Miracle-dz/UniFAR-FTUs huggingface dataset:
Aerobic exercise training in Kartagener’s syndrome: case report

Kartagener’s syndrome is a rare, autosomal recessive inherited disease, which is characterized by a triad of chronic sinusitis, bronchiectasis, and situs inversus. In this report, we aimed to represent the effect of aerobic exercise training in addition to chest physiotherapy in an outpatient with Kartagener’s syndrome. An 18-year-old female diagnosed with Kartagener’s syndrome applied with the complaints of productive cough and dyspnea with exertion and attended pulmonary rehabilitation program comprising exercise training in addition to standard treatment. Aerobic exercise training was performed three times weekly at 80% of the peak heart rate, for 8 weeks as supervised sessions. Respiratory physiotherapy and postural exercises were taught to the patient to be performed at home each day of the week. Before and after pulmonary rehabilitation program, incremental shuttle walk test (ISWT) was performed; dyspnea and fatigue were assessed using Borg Scale. Pulmonary function test was evaluated using spirometer. The patient wore activity monitor for 7 consecutive days before and after training. After pulmonary rehabilitation program, 90-m increase in ISWT was observed. We recommend exercise training in patients with Kartagener’s syndrome to increase exercise capacity. Further randomized control trial is needed to clarify the effects.
RocA Binds CsrS To Modulate CsrRS-Mediated Gene Regulation in Group A Streptococcus

Bacterial two-component regulatory systems, comprising a membrane-bound sensor kinase and cytosolic response regulator, are critical in coordinating the bacterial response to changing environmental conditions. More recently, auxiliary regulators which act to modulate the activity of two-component systems, allowing integration of multiple signals and fine-tuning of bacterial responses, have been identified. RocA is a regulatory protein encoded by all serotypes of the important human pathogen group A Streptococcus. Although RocA is known to exert its regulatory activity via the streptococcal two-component regulatory system CsrRS, the mechanism by which it functions was unknown. Based on new experimental evidence, we propose a model whereby RocA interacts with CsrS in the streptococcal cell membrane to enhance CsrS autokinase activity and subsequent phosphotransfer to the response regulator CsrR, which mediates transcriptional repression of target genes. ABSTRACT The orphan regulator RocA plays a critical role in the colonization and pathogenesis of the obligate human pathogen group A Streptococcus. Despite multiple lines of evidence supporting a role for RocA as an auxiliary regulator of the control of virulence two-component regulatory system CsrRS (or CovRS), the mechanism of action of RocA remains unknown. Using a combination of in vitro and in vivo techniques, we now find that RocA interacts with CsrS in the streptococcal membrane via its N-terminal region, which contains seven transmembrane domains. This interaction is essential for RocA-mediated regulation of CsrRS function. Furthermore, we demonstrate that RocA forms homodimers via its cytoplasmic domain. The serotype-specific RocA truncation in M3 isolates alters this homotypic interaction, resulting in protein aggregation and impairment of RocA-mediated regulation. Taken together, our findings provide insight into the molecular requirements for functional interaction of RocA with CsrS to modulate CsrRS-mediated gene regulation. IMPORTANCE Bacterial two-component regulatory systems, comprising a membrane-bound sensor kinase and cytosolic response regulator, are critical in coordinating the bacterial response to changing environmental conditions. More recently, auxiliary regulators which act to modulate the activity of two-component systems, allowing integration of multiple signals and fine-tuning of bacterial responses, have been identified. RocA is a regulatory protein encoded by all serotypes of the important human pathogen group A Streptococcus. Although RocA is known to exert its regulatory activity via the streptococcal two-component regulatory system CsrRS, the mechanism by which it functions was unknown. Based on new experimental evidence, we propose a model whereby RocA interacts with CsrS in the streptococcal cell membrane to enhance CsrS autokinase activity and subsequent phosphotransfer to the response regulator CsrR, which mediates transcriptional repression of target genes.
Patterns of richness of freshwater mollusks from Chile: predictions of its distribution based on null models

