Miracle-dz/UniFAR-FTUs huggingface dataset:
Sirt1 Antisense Long Noncoding RNA Promotes Cardiomyocyte Proliferation by Enhancing the Stability of Sirt1

Background Antisense long noncoding RNAs (lncRNAs) are single‐stranded RNAs that overlapped gene‐coding regions on the opposite DNA strand and play as critical regulators in cardiovascular diseases. The high conservation and stability may be good advantages for antisense lncRNAs. However, the roles of antisense lncRNAs in cardiomyocyte proliferation and cardiac regeneration are still unknown. Methods and Results In this study, we found that Silent information regulator factor 2 related enzyme 1 (Sirt1) antisense lncRNA expression was significantly increased during heart development. By gain and loss function of Sirt1 antisense lncRNA using adenovirus and locked nucleic acid, respectively, we demonstrated that Sirt1 antisense lncRNA promoted cardiomyocyte proliferation in vitro and in vivo, and the suppression of Sirt1 antisense lncRNA inhibited cardiomyocyte proliferation. Moreover, overexpression of Sirt1 antisense lncRNA enhanced cardiomyocyte proliferation, attenuated cardiomyocyte apoptosis, improved cardiac function, and decreased mortality rate after myocardial infarction. Furthermore, Sirt1 antisense lncRNA can bind the Sirt1 3′‐untranslated region, enhancing the stability of Sirt1 and increasing Sirt1 abundance at both the mRNA and protein levels. Finally, we found that Sirt1 was involved in Sirt1 antisense lncRNA‐induced cardiomyocyte proliferation. Conclusions The present study identified Sirt1 antisense lncRNA as a novel regulator of cardiomyocyte proliferation and cardiac regeneration by interacting and stabilizing Sirt1 mRNA, which may serve as an effective gene target for preventing myocardial infarction.
Artificial Selection for Pathogenicity Mutations in Staphylococcus aureus Identifies Novel Factors Relevant to Chronic Infection

Adaptation of Staphylococcus aureus to host microenvironments during chronic infection involves spontaneous mutations, yet changes underlying adaptive phenotypes remain incompletely explored. Here, we employed artificial selection and whole-genome sequencing to better characterize spontaneous chromosomal mutations that alter two pathogenicity phenotypes relevant to chronic infection in S. aureus: intracellular invasiveness and intracellular cytotoxicity. ABSTRACT Adaptation of Staphylococcus aureus to host microenvironments during chronic infection involves spontaneous mutations, yet changes underlying adaptive phenotypes remain incompletely explored. Here, we employed artificial selection and whole-genome sequencing to better characterize spontaneous chromosomal mutations that alter two pathogenicity phenotypes relevant to chronic infection in S. aureus: intracellular invasiveness and intracellular cytotoxicity. We identified 23 genes whose alteration coincided with enhanced virulence, 11 that were previously known and 12 (52%) that had no previously described role in S. aureus pathogenicity. Using precision genome editing, transposon mutants, and gene complementation, we empirically assessed the contributions of individual genes to the two virulence phenotypes. We functionally validated 14 of 21 genes tested as measurably influencing invasion and/or cytotoxicity, including 8 newly implicated by this study. We identified inactivating mutations (murA, ndhC, and a hypothetical membrane protein) and gain-of-function mutations (aroE Thr182Ile, yhcF Thr74Ile, and Asp486Glu in a hypothetical peptidase) in previously unrecognized S. aureus virulence genes that enhance pathogenesis when introduced into a clean genetic background, as well as a novel activating mutation in the known virulence regulator gene saeS (Ala106Thr). Investigation of potentially epistatic interactions identified a tufA mutation (Ala271Val) that enhances virulence only in the context of purine operon repressor gene (purR) inactivation. This project reveals a functionally diverse range of genes affected by gain- or loss-of-function mutations that contribute to S. aureus adaptive virulence phenotypes. More generally, the work establishes artificial selection as a means to determine the genetic mechanisms underlying complex bacterial phenotypes relevant to adaptation during infection.
ROMO1 is a constituent of the human presequence translocase required for YME1L protease import

