Miracle-dz/UniFAR-FTUs huggingface dataset:
A comprehensive genomic history of extinct and living elephants

Significance Elephantids were once among the most widespread megafaunal families. However, only three species of this family exist today. To reconstruct their evolutionary history, we generated 14 genomes from living and extinct elephantids and from the American mastodon. While previous studies examined only simple bifurcating relationships, we found that gene flow between elephantid species was common in the past. Straight-tusked elephants descend from a mixture of three ancestral populations related to the ancestor of African elephants, woolly mammoths, and present-day forest elephants. We detected interbreeding between North American woolly and Columbian mammoths but found no evidence of recent gene flow between forest and savanna elephants, demonstrating that both gene flow and isolation have been central in the evolution of elephantids. Elephantids are the world’s most iconic megafaunal family, yet there is no comprehensive genomic assessment of their relationships. We report a total of 14 genomes, including 2 from the American mastodon, which is an extinct elephantid relative, and 12 spanning all three extant and three extinct elephantid species including an ∼120,000-y-old straight-tusked elephant, a Columbian mammoth, and woolly mammoths. Earlier genetic studies modeled elephantid evolution via simple bifurcating trees, but here we show that interspecies hybridization has been a recurrent feature of elephantid evolution. We found that the genetic makeup of the straight-tusked elephant, previously placed as a sister group to African forest elephants based on lower coverage data, in fact comprises three major components. Most of the straight-tusked elephant’s ancestry derives from a lineage related to the ancestor of African elephants while its remaining ancestry consists of a large contribution from a lineage related to forest elephants and another related to mammoths. Columbian and woolly mammoths also showed evidence of interbreeding, likely following a latitudinal cline across North America. While hybridization events have shaped elephantid history in profound ways, isolation also appears to have played an important role. Our data reveal nearly complete isolation between the ancestors of the African forest and savanna elephants for ∼500,000 y, providing compelling justification for the conservation of forest and savanna elephants as separate species.
RVX-208, an Inducer of ApoA-I in Humans, Is a BET Bromodomain Antagonist

Increased synthesis of Apolipoprotein A-I (ApoA-I) and HDL is believed to provide a new approach to treating atherosclerosis through the stimulation of reverse cholesterol transport. RVX-208 increases the production of ApoA-I in hepatocytes in vitro, and in vivo in monkeys and humans, which results in increased HDL-C, but the molecular target was not previously reported. Using binding assays and X-ray crystallography, we now show that RVX-208 selectively binds to bromodomains of the BET (Bromodomain and Extra Terminal) family, competing for a site bound by the endogenous ligand, acetylated lysine, and that this accounts for its pharmacological activity. siRNA experiments further suggest that induction of ApoA-I mRNA is mediated by BET family member BRD4. These data indicate that RVX-208 increases ApoA-I production through an epigenetic mechanism and suggests that BET inhibition may be a promising new approach to the treatment of atherosclerosis.
The Major Birch Pollen Allergen Bet v 1 Induces Different Responses in Dendritic Cells of Birch Pollen Allergic and Healthy Individuals

