Miracle-dz/UniFAR-FTUs huggingface dataset:
ETS variant transcription factor 5 and c-Myc cooperate in derepressing the human telomerase gene promoter via composite ETS/E-box motifs

The human telomerase gene (hTERT) is repressed in most somatic cells. How transcription factors activate the hTERT promoter in its repressive chromatin environment is unknown. Here, we report that the ETS family protein ETS variant transcription factor 5 (ETV5) mediates epidermal growth factor (EGF)-induced hTERT expression in MCF10A cells. This activation required MYC proto-oncogene bHLH transcription factor (c-Myc) and depended on the chromatin state of the hTERT promoter. Using chromatinized bacterial artificial chromosome (BAC) reporters in human fibroblasts, we found that ETV5 and c-Myc/MYC-associated factor X (MAX) synergistically activate the hTERT promoter via two identical, but inverted, composite Ets/E-box motifs enclosing the core promoter. Mutations of Ets or E-box sites in either DNA motif abolished the activation and reduced or eliminated the synergism. ETV5 and c-Myc facilitated each other's binding to the hTERT promoter. ETV5 bound to the hTERT promoter in both telomerase-negative and -positive cells, but it activated the repressed hTERT promoter and altered histone modifications only in telomerase-negative cells. The synergistic ETV5/c-Myc activation disappeared when hTERT promoter repression became relieved because of the loss of distal regulatory elements in chimeric human/mouse BAC reporters. Our results suggest that the binding of c-Myc and ETS family proteins to the Ets/E-box motifs derepresses the hTERT promoter by inducing an active promoter configuration, providing a mechanistic insight into hTERT activation during tumorigenesis.
Combining Imaging and Genetics to Predict Recurrence of Anticoagulation-Associated Intracerebral Hemorrhage

Supplemental Digital Content is available in the text. Background and Purpose: For survivors of oral anticoagulation therapy (OAT)–associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the apolipoprotein E (APOE) gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and APOE genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest. Methods: Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and APOE genotype predict ICH recurrence. We then developed and validated a combined APOE-MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis. Results: Cortical superficial siderosis, cerebral microbleed, and APOE ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all P<0.05). Combining APOE genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, P=0.033). In the MGH (training) data set, CSS, cerebral microbleed, and APOE ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH. Conclusions: Combining MRI and APOE genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined APOE-MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.
Nudging in Public Health Lifestyle Interventions: A Systematic Literature Review and Metasynthesis

Nudging is increasingly used in public health interventions in Western societies to produced health-promoting behavior changes; however, there is lack of clarity as to what constitutes a nudge, scant knowledge of the effectiveness of nudging techniques in public health lifestyle interventions and a number of ethical and value-based concerns. The aim of this review is to address these research lacunae and identify the characteristics of nudges in empirical research on public health interventions intended to induce healthy lifestyle changes, including whether they are effective. We conducted systematic searches for relevant articles published between January 2008 and April 2019 in three databases, PubMed, CINAHL and PsycINFO, and combined this with a metasynthesis to construct interpretative explanations. A total of 66 original studies met the inclusion criteria. The findings of the systematic review showed that most nudging interventions involved diet/nutrition, most were carried out as single experiments, and the majority had the intended effects. Specific nudging techniques were identified with respect to the broader nudging categories of accessibility, presentation, using messages and pictures, technology-supported information, financial incentives, affecting the senses, and cognitive loading; several studies included more than one nudging technique. Although many nudging techniques had the intended effects, it is unclear whether they would work outside the study setting. The synthesis revealed that the studies lacked critical reflection on the assumptions about health that were implicit in nudging interventions, the cultural acceptability of nudges, the context-free assumptions of nudging theory, and the implications of these aspects for the public health context.
A Highly Stretchable Sheath-Core Yarn for Multifunctional Wearable Electronics.

