, one of the best biomarkers of mitochondrial dysfunction. SUBJECTS AND METHODS This study included 56 children aged 6-16 years who were diagnosed with ADHD for the first time and 56 age- and sex-matched children without ADHD. Real-time PCR was performed to determine the relative mtDNA copy number in each study participant. RESULTS The mean mtDNA copy number of the case group was 57.623±24.827 and that of the control group was 44.204±18.926 (p=0.002). The mtDNA copy number of the case group was higher than that of the control group. Results of ROC curve analysis provided a mtDNA cutoff value of 45. CONCLUSION Significantly higher mtDNA copy number in ADHD group may suggest mitochondrial dysfunction in the etiopathogenesis of ADHD.
Integrated Framework of the Immune-Defense Transcriptional Signatures in the Arabidopsis Shoot Apical Meristem

The growing tips of plants grow sterile; therefore, disease-free plants can be generated from them. How plants safeguard growing apices from pathogen infection is still a mystery. The shoot apical meristem (SAM) is one of the three stem cells niches that give rise to the above ground plant organs. This is very well explored; however, how signaling networks orchestrate immune responses against pathogen infections in the SAM remains unclear. To reconstruct a transcriptional framework of the differentially expressed genes (DEGs) pertaining to various SAM cellular populations, we acquired large-scale transcriptome datasets from the public repository Gene Expression Omnibus (GEO). We identify here distinct sets of genes for various SAM cellular populations that are enriched in immune functions, such as immune defense, pathogen infection, biotic stress, and response to salicylic acid and jasmonic acid and their biosynthetic pathways in the SAM. We further linked those immune genes to their respective proteins and identify interactions among them by mapping a transcriptome-guided SAM-interactome. Furthermore, we compared stem-cells regulated transcriptome with innate immune responses in plants showing transcriptional separation among their DEGs in Arabidopsis. Besides unleashing a repertoire of immune-related genes in the SAM, our analysis provides a SAM-interactome that will help the community in designing functional experiments to study the specific defense dynamics of the SAM-cellular populations. Moreover, our study promotes the essence of large-scale omics data re-analysis, allowing a fresh look at the SAM-cellular transcriptome repurposing data-sets for new questions.
SERINC5 Inhibits HIV-1 Infectivity by Altering the Conformation of gp120 on HIV-1 Particles

SERINC5 is a host cell protein that inhibits the infectivity of HIV-1 by a novel and poorly understood mechanism. Here, we provide evidence that the SERINC5 protein alters the conformation of the HIV-1 Env proteins and that this action is correlated with SERINC5’s ability to inhibit HIV-1 infectivity. Defining the specific effects of SERINC5 on the HIV-1 glycoprotein conformation may be useful for designing new antiviral strategies targeting Env. ABSTRACT SERINC5 is a 10-transmembrane-domain cellular protein that is incorporated into budding HIV-1 particles and reduces HIV-1 infectivity by inhibiting virus-cell fusion. HIV-1 susceptibility to SERINC5 is determined by sequences in the viral Env glycoprotein gp120, and the antiviral effect of SERINC5 is counteracted by the viral accessory protein Nef. While the precise mechanism by which SERINC5 inhibits HIV-1 infectivity is unclear, previous studies have suggested that SERINC5 affects Env conformation. To define the effects of SERINC5 on Env conformation, we quantified the binding of HIV-1 particles to immobilized Env-specific monoclonal antibodies. We observed that SERINC5 reduced the binding of HIV-1 particles bearing a SERINC5-susceptible Env to antibodies that recognize the V3 loop, a soluble CD4 (sCD4)-induced epitope, and an N-linked glycan. In contrast, SERINC5 did not alter the capture of HIV-1 particles bearing the SERINC5-resistant Env protein. Moreover, the effect of SERINC5 on antibody-dependent virus capture was abrogated by Nef expression. Our results indicate that SERINC5 inhibits HIV-1 infectivity by altering the conformation of gp120 on virions and/or physical masking of specific HIV-1 Env epitopes. IMPORTANCE SERINC5 is a host cell protein that inhibits the infectivity of HIV-1 by a novel and poorly understood mechanism. Here, we provide evidence that the SERINC5 protein alters the conformation of the HIV-1 Env proteins and that this action is correlated with SERINC5’s ability to inhibit HIV-1 infectivity. Defining the specific effects of SERINC5 on the HIV-1 glycoprotein conformation may be useful for designing new antiviral strategies targeting Env.
Influence of Photoperiod on the Accumulation of Metabolites during Diapause Induction in Cotesia vestalis (Haliday) (Hymenoptera: Braconidae)