The mitochondrial presequence translocation machinery (TIM23 complex) is conserved between the yeast Saccharomyces cerevisiae and humans; however, functional characterization has been mainly performed in yeast. Here, we define the constituents of the human TIM23 complex using mass spectrometry and identified ROMO1 as a new translocase constituent with an exceptionally short half-life. Analyses of a ROMO1 knockout cell line revealed aberrant inner membrane structure and altered processing of the GTPase OPA1. We show that in the absence of ROMO1, mitochondria lose the inner membrane YME1L protease, which participates in OPA1 processing and ROMO1 turnover. While ROMO1 is dispensable for general protein import along the presequence pathway, we show that it participates in the dynamics of TIM21 during respiratory chain biogenesis and is specifically required for import of YME1L. This selective import defect can be linked to charge distribution in the unusually long targeting sequence of YME1L. Our analyses establish an unexpected link between mitochondrial protein import and inner membrane protein quality control.
OCRL deficiency impairs endolysosomal function in a humanized mouse model for Lowe syndrome and Dent disease

Mutations in OCRL encoding the inositol polyphosphate 5-phosphatase OCRL (Lowe oculocerebrorenal syndrome protein) disrupt phosphoinositide homeostasis along the endolysosomal pathway causing dysfunction of the cells lining the kidney proximal tubule (PT). The dysfunction can be isolated (Dent disease 2) or associated with congenital cataracts, central hypotonia and intellectual disability (Lowe syndrome). The mechanistic understanding of Dent disease 2/Lowe syndrome remains scarce due to limitations of animal models of OCRL deficiency. Here, we investigate the role of OCRL in Dent disease 2/Lowe syndrome by using OcrlY/- mice, where the lethal deletion of the paralogue Inpp5b was rescued by human INPP5B insertion, and primary culture of proximal tubule cells (mPTCs) derived from OcrlY/- kidneys. The OcrlY/- mice show muscular defects with dysfunctional locomotricity and present massive urinary losses of low-molecular-weight proteins and albumin, caused by selective impairment of receptor-mediated endocytosis in PT cells. The latter was due to accumulation of phosphatidylinositol 4,5-bisphosphate PI(4,5)P2 in endolysosomes, driving local hyper-polymerization of F-actin and impairing trafficking of the endocytic LRP2 receptor, as evidenced in OcrlY/- mPTCs. The OCRL deficiency was also associated with a disruption of the lysosomal dynamic and proteolytic activity. Partial convergence of disease-pathways and renal phenotypes observed in OcrlY/- and Clcn5Y/- mice suggest shared mechanisms in Dent diseases 1 and 2. These studies substantiate the first mouse model of Lowe syndrome and give insights into the role of OCRL in cellular trafficking of multiligand receptors. These insights open new avenues for therapeutic interventions in Lowe syndrome and Dent disease.
Honey bee colony‐level exposure and effects in realistic landscapes: An application of BEEHAVE simulating clothianidin residues in corn pollen

Discerning potential effects of insecticides on honey bee colonies in field studies conducted under realistic conditions can be challenging because of concurrent interactions with other environmental conditions. Honey bee colony models can control exposures and other environmental factors, as well as assess links among pollen and nectar residues in the landscape, their influx into the colony, and the resulting exposures and effects on bees at different developmental stages. We extended the colony model BEEHAVE to represent exposure to the insecticide clothianidin via residues in pollen from treated cornfields set in real agricultural landscapes in the US Midwest. We assessed their potential risks to honey bee colonies over a 1‐yr cycle. Clothianidin effects on colony strength were only observed if unrealistically high residue levels in the pollen were simulated. The landscape composition significantly impacted the collection of pollen (residue exposure) from the cornfields, resulting in higher colony‐level effects in landscapes with lower proportions of semi‐natural land. The application of the extended BEEHAVE model with a pollen exposure‐effects module provides a case study for the application of a mechanistic honey bee colony model in pesticide risk assessment integrating the impact of a range of landscape compositions. Environ Toxicol Chem 2019;38:423–435. © 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Natural and semisynthetic polymers blended orodispersible films of citalopram