Integrated flexible devices simultaneously with strain sensing and energy storage functions are urgently desirable to detect human motion for potential wearable applications. Herein, this paper reports the fabrication of cotton/carbon nanotube (CNTs) sheath-core yarn deposited with poly-pyrrole (PPy) for highly multifunctional stretchable wearable electronics. The microscopic structures and morphologies of prepared sheath-core yarn were characterized by SEM and FTIR. Mechanical experiment has demonstrated the excellent stretchable capacity due to the unique spring-like structure. We demonstrate that the sheath-core yarn can be used as wearable strain sensors, exhibiting ultrahigh strain sensing range (0-350%) and excellent stability. The sheath-core yarn can be used in highly sensitive real-time monitoring towards both subtle and large human motions under different conditions. Furthermore, the electrochemical performance of sheath-core yarn was characterized by cyclic voltammetry (CV), galvanostatic charge-discharge (GCD), electrochemical impedance spectroscopy (EIS). The measured areal capacitance is 761.2 mF/cm2at the scanning rate of 1 mV/s. The method of spinning technology may lead to new exploitation for CNTs and PPy in future wearable electronic device applications.
Fibroblast growth factor 2 contributes to the effect of salidroside on dendritic and synaptic plasticity after cerebral ischemia/reperfusion injury

Ischemic stroke, a serious neurological disease, is associated with cell death, axonal and dendritic plasticity, and other activities. Anti-inflammatory, anti-apoptotic, promote dendritic and synaptic plasticity are critical therapeutic targets after ischemic stroke. Fibroblast growth factor-2 (FGF2), which is involved in the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/CAMP response element (CRE)-binding protein (CREB) pathway, has been shown to facilitate dendritic and synaptic plasticity. Salidroside (Sal) has been reported to have anti-inflammatory, anti-oxidative, and anti-apoptotic effects; however, the underlying mechanisms of Sal in promoting dendritic and synaptic plasticity remain unclear. Here, the anti-inflammatory, anti-apoptotic, dendritic and synaptic plasticity effects of Sal were investigated in vitro in PC12 cells under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions and in vivo in rats with middle cerebral artery occlusion/reperfusion (MCAO/R). We investigated the role of Sal in promoting dendritic and synaptic plasticity in the ischemic penumbra and whether the FGF2-mediated cAMP/PKA/CREB pathway was involved in this process. The present study demonstrated that Sal could significantly inhibit inflammation and apoptosis, and promote dendritic and synaptic plasticity. Overall, our study suggests that Sal is an effective treatment for ischemic stroke that functions via the FGF2-mediated cAMP/PKA/CREB pathway to promote dendritic and synaptic plasticity.
Tombusvirus p19 Captures RNase III-Cleaved Double-Stranded RNAs Formed by Overlapping Sense and Antisense Transcripts in Escherichia coli

Antisense transcription is widespread in bacteria. By base pairing with overlapping sense RNAs, antisense RNAs (asRNA) can form double-stranded RNAs (dsRNA), which are cleaved by RNase III, a dsRNA endoribonuclease. The ectopic expression of plant Tombusvirus p19 in Escherichia coli stabilizes ∼21-nucleotide (nt) dsRNA RNase III decay intermediates, which enabled us to characterize otherwise highly unstable asRNA by deep sequencing of p19-captured dsRNA. RNase III-produced small dsRNA were formed at most bacterial genes in the bacterial genome and in a plasmid. ABSTRACT Antisense transcription is widespread in bacteria. By base pairing with overlapping sense RNAs, antisense RNAs (asRNA) can form double-stranded RNAs (dsRNA), which are cleaved by RNase III, a dsRNA endoribonuclease. The ectopic expression of plant Tombusvirus p19 in Escherichia coli stabilizes ∼21-nucleotide (nt) dsRNA RNase III decay intermediates, which enabled us to characterize otherwise highly unstable asRNA by deep sequencing of p19-captured dsRNA. RNase III-produced small dsRNA were formed at most bacterial genes in the bacterial genome and in a plasmid. We classified the types of asRNA in genomic clusters producing the most abundant p19-captured dsRNA and confirmed RNase III regulation of asRNA and sense RNA decay at three type I toxin-antitoxin loci and at a coding gene, rsd. Furthermore, we provide potential evidence for the RNase III-dependent regulation of CspD protein by asRNA. The analysis of p19-captured dsRNA revealed an RNase III sequence preference for AU-rich sequences 3 nucleotides on either side of the cleavage sites and for GC-rich sequences in the 2-nt overhangs. Unexpectedly, GC-rich sequences were enriched in the middle section of p19-captured dsRNA, suggesting some unexpected sequence bias in p19 protein binding. Nonetheless, the ectopic expression of p19 is a sensitive method for identifying antisense transcripts and RNase III cleavage sites in dsRNA formed by overlapping sense and antisense transcripts in bacteria.
Automated Feeding Behaviors Associated with Subclinical Respiratory Disease in Preweaned Dairy Calves