Dendritic cells play a fundamental role in shaping the immune response to allergens. The events that lead to allergic sensitization or tolerance induction during the interaction of the major birch pollen allergen Bet v 1 and dendritic cells are not very well studied. Here, we analyzed the uptake of Bet v 1 and the cross-reactive celery allergen Api g 1 by immature monocyte-derived dendritic cells (iMoDCs) of allergic and normal donors. In addition, we characterized the allergen-triggered intracellular signaling and transcriptional events. Uptake kinetics, competitive binding, and internalization pathways of labeled allergens by iMoDCs were visualized by live-cell imaging. Surface-bound IgE was detected by immunofluorescence microscopy and flow cytometry. Allergen- and IgE-induced gene expression of early growth response genes and Th1 and Th2 related cytokines and chemokines were analyzed by real-time PCR. Phosporylation of signaling kinases was analyzed by Western blot. Internalization of Bet v 1 by iMoDCs of both donor groups, likely by receptor-mediated caveolar endocytosis, followed similar kinetics. Bet v 1 outcompeted Api g 1 in cell surface binding and uptake. MoDCs of allergic and healthy donors displayed surface-bound IgE and showed a pronounced upregulation of Th2 cytokine- and NFκB-dependent genes upon non-specific Fcε receptor cross-linking. In contrast to these IgE-mediated responses, Bet v 1-stimulation increased transcript levels of the Th2 cytokines IL-4 and IL-13 but not of NFκB-related genes in MoDCs of BP allergic donors. Cells of healthy donors were either unresponsive or showed elevated mRNA levels of Th1-promoting chemokines. Moreover, Bet v 1 was able to induce Erk1/2 and p38 MAPK activation in BP allergics but only a slight p38 activation in normal donors. In conclusion, our data indicate that Bet v 1 favors the activation of a Th2 program only in DCs of BP allergic individuals.
DPP-4 Inhibitors as Therapeutic Modulators of Immune Cell Function and Associated Cardiovascular and Renal Insulin Resistance in Obesity and Diabetes

The prevalence of obesity and diabetes continues to rise in the United States and worldwide. These findings parallel the expansion of childhood obesity and diabetes. Obesity is a central component of the cardiorenal metabolic syndrome (CRS) which increases the risk for cardiovascular disease (CVD) and chronic kidney disease (CKD). The hallmark of obesity, CRS, and early type 2 diabetes is insulin resistance, a result of decreased insulin metabolic signaling due, in part, to enhanced serine phosphorylation and/or proteasome-mediated degradation of the insulin receptor substrate. Cardiovascular and renal insulin resistance significantly contributes to endothelial dysfunction, impaired cardiac diastolic and vascular relaxation, glomerular injury, and tubular dysfunction. In this context, multiple factors including oxidative stress, increased inflammation, and inappropriate activation of the renin-angiotensin-aldosterone and the sympathetic nervous system contribute to overweight- and obesity-induced systemic and tissue insulin resistance. One common link between obesity and the development of insulin resistance appears to be a low-grade inflammatory response resulting from dysfunctional innate and adaptive immunity. In this regard, there has been recent work on the role of dipeptidyl peptidase-4 (DPP-4) in modulating innate and adaptive immunity. The direct effects of DPP-4 on immune cells and the indirect effects through GLP-1-dependent and -independent pathways suggest effects of DPP-4 inhibition may have beneficial effects beyond glycemic control in improving CVD and renal outcomes. Accordingly, this review addresses new insights into the role of DPP-4 in immune modulation and the potential beneficial effects of DPP-4 inhibitors in insulin resistance and associated CVD and CKD prevention.
Augmenting mHealth With Human Support: Notes From Community Care of People With Serious Mental Illnesses

Topic: This article describes the activities of 2 mHealth specialists who supported the deployment of FOCUS—a smartphone self-management application for individuals with serious mental illnesses. Purpose: Several support activities have been identified as potentially advantageous for individuals using mHealth interventions: facilitation of user engagement, data utilization to enhance care, and promotion of meaningful use. We present 3 examples to demonstrate the implementation of these activities during a 12-week smartphone intervention. Sources Used: The personal experiences of 2 mHealth specialists are shared within the context of 3 examples of individuals who participated in the smartphone intervention. Conclusions and Implications for Practice: The application of these support activities highlights the future opportunities that mHealth interventions could offer to individuals with serious mental illnesses and their providers. Additionally, these examples call for conversation about technology support roles and where they belong in the context of community-based care.
Transcatheter closure of secundum atrial septal defects: has fear of device erosion altered outcomes?