Abstract Most insects must accumulate certain metabolites before entering diapause by virtue of photoperiodic regulation. Photoperiods influence diapause beyond the maternal generation in Cotesia vestalis (Haliday) (Hymenoptera: Braconidae), which is one of the most important larval endoparasitoid of Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae). The accumulation of metabolites in the non-diapausing prepupae, adults, and eggs (before and after oviposition) in progeny from C. vestalis cultures reared at 25°C under three photoperiods (8:16, 12:12, and 16:8 (L:D) hr), along with diapausing prepupae were measured to investigate the effects of photoperiod on the accumulation of metabolites during diapause induction. Compared with those of non-diapausing prepupae, free water, trehalose, total lipid titer, and total polyol contents in diapausing prepupae showed no significant differences; but weight, bound water, total sugar, glycogen, triglyceride, and protein contents were significantly higher. Under 8 hr short days, non-diapausing prepupae and adult females were significantly heavier, and held more bound water content, however, had less free water content than those under 16 hr long days; during diapause induction from maternal generation to progeny, the variation trends of triglyceride and protein contents were irregular, such as at one stage the contents under 8 hr short lights were higher, at another stage were lower, and there was even no difference at the other stage with those under long light. Total polyol (except at prepupal stage) increased with the increase of light period, but glycogen contents increased as the light period was reduced from prepupal, adult stages to egg stages (before and after oviposition) in progeny. These results revealed that in C. vestalis, the parasitoids might start accumulating glycogen, rather than other metabolites, before entering diapause, even at maternal generation influenced by short photoperiod. Meanwhile, lower total polyol content, and higher bound water content, dry weight under short light may be prepared for surviving adverse environments (desiccation and cold) after diapause. The condition experienced by maternal generation must be concerned during diapause induction.
Developments in the psychological treatment of anorexia nervosa and their implications for daily practice

Purpose of review Our aim is to give an overview of the recent literature on psychological treatment for young adults and adults with anorexia nervosa and to discuss the implications of the findings for clinical practice. Recent findings Three systematic reviews and meta-analyses have recently been published on psychological treatments for anorexia nervosa. Treatment outcomes are still modest and mainly focus on weight outcome, although outcomes for eating disorder disease and quality of life have also been reported. Adhering to a treatment protocol might lead to faster and better results. Summary For children and adolescents with anorexia nervosa, the major guidelines recommend a family-based treatment. The treatments of choice for young adults and adults with anorexia nervosa are the Maudsley Anorexia Nervosa Treatment for Adults (MANTRA), Cognitive Behaviour Therapy-Enhanced (CBT-E) and Specialist Supportive Clinical Management (SSCM), but none of these treatments seem to be superior. In search of other ways to improve outcome, shared decision making may be a way to help patients become more involved in their treatment, enhance their motivation and consequently improve the outcome.
HDAC6 regulates antibody-dependent intracellular neutralization of viruses via deacetylation of TRIM21

Tripartite motif–containing protein 21 (TRIM21) is a cytosolic antibody receptor that targets the internalized virus–antibody complex to the proteasome for degradation. However, the precise mechanism regulating TRIM21 activity is unknown. Here we show that TRIM21 is a substrate of histone deacetylase 6 (HDAC6) and that its function is regulated by acetylation. HDAC6 interacts with TRIM21 through its PRYSPRY motif and deacetylates TRIM21 at lysine 385 and lysine 387, thus promoting its homodimerization. Inhibiting HDAC6 activity increases TRIM21 acetylation, and hyperacetylation blocks TRIM21 dimerization and ubiquitination, preventing its binding to the virus–antibody complex and its degradation via the ubiquitin–proteasome pathway. HDAC6 depletion or inhibition increases virus accumulation in cells, indicative of an impaired capacity for antibody-dependent intracellular neutralization of viruses, whereas TRIM21 acetylation-deficient K385/387R mutant rescues HDAC6 depletion–caused ADIN impairment. These findings provide evidence for HDAC6 as a novel regulator of TRIM21-mediated intracellular innate immunity.
Heterologous expression of a glycosyl hydrolase and cellular reprogramming enable Zymomonas mobilis growth on cellobiose