The freshwater mussels from Chile are characterized by a high percentage of endemism and a fragmented latitudinal diversity, which has been attributed to the features and geomorphological history sculpted by the hydrographic basins. In this work, a set of hypothesis under a macroecological approach is addressed, with the aim to explore environmental, topographic and hydrological factors that define the latitudinal distribution of this mussel group. In order to achieve this goal, Rapoport’s rule, geometrics limits and co-ocurrence were evaluated. In addition, we analyze the source and sink hypotheses through the nested analysis. We observed a noticeable mid-domain effect (MDE), where a major richness than expected was randomly observed between 40 and 41°S. The results revealed that the distribution pattern was not concordant with Rapoport’s rule (r = 0.123; p = 0.128). Regarding to historical dynamic of the distribution, the results show a significant nestedness pattern, suggesting a source-sink dynamic, that is, poorer communities are a subset of richer communities in species. According to the co-occurrence analysis, an aggregate pattern existed, suggesting potential regulatory mechanisms. The specific richness pattern is explained by the variable seasonality of the temperature with a variance percentage explained of 35%. The full model indicated that variables which characterize the heterogeneity of habitat (i.e. range, Shannon), water availability (i.e., precipitation, density of water bodies) and topography (i.e., altitude area available) jointly explain 40% of the variability of the observed richness. This study shows that the geographical distribution of mollusc richness is mainly explained by mainly climatic and topographical environmental components, as well as by the source-sink dynamics.
Genome-wide identification and expression profiling of the C2H2-type zinc finger protein genes in the silkworm Bombyx mori

Cys2-His2 zinc finger (C2H2-ZF) proteins comprise the largest class of putative eukaryotic transcription factors. The zinc finger motif array is highly divergent, indicating that most proteins will have distinctive binding sites and perform different functions. However, the binding sites and functions of the majority of C2H2-ZF proteins remain unknown. In this study, we identified 327 C2H2-ZF protein genes in the silkworm, 290 in the monarch butterfly, 243 in the fruit fly, 107 in elegans, 673 in mouse, and 1,082 in human. The C2H2-ZF protein genes of the silkworm were classified into three main grouping clades according to a phylogenetic classification, and 312 of these genes could be mapped onto 27 chromosomes. Most silkworm C2H2-ZF protein genes exhibited specific expression in larval tissues. Furthermore, several C2H2-ZF protein genes had sex-specific expression during metamorphosis. In addition, we found that some C2H2-ZF protein genes are involved in metamorphosis and female reproduction by using expression clustering and gene annotation analysis. Among them, five genes were selected, BGIBMGA002091 (CTCF), BGIBMGA006492 (fru), BGIBMGA006230 (wor), BGIBMGA004640 (lola), and BIGBMGA004569, for quantitative real-time PCR analysis from larvae to adult ovaries. The results showed that the five genes had different expression patterns in ovaries, among which BGIBMGA002091 (CTCF) gene expression level was the highest, and its expression level increased rapidly in late pupae and adult stages. These findings provide a basis for further investigation of the functions of C2H2-ZF protein genes in the silkworm, and the results offer clues for further research into the development of metamorphosis and female reproduction in the silkworm.
An Undergraduate Research Project Utilizing CRISPR-Cas9 Gene Editing Technology to Study Gene Function in Arabidopsis thaliana†

The CRISPR-Cas9 system functions in microbial viral pathogen recognition pathways by identifying and targeting foreign DNA for degradation. Recently, biotechnological advances have allowed scientists to use CRISPR-Cas9-based elements as a molecular tool to selectively modify DNA in a wide variety of other living systems. Given the emerging need to bring engaging CRISPR-Cas9 laboratory experiences to an undergraduate audience, we incorporated a CRISPR-based research project into our Genetics class laboratories, emphasizing its use in plants. Our genetic manipulations were designed for Arabidopsis thaliana, which despite serving as a plant research model, has traditionally been difficult to use in a classroom setting. For this project, students transformed plasmid DNA containing the essential CRISPR-Cas9 gene editing elements into A. thaliana. Expression of these elements in the plant genome was expected to create a deletion at one of six targeted genes. The genes we chose had a known seedling and/or juvenile loss-of-function phenotype, which made genetic analysis by students with a limited background possible. It also allowed the project to reach completion in a typical undergraduate semester timeframe. Assessment efforts demonstrated several learning gains, including students’ understanding of CRISPR-Cas9 content, their ability to apply CRISPR-Cas9 gene editing tools using bioinformatics and genetics, their ability to employ elements of experimental design, and improved science communication skills. They also felt a stronger connection to their scientific education and were more likely to continue on a STEM career path. Overall, this project can be used to introduce CRISPR-Cas9 technology to undergraduates using plants in a single-semester laboratory course.
Undergraduates Phenotyping Arabidopsis Knockouts in a Course-Based Undergraduate Research Experience: Exploring Plant Fitness and Vigor Using Quantitative Phenotyping Methods