Simple Summary Pneumonia in dairy calves impacts animal welfare and is costly to producers. Feeding behavior might be a useful aide for early disease detection before the clinical signs of disease are apparent. This study compared feeding behavior among calves with either pneumonia and no outward signs of respiratory disease, pneumonia plus outward signs of disease, and calves without any respiratory disease. Although unaffected calves and calves with inapparent pneumonia had similar feeding behaviors, we found that calves with pneumonia plus visible signs of respiratory disease drank slower than the others. Therefore, feeding behavior may not be useful to detect calves with pneumonia before clinical signs are apparent. Abstract Little is known about feeding behaviors in young dairy calves with subclinical respiratory disease (SBRD). The objective of this study was to determine if calves with their first case of SBRD exhibit different feeding behaviors during the 7 d around detection, compared to calves with their first case of clinical BRD (CBRD) or without BRD (NOBRD). Preweaned, group-housed dairy calves (n = 103; 21 ± 6 d of age) underwent twice weekly health exams (lung ultrasound and clinical respiratory score; CRS); health exams were used to classify the BRD status for each calf: SBRD (no clinical signs and lung consolidation ≥ 1cm2; n = 73), CBRD (clinical signs and lung consolidation ≥ 1cm2; n = 18), or NOBRD (never had lung consolidation ≥ 1cm2 or CRS+; n = 12). Feeding behavior data (drinking speed, number of visits, and intake volume) were collected automatically. Calves with SBRD and calves with NOBRD had similar drinking speeds (782 vs. 844 mL/min). Calves with CBRD drank slower than both calves with SBRD (688 vs. 782 mL/min) and NOBRD (688 vs. 844 mL/min). There was no effect of BRD status on any other behavior. Feeding behavior was not an effective means of identifying calves with SBRD.
Oleanolic Acid Suppressed DMBA-Induced Liver Carcinogenesis through Induction of Mitochondrial-Mediated Apoptosis and Autophagy

Abstract Phytochemicals appeared as a rich source of efficient and safe agents against many diseases like cancer. Various herbal sources are rich in oleanolic acid (OA). The scope of this study was to assess the biochemical and molecular mechanisms implicated in the ameliorative potency of OA against DMBA-induced liver carcinogenesis. Forty-eight male albino mice were assigned randomly to five groups (eight mice each) as follows: control healthy group, olive oil group, OA group, DMBA group, and DMBA with OA. Apoptosis, autophagy, inflammation, proliferation, and angiogenesis were investigated in the tissue samples. Histopathological examination was carried out as well as liver enzymes activity and other hepatic antioxidant and inflammatory biomarkers. The treatment with OA effectively suppressed the DMBA-initiated liver carcinogenesis via modulation of antioxidant status, induction of apoptosis and autophagy through modulating the expression of Caspase-3, Bcl-2 and Beclin-1, inhibiting angiogenesis (VEGF), proliferation (PCNA), and improved liver function and histological picture with a reduction in AFP level. Additionally, OA applies its antitumor effects by inhibition of proinflammatory transcription factor NF-κB and inflammatory markers (TNF-α and Cox-2) associated with DMBA administration. The present study shows that OA treatment efficiently suppressed the DMBA-initiated liver carcinogenesis through induction of mitochondrial-mediated apoptosis and autophagy and modulating inflammation.
Estimating the Relationship Between Perceived Stigma and Victimization of People With Mental Illness