Plant-derived fuels and chemicals from renewable biomass have significant potential to replace reliance on petroleum and improve global carbon balance. However, plant biomass contains significant fractions of oligosaccharides that are not usable natively by many industrial microorganisms, including Escherichia coli, Saccharomyces cerevisiae, and Zymomonas mobilis. Even after chemical or enzymatic hydrolysis, some carbohydrate remains as non-metabolizable oligosaccharides (e.g., cellobiose or longer cellulose-derived oligomers), thus reducing the efficiency of conversion to useful products. To begin to address this problem for Z. mobilis, we engineered a strain (Z. mobilis GH3) that expresses a glycosyl hydrolase (GH) with β-glucosidase activity from a related α-proteobacterial species, Caulobacter crescentus, and subjected it to an adaptation in cellobiose medium. Growth on cellobiose was achieved after a prolonged lag phase in cellobiose medium that induced changes in gene expression and cell composition, including increased expression and extracellular release of GH. These changes were reversible upon growth in glucose-containing medium, meaning they did not result from genetic mutation but could be retained upon transfer of cells to fresh cellobiose medium. After adaptation to cellobiose, our GH-expressing strain was able to convert about 50% of cellobiose to glucose within 24 h and use it for growth and ethanol production. Alternatively, pre-growth of Z. mobilis GH3 in sucrose medium enabled immediate growth on cellobiose. Proteomic analysis of cellobiose- and sucrose-adapted strains revealed upregulation of secretion-, transport-, and outer membrane-related proteins, which may aid release or surface display of GHs, entry of cellobiose into the periplasm, or both. Our two key findings are that Z. mobilis can be reprogrammed to grow on cellobiose as a sole carbon source and that this reprogramming is related to a natural response of Z. mobilis to sucrose that promotes sucrase production.
Near normalization of peripheral blood markers in HIV-infected patients on long-term suppressive antiretroviral therapy: a case-control study.

OBJECTIVE To explore the differences in peripheral blood markers between HIV well-controlled patients on long-term suppressive antiretroviral therapy (HIV-group) and age-matched healthy controls (HC), to evaluate the benefits of virological suppression in those patients. METHODS We performed a case-control study in 22 subjects in HIV-group and 14 in HC-group. RNA-seq analysis was performed from peripheral blood mononuclear cells (PBMCs). Peripheral blood T-cell subsets were evaluated by flow cytometry and plasma biomarkers by immunoassays. All p-values were corrected by the false discovery rate (FDR, q-values). RESULTS Only the serine/arginine repetitive matrix 4 (SRRM4) gene, which is involved in alternative RNA splicing events, was differentially expressed between HIV and HC groups (q-value≤0.05 and fold-change≥2). However, 147 differentially expressed genes were found with a more relaxed threshold (p-value≤0.05 and fold-change≥1.5), of which 67 genes with values of variable importance in projection (VIP)≥1 were selected for pathway analysis. We found that six ribosomal genes represented significant Ribosome-related pathways, all of them downregulated in the HIV-group, which may be a strategy to facilitate viral production. T-cells subset and plasma biomarkers did not show significant differences after FDR correction (q-value> 0.05), but a non-corrected analysis showed higher values of CD4 Treg cells (CD4CD25CD127), MCP-1, and sVEGF-R1 in the HIV-group (p-value≤0.05). CONCLUSIONS T-cell subsets, plasma biomarkers, and gene expression were close to normalization in HIV-infected patients on long-term suppressive cART compared to healthy controls. However, residual alterations remain, mainly at the gene expression, which still reveals the impact of HIV infection in these patients.
MiR‐134‐5p targeting XIAP modulates oxidative stress and apoptosis in cardiomyocytes under hypoxia/reperfusion‐induced injury

MicroRNA‐134‐5p (MiR‐134‐5p) has been proposed as a promising novel biomarker for the diagnosis of acute myocardial infarction (AMI). However, the biological role of miR‐134‐5p in ischemic cardiomyocytes has been little disclosed yet. Expression of miR‐134‐5p and X‐linked inhibitor of apoptosis protein (XIAP) was detected using RT‐qPCR and western blot. Oxidative stress and cell apoptosis were determined by enzyme‐linked immunosorbent assays, 3‐(4, 5‐dimethylthiazole‐2‐y1)‐2, 5‐biphenyl tetrazolium bromide assay, flow cytometry, western blot, and terminal‐deoxynucleoitidyl transferase‐mediated nick end labeling (TUNEL). The interaction between miR‐134‐5p and XIAP was confirmed by luciferase reporter assay. Expression of miR‐134‐5p was upregulated in serum of AMI patients and hypoxia/reoxygenation (H/R)‐induced cardiomyocytes (AC16 and HCM). MiR‐134‐5p downregulation could inhibit H/R‐mediated release of lactic dehydrogenase enzyme (LDH) and malondialdehyde (MDA), and promote superoxide dismutase (SOD) and glutathione peroxidase (GSH‐PX) levels. Meanwhile, cell viability was increased, while the apoptosis rate and TUNEL positive cells were inhibited by miR‐134‐5p downregulation in H/R‐treated AC16 and HCM cells. Mechanically, XIAP was downregulated and targeted by miR‐134‐5p in H/R‐induced cardiomyocytes in vitro. Overexpression of XIAP inhibited oxidative stress and cell apoptosis in H/R‐treated AC16 and HCM cells, which was similar to miR‐134‐5p knockdown. Moreover, downregulation of XIAP could partially reverse the effect of miR‐134‐5p knockdown in H/R‐induced cardiomyocytes. Knockdown of miR‐134‐5p protected cardiomyocytes from H/R‐induced oxidative stress and apoptosis in vitro through targeting XIAP.
Bone metastasis classification using whole body images from prostate cancer patients based on convolutional neural networks application

