Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Antioxidative Activity for Extracts from Defatted Rice Bran Using 5-Axe Cobweb Chart

Defatted rice bran was treated at 230°C for 5 min with distilled water or 40% (v/v) acetone to produce the corresponding extracts. Acetone-soluble substances were fractionated from the extracts. The antioxidative activities against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl and peroxyl radicals, and the hypochlorite and peroxynitrite ions of the extracts and acetone-soluble substances were examined, and the activities were comprehensively characterized using the 5-axe cobweb chart. The 40% acetone extract exhibited higher activity than the water extract. Fractionation of acetone-soluble substances from extracts increased activity. The acetone-soluble substances from the extract with 40% acetone exhibited the highest activity among the extracts and acetone-soluble substances.
Fragile X Mental Retardation Protein Bidirectionally Controls Dendritic Ih in a Cell Type-Specific Manner between Mouse Hippocampus and Prefrontal Cortex

Channelopathies are implicated in Fragile X syndrome (FXS), yet the dysfunction of a particular ion channel varies with cell type. We previously showed that HCN channel function is elevated in CA1 dendrites of the fmr1–/y mouse model of FXS, but reduced in L5 PFC dendrites. Using male mice, we tested whether Fragile X Mental Retardation Protein (FMRPO), the protein whose absence causes FXS, differentially modulates HCN channels in CA1 versus L5 PFC dendrites. Using a combination of viral tools, intracellular peptide, and dendritic electrophysiology, we found that FMRP regulates HCN channels via a cell-autonomous protein–protein interaction. Virally expressed FMRP restored WT HCN channel-related dendritic properties in both CA1 and L5 neurons. Rapid intracellular perfusion of the non-mRNA binding N-terminal fragment, FMRP1-298, similarly restored dendritic function. In support of a protein–protein interaction, we found that FMRP associated with HCN-TRIP8b complexes in both hippocampus and PFC. Finally, voltage-clamp recordings showed that FMRP modulated Ih by regulating the number of functional dendritic HCN channels rather than individual channel properties. Together, these represent three novel findings as to the nature of the changes in dendritic function in CA1 and PFC neurons based on the presence or absence of FMRP. Moreover, our findings provide evidence that FMRP can regulate its targets in opposite directions depending upon the cellular milieu. SIGNIFICANCE STATEMENT Changes in dendritic function, and voltage-gated ion channels in particular, are increasingly the focus of neurological disorders. We, and others, previously identified cell type-specific channelopathies in a mouse of model of Fragile X syndrome. The present study shows that replacing Fragile X Mental Retardation Protein, which is absent in Fragile X syndrome, in adult CA1 and L5 PFC neurons regulates the number of functional dendritic HCN channels in a cell type-specific manner. These results suggest that Fragile X Mental Retardation Protein regulates dendritic HCN channels via a cell-autonomous protein--protein mechanism.
Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma

Key Points Question Is savolitinib monotherapy more effective than sunitinib monotherapy on progression-free survival (PFS) in patients with MET-driven, unresectable and locally advanced, or metastatic papillary renal cell carcinoma (PRCC)? Findings In this phase 3, open-label, randomized clinical multicenter study including 60 patients with MET-driven PRCC, the primary end point was PFS. Although study enrollment was closed early, PFS was not statistically different for patients who received savolitinib or sunitinib, and the safety profile was superior with savolitinib. Meaning Further investigation of savolitinib as a treatment option for MET-driven PRCC is warranted.
Aspects of Parent–Child Interaction from Infancy to Late Adolescence are Associated with Severity of Childhood Maltreatment through Age 18

Childhood maltreatment (CM) is a pervasive public health problem worldwide, with negative health consequences across the lifespan. Despite these adverse outcomes, identifying children who are being maltreated remains a challenge. Thus, there is a need to identify reliably observable features of parent–child interaction that indicate risk for CM and that can instigate strategically targeted family supports. The aim of this longitudinal study was to assess multiple aspects of observed mother–child interaction from infancy to late adolescence as risk indicators of the overall severity of CM by age 18. Mother–child dyads were assessed in infancy (N = 56), at age 7 years (N = 56), and at age 19 years (N = 56/110). Severity of CM through age 18 was indexed by combined prospective and retrospective assessments. Interactions associated with severity of CM by age 18 included maternal hostility in infancy, maternal withdrawal in infancy and middle childhood, child disorganized attachment behavior in middle childhood and late adolescence, as well as hostile and role-confused interactions in late adolescence. This study identifies new indices of maternal and child behavior as important risk indicators for the severity of CM. These indices could be used to improve early identification and tailor preventive interventions for families at risk for CM.
The domesticated transposase ALP2 mediates formation of a novel Polycomb protein complex by direct interaction with MSI1, a core subunit of Polycomb Repressive Complex 2 (PRC2)