Over the past two decades, we have substantially increased our understanding of violence committed by individuals with mental illness, while comparatively less is known about the victimization experiences of this population. What has been established in the literature is that individuals with mental illness are more likely to experience victimization than the general public, and certain risk factors influence the likelihood of victimization. What remains unexplored is the possibility that a person with mental illness’ perception that mental illness is stigmatized may be significantly associated with victimization experiences. Thus, the purpose of the current study is to examine whether stigma and victimization are associated, and in what direction. In other words, does perceived stigma lead to victimization? Or does victimization lead to perceived stigma? To assess these research questions, data from the Community Outcomes of Assisted Outpatient Treatment study are used, which is a longitudinal study of individuals with serious mental illness (n = 184). A variety of methods are employed to assess the association between victimization and perceived stigma including logistic and ordinary least squares regression models. Results from the logistic regression model indicate that perceived stigma is associated with an increase in the odds that a person with mental illness will experience victimization at later follow-ups. Results from the ordinary least squares regression analysis, however, show that victimization at baseline does not predict perceived stigma at later times. Implications regarding future research and clinical practice are discussed.
Caenorhabditis elegans AF4/FMR2 Family Homolog affl-2 Regulates Heat-Shock-Induced Gene Expression

To mitigate the deleterious effects of temperature increases on cellular organization and proteotoxicity, organisms have developed mechanisms to respond to heat stress. In eukaryotes, HSF1 is the master regulator of the heat shock transcriptional response, but the heat shock response pathway is not yet fully understood. From a forward genetic screen for suppressors of heat-shock-induced gene expression in Caenorhabditis elegans, we found a new allele of hsf-1 that alters its DNA-binding domain, and we found three additional alleles of sup-45, a previously molecularly uncharacterized genetic locus. We identified sup-45 as one of the two hitherto unknown C. elegans orthologs of the human AF4/FMR2 family proteins, which are involved in regulation of transcriptional elongation rate. We thus renamed sup-45 as affl-2 (AF4/FMR2-Like). Through RNA-seq, we demonstrated that affl-2 mutants are deficient in heat-shock-induced transcription. Additionally, affl-2 mutants have herniated intestines, while worms lacking its sole paralog (affl-1) appear wild type. AFFL-2 is a broadly expressed nuclear protein, and nuclear localization of AFFL-2 is necessary for its role in heat shock response. affl-2 and its paralog are not essential for proper HSF-1 expression and localization after heat shock, which suggests that affl-2 may function downstream of, or parallel to, hsf-1. Our characterization of affl-2 provides insights into the regulation of heat-shock-induced gene expression to protect against heat stress.
RICE FIELDS AS TEMPORARY WETLANDS: A REVIEW

Rice fields are temporary wetlands that harbor many of the same species that breed in natural temporary ponds. Therefore the rice agroecosystem has the potential to help sustain the regional biodiversity of many invertebrates and vertebrates. Like natural areas of wetlands, rice cultivation provides a habitat mosaic of temporary and more permanent waters. Because of their low floral diversity and because their species composition will rarely overlap completely with that of natural ponds, rice fields are not substitutes for natural temporary ponds. However, they are important in sustaining populations of several species, including wading birds and frogs. Farming methods vary widely, and different practices can alter the suitability of rice fields as habitats. Farmers use water management, pesticides, and sometimes fish to control crop pests and mosquitoes, and other taxa may be affected as well. Farmers may irrigate rice intermittently to control pests, and intermittent habitat holds fewer species than are.
Teacher Harassment Victimization in Adolescents with High-Functioning Autism Spectrum Disorder: Related Factors and Its Relationships with Emotional Problems