Bone metastasis is one of the most frequent diseases in prostate cancer; scintigraphy imaging is particularly important for the clinical diagnosis of bone metastasis. Up to date, minimal research has been conducted regarding the application of machine learning with emphasis on modern efficient convolutional neural networks (CNNs) algorithms, for the diagnosis of prostate cancer metastasis from bone scintigraphy images. The advantageous and outstanding capabilities of deep learning, machine learning's groundbreaking technological advancement, have not yet been fully investigated regarding their application in computer-aided diagnosis systems in the field of medical image analysis, such as the problem of bone metastasis classification in whole-body scans. In particular, CNNs are gaining great attention due to their ability to recognize complex visual patterns, in the same way as human perception operates. Considering all these new enhancements in the field of deep learning, a set of simpler, faster and more accurate CNN architectures, designed for classification of metastatic prostate cancer in bones, is explored. This research study has a two-fold goal: to create and also demonstrate a set of simple but robust CNN models for automatic classification of whole-body scans in two categories, malignant (bone metastasis) or healthy, using solely the scans at the input level. Through a meticulous exploration of CNN hyper-parameter selection and fine-tuning, the best architecture is selected with respect to classification accuracy. Thus a CNN model with improved classification capabilities for bone metastasis diagnosis is produced, using bone scans from prostate cancer patients. The achieved classification testing accuracy is 97.38%, whereas the average sensitivity is approximately 95.8%. Finally, the best-performing CNN method is compared to other popular and well-known CNN architectures used for medical imaging, like VGG16, ResNet50, GoogleNet and MobileNet. The classification results show that the proposed CNN-based approach outperforms the popular CNN methods in nuclear medicine for metastatic prostate cancer diagnosis in bones.
Blind Monaural Source Separation on Heart and Lung Sounds Based on Periodic-Coded Deep Autoencoder

Auscultation is the most efficient way to diagnose cardiovascular and respiratory diseases. To reach accurate diagnoses, a device must be able to recognize heart and lung sounds from various clinical situations. However, the recorded chest sounds are mixed by heart and lung sounds. Thus, effectively separating these two sounds is critical in the pre-processing stage. Recent advances in machine learning have progressed on monaural source separations, but most of the well-known techniques require paired mixed sounds and individual pure sounds for model training. As the preparation of pure heart and lung sounds is difficult, special designs must be considered to derive effective heart and lung sound separation techniques. In this study, we proposed a novel periodicity-coded deep auto-encoder (PC-DAE) approach to separate mixed heart-lung sounds in an unsupervised manner via the assumption of different periodicities between heart rate and respiration rate. The PC-DAE benefits from deep-learning-based models by extracting representative features and considers the periodicity of heart and lung sounds to carry out the separation. We evaluated PC-DAE on two datasets. The first one includes sounds from the Student Auscultation Manikin (SAM), and the second is prepared by recording chest sounds in real-world conditions. Experimental results indicate that PC-DAE outperforms several well-known separation works in terms of standardized evaluation metrics. Moreover, waveforms and spectrograms demonstrate the effectiveness of PC-DAE compared to existing approaches. It is also confirmed that by using the proposed PC-DAE as a pre-processing stage, the heart sound recognition accuracies can be notably boosted. The experimental results confirmed the effectiveness of PC-DAE and its potential to be used in clinical applications.
The Michael J. Fox Foundation’s Strategies for Accelerating Translation of LRRK2 into Therapies for Parkinson Disease

Since 2005, The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has invested significant funding and non-funding effort to accelerate research and drug development activity around the Parkinson disease (PD)-associated protein LRRK2. MJFF has spearheaded multiple public/private pre-competitive collaborations that have contributed to our understanding of LRRK2 function; de-risked potential safety questions around the therapeutic use of LRRK2 kinase inhibitors; and generated critical research tools, biosamples, and data for the field. Several LRRK2-targeted therapies are now in human testing due to the hard work of so many in the PD community. In this perspective, we present a holistic description and model of how our Foundation’s support targeted important barriers to LRRK2 research and helped move the field into clinical trials.