Abstract Background Transcatheter device closure has become the established standard of care for suitable atrial septal defects. Device erosion has been a recent focus and has prompted changes in the Instructions for Users documentation released by device companies. We reviewed our entire local experience with atrial septal defect device closure, focussing on the evolution of this procedure in our centre and particularly on complications. Methods We carried out a retrospective review of 581 consecutive patients undergoing attempted transcatheter device closure of an atrial septal defect in Auckland from December 1997 to June 2014. We reviewed all complications recorded and compared our outcomes with the current literature. We sought to understand the impact of the evolution in recommendations and clinical practice on patient outcomes in our programme. Results There were a total of 24 complications (4.1%), including 10 device embolisations (1.7%), nine arrhythmias (1.5%), two significant vascular access-related complications (0.3%), one device erosion (0.2%), one malposed device (0.2%), and one probable wire perforation of the left atrial appendage (0.2%). There was one mortality related to device embolisation. All device embolisations occurred following the change in Instructions for Users after publication of the first device erosion report in 2004. This increase in embolisation rate was statistically significant (p-value 0.015). Conclusions In our series, the incidence of device embolisation was higher than that anticipated, with a significant increase following changes to the Instructions for Users. This highlights the need for ongoing data collection on complication incidence and for ongoing review of the impact of changes in clinical practice on complication rates.
C-Reactive Protein Concentration Predicts Change in Body Mass Index during Childhood

Objective Inflammation may constitute an underlying mechanism for increased risk of developing chronic diseases in later years, but few prospective studies have assessed the influence of low-grade inflammation on body weight gain, particularly among children in low- to middle-income settings with lower prevalence of overweight and obesity. We aimed to investigate whether C-reactive protein (CRP), as a biomarker of low-grade inflammation, predicts changes in body mass index-for-age z scores (BAZ) during childhood. Methods A population-based longitudinal study was conducted in the Brazilian Amazon among children aged ≤10 years in 2007, with follow-up visits in 2009 and 2012. Outcome was annual change in BAZ. As the main exposure of interest, CRP concentrations were divided into four categories, with values <1 mg/L divided in tertiles plus a fourth category with values ranging from 1 to 10 mg/L. Children were simultaneously screened for iron and vitamin A deficiencies, diarrhea, and wheezing. We used mixed-effect linear regression models to measure the effect of CRP concentrations on annual BAZ change and linear regression models to explore CRP predictors at baseline. Results At baseline, 1007 children had CRP and anthropometric data [mean (SD) age: 5.3 (2.9) years; 50.9% male, 84.5% mulatto/mixed-race, 14.0% at risk for overweight or obesity, 4.8% stunted]; 737 were successfully followed up. Morbidities and nutritional deficiencies were widespread. Among participants aged >5 years, children in the highest tertile of CRP <1 mg/L at baseline, regarded as an indicator of low-grade inflammation, had a 0.04 z/y higher gain in BAZ (95% CI: 0.01, 0.09 z/y) during follow-up. CRP was positively associated with household poverty and worse nutritional indicators. Conclusions We found evidence of a role for low-grade inflammation in predicting annual BAZ gain among children aged >5 years.
Experimental study of granular convection in (real) two- dimension Brazil-nut effect

Brazil-nut Effect (BNE) experiment in (real) two-dimension is conducted. Container, bed particles, and intruder are made from the same material, i.e. 2 mm thickness acrylic plate. Dimensionless acceleration r and vibration frequency f are in the range of 2-4 and 13-17 Hz, respectively. It is observed that rise time Trise decreases with the increase of Γ similar to reported by others, but there is a range of f and Γ, where Trise increases with the increase of Γ due to occurrence of Leidenfrost effect, which reduces convection flow of granular particles.
Development and Preliminary Validation of Chinese Preschoolers’ Eating Behavior Questionnaire