Abstract This study was aimed at developing orodispersible films of citalopram using combination of natural and semisynthetic polymers for patients with swallowing problem. Okra biopolymer and moringa gum were utilized in combination with hydroxypropyl methylcellulose (HPMC) and pullulan. The disintegration time was less than 30 seconds and the drug content uniformity was 97.89–102.05% for all film formulations. Films formulated with HPMC (K15 and K4M) combination (F1) and combination of okra and HPMC K15 (F2) had superior mechanical properties as compared with F3 (okra and pullulan) and F4 (moringa gum and HPMC). Thermal analysis revealed stable formulations over the studied temperature range and the crystalline citalopram was completely or partially transformed into amorphous form as revealed by the differential thermal analysis, X-ray diffraction and scanning electron microscopy images. In conclusion, okra biopolymer could be used in combination with HPMC for the development of orodispersible films. Graphical Abstract
Compositional reorganization of the nucleolus in budding yeast mitosis

The nucleolus is a membraneless organelle of the nucleus and the site of rRNA synthesis, maturation, and assembly into preribosomal particles. The nucleolus, organized around arrays of rRNA genes (rDNA), dissolves during prophase of mitosis in metazoans, when rDNA transcription ceases, and reforms in telophase, when rDNA transcription resumes. No such dissolution and reformation cycle exists in budding yeast, and the precise course of nucleolar segregation remains unclear. By quantitative live-cell imaging, we observed that the yeast nucleolus is reorganized in its protein composition during mitosis. Daughter cells received equal shares of preinitiation factors, which bind the RNA polymerase I promoter and the rDNA binding barrier protein Fob1, but only about one-third of RNA polymerase I and the processing factors Nop56 and Nsr1. The distribution bias was diminished in nonpolar chromosome segregation events observable in dyn1 mutants. Unequal distribution, however, was enhanced by defects in RNA polymerase I, suggesting that rDNA transcription supports nucleolar segregation. Indeed, quantification of pre-rRNA levels indicated ongoing rDNA transcription in yeast mitosis. These data, together with photobleaching experiments to measure nucleolar protein dynamics in anaphase, consolidate a model that explains the differential partitioning of nucleolar components in budding yeast mitosis.
Management of N0 neck in early oral squamous cell carcinoma: A systematic review and meta‐analysis

The role of elective neck dissection (END) in patients with stage I (T1N0) and II (T2N0) squamous cell carcinoma of the oral cavity remains a controversial topic. We investigate the need for END by establishing a true incidence of occult nodal disease as a function of T stage
FPGA Based Torque and Flux Estimator of Direct Torque Control for Induction Machine Drives

This paper presents a new design of the torque and stator flux estimators for Direct Torque control (DTC) for Field Programmable Gate Array (FPGA) implementation, which permit very fast calculations.An alternative variable word-size approach in two’s complement fixed-point format is used for the implementation, in order to minimize calculation errors and the hardware resource usage. The simulation results of DTC model in Matlab, which performed double-precision calculations, are used as references to digital computations executed in FPGA implementation.The Hardware-in-the-loop (HIL) method is used to verify the minimal error between Matlab simulation and the experimental results, and thus the well-functionality of the implemented estimators. Keywords: FPGA, DTC, HIL
Does the Severity of Students’ Pre-Intervention Math Deficits Affect Responsiveness to Generally Effective First-Grade Intervention?

The purpose of this analysis was to assess whether effects of first-grade mathematics intervention apply across the range of at-risk learners’ initial skill levels. Students were randomly assigned to control (n = 213) and two variants of intervention (n = 385) designed to improve arithmetic. Of each 30-minute intervention session (48 over 16 weeks), 25 minutes were identical in the two variants, focused on number knowledge that provides the conceptual bases for arithmetic. The other five minutes provided nonspeeded conceptual practice (n = 196) or speeded strategic practice (n = 199). Contrasts tested effects of intervention (combined across variants) versus control and effects between the variants. Moderation analysis indicated no significant interactions between at-risk children’s pre-intervention mathematics skill and either contrast on any outcome. Across pre-intervention math skill, effects favored intervention over control on arithmetic and transfer to double-digit calculations and number knowledge, and favored speeded over nonspeeded practice on arithmetic.
Souvislosti reálné a virtuální identity dospívajících

