bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imatinib mesylate induces necroptotic cell death and impairs autophagic flux in human cardiac progenitor cells
Authors: Walmsley Robert , Steele Derek S. , Ellison-Hughes Georgina M. , Smith Andrew J. 
Published: April 2021

AbstractThe receptor tyrosine kinase inhibitor imatinib mesylate has improved patient cancer survival rates but has been linked to long-term cardiotoxicity. This study investigated the effects of imatinib on cell viability, apoptosis, autophagy and necroptosis in human cardiac progenitor cells in vitro. After 24 hours, imatinib significantly reduced cell viability (75.9±2.7% vs._100.0±0.0%, n=5, p<0.05) at concentrations comparable to peak plasma levels (10 µM). Further investigation showed no increase in caspase 3 or 7 activation. Imatinib also significantly reduced the fluorescence of cells stained with TMRM (74.6±6.5% vs. 100.0±0.0%, n=5, p<0.05), consistent with mitochondrial depolarization. Imatinib increased lysosome and autophagosome content relative to the control, as indicated by changes in acridine orange fluorescence (46.0±5.4% vs. 9.0±3.0, n=7, p<0.001) and expression of LAMP2 (2.4±0.3 fold, n=3, p<0.05) after 24 hours treatment. Although imatinib increased the expression of proteins associated with autophagy, it also impaired the autophagic flux, as demonstrated by the proximity ligation assay staining for LAMP2 (lysosome marker) and LC3II (autophagosome marker), with control cells showing 11.3±2.1 puncta per cell and 48 hours of imatinib treatment reducing the visible puncta to 2.7±0.7 per cell (n=10, p<0.05). Cell viability was partially recovered by autophagosome inhibition by wortmannin, with a 91.8±8.2% (n=5, p>0.05) increase in viability after imatinib and wortmannin co-treatment. Imatinib-induced necroptosis was associated with an 8.5±2.5-fold increase in activation of mixed lineage kinase domain-like pseudokinase. Imatinib-induced toxicity was rescued by RIP1 inhibition relative to the control; 88.6±3.0% vs. 100.0±0.0% (n=4, p>0.05). In summary, imatinib applied to human cardiac progenitor cells depolarizes mitochondria and induces cell death through necroptosis, which can be recovered by inhibition of RIP1, with an additional partial role for autophagy in the cell death pathway. These data provide two possible targets for co-therapies to address imatinib-induced long-term cardiotoxicity.
Adipose mitochondrial metabolism controls body growth by modulating cytokine and insulin signaling
Authors: Sriskanthadevan-Pirahas Shrivani , Turingan Michael J , Chahal Joel S , Thorson Erin , Grewal Savraj S 
Published: April 2021

SummaryAnimals need to adapt their growth to fluctuations in nutrient availability to ensure proper development and survival. These adaptations often rely on specific nutrient-sensing tissues and their control of whole-body physiology through inter-organ communication. While the signaling mechanisms that underlie this communication are well studied, the contributions of metabolic alterations in the nutrient-sensing tissues are less clear. Here, we show how reprogramming of adipose mitochondrial metabolism controls whole-body growth inDrosophilalarvae. We find that dietary nutrients alter fat body mitochondrial morphology to lower their bioenergetic activity, which we see can rewire fat body glucose metabolism. Strikingly, we find that genetic reduction of mitochondrial bioenergetics just in the fat body is sufficient to accelerate body growth and development. These growth effects are caused by inhibition of the fat-derived adipokine, TNFα/Eiger, which leads to enhanced systemic insulin signaling, the main hormonal stimulator of body growth. Our work reveals how reprogramming of mitochondrial metabolism in one nutrient-sensing tissue is able to couple whole body growth to nutrient availability.
Associations between Infant-Mother Physiological Synchrony and 4- to 6-Month-Old Infants’ Emotion Regulation
Authors: Abney Drew H. , daSilva Elizabeth B. , Bertenthal Bennett I. 
Published: April 2021

