cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5125411
title: Supplementary Material for: From Structure to Function: Mitochondrial Morphology, Motion and Shaping in Vascular Smooth Muscle

description: The diversity of mitochondrial arrangements, which arise from the organelle being static or moving, or fusing and dividing in a dynamically reshaping network, is only beginning to be appreciated. While significant progress has been made in understanding the proteins that reorganise mitochondria, the physiological significance of the various arrangements is poorly understood. The lack of understanding may occur partly because mitochondrial morphology is studied most often in cultured cells. The simple anatomy of cultured cells presents an attractive model for visualizing mitochondrial behaviour but contrasts with the complexity of native cells in which elaborate mitochondrial movements and morphologies may not occur. Mitochondrial changes may take place in native cells (in response to stress and proliferation), but over a slow time-course and the cellular function contributed is unclear. To determine the role mitochondrial arrangements play in cell function, a crucial first step is characterisation of the interactions among mitochondrial components. Three aspects of mitochondrial behaviour are described in this review: (1) morphology, (2) motion and (3) rapid shape changes. The proposed physiological roles to which various mitochondrial arrangements contribute and difficulties in interpreting some of the physiological conclusions are also outlined.
DOI: 10.6084/m9.figshare.5125396
title: Supplementary Material for: The Role of Hemocytes in <b><i>Anopheles gambiae</i></b> Antiplasmodial Immunity

description: Hemocytes synthesize key components of the mosquito complement-like system, but their role in the activation of antiplasmodial responses has not been established. The effect of activating <i>Toll</i> signaling in hemocytes on <i>Plasmodium </i>survival was investigated by transferring hemocytes or cell-free hemolymph from donor mosquitoes in which the suppressor <i>cactus </i>was silenced. These transfers greatly enhanced antiplasmodial immunity, indicating that hemocytes are active players in the activation of the complement-like system, through an effector/effectors regulated by the <i>Toll</i> pathway. A comparative analysis of hemocyte populations between susceptible G3 and the refractory L3-5 <i>Anopheles gambiae</i> mosquito strains did not reveal significant differences under basal conditions or in response to <i>Plasmodium berghei</i> infection. The response of susceptible mosquitoes to different <i>Plasmodium</i> species revealed similar kinetics following infection with <i>P. berghei,</i><i>P. yoelii</i> or <i>P. falciparum,</i> but the strength of the priming response was stronger in less compatible mosquito-parasite pairs. The <i>Toll, Imd,</i><i>STAT</i> or <i>JNK</i> signaling cascades were not essential for the production of the hemocyte differentiation factor (HDF) in response to <i>P. berghei </i>infection, but disruption of <i>Toll, STAT</i> or <i>JNK </i>abolished hemocyte differentiation in response to HDF. We conclude that hemocytes are key mediators of <i>A. gambiae</i> antiplasmodial responses.
DOI: 10.6084/m9.figshare.5125399
title: Supplementary Material for: The Tonal Space of Contrastive Five Level Tones

description: Multiple-level tone contrasts are typologically disfavoured because they violate the dispersion principles of maximizing perceptual distance and minimizing articulatory effort. This study investigates the tonal dispersion of a multiple-level tone system by exploring the cues used in producing and perceiving the five level tones of Black Miao. Both production and perception experiments show that non-modal phonations are very important cues for these tonal contrasts. Non-modal phonations significantly contribute to the dispersion of the five level tones in two ways: either by enhancing pitch contrasts or by providing an additional contrastive cue. Benefiting from more than one cue, the level tones T11, T33 and T55 are well distinguished in the tonal space; by contrast, the level tones T22 and T44, only contrasting in pitch, are the most confusable tones. The tonal registers model proposed in this article sheds light on the different uses of non-modal phonations across languages.
DOI: 10.6084/m9.figshare.5125402
title: Supplementary Material for: Aging-Related Genes in Mesenchymal Stem Cells: A Mini-Review