A large fraction of plant genomes is composed of transposable elements (TE), which provide a potential source of novel genes through “domestication”–the process whereby the proteins encoded by TE diverge in sequence, lose their ability to catalyse transposition and instead acquire novel functions for their hosts. In Arabidopsis, ANTAGONIST OF LIKE HETEROCHROMATIN PROTEIN 1 (ALP1) arose by domestication of the nuclease component of Harbinger class TE and acquired a new function as a component of POLYCOMB REPRESSIVE COMPLEX 2 (PRC2), a histone H3K27me3 methyltransferase involved in regulation of host genes and in some cases TE. It was not clear how ALP1 associated with PRC2, nor what the functional consequence was. Here, we identify ALP2 genetically as a suppressor of Polycomb-group (PcG) mutant phenotypes and show that it arose from the second, DNA binding component of Harbinger transposases. Molecular analysis of PcG compromised backgrounds reveals that ALP genes oppose silencing and H3K27me3 deposition at key PcG target genes. Proteomic analysis reveals that ALP1 and ALP2 are components of a variant PRC2 complex that contains the four core components but lacks plant-specific accessory components such as the H3K27me3 reader LIKE HETEROCHROMATION PROTEIN 1 (LHP1). We show that the N-terminus of ALP2 interacts directly with ALP1, whereas the C-terminus of ALP2 interacts with MULTICOPY SUPPRESSOR OF IRA1 (MSI1), a core component of PRC2. Proteomic analysis reveals that in alp2 mutant backgrounds ALP1 protein no longer associates with PRC2, consistent with a role for ALP2 in recruitment of ALP1. We suggest that the propensity of Harbinger TE to insert in gene-rich regions of the genome, together with the modular two component nature of their transposases, has predisposed them for domestication and incorporation into chromatin modifying complexes.
The Mediator CDK8-Cyclin C complex modulates Dpp signaling in Drosophila by stimulating Mad-dependent transcription

Dysregulation of CDK8 (Cyclin-Dependent Kinase 8) and its regulatory partner CycC (Cyclin C), two subunits of the conserved Mediator (MED) complex, have been linked to diverse human diseases such as cancer. Thus, it is essential to understand the regulatory network modulating the CDK8-CycC complex in both normal development and tumorigenesis. To identify upstream regulators or downstream effectors of CDK8, we performed a dominant modifier genetic screen in Drosophila based on the defects in vein patterning caused by specific depletion or overexpression of CDK8 or CycC in developing wing imaginal discs. We identified 26 genomic loci whose haploinsufficiency can modify these CDK8- or CycC-specific phenotypes. Further analysis of two overlapping deficiency lines and mutant alleles led us to identify genetic interactions between the CDK8-CycC pair and the components of the Decapentaplegic (Dpp, the Drosophila homolog of TGFβ, or Transforming Growth Factor-β) signaling pathway. We observed that CDK8-CycC positively regulates transcription activated by Mad (Mothers against dpp), the primary transcription factor downstream of the Dpp/TGFβ signaling pathway. CDK8 can directly interact with Mad in vitro through the linker region between the DNA-binding MH1 (Mad homology 1) domain and the carboxy terminal MH2 (Mad homology 2) transactivation domain. Besides CDK8 and CycC, further analyses of other subunits of the MED complex have revealed six additional subunits that are required for Mad-dependent transcription in the wing discs: Med12, Med13, Med15, Med23, Med24, and Med31. Furthermore, our analyses confirmed the positive roles of CDK9 and Yorkie in regulating Mad-dependent gene expression in vivo. These results suggest that CDK8 and CycC, together with a few other subunits of the MED complex, may coordinate with other transcription cofactors in regulating Mad-dependent transcription during wing development in Drosophila.
TARGET DISCRIMINATION BY AN ECHOLOCATING FINLESS PORPOISE, NEOPHOCAENA PHOCAENOIDES