We present a curriculum description, an initial student outcome investigation, and sample scientific results for a representative Course-Based Undergraduate Research Experience (CURE) that is part of the “Undergraduates Phenotyping Arabidopsis Knockouts” (unPAK) network. CUREs in the unPAK network characterize quantitative phenotypes of the model plant Arabidopsis from across environments to uncover connections between genotype and phenotype. Students in unPAK CUREs grow plants in a replicated block design and make quantitative measurements throughout the semester. This CURE enables students to answer plant science questions that draw from fields such as environmental science, genetics, ecology, and evolution. Findings indicate that this experience provides students with opportunities to make relevant scientific discoveries. Eighty percent of student datasets produced from the CURE met criteria for inclusion in the project database, indicative of student learning in data collection and analysis of quantitative plant traits. Student datasets uncovered novel effects of mutation on plant form. In addition, students’ science self-efficacy increased as a result of course participation, and faculty feedback on course implementation was positive. We present unPAK as a new network that supports CUREs and research experiences focused on collecting biological data made publicly available to the scientific community. The unPAK CUREs can be tailored to address instructor interests or pedagogical needs while involving students in research investigating quantitative plant phenotypes.
Dorsal Striatal Circuits for Habits, Compulsions and Addictions

Here, we review the neural circuit bases of habits, compulsions, and addictions, behaviors which are all characterized by relatively automatic action performance. We discuss relevant studies, primarily from the rodent literature, and describe how major headway has been made in identifying the brain regions and neural cell types whose activity is modulated during the acquisition and performance of these automated behaviors. The dorsal striatum and cortical inputs to this structure have emerged as key players in the wider basal ganglia circuitry encoding behavioral automaticity, and changes in the activity of different neuronal cell-types in these brain regions have been shown to co-occur with the formation of automatic behaviors. We highlight how disordered functioning of these neural circuits can result in neuropsychiatric disorders, such as obsessive-compulsive disorder (OCD) and drug addiction. Finally, we discuss how the next phase of research in the field may benefit from integration of approaches for access to cells based on their genetic makeup, activity, connectivity and precise anatomical location.
Clinical outcomes of inpatient cardiac rehabilitation for patients with treated left ventricular assist device in Korea: 1-year follow-up