description: Adult stem cells in mammalian organs play pivotal roles in the maintenance and repair of these organs throughout the life of the adult and maintain the proper homeostasis of a tissue or organ. Among the adult stem cells described to date, mesenchymal stem cells (MSCs) are highlighted for clinical applications because MSCs have many advantages for cell therapy, including multilineage differentiation, homing, immune modulation and wound-healing effects. However, as the aging of MSCs leads to an age-associated decline in their number and function, it is important to clarify the age-associated factors and regulatory mechanism associated with the MSC aging process.<b> </b>In this review, we amass and discuss the recent data related to age-associated genes in MSCs. In particular, the activities of epigenetic regulatory factors, including histone acetylase and DNA methyltransferase, modulate gene expression and crosstalk with each other during the MSC senescence process. p16<sup>INK4A</sup> and high-mobility group A2 play important age-associated roles in the regulation of MSC stemness, and lamin A- and prelamin A-dependent nuclear abnormalities have significant biological relevance in MSC aging. Taken together, the information described here, including the epigenetic regulatory factors, transcription factors and cell signaling, could be used toward the development of treatments for MSC aging and related defects.
DOI: 10.6084/m9.figshare.5125408.v1
title: Supplementary Material for: Individual Genetic Variations Related to Satiety and Appetite Control Increase Risk of Obesity in Preschool-Age Children in the STRONG Kids Program

description: <b><i>Background/Aims:</i></b> The burden of the childhood obesity epidemic is well recognized; nevertheless, the genetic markers and gene-environment interactions associated with the development of common obesity are still unknown. In this study, candidate genes associated to satiety and appetite control pathways with obesity-related traits were tested in Caucasian preschoolers from the STRONG Kids project. <b><i>Methods:</i></b> Eight genetic variants in genes related to obesity (BDNF, LEPR, FTO, PCSK1, POMC, TUB, LEP, and MC4R) were genotyped in 128 children from the STRONG Kids project (mean age 39.7 months). Data were analyzed for individual associations and to test for genetic predisposition scores (GPSs) with body mass index (BMI) and anthropometric traits (Z-scores, e.g. height-for-age Z-score, HAZ). Covariates included age, sex, and breastfeeding (BF) duration. <b><i>Results:</i></b> Obesity and overweight prevalence was 6.3 and 19.5%, respectively, according to age- and sex-specific BMI percentiles. Individual genetic associations of MC4R and LEPR markers with HAZ were strengthened when BF duration was included as a covariate. Our GPSs show that, as the number of risk alleles increased, the risk of higher BMI and HAZ also increased. Overall, the GPSs assembled were able to explain 2-3% of the variability in BMI and HAZ phenotypes. <b><i>Conclusion:</i></b> Genetic associations with common obesity-related phenotypes were found in the STRONG Kids project. GPSs assembled for specific candidate genes were associated with BMI and HAZ phenotypes.
DOI: 10.6084/m9.figshare.5125414.v1
title: Supplementary Material for: Low Birthweight and Premature Birth Are Risk Factors for Podocytopenia and Focal Segmental Glomerulosclerosis

description: <b><i>Background:</i></b> Recent reports suggest that low birthweight (LBW) is a risk factor for kidney diseases, including focal segmental glomerulosclerosis (FSGS), although the underlying pathological mechanism remains unknown. Podocyte loss triggers glomerulosclerosis; however, whether FSGS in LBW children is associated with podocytopenia is unclear. <b><i>Methods:</i></b> We reviewed the birthweights and gestational age of all patients who underwent renal biopsies from 1995 to 2011 at our Institute. Sixteen patients had FSGS, of which 6 (37.5%) had LBW; this LBW rate was significantly higher than the overall LBW rate in Japan (9.7%). The incidence of LBW was also high in patients with minimal change nephrotic syndrome (MCNS; 12.5%). The glomerular cell numbers in biopsy sections were calculated using computer image analysis and compared with FSGS of normal birthweight (NBW-FSGS). Biopsy specimens from age-matched patients with MCNS were also compared. Wilms' tumor-1 (WT1) immunohistochemistry was performed to enumerate the podocytes. <b><i>Results:</i></b> All patients in the LBW-FSGS group were also preterm, with an average gestational age of 25.8 weeks. The number of podocytes per glomerulus in the LBW-FSGS patients was 34 and 24% lower as compared to that in the MCNS patients (p &lt; 0.01) and the NBW-FSGS patients (p &lt; 0.05), respectively. Similar results were observed for the WT1-positive glomerular cell number. <b><i>Conclusion:</i></b> LBW and premature birth were associated with FSGS development. The possibility that LBW and premature birth may be predisposing factors for severe podocytopenia in children with FSGS warrants further investigation.
DOI: 10.6084/m9.figshare.5125393
title: Supplementary Material for: Chronic Kidney Disease Causes Disruption of Gastric and Small Intestinal Epithelial Tight Junction