The ability of a finless porpoise (Neophocaena phocaenoides) to discriminate the material and size of a target by echolocation was investigated. The porpoise was required to choose a standard target of a 15-mm diameter solid steel cylinder from two stimuli, a standard and a comparison target, presented simultaneously. The porpoise could distinguish a standard cylinder from acrylic resin and brass targets, but had difficulties distinguishing it from an aluminum cylinder. In size discrimination, the porpoise could distinguish the standard from 12-, 18-, and 20-mm diameter cylinders, but had difficulties distinguishing it from a 14-mm diameter cylinder. Echo measurements suggest that the porpoise is able to detect: (1) time difference between two echo highlights to within approximately 1 μS, (2) frequency shifts of approximately 7 kHz in a broadband echo having a peak frequency of nearly 140 kHz, (3) time-separation pitch of approximately 30 kHz, and (4) target strength differences of approximately 1 dB.
A concise history of genome-wide association studies

Genome-wide association studies (GWASs) have had a tremendous impact on the pace of genomic research of common diseases. The number of identified genetic variants associated has grown exponentially. For some diseases, such as coronary heart disease (CHD), the number of known susceptibility genes has grown from a handful to more than 45. A substantial number of genes point to unexpected mechanism involved, and functional data from the Encyclopedia of Deoxyribonucleic Acid Elements (ENCODE) project is helpful in uncovering the functional relevance to diseases. The rapidly evolving techniques have made the shift from family-based linkage studies to GWASs possible. Advanced single nucleotide polymorphism (SNP) arrays containing hundreds of thousands of variants efficiently assess the extent of genome-wide disease-associated genetic variation. Along with SNP arrays came breakthroughs in statistical analyses and study designs leading to the exponential growth of the GWAS catalog. Pathway analyses of GWASs results with manually curated software programs have been insightful. Next-generation sequencing (NGS) of the exome or even the whole genome will undoubtedly shift the balance in focus from common variants to more rare variations impacting common diseases. Moreover, the combined power of GWASs, sequencing, pathway analysis, and functional data to study common disease shall only be limited by our ability to comprehend.
How to implement the framework for the elimination of mother-to-child transmission of HIV, syphilis, hepatitis B and Chagas (EMTCT Plus) in a disperse rural population from the Gran Chaco region: A tailor-made program focused on pregnant women

1 Fundación Mundo Sano, Buenos Aires, Argentina, 2 Asociación para el Desarrollo Sanitario Regional (ADESAR), San Antonio de Areco, Buenos Aires, Argentina, 3 Consejo Nacional de Investigaciones Cientı́ficas y Técnicas (CONICET), Centro de Educación Médica e Investigaciones Clı́nicas “Norberto Quirno” (CEMIC), Buenos Aires, Argentina, 4 Instituto de Parasitologı́a “Dr. Mario Fatala Chaben,” Administración Nacional de Laboratorios e Institutos de Salud (ANLIS), Buenos Aires, Argentina, 5 Centro Nacional de Diagnóstico e Investigaciones en Endemo-epidemias (CeNDIE), ANLIS, Buenos Aires, Argentina, 6 Universidad Nacional de San Antonio de Areco, San Antonio de Areco, Buenos Aires, Argentina, 7 Ministerio de Salud Pública de Salta, Salta, Argentina, 8 Ministerio de Primera Infancia, Salta, Argentina, 9 Dirección de Salud, Gobierno Autónomo Regional del Gran Chaco, Bolivia, 10 XVI Región Sanitaria Boquerón, Ministerio de Salud Pública y Bienestar Social, Mariscal José Félix Estigarribia, Paraguay, 11 Consejo Nacional de Investigaciones Cientı́fica y Técnicas (CONICET), Instituto de Investigaciones en Enfermedades Tropicales (IIET), Universidad de Salta – Sede Regional Orán, San Ramón de Orán, Salta, Argentina, 12 Consejo Nacional de Investigaciones Cientı́fica y Técnicas (CONICET), Fundación Mundo Sano, Buenos Aires, Argentina
Prevalence of Familial Hypercholesterolemia Among the General Population and Patients With Atherosclerotic Cardiovascular Disease