V nasem přispěvku se zaměřujeme na prokazani souvislosti mezi realnou a virtualni identitou dospivajicich, respektive chovanim adolescentů ve virtualnim prostředi. Jako teoretický koncept identity jsme v navaznosti na kvalitativni výzkum zvolili teorii Marcii. Ve výzkumu si klademe otazku, zda se dospivajici ve statusu předcasně uzavřene identity chovaji v souladu s normami a ocekavanimi rodiců take ve virtualnim světě. U dospivajicich nachazejicich se ve statusu moratoria se zabývame otazkou, zda castěji experimentuji se svoji on-line identitou, do jake miry použivaji internet k ujasněni svých životnich hodnot a postojů a jak se chovaji on-line ve vztahu k normam. U dospivajicich ve statusu dosaženi identity se ptame, zda využivaji internet pro ujasněni svých hodnot a postojů, ackoliv v realitě tyto hodnoty a postoje vydavaji spise za ujasněne.
What is an autonomy supportive environment in geriatric care units? Focus group interviews with healthcare professionals

OBJECTIVES Grounded in Self-Determination Theory (SDT), the aim of the study was to define an autonomy supportive environment through the perceptions of different healthcare professionals in three geriatric care units within French public and private hospitals. STUDY DESIGN Four focus groups were conducted with healthcare professionals. Each focus group was videotaped and audio-recorded and transcribed verbatim. METHODS An inductive approach was used, and data analysis was carried out using NVivo 10 software for Mac-QSR International. RESULTS Three themes were highlighted (a) building a relationship of trust with older people; (b) encouraging them to express themselves and (c) promoting progress. CONCLUSION The present study provides some information and a reflection for healthcare professionals who might be interested in using a more autonomy-supportive motivating style in their practice.
Identification of prognostic biomarkers for patients withhepatocellular carcinoma after hepatectomy

Hepatocellular carcinoma (HCC) is a lethal malignancy with high morbidity and mortality rates worldwide. The identification of prognosis‑associated biomarkers is crucial to improve HCC patient survival. The present study aimed to explore potential predictive biomarkers for HCC. Differentially expressed genes (DEGs) were analyzed in the GSE36376 dataset using GEO2R. Hub genes were identified and further investigated for prognostic value in HCC patients. A risk score model and nomogram were constructed to predict HCC prognosis using the prognosis‑associated genes and clinical factors. Pearson's correlation was employed to show interactions among hub genes. Gene enrichment analysis was performed to identify detailed biological processes and pathways. A total of 71 DEGs were obtained and seven (ADH4, CYP2C8, CYP2C9, CYP8B1, SLC22A1, TAT and HSD17B13, all adjusted P≤0.05) of the 10 hub genes were identified as prognosis‑related genes for survival analysis in HCC patients, including alcohol dehydrogenase 4 (class II), pi polypeptide (ADH4), cytochrome p450 family 2 subfamily C member 8 (CYP2C8), cytochrome P450 family 2 subfamily C member 9 (CYP2C9), cytochrome P450 family 8 subfamily B member 1 (CYP8B1), solute carrier family 22 member 1 (SLC22A1), tyrosine aminotransferase (TAT) and hydroxysteroid 17‑β dehydrogenase 13 (HSD17B13). The risk score model could predict HCC prognosis and the nomogram visualized gene expression and clinical factors of probability for HCC prognosis. The majority of genes showed significant Pearson's correlations with others (41 Pearson correlations P≤0.01, four Pearson correlations P>0.05). GO analysis revealed that terms such as 'chemical carcinogenesis' and 'drug metabolism‑cytochrome P450' were enriched and may prove helpful to elucidate the mechanisms of hepatocarcinogenesis. Hub genes ADH4, CYP2C8, CYP2C9, CYP8B1, SLC22A1, TAT and HSD17B13 may be useful as predictive biomarkers for HCC prognosis.
Analysis of genetic and serology of hepatitis A virus infection during and after outbreak in two junior high schools in Surabaya, Indonesia