This study aimed to examine the prevalence, related factors, and emotional problems associated with teacher harassment victimization in adolescents with autism spectrum disorder (ASD) assessed by self-reports and parent reports. A total of 219 adolescents with ASD participated in this study. The self-reported and parent-reported rates of teacher harassment victimization were calculated. Sociodemographic characteristics, parent-reported social communication deficits, attention-deficit and hyperactivity disorder (ADHD) symptoms, oppositional defiant disorder (ODD) symptoms, self-reported depression and anxiety symptoms, and suicidality were surveyed. In total, 26 (11.9%) adolescents with ASD experienced teacher harassment based on self-reports or parent reports; the convergence between adolescent and parent reports on adolescent experiences of teacher harassment was low. Victims of teacher harassment exhibited more severe social communication deficits and ODD symptoms than nonvictims of teacher harassment. Victims of teacher harassment displayed more severe depression and anxiety and were more likely to have suicidality. Socio-communication deficits and ODD symptoms were related to teacher harassment victimization, which in turn was significantly associated with emotional problems among adolescents with ASD.
Quantifying Spatiotemporal Gait Parameters with HoloLens in Healthy Adults and People with Parkinson’s Disease: Test-Retest Reliability, Concurrent Validity, and Face Validity

Microsoft’s HoloLens, a mixed-reality headset, provides, besides holograms, rich position data of the head, which can be used to quantify what the wearer is doing (e.g., walking) and to parameterize such acts (e.g., speed). The aim of the current study is to determine test-retest reliability, concurrent validity, and face validity of HoloLens 1 for quantifying spatiotemporal gait parameters. This was done in a group of 23 healthy young adults (mean age 21 years) walking at slow, comfortable, and fast speeds, as well as in a group of 24 people with Parkinson’s disease (mean age 67 years) walking at comfortable speed. Walking was concurrently measured with HoloLens 1 and a previously validated markerless reference motion-registration system. We comprehensively evaluated HoloLens 1 for parameterizing walking (i.e., walking speed, step length and cadence) in terms of test-retest reliability (i.e., consistency over repetitions) and concurrent validity (i.e., between-systems agreement), using the intraclass correlation coefficient (ICC) and Bland–Altman’s bias and limits of agreement. Test-retest reliability and between-systems agreement were excellent for walking speed (ICC ≥ 0.861), step length (ICC ≥ 0.884), and cadence (ICC ≥ 0.765), with narrower between-systems than over-repetitions limits of agreement. Face validity was demonstrated with significantly different walking speeds, step lengths and cadences over walking-speed conditions. To conclude, walking speed, step length, and cadence can be reliably and validly quantified from the position data of the wearable HoloLens 1 measurement system, not only for a broad range of speeds in healthy young adults, but also for self-selected comfortable speed in people with Parkinson’s disease.
Nano-Vesicle Based Anti-Fungal Formulation Shows Higher Stability, Skin Diffusion, Biosafety and Anti-Fungal Efficacy In Vitro

Opportunistic fungal infections are responsible for over 1.5 million deaths per year. This has created a need for highly effective antifungal medication to be as potent as possible. In this study, we improved the efficacy of a common over the counter (OTC) antifungal skin medication, miconazole, by encapsulating nano-molecules of the drug in cholesterol/sodium oleate nano-vesicles. These nano-vesicles were characterized to optimize their size, zeta potential, polydispersity index and encapsulation efficiency. Furthermore, these nano-vesicles were compared to a conventional miconazole-based commercially available cream to determine potential improvements via permeation through the stratum corneum, cytotoxicity, and antifungal capabilities. Our results found that the vesicle size was within the nano range (~300 nm), with moderate polydispersity and stability. When compared with the commercially available cream, Actavis, as well as free miconazole, the miconazole nano-vesicle formulation displayed enhanced fungal inhibition by a factor of three or more when compared to free miconazole. Furthermore, with smaller nanoparticle (NP) sizes, higher percentages of miconazole may be delivered, further enhancing the efficacy of miconazole’s antifungal capability. Cytotoxicity studies conducted with human dermal fibroblast cells confirm its biosafety and biocompatibility, as cell survival rate was observed to be twofold higher in nano-vesicle formulation than free miconazole. This formulation has the potential to treat fungal infections through increasing the retention time in the skin, improving the treatment approach, and by enhancing the efficacy via the use of nano-vesicles.