Supplemental Digital Content is available in the text. Background: Contemporary studies suggest that familial hypercholesterolemia (FH) is more frequent than previously reported and increasingly recognized as affecting individuals of all ethnicities and across many regions of the world. Precise estimation of its global prevalence and prevalence across World Health Organization regions is needed to inform policies aiming at early detection and atherosclerotic cardiovascular disease (ASCVD) prevention. The present study aims to provide a comprehensive assessment and more reliable estimation of the prevalence of FH than hitherto possible in the general population (GP) and among patients with ASCVD. Methods: We performed a systematic review and meta-analysis including studies reporting on the prevalence of heterozygous FH in the GP or among those with ASCVD. Studies reporting gene founder effects and focused on homozygous FH were excluded. The search was conducted through Medline, Embase, Cochrane, and Global Health, without time or language restrictions. A random-effects model was applied to estimate the overall pooled prevalence of FH in the general and ASCVD populations separately and by World Health Organization regions. Results: From 3225 articles, 42 studies from the GP and 20 from populations with ASCVD were eligible, reporting on 7 297 363 individuals/24 636 cases of FH and 48 158 patients/2827 cases of FH, respectively. More than 60% of the studies were from Europe. Use of the Dutch Lipid Clinic Network criteria was the commonest diagnostic method. Within the GP, the overall pooled prevalence of FH was 1:311 (95% CI, 1:250–1:397; similar between children [1:364] and adults [1:303], P=0.60; across World Health Organization regions where data were available, P=0.29; and between population-based and electronic health records–based studies, P=0.82). Studies with ≤10 000 participants reported a higher prevalence (1:200–289) compared with larger cohorts (1:365–407; P<0.001). The pooled prevalence among those with ASCVD was 18-fold higher than in the GP (1:17 [95% CI, 1:12–1:24]), driven mainly by coronary artery disease (1:16; [95% CI, 1:12–1:23]). Between-study heterogeneity was large (I2>95%). Tests assessing bias were nonsignificant (P>0.3). Conclusions: With an overall prevalence of 1:311, FH is among the commonest genetic disorders in the GP, similarly present across different regions of the world, and is more frequent among those with ASCVD. The present results support the advocacy for the institution of public health policies, including screening programs, to identify FH early and to prevent its global burden.
In situ Bioassays of Brook Trout (Salvelinus fontinalis) and Blacknose Dace (Rhinichthys atratulus) in Adirondack Streams Affected by Episodic Acidification

In situ bioassays were conducted using native Adirondack brook trout (Salvelinus fontinalis) and blacknose dace (Rhinichthys atratulus) in four headwater streams. Conductivity, pH, temperature, and stage height were monitored continuously, and water samples for laboratory analysis were collected during hydrologic episodes. Fish survived well during baseflow conditions, but during periods of spring snowmelt or large precipitation events, survival was poor. Blacknose dace were more sensitive than brook trout, and mortality was best correlated with the log of median inorganic monomeric aluminum (Alim) concentration. Brook trout mortality was best correlated with a two-variable model that included dissolved organic carbon (DOC) and a concentration–duration variable (median Alim during the episode times the duration of the episode). Brook trout mortality was inversely correlated with DOC. Bioassay fish that had been in the streams 15–24 d survived episodes better than fish that had either not become acclimatiz.
Telomere DNA Damage Signaling Regulates Prostate Cancer Tumorigenesis