Background The objective of this study was to develop a questionnaire for caregivers to assess the eating behavior of Chinese preschoolers. Methods To assess children’s eating behaviors, 152 items were derived from a broad review of the literature related to epidemiology surveys and the assessment of children’s eating behaviors. All of these items were reviewed by 50 caregivers of preschoolers and 10 experienced pediatricians. Seventy-seven items were selected for use in a primary questionnaire. After conducting an exploratory factor analysis and a variability analysis on the data from 313 preschoolers used to evaluate this primary questionnaire, we deleted 39 of these 77 items. A Chinese Preschoolers’ Eating Behavior Questionnaire (CPEBQ) was finally established from the remaining 38 items. The structure of this questionnaire was explored by factor analysis, and its reliability, validity and discriminative ability were evaluated with data collected from caregivers of 603 preschoolers. Results The CPEBQ consisted of 7 dimensions and 38 items. The 7 dimensions were food fussiness, food responsiveness, eating habit, satiety responsiveness, exogenous eating, emotional eating and initiative eating. The Cronbach’s α coefficient for the questionnaire was 0.92, and the test-retest reliability was 0.72. There were significant differences between the scores of normal-weight, overweight and obese preschoolers when it was referred to food fussiness, food responsiveness, eating habits, satiety responsiveness and emotional eating (p<0.05). Differences in caregiver’s education levels also had significant effects on scores for food fussiness, eating habits and exogenous eating (p<0.05). Conclusions The CPEBQ satisfies the conditions of reliability and validity, in accordance with psychometric demands. The questionnaire can be employed to evaluate the characteristics of Chinese preschoolers’ eating behaviors; therefore, it can be used in child health care practice and research.
SILAC-Based Proteomic Profiling of the Human MDA-MB-231 Metastatic Breast Cancer Cell Line in Response to the Two Antitumoral Lactoferrin Isoforms: The Secreted Lactoferrin and the Intracellular Delta-Lactoferrin

Background Lactoferrins exhibit antitumoral activities either as a secretory lactoferrin or an intracellular delta-lactoferrin isoform. These activities involve processes such as regulation of the cell cycle and apoptosis. While lactoferrin has been shown to exert its function by activating different transduction pathways, delta-lactoferrin has been proven to act as a transcription factor. Like many tumor suppressors, these two proteins are under-expressed in several types of cancer, particularly in breast cancer. Methodology/Principal Findings In order to compare the differential effects of the re-introduction of lactoferrin isoforms in breast cancer cells we chose the cancerous mammary gland MDA-MB-231 cell line as a model. We produced a cell line stably expressing delta-lactoferrin. We also treated these cells with fresh purified human breast lactoferrin. We performed two quantitative proteomic studies in parallel using SILAC coupled to mass spectrometry in order to compare the effects of different doses of the two lactoferrin isoforms. The proteome of untreated, delta-lactoferrin expressing and human lactoferrin treated MDA-MB-231 cells were compared. Overall, around 5300 proteins were identified and quantified using the in-house developed MFPaQ software. Among these, expression was increased by 1.5-fold or more for around 300 proteins in delta-lactoferrin expressing cells and 190 proteins in lactoferrin treated cells. At the same time, about 200 and 40 proteins were found to be downregulated (0-0.7-fold) in response to delta-lactoferrin and lactoferrin, respectively. Conclusions/Significance Re-introduction of delta-lactoferrin and lactoferrin expression in MDA-MB-231 mainly leads to modifications of protein profiles involved in processes such as proliferation, apoptosis, oxidative stress, the ubiquitin pathway, translation and mRNA quality control. Moreover, this study identified new target genes of delta-lactoferrin transcriptional activity such as SelH, GTF2F2 and UBE2E1.
Detection of human immunoglobulin G based on poly(pyrrole-3-carboxylic acid) thin film using electrochemical-surface plasmon optical technique