description: <b><i>Background:</i></b> Integrity of the tight junction (TJ) which seals the gap between the epithelial cells of the gastrointestinal tract is critical in preventing the entry of the microbial toxins, antigens, and other harmful products in the subepithelial tissues and the internal milieu. By enabling the absorption of these products, impairment of the intestinal epithelial barrier leads to local and systemic inflammation. We have recently found depletion of the key protein constituents of colonic epithelial TJ in animals with chronic kidney disease (CKD). Postmortem studies have revealed the presence of inflammation throughout the gastrointestinal tract in uremic humans. This observation suggests that uremia may cause disruption of the epithelial barrier in all segments of the gastrointestinal tract including the stomach, jejunum, and ileum. The present study was undertaken to explore this possibility. <b><i>Methods:</i></b> Sprague-Dawley rats were randomized to CKD or control groups. The CKD group was subjected to 5/6 nephrectomy while the control group underwent a sham operation. The animals were observed for 10 weeks at which time they were euthanized and their stomachs, jejunums, and ileums were removed and processed for measurement of TJ proteins. <b><i>Results:</i></b> The CKD rats showed marked azotemia, systemic oxidative stress, and marked depletion of the key protein constituents of the epithelial TJ (claudin-1, occludin, and ZO1) in the stomach, jejunum, and ileum. <b><i>Conclusions:</i></b> The present study extends the earlier finding of uremia-induced disruption of colonic epithelial TJ by documenting the involvement of the stomach, jejunum, and ileum as well.
DOI: 10.6084/m9.figshare.5125390
title: Supplementary Material for: Pubertal Growth and Serum Testosterone and Estradiol Levels in Boys

description: <b><i>Background/Aims:</i></b> To study serum testosterone and estradiol in healthy boys in relation to growth during puberty up to peak height velocity (PHV). <b><i>Methods:</i></b> Growth velocity was analyzed through testosterone (n = 41) and 17β-estradiol (n = 37) 24-hour profiles in a dose-response model. Participants were 26 healthy boys admitted for short or tall stature or participating as healthy volunteers at the Queen Silvia Children's Hospital. Other inclusion criteria included the following: gestational age 37-42 weeks, birth weight and length &gt;-2 standard deviation score (SDS) and prepubertal height and weight within ±3 SDS. Testosterone was measured using a modified radioimmunoassay (RIA) with a detection limit of 0.03 nmol/l. Estradiol was determined using an ultrasensitive extraction RIA with a detection limit 4 pmol/l. A sixth-grade polynomial was fitted to each child's growth data, giving growth velocity and age at PHV. <b><i>Results:</i></b> Growth velocity increased by 50% from prepubertal growth to PHV at a morning testosterone level of 3.1 nmol/l (95% confidence interval 2.4-4.2), EC<sub>50</sub>. The corresponding EC<sub>50</sub> of 17β-estradiol was 6.5 pmol/l (3.2-13). Boys approaching PHV (&lt;4% remaining) had morning testosterone levels &gt;10 nmol/l and 17β-estradiol &gt;9 pmol/l. <b><i>Conclusion:</i></b> Observed early puberty/initial mid puberty morning testosterone levels of 2.4-4.2 nmol/l are associated with a 50% increase in growth velocity from prepubertal growth to PHV in healthy boys.
DOI: 10.6084/m9.figshare.5125396.v1
title: Supplementary Material for: The Role of Hemocytes in <b><i>Anopheles gambiae</i></b> Antiplasmodial Immunity

description: Hemocytes synthesize key components of the mosquito complement-like system, but their role in the activation of antiplasmodial responses has not been established. The effect of activating <i>Toll</i> signaling in hemocytes on <i>Plasmodium </i>survival was investigated by transferring hemocytes or cell-free hemolymph from donor mosquitoes in which the suppressor <i>cactus </i>was silenced. These transfers greatly enhanced antiplasmodial immunity, indicating that hemocytes are active players in the activation of the complement-like system, through an effector/effectors regulated by the <i>Toll</i> pathway. A comparative analysis of hemocyte populations between susceptible G3 and the refractory L3-5 <i>Anopheles gambiae</i> mosquito strains did not reveal significant differences under basal conditions or in response to <i>Plasmodium berghei</i> infection. The response of susceptible mosquitoes to different <i>Plasmodium</i> species revealed similar kinetics following infection with <i>P. berghei,</i><i>P. yoelii</i> or <i>P. falciparum,</i> but the strength of the priming response was stronger in less compatible mosquito-parasite pairs. The <i>Toll, Imd,</i><i>STAT</i> or <i>JNK</i> signaling cascades were not essential for the production of the hemocyte differentiation factor (HDF) in response to <i>P. berghei </i>infection, but disruption of <i>Toll, STAT</i> or <i>JNK </i>abolished hemocyte differentiation in response to HDF. We conclude that hemocytes are key mediators of <i>A. gambiae</i> antiplasmodial responses.
DOI: 10.6084/m9.figshare.5125381
title: Supplementary Material for: Pilot Study Using Proteomics to Identify Predictive Biomarkers of Necrotizing Enterocolitis from Buccal Swabs in Very Low Birth Weight Infants