In Korea, the first patient with a left ventricular assist device (LVAD) for destination therapy had successful implantation of a continuous-flow model in 2012. We investigated the safety and efficacy of exercise therapy with LVAD implantation 15 Korean patients. We retrospectively reviewed 15 patients (mean age, 67.4±11.6 years; 10 males, 5 female, left ventricular ejection fraction 23.6%±7.1%), including 4 with implanted continuous-flow and 11 an axial-flow LVAD. The New York Heart Association functional classification, ejection fraction, and quality of life were obtained. Survival rate, adverse events, admission rates, and enrollment rates in cardiac rehabilitation were investigated. Survival at 6 and 12 months was 100% and 89%, respectively. The New York Heart Association functional classification improved from 3.4±0.5 to 2.3±0.05 at 12 months postoperatively (P<0.0001). The ejection fraction significantly increased from 23.6%±7.2% on the preoperative day to 35.4%±14.2% at 1 year (P<0.0018). The quality of life was also improved at 1 year (P<0.0001). The most common adverse events were bleeding (56%) and dyspnea (44%). The number of admissions was 3.2 per patient-year. LVAD therapy is a safe and effective treatment option with exercise intervention for Korean patients waiting for heart transplantation or those who were ineligible for heart transplantation. A larger study with longer follow-up is needed to determine details clinical outcomes after LVAD.
Survival Analysis of Multi-Omics Data Identifies Potential Prognostic Markers of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is the most common and among the deadliest of pancreatic cancers. Its 5-year survival is only ∼8%. Pancreatic cancers are a heterogeneous group of diseases, of which PDAC is particularly aggressive. Like many other cancers, PDAC also starts as a pre-invasive precursor lesion (known as pancreatic intraepithelial neoplasia, PanIN), which offers an opportunity for both early detection and early treatment. Even advanced PDAC can benefit from prognostic biomarkers. However, reliable biomarkers for early diagnosis or those for prognosis of therapy remain an unfulfilled goal for PDAC. In this study, we selected 153 PDAC patients from the TCGA database and used their clinical, DNA methylation, gene expression, and micro-RNA (miRNA) and long non-coding RNA (lncRNA) expression data for multi-omics analysis. Differential methylations at about 12,000 CpG sites were observed in PDAC tumor genomes, with about 61% of them hypermethylated, predominantly in the promoter regions and in CpG-islands. We correlated promoter methylation and gene expression for mRNAs and identified 17 genes that were previously recognized as PDAC biomarkers. Similarly, several genes (B3GNT3, DMBT1, DEPDC1B) and lncRNAs (PVT1, and GATA6-AS) are strongly correlated with survival, which have not been reported in PDAC before. Other genes such as EFR3B, whose biological roles are not well known in mammals are also found to strongly associated with survival. We further identified 406 promoter methylation target loci associated with patients survival, including known esophageal squamous cell carcinoma biomarkers, cg03234186 (ZNF154), and cg02587316, cg18630667, and cg05020604 (ZNF382). Overall, this is one of the first studies that identified survival associated genes using multi-omics data from PDAC patients.
Distribution, Function and Regulation of Type 6 Secretion Systems of Xanthomonadales

Members of the Xanthomonadales order include several plant pathogens of significant economic and agricultural impact, such as Xanthomonas spp. Type 6 secretion systems (T6SSs) are contractile nanomachines used by many bacterial species to inject protein effectors into target prokaryotic and eukaryotic cells and provide a competitive advantage for bacteria in different environments. Effectors with antibacterial properties include peptidoglycan hydrolases, lipases and phospholipases that break down structural components of the cell envelope, promoting target-cell lysis; and RNases, DNAses, and NADases that affect target-cell metabolism, arresting growth. Effectors with anti-eukaryotic properties are functionally more diverse. The T6SS of Xanthomonas citri is the only example experimentally characterized so far within the Xanthomonadales order and displays anti-eukaryotic function by providing resistance to predation by amoeba. This T6SS is regulated at the transcriptional level by a signaling cascade involving a Ser/Thr kinase and an extracytoplasmic function (ECF) sigma factor. In this review, we performed in silico analyses of 35 genomes of Xanthomonadales and showed that T6SSs are widely distributed and phylogenetically classified into three major groups. In silico predictions identified a series of proteins with known toxic domains as putative T6SS effectors, suggesting that the T6SSs of Xanthomonadales display both anti-prokaryotic and anti-eukaryotic properties depending on the phylogenetic group and bacterial species.
Hepatitis C subtype distribution in chronically infected patients with mild liver fibrosis in France: the GEMHEP study