An electrochemically controlled PP3C-based surface plasmon optical technique was employed to study an optical and electrical property of the PP3C film and a label-free detection of the interaction between anti-IgG and IgG. In this study, electropolymerization was employed to fabricate poly(pyrrole-3-carboxylic acid) (PP3C) film on a gold surface of substrate using pyrrole-3-carboxylic acid (P3C) monomer solution in 0.5 M H2SO4. Electrochemical-surface plasmon resonance (ECSPR) and electrochemical-transmission surface plasmon resonance (EC-TSPR) spectroscopy were carried out to study the kinetic property and electroactivity property of the PP3C film in a real-time. Various constant applied potentials were applied to the PP3C films in neutral phosphate-buffered saline (PBS) solution to study the electroactivity property. Moreover, Ultraviolet-visible (UV-vis) spectroscopy and
DARC alleles and Duffy phenotypes in African Americans

BACKGROUND: The DARC (Duffy blood group, chemokine receptor) gene encodes for a transmembrane glycoprotein that functions as a chemokine transporter, is a receptor for Plasmodium vivax and P. knowlesi, and expresses the Duffy blood group antigens (Fy). The Fy(a−b−) phenotype found in people of African descent is typically associated with a −67t>c mutation in the 5′‐untranslated region (UTR), which prevents red blood cells being invaded by P. vivax and P. knowlesi. The aim of this study was to establish DARC allele frequencies in an African American blood donor cohort, determine a phylogenetic tree for DARC, and compare human and Neandertal DARC genes.
Lapita Diet in Remote Oceania: New Stable Isotope Evidence from the 3000-Year-Old Teouma Site, Efate Island, Vanuatu

Remote Oceania was colonized ca. 3000 BP by populations associated with the Lapita Cultural Complex, marking a major event in the prehistoric settlement of the Pacific Islands. Although over 250 Lapita sites have been found throughout the Western Pacific, human remains associated with Lapita period sites are rare. The site of Teouma, on Efate Island, Vanuatu has yielded the largest burial assemblage (n = 68 inhumations) of Lapita period humans ever discovered, providing a unique opportunity for assessing human adaptation to the environment in a colonizing population. Stable isotope ratios (δ13C, δ15N, δ34S) of human bone collagen from forty-nine Teouma adults were analyzed against a comprehensive dietary baseline to assess the paleodiet of some of Vanuatu's earliest inhabitants. The isotopic dietary baseline included both modern plants and animals (n = 98) and prehistoric fauna from the site (n = 71). The human stable isotope data showed that dietary protein at Teouma included a mixture of reef fish and inshore organisms and a variety of higher trophic marine (e.g. marine turtle) and terrestrial animals (e.g. domestic animals and fruit bats). The domestic pigs and chickens at Teouma primarily ate food from a C3 terrestrial environment but their δ15N values indicated that they were eating foods from higher trophic levels than those of plants, such as insects or human fecal matter, suggesting that animal husbandry at the site may have included free range methods. The dietary interpretations for the humans suggest that broad-spectrum foraging and the consumption of domestic animals were the most important methods for procuring dietary protein at the site. Males displayed significantly higher δ15N values compared with females, possibly suggesting dietary differences associated with labor specialization or socio-cultural practices relating to food distribution.
Smartphone accelerometers for the detection of heart rate

ABSTRACT Introduction: Micro-electro-mechanical systems technology, now embedded into smartphones, potentially allows measuring heart mechanical activity by positioning the phone on the body and acquiring vibrational signals, without the need for additional peripherals or interfaces. However, lack of standardization in experimental protocol, processing methodology and validation procedures, together with the wide range of available smartphones on the market, impact on the comparability of results and their general validity. The aim of this review is to provide information on the state-of-the art of research in this field, with current limitations and potentials, thus potentially serving as a basis for the creation of a standard based on current experiences. Areas covered: The review focused on studies relevant to the extraction of the heart rate using accelerometric technology, searching for relevant literature (papers or conference proceedings) both in Pubmed and IEEE eXplore engines. Expert commentary: From the results of this review, the smartphone can be considered a powerful device able to accurately measure the resting heart rate, thanks to embedded accelerometer technology. However, lack of a shared standard in the acquisition protocol and analysis procedure, thus affecting user-collected data reliability, could limit clinical acceptability and prevent recommending this approach as a self-tracking tool in patients.