description: <b><i>Background:</i></b> Necrotizing enterocolitis (NEC) is a major cause of death and morbidity in very low birth weight infants. <b><i>Objective:</i></b> To identify biomarker(s) that would predict NEC using buccal swab samples utilizing a proteomic approach. <b><i>Methods:</i></b> Cumulative buccal swab samples derived from very low birth weight preterm infants (&lt;32 weeks' gestational age and &lt;1,250 g) at 1, 2 and 3 weeks prior to the development of NEC and matched controls were subjected to two-dimensional difference gel electrophoresis and LC-MS/MS analysis for proteomic protein discovery. After identification of 21 altered proteins, we chose 3 candidate proteins using a broad systems biologic analysis approach that suggested several altered cellular processes that could be associated with NEC. <b><i>Results:</i></b> Preliminary validation studies using Western blots on these samples and 10 additional NEC and 10 matched control buccal samples collected within 2 or 3 weeks before NEC diagnosis analysis showed lower interleukin-1 receptor antagonist. <b><i>Conclusion:</i></b> Our results suggest that interleukin-1 receptor antagonist is worthy of further studies to determine its utility in helping predict NEC.
DOI: 10.6084/m9.figshare.5125384
title: Supplementary Material for: Genome-Wide Transcriptional Analysis of <b><i>Drosophila</i></b> Larvae Infected by Entomopathogenic Nematodes Shows Involvement of Complement, Recognition and Extracellular Matrix Proteins

description: <i>Heterorhabditis bacteriophora</i> is an entomopathogenic nematode (EPN) which infects its host by accessing the hemolymph where it releases endosymbiotic bacteria of the species <i>Photorhabdus luminescens</i>. We performed a genome-wide transcriptional analysis of the <i>Drosophila</i> response to EPN infection at the time point at which the nematodes reached the hemolymph either via the cuticle or the gut and the bacteria had started to multiply. Many of the most strongly induced genes have been implicated in immune responses in other infection models. Mapping of the complete set of differentially regulated genes showed the hallmarks of a wound response, but also identified a large fraction of EPN-specific transcripts. Several genes identified by transcriptome profiling or their homologues play protective roles during nematode infections. Genes that positively contribute to controlling nematobacterial infections encode: a homolog of thioester-containing complement protein 3, a basement membrane component (glutactin), a recognition protein (GNBP-like 3) and possibly several small peptides. Of note is that several of these genes have not previously been implicated in immune responses.
DOI: 10.6084/m9.figshare.5125390.v1
title: Supplementary Material for: Pubertal Growth and Serum Testosterone and Estradiol Levels in Boys

description: <b><i>Background/Aims:</i></b> To study serum testosterone and estradiol in healthy boys in relation to growth during puberty up to peak height velocity (PHV). <b><i>Methods:</i></b> Growth velocity was analyzed through testosterone (n = 41) and 17β-estradiol (n = 37) 24-hour profiles in a dose-response model. Participants were 26 healthy boys admitted for short or tall stature or participating as healthy volunteers at the Queen Silvia Children's Hospital. Other inclusion criteria included the following: gestational age 37-42 weeks, birth weight and length &gt;-2 standard deviation score (SDS) and prepubertal height and weight within ±3 SDS. Testosterone was measured using a modified radioimmunoassay (RIA) with a detection limit of 0.03 nmol/l. Estradiol was determined using an ultrasensitive extraction RIA with a detection limit 4 pmol/l. A sixth-grade polynomial was fitted to each child's growth data, giving growth velocity and age at PHV. <b><i>Results:</i></b> Growth velocity increased by 50% from prepubertal growth to PHV at a morning testosterone level of 3.1 nmol/l (95% confidence interval 2.4-4.2), EC<sub>50</sub>. The corresponding EC<sub>50</sub> of 17β-estradiol was 6.5 pmol/l (3.2-13). Boys approaching PHV (&lt;4% remaining) had morning testosterone levels &gt;10 nmol/l and 17β-estradiol &gt;9 pmol/l. <b><i>Conclusion:</i></b> Observed early puberty/initial mid puberty morning testosterone levels of 2.4-4.2 nmol/l are associated with a 50% increase in growth velocity from prepubertal growth to PHV in healthy boys.
DOI: 10.6084/m9.figshare.5125372
title: Supplementary Material for: Risk of Vascular Events after Nondisabling Small and Large Vessel Cerebral Ischemia