Outbreaks of hepatitis A have occurred in some cities in Indonesia. In Surabaya, the capital city of East Java province, Indonesia, hepatitis A outbreaks have been reported since2013, with a marked increase in the number of cases in 2015. The aim of the present study was to analyze the genetic and serology of acute symptomatic cases (early infection) during a hepatitis A outbreak and asymptomatic cases after the outbreak in two junior high schools in Surabaya in 2015 to 2016. Students with acute symptomatic hepatitis A during the outbreak and other students who were asymptomatic 3 to 4 months after the outbreak were enrolled. Asymptomatic students had no symptoms from the outbreak until they were enrolled. Sera were collected to identify anti‐hepatitis A virus (HAV) IgM (by enzyme‐linked immunosorbent assay) and HAV genetic variations/genotypes (using polymerase chain reaction [PCR]‐sequencing and phylogenetic analysis). A total of 33 (97.1%) out of 34 sera of students with acute symptoms were positive for anti‐HAV IgM and 18% of them were positive by PCR, identified as HAV subgenotype IA. No prominent amino acid variations were observed from reported HAV sequences from Indonesia. Among 38 sera of asymptomatic students, most (55.3%) were positive for anti‐HAV IgM, while none were positive by PCR. In conclusion, HAV‐IA was the only subgenotype identified in acute symptomatic cases during the outbreak. The percentage of HAV‐specific IgM‐positive cases was very high among acute symptomatic students, but that was also high among asymptomatic students, which might contribute as the important source of infection during the outbreak.
Identification of novel urease inhibitors: pharmacophore modeling, virtual screening and molecular docking studies

Abstract Pharmacophore modeling and atom-based three-dimensional quantitative structure–activity relationship (3D-QSAR) have been developed on N-acylglycino- and hippurohydroxamic acid derivatives, which are known potential inhibitors of urease. This is followed by virtual screening and ADMET (absorption, distribution, metabolism, excretion and toxicity) studies on a large library of known drugs in order to get lead molecules as Helicobacter pylori urease inhibitors. A suitable three-featured pharmacophore model comprising one H-bond acceptor and two H-bond donor features (ADD.10) has been found to be the best QSAR model. An external library of compounds (∼3000 molecules), pre-filtered using Lipinski’s rule of five, has been further screened using the pharmacophore model ADD.10. By analyzing the fitness of the hits with respect to the pharmacophore model and their binding interaction inside the urease active site, four molecules have been predicted to be extremely good urease inhibitors. Two of these have significant potential and should be taken up for further drug-designing process.
cd44 deletion suppresses atypia in the precancerous mouse testis

Loss‐of‐function of RHAMM causes hypofertility and testicular atrophy in young mice, followed by germ cell neoplasia in situ (GCNIS) of the testis, cellular atypia, and development of the testicular germ cell tumor (TGCT) seminoma. These pathologies reflect the risk factors and phenotypes that precede seminoma development in humans and—given the high prevalence of RHAMM downregulation in human seminoma—link RHAMM dysfunction with the aetiology of male hypofertility and GCNIS‐related TGCTs. The initiating event underlying these pathologies, in RHAMM mutant testis, is premature displacement of undifferentiated progenitors from the basal compartment. We hypothesized that cd44 (both cancer initiating cell‐ and oncogenic progression marker) will drive GCNIS development, induced by RHAMM‐loss‐of‐function in the mouse. We report that cd44 is expressed in a specific subset of GCNIS testes. Its genetic deletion has no effect on GCNIS onset, but it ameliorates oncogenic progression. We conclude that cd44 expression, combined with RHAMM dysfunction, promotes oncogenic progression in the testis.
Interaction between C-Tb and PPD given concomitantly in a split-body randomised controlled trial.

SETTING Seven tuberculosis (TB) clinics in South Africa. OBJECTIVE As both purified protein derivative (PPD) and a Mycobacterium tuberculosis-specific skin test (C-Tb) contain region of difference 1 (RD1) antigens, we conducted a study to evaluate whether there was any interaction between the two during concomitant and separate administration in patients with newly diagnosed culture-positive TB. DESIGN Adult patients with active TB (n = 456, 20% human immunodeficiency virus infected) were randomised to receive only C-Tb, only PPD, or concomitant injection of both C-Tb and PPD using the Mantoux technique. Indurations were read after 48-72 h. QuantiFERON®-TB Gold In-Tube (QFT) was performed in tandem. RESULTS Of the 456 study participants, 154 simultaneously received both C-Tb and PPD, 153 only C-Tb and 149 only PPD. There was no effect of concomitant injection of PPD on the mean C-Tb induration (19 mm, 95%CI 17-22 vs. 18 mm, 95%CI 16-21; P = 0.91). In patients with active TB, C-Tb sensitivity (78%) was similar to PPD (81%) and QFT (84%; excluding 82/429 [19%] indeterminate results). All tests showed reduced sensitivity in participants with CD4 <100 cells/μl. CONCLUSION In patients with active TB, there was no interaction between C-Tb and PPD during concomitant injection of both agents. Sensitivities were similar for PPD and C-Tb.