Abstract Treatment options for Hepatitis C infection have greatly improved with direct-acting antiviral (DAA) combinations achieving high cure rates. Nevertheless, the cost of this treatment is still high and access to treatment in many countries has been preferentially reserved for patients with more severe fibrosis (F3 and F4). In this French nationwide study, we investigated the epidemiological characteristics and genotype distribution of hepatitis C virus (HCV) in treatment-naive patients with METAVIR fibrosis stages between F0 and F2 in order to identify patient profiles that became eligible for unrestricted treatment in a second period. Between 2015 and 2016 we collected data from nine French university hospitals on a total of 584 HCV positive patients with absent, mild or moderate liver fibrosis. The most represented genotypes were genotype 1b (159/584; 27.2%), followed by genotype 1a (150/584; 25.7%); genotype 3 (87/584: 14.9%); genotype 4 (80/584; 13.7%). Among genotype 4: 4a was predominantly encountered with 22 patients (27.5% of genotype 4). Genotypes 1b and 1a are currently the most frequent virus types present in treatment-naive patients with mild fibrosis in France. They can be readily cured using the available DAA. Nevertheless, non-a/non-d genotype 4 is also frequent in this population and clinical data on the efficacy of DAA on these subtypes is missing. The GEMHEP is the French group for study and evaluation of viral hepatitis on a national scale. Data collection on epidemiological and molecular aspects of viral hepatitis is performed on a regular basis in all main French teaching hospitals and serves as a basis for surveillance of these infections. Analysis and trends are regularly published on behalf of the GEMHEP group. Data collection was performed retrospectively over the 2015–2016 period, covering nine main university hospitals in France. A total of 584 hepatitis C positive patients were included in this study. Genotyping of the circulating viruses showed a high prevalence of genotypes 1b and 1a in our population. The epidemiology of hepatitis C is slowly changing in France, particularly as a consequence of the rise of ‘non-a non-d’ genotype 4 viruses mainly originating from African populations. More data concerning treatment efficacy of these genotypes is needed in order to guide clinical care.
The Capsid Protein VP1 of Coxsackievirus B Induces Cell Cycle Arrest by Up-Regulating Heat Shock Protein 70

Manipulating cell cycle is one of the common strategies used by viruses to generate favorable cellular environment to facilitate viral replication. Coxsackievirus B (CVB) is one of the major viral pathogens of human myocarditis and cardiomyopathy. Because of its small genome, CVB depends on cellular machineries for productive replication. However, how the structural and non-structural components of CVB would manipulate cell cycle is not clearly understood. In this study, we demonstrated that the capsid protein VP1 of CVB type 3 (CVB3) induced cell cycle arrest at G1 phase. G1 arrest was the result of the decrease level of cyclin E and the accumulation of p27Kip1. Study on the gene expression profile of the cells expressing VP1 showed that the expression of both heat shock protein 70-1 (Hsp70-1) and Hsp70-2 was significantly up-regulated. Knockdown of Hsp70 resulted in the increased level of cyclin E and the reduction of p27Kip1. We further demonstrated that the phosphorylation of the heat shock factor 1, which directly promotes the expression of Hsp70, was also increased in the cell expressing VP1. Moreover, we show that CVB3 infection also induced G1 arrest, likely due to dysregulating Hsp70, cyclin E, and p27, while knockdown of Hsp70 dramatically inhibited viral replication. Cell cycle arrest at G1 phase facilitated CVB3 infection, since viral replication in the cells synchronized at G1 phase dramatically increased. Taken together, this study demonstrates that the VP1 of CVB3 induces cell cycle arrest at G1 phase through up-regulating Hsp70. Our findings suggest that the capsid protein VP1 of CVB is capable of manipulating cellular activities during viral infection.
Learning to Generate Industrial SAT Instances

In this paper, we present Satgen, the first implicit generative model of real-world Boolean Satisfiability (SAT) formulas. Our approach uses unsupervised machine learning techniques to generate new formulas by mimicking the structural properties of a given input formula Phi. We proceed in two phases: first, we construct the Literal-Incidence Graph (LIG) of Phi. This is used by a Generative Adversarial Network (GAN) to generate new LIGs that exhibit graph-theoretic properties similar to those of the LIG of Phi. In the second phase, we extract a formula whose LIG would correspond to the generated graph. We show that generating such a formula is equivalent to finding a minimal clique edge cover of the given graph, which we tackle efficiently using a greedy hill-climbing algorithm. We verify experimentally that our approach generates formulas that closely resemble a given real-world SAT instance, as measured by a range of different metrics.