description: <b><i>Background:</i></b> Small- and large-vessel disease (SVD and LVD, respectively) might have a different pathogenesis and prognosis but the long-term risk of death and recurrent stroke appears to be similar in previous studies. In this study, we investigated the long-term vascular prognosis of patients with LVD and SVD in a large cohort of well-documented patients. <b><i>Methods:</i></b> We included 971 patients with transient ischemic attack (TIA) or nondisabling ischemic stroke of atherosclerotic origin referred to a university hospital in the Netherlands between 1994 and 2005 and followed them for the occurrence of vascular events or death. The primary outcome was a composite of stroke, myocardial infarction and vascular death, whichever happened first. Classification of SVD/LVD was primarily based on brain imaging. We used regression analyses to generate hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses were performed in subsets of the population, i.e. patients with subtype classification based on imaging, excluding TIA patients, first-ever stroke patients and LVD patients without a symptomatic carotid stenosis. <b><i>Results:</i></b> During a mean follow-up of 6.3 years, new vascular events occurred in 56 of 312 SVD patients (3.3%/year) and in 128 of 659 LVD patients (2.9%/year). These were ischemic strokes in 33 of the 56 events in SVD patients (2.0%/year) and 54 of the 128 events in LVD patients (1.2%/year). The corresponding age- and sex-adjusted HR for all new vascular events for LVD versus SVD was 0.76 (95% CI 0.56-1.05) for the total follow-up period. When this risk was split into early risk (&lt;1 year) and late risk (&gt;1 year), it was not significantly different for the 1-year risk of vascular events (HR 1.04, 95% CI 0.57-1.91); however, after 1 year of follow-up, LVD patients had fewer outcome events compared with SVD patients (HR 0.66, 95% CI 0.46-0.96). For ischemic strokes, the overall HR was 0.60 (95% CI 0.39-0.94). As with the primary outcome, here also the 1-year risk was not significantly different from &gt;1-year risk (HR 1.31, 95% CI 0.62-2.81, and HR 0.36, 95% CI 0.21-0.63, respectively). The sensitivity analyses showed virtually the same results. <b><i>Conclusion:</i></b> In patients with nondisabling cerebrovascular disease, we found, despite no differences at baseline in terms of vascular risk factors, a better long-term prognosis for patients with LVD for all vascular events, especially for recurrent strokes. Our observations support a different pathogenesis in SVD and LVD patients, and optimal prevention is indicated for patients with what was formerly regarded as ‘benign' SVD stroke.
DOI: 10.6084/m9.figshare.5125378
title: Supplementary Material for: Effectiveness of Collaborative Stepped Care for Anxiety Disorders in Primary Care: A Pragmatic Cluster Randomised Controlled Trial

description: <b><i>Background:</i></b> Collaborative stepped care (CSC) may be an appropriate model to provide evidence-based treatment for anxiety disorders in primary care. <b><i>Methods:</i></b> In a<b> </b>cluster randomised controlled trial, the effectiveness of CSC compared to care as usual (CAU) for adults with panic disorder (PD) or generalised anxiety disorder (GAD) in primary care was evaluated. Thirty-one psychiatric nurses who provided their services to 43 primary care practices in the Netherlands were randomised to deliver CSC (16 psychiatric nurses, 23 practices) or CAU (15 psychiatric nurses, 20 practices). CSC was provided by the psychiatric nurses (care managers) in collaboration with the general practitioner and a consultant psychiatrist. The intervention consisted of 3 steps, namely guided self-help, cognitive behavioural therapy and antidepressants. Anxiety symptoms were measured with the Beck Anxiety Inventory (BAI) at baseline and after 3, 6, 9 and 12 months. <b><i>Results:</i></b> We recruited 180 patients with a DSM-IV diagnosis of PD or GAD, of whom 114 received CSC and 66 received usual primary care. On the BAI, CSC was<b> </b>superior to CAU [difference in gain scores from baseline to 3 months: -5.11, 95% confidence interval (CI) -8.28 to -1.94; 6 months: -4.65, 95% CI -7.93 to -1.38; 9 months: -5.67, 95% CI -8.97 to -2.36; 12 months: -6.84, 95% CI -10.13 to -3.55]. <b><i>Conclusions:</i></b> CSC, with guided self-help as a first step, was more effective than CAU for primary care patients with PD or GAD.