Telomere shortening has been demonstrated in benign prostatic hypertrophy (BPH), which is associated with prostate epithelial cell senescence. Telomere shortening is the most frequently observed genetic alteration in prostatic intraepithelial neoplasia, and is associated with poor clinical outcomes in prostate cancer. Gene expression database analysis revealed decreased TRF2 expression during malignant progression of the prostate gland. We reasoned that reduced TRF2 expression in prostate epithelium, by activating the telomere DNA damage response, would allow us to model both benign and malignant prostate disease. Prostate glands with reduced epithelial TRF2 expression developed age- and p53-dependent hypertrophy, senescence, ductal dilation, and smooth muscle hyperplasia similar to human BPH. Prostate tumors with reduced TRF2 expression were classified as high-grade androgen receptor–negative adenocarcinomas, which exhibited decreased latency, increased proliferation, and distant metastases. Prostate cancer stem cells with reduced TRF2 expression were highly tumorigenic and maintained telomeres both by telomerase and alternative lengthening (ALT). Telomerase inhibition in prostate glands with reduced TRF2 expression produced significant reduction in prostate tumor incidence by halting progression at intraepithelial neoplasia (PIN). These lesions were highly differentiated, exhibited low proliferation index, and high apoptotic cell fraction. Prostate tumors with reduced TRF2 expression and telomerase inhibition failed to metastasize and did not exhibit ALT. Implications: Our results demonstrate that the telomere DNA damage response regulates BPH, PIN, and prostate cancer and may be therapeutically manipulated to prevent prostate cancer progression.
Accuracy of Underwater Counts of Juvenile Chinook Salmon, Coho Salmon, and Steelhead

Abstract Underwater observers counted juvenile salmonids in study areas on mid-Columbia River tributaries, and the accuracy of these counts was examined. We compared counts taken by two to six experienced snorkelers with counts obtained after use of sodium cyanide in the same sites at stream temperatures that ranged from 5.6 to 18.3°C. We found no significant relationships between the accuracy of visual counts of juvenile salmonids and discharge, surface area, or time of day that we snorkeled. However, the accuracy of visual counts of age-0 chinook salmon Oncorhynchus tshawytscha, age-0 steelhead O. mykiss, and age-1 and older (age-1+) steelhead, but not of age-0 coho salmon O. kisutch. declined significantly with decreased temperatures. At temperatures above 14°C, snorkelers counted about 70% of the juvenile salmonids present. Below 14°C, most counts included under half the fish present, and below 9°C, snorkelers observed less than 20% of the fish present. At temperatures above 14°C, accuracy of snorkel .
The Exploration of How Social Media Cultivate College Student Smokers: Theorizing Valence of Communication, Impression Management, and Perceived Risks and Benefits of Smoking in the O1-S-R1-O2-R2 Model

ABSTRACT The purpose of this study is to build a theoretical framework to account for how social media lead college students to smoke. Arguing critical concepts, such as valence of communication, impression management, perceived risks and benefits, this study develops the O 1 -S-R 1 -O 2 -R 2 model. For this, we test a separated model for smokers and nonsmokers. For smokers, the effect of exposure to pro-smoking content on smoking behavior is mediated by an impression of smokers, a favorable expression about smoking, and perceived benefits. And, the effect of exposure to anti-smoking content on smoking behavior is mediated by an unfavorable expression about smoking and perceived risks. However, such mediation processes cannot be observed for nonsmokers; namely, the effect of exposure to pro-smoking content on smoking intention is only mediated by a favorable expression about smoking. Considering the separated path models for smokers and nonsmokers, theoretical and practical implications are suggested for future study. Methodological limitations are discussed as well.
Development of an Outcome Measure of Observable Signs of Health and Well-Being in Infants With Orofacial Clefts

Objective: To develop an outcomes instrument that assesses observations that can be reliably reported by caregivers and can be used to assess health of infants with a cleft lip or cleft lip and cleft palate (CL±P) and impacts of treatments. Design: Cross-sectional, mixed methods study. Setting: Caregivers and health-care providers were recruited from 3 academic craniofacial centers and national advertisements. Most interviews were conducted by telephone, and surveys were completed online. Participants: Caregivers had a child less than 3 years of age with CL±P and spoke either English or Spanish. Health-care providers were members of a cleft team. Caregivers (n = 492) and health-care professionals (n = 75) participated in at least one component of this study. Main Outcome Measure(s): Caregivers and health-care providers participated in tasks related to instrument development: concept elicitation for items within relevant health domains, prioritization of items, and item review. Results: We identified 295 observations of infant well-being across 9 health areas. Research staff and specialists evaluated items for clarity, specificity to CL±P, and responsiveness to treatment. Caregivers and health-care providers rated the resulting list of 104 observations and developed the final instrument of 65 items. Conclusions: In this phase of development of the Infant with Clefts Observation Outcomes (iCOO) instrument, items were developed to collect caregiver observations about indicators of children’s health and well-being across multiple domains allowing for psychometric testing, sensitivity to changes associated with treatment, and documentation of the effects of treatment.