AbstractIn this study we assessed whether physiological synchrony between infants and mothers contributes to infants’ emotion regulation following a mild social stressor. Infants between 4- to 6-months of age and their mothers were tested in the Face-to-Face-Still-Face paradigm, and were assessed for behavioral and physiological self-regulation during and following the stressor. Physiological synchrony was calculated from a continuous measure of respiratory sinus arrhythmia (RSA) enabling us to cross-correlate the infants’ and mothers’ RSA responses. Without considering physiological synchrony, the evidence suggested that infants’ distress followed the prototypical pattern of increasing during the Still Face episode and then decreasing during the Reunion episode. Once physiological synchrony was added to the model, we observed that infants’ emotion regulation improved if mother-infant synchrony was positive, but not if it was negative. This result was qualified further by whether or not infants suppressed their RSA response during the Still Face episode. In sum, these findings highlight how individual differences in infants’ physiological responses contribute significantly to their self-regulation abilities.
P5A-ATPase controls the ER translocation of Wnt in neuronal migration
Authors: Li Tingting , Yang Xiaoyan , Feng Zhigang , Nie Wang , Zou Yan 
Published: April 2021

SummaryWnt family are conserved secretory proteins required for developmental patterning and tissue homeostasis. The mechanisms underlying intracellular maturation and intercellular signal transduction of Wnt proteins have been extensively studied. However, how Wnt is targeted to the endoplasmic reticulum (ER) for processing and secretion remains elusive. Here we report that CATP-8/P5A-ATPase directs neuronal migration non-cell autonomously inC. elegansby regulating EGL-20/Wnt biogenesis. CATP-8 functions as a translocase to translocate EGL-20/Wnt nascent polypeptide into the ER by interacting with the hydrophobic core region of EGL-20 signal sequence. Such regulation of Wnt biogenesis by P5A-ATPase is conserved in human cells. These findings reveal physiological roles of P5A-ATPase in neural development and identify Wnt proteins as direct substrates of P5A-ATPase for ER translocation.
Intermittent Fasting Enhances Hippocampal Npy Expression to Promote Neurogenesis Following Traumatic Brain Injury
Authors: Cao Shuqiang , Li Manrui , Sun Yuwen , Yang Wenjie , Dai Hao , Guo Yadong , Ye Yi , Wang Zheng , Xie Xiaoqi , Chen Xiameng , Liang Weibo 
Published: April 2021

AbstractInterventions for preventing cognitive dysfunction post traumatic brain injury (TBI) is limited. Given that adult hippocampal neurogenesis (AHN) after brain injury contributes to cognitive recovery, and that the AHN is potentially affected by nutritional factors, we asked whether fasting could promote AHN and thus ameliorates cognitive defects after TBI. Here we show that a one-month intermittent fasting (IF) regimen enhanced proliferation of neural stem cells (NSCs) in the subgranular zone (SGZ) of hippocampus 3 days post TBI, as well as improved cognitive performance in Morris water maze (MWM) test. Furthermore, an increase in hippocampal Npy expression was detected in IF group after injury, compared to the mice fed ad libitum (AL), and locally knock-down of Npy in vivo attenuated the aforementioned effects of IF in TBI. These findings suggest that IF promotes AHN following TBI by a mechanism involving enhancement of Npy expression, which may offer novel interventions that might prevent cognitive dysfunction caused by injury.
Adolescent Binge Drinking is Associated with Accelerated Decline of Gray Matter Volume
Authors: Infante M.A. , Zhang Y. , Brumback T. , Brown S.A. , Colrain I.M. , Baker F.C. , Clark D.B. , Goldston D. , Nagel B.J. , Nooner K.B. , Zhao Q. , Pohl K.M. , Sullivan E.V. , Pfefferbaum A. , Tapert S.F. , Thompson W.K. 
Published: April 2021

AbstractThe age- and time-dependent effects of binge-drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume development was examined using longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA). Non-binge drinkers (n=177) were matched to binge drinkers (n=164) on potential confounders. Number of binge drinking episodes in the past year was linked to decreased volumes for total gray matter, frontal, parietal, temporal, and occipital lobes (ps<.001). Interactions of binge drinking episodes and age demonstrated stronger effects in younger subjects for total gray matter, frontal, temporal, and occipital lobes (ps<.001). Subsequent models included binge drinking coded in multiple ways. Models sensitive to number of episodes and temporal proximity to outcomes provided the best fits. Declines in gray matter volume association with binge drinking are potentially related to changes in cognition frequently reported among binge drinking adolescents. Results underscore the potential importance of delaying initiation of binge drinking and provide evidence for a dose-response relationship of binge drinking to gray matter decline. Temporally proximal binge drinking was associated more strongly with gray matter decline, suggesting the potential for recovery.
The RNA-binding protein RBP42 regulates cellular energy metabolism in mammalian-infectiveTrypanosoma brucei
Authors: Das Anish , Liu Tong , Li Hong , Husain Seema 
Published: April 2021

AbstractRNA-binding proteins are key players in coordinated post-transcriptional regulation of functionally related genes, defined as RNA regulons. RNA regulons play particularly critical roles in parasitic trypanosomes, which exhibit unregulated co-transcription of long arrays of unrelated genes. In this report, we present a systematic analysis of an essential RNA-binding protein, RBP42, in the mammalian-infective slender bloodstream form of African trypanosome, and we show that RBP42 is a key regulator of parasite’s central carbon and energy metabolism. Using individual-nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP) to identify genome-wide RBP42-RNA interactions, we show that RBP42 preferentially binds within the coding region of mRNAs encoding core metabolic enzymes. Using global quantitative transcriptomic and proteomic analyses, we also show that loss of RBP42 reduces the abundance of target mRNA-encoded proteins, but not target mRNA, suggesting a plausible role of RBP42 as a positive regulator of target mRNA translation. Analysis reveals significant changes in central carbon metabolic intermediates following loss of RBP42, further supporting its critical role in cellular energy metabolism.
Visual Thalamocortical Mechanisms of Waking State Dependent Activity and Alpha Oscillations
Authors: Nestvogel Dennis B. , McCormick David A. 
Published: April 2021

SummaryThe brain exhibits distinct patterns of recurrent activity closely related to the behavioral state of the animal. The neural mechanisms that underlie state-dependent activity in the awake animal are incompletely understood. Here, we demonstrate that two types of state-dependent activity - rapid arousal/movement related signals and a 3-5 Hz alpha-like rhythm - in the primary visual cortex (V1) of mice strongly correlate with activity in the visual thalamus. Inactivation of V1 does not interrupt arousal/movement related signals in most visual thalamic neurons, but it abolishes the 3-5 Hz oscillation. Silencing of the visual thalamus similarly eradicates the alpha-like rhythm and perturbs arousal/movement-related activation in V1. Finally, we observed that whisker movement or locomotion is not required for rapid increases in cortical activation. Our results indicate that thalamocortical interactions together with cell-intrinsic properties of thalamocortical cells play a crucial role in shaping state-dependent activity in V1 of the awake animal.HighlightsWhisker movements correlate with rapid synaptic activation in V1 and visual thalamusSilencing of V1 does not abolish movement related activation in most dLGN or LP cellsSilencing of visual thalamus strongly reduces movement related activation in V1Thalamocortical interactions generate state-dependent alpha frequency oscillationVisual thalamic cells exhibit LTS firing during alpha oscillation in the awake mouse
Viral diversity in Phytophthora cactorum population infecting strawberry
Authors: Poimala Anna , Parikka Päivi , Hantula Jarkko , Vainio Eeva J. 
Published: April 2021

SummaryEighty‐eight Phytophthora cactorum strains isolated from crown or leather rot of strawberry in 1971–2019 were screened for viruses using RNA‐seq and RT‐PCR. Remarkably, all but one isolate were virus‐infected, most of them harbouring more than one virus of different genera or species. The most common virus occurring in 94% of the isolates was the Phytophthora cactorum RNA virus 1 (PcRV1) resembling members of Totiviridae. Novel viruses related to members of Endornaviridae, named Phytophthora cactorum alphaendornaviruses 1‐3 (PcAEV1‐3), were found in 57% of the isolates. Four isolates hosted viruses with affinities to Bunyaviridae, named Phytophthora cactorum bunyaviruses 1‐3 (PcBV1‐3), and a virus resembling members of the proposed genus ‘Ustivirus’, named Phytophthora cactorum usti‐like virus (PcUV1), was found in a single isolate. Most of the virus species were represented by several distinct strains sharing ≥81.4% aa sequence identity. We found no evidence of spatial differentiation but some temporal changes in the P. cactorum virus community were observed. Some isolates harboured two or more closely related strains of the same virus (PcAEV1 or PcRV1) sharing 86.6%–96.4% nt identity in their polymerase sequence. This was surprising as viruses with such a high similarity are typically mutually exclusive.
Challenges to the co‐management of biodiversity in a reflexive modernity
Authors: Bardsley Douglas K , Bardsley Annette M , Moskwa Emily , Weber Delene , Robinson Guy M 
Published: April 2021

AbstractThe marginalisation of people from natural areas has dominated conservation approaches in post‐colonial societies such as Australia. Yet the approach is limited, in part because people are also excluded from co‐managing their local environments, an effect that raises important questions about the future of conservation in a reflexive era where account must also be taken of how to manage risks such as bushfires. To address the complexity of social processes that influence conservation, new forms of co‐management between governments and community stakeholders are evolving but do not always achieve their participatory aims. In this article, discrepancies between perceptions of conservation governance and the responsibilities and activities of the South Australian Government are examined by reference to original research involving a residential survey and a follow‐up focus group discussion with local community and non‐profit environmental organisations. Findings suggest that local environmental groups are knowledge‐rich and strong relationships exist between local conservation actors and government officers, but those partnerships receive only limited support. In addition, opportunities for co‐management between government and non‐governmental environmental organisations are hindered by insufficient acknowledgement within government of the importance of unique, actionable local knowledge; an inability to effectively coordinate activities across and between government and non‐government actors; and an unwillingness to engage with stakeholders in a manner that develops and maintains trust.
Metabolic responses in neonatal sepsis—A systematic review of human metabolomic studies
Authors: Bjerkhaug Aline U. , Granslo Hildegunn Norbakken , Klingenberg Claus 
Published: April 2021

AbstractAimTo systematically review human metabolomic studies investigating metabolic responses in septic neonates.MethodsA systematic literature search was performed in the databases MEDLINE, EMBASE and Cochrane library up to the 1st of January 2021. We included studies that assessed neonatal sepsis and the following outcomes; (1) change in the metabolism compared to healthy neonates and/or (2) metabolomics compared to traditional diagnostic tools of neonatal sepsis. The screened abstracts were independently considered for eligibility by two researchers. PROSPERO ID: CRD42020164454.ResultsThe search identified in total 762 articles. Fifteen articles were assessed for eligibility. Four studies were included, with totally 78 neonates. The studies used different diagnostic criteria and had between 1 and 16 sepsis cases. All studies with bacterial sepsis found alterations in the glucose and lactate metabolism, reflecting possible redistribution of glucose consumption from mitochondrial oxidative phosphorylation to the lactate and pentose phosphate pathway. We also found signs of increased oxidative stress and fatty acid oxidation in sepsis cases.ConclusionWe found signs of metabolomic signatures in neonatal sepsis. This may lead to better understanding of sepsis pathophysiology and detection of new candidate biomarkers. Results should be validated in large‐scale multicentre studies.
Parents want Swedish child health services to focus more on motor development and practical advice
Authors: Lång Christina , Tell Johanna , Johansen Kine 
Published: April 2021

AbstractAimParents’ experiences and expectations are key to developing evidence‐based approaches that respond to family needs. However, little is known about how parents regard the motor assessments in well‐child surveillance and what they need to support their child's motor development. This study explored their experiences.MethodsWe conducted 11 semi‐structured interviews with Swedish‐speaking parents whose children had been referred to a physiotherapist by child health services (CHS) before 18 months of age. Consecutive sampling was conducted from March to November 2018. The data were analysed using systematic text condensation.ResultsThe three themes that emerged were that that parents liked the CHS setting, but had concerns about the lack of focus on motor development during routine health visits and wanted more dialogue about this area. The parents said that the assessments varied considerably and that their concerns were not always taken seriously. They wanted to know more about the professionals’ observations, how their child was expected to develop and what they could do to support their motor development.ConclusionParents wanted a greater focus on motor development during routine health visits. This included advice on how they could support their child's development.
Rifampicin induces the bone form of alkaline phosphatase in humans
Authors: Nabil Heba , Kummu Outi , Lehenkari Petri , Rysä Jaana , Risteli Juha , Hakkola Jukka , Hukkanen Janne 
Published: April 2021

AbstractPregnane X receptor (PXR) is a xenobiotic‐sensing nuclear receptor that regulates drug metabolism in the liver and intestine. In our clinical trials on healthy volunteers to discover novel metabolic functions of PXR activation, we observed that rifampicin, a well‐established ligand for human PXR, 600 mg daily for a week, increased the plasma alkaline phosphatase (ALP) significantly compared with the placebo. Further analysis with lectin affinity electrophoresis revealed that especially the bone form of ALP was elevated. To investigate the mechanism(s) of bone ALP induction, we employed osteoblast lineage differentiated from human primary bone marrow–derived mesenchymal stromal cells. Rifampicin treatment increased ALP activity and mRNA level of bone biomarker genes (ALP, MGP, OPN and OPG). PXR expression was detected in the cells, but the expression was very low compared with the human liver. To further investigate the potential role of PXR in the ALP induction, we treated mice and rats with a rodent PXR ligand pregnenolone 16α‐carbonitrile (PCN). However, PCN treatment did not increase plasma ALP activity or bone ALP mRNA expression. In conclusion, rifampicin treatment induces the bone form of ALP in the serum of healthy human volunteers. Further studies are required to establish the mechanism of this novel finding.
The stability of implants and microbiological effects following photobiomodulation therapy with one‐stage placement: A randomized, controlled, single‐blinded, and split‐mouth clinical study
Authors: Bozkaya Suleyman , Uraz Ahu , Guler Berceste , Kahraman Sevil Altundağ , Turhan Bal Bilge 
Published: April 2021

AbstractBackgroundStudies have reported a positive effect on bone healing and the elimination of microorganisms placed on the titanium implants, while others have not confirmed the positive photobiomodulation therapy (PBMT) effects on bone regeneration and bone structure around the implants.PurposeThe aim of the present study was to address the following questions: Does PBMT improve implant stability and affect microbiota around dental implants in the early stage of osseointegration?Materials and MethodsThis study was designed as randomized‐controlled prospective, split mouth, single‐blinded clinical trial. Implants were randomly divided into two groups and implants placed in the test group were treated with Gallium‐aluminum‐arsenide (GaAlAs) diode laser with PBMT immediately after surgery and for 15 days (n = 47). In the control group, implants were not irradiated(n = 46). The primary stability of the implants was measured by the Resonance frequency analysis (RFA) after insertion and the secondary stability values were recorded at 30th, 60th, and 90th days after surgery as implant stability quotient (ISQ). The hand‐held RFA was held perpendicular to the jaw line as indicated by the manufacturer for buccal‐lingual (BL), mesial‐distal (MD), and lingual‐buccal (LB) measurement and different measurements were analyzed as separately.ResultsSignificantly higher magnetic RFA values were achieved on the 90th day in all measurement sides for both groups. ISQ levels in groups at baseline and the day‐30, 60, and 90. ISQ readings were not statistically significant between test and control groups for each time point. A statistically significant increase in ISQ reading for BL, MD, and LB dimensions in both groups was noted from baseline to the day‐90 (P < .05).ConclusionIt was concluded that PBMT did not have a clinically significant effect on implant stabilization, especially in terms of ISQ values at early alveolar bone healing term. Clinical trial number is NCT04495335.
It's a family affair: How social identification influences family CEO compensation
Authors: Mueller Elisabeth F. , Flickinger Miriam 
Published: April 2021

AbstractResearch Question/IssueThis study analyzes the heterogeneity of CEO compensation in family firms. Specifically, we investigate the relationship between a family CEO's social identification with the family firm and the level of her or his compensation.Research Findings/InsightsUsing a sample of S&P 500 family firms between 2006 and 2014, we find that levels of social identification among family CEOs explain the heterogeneous patterns of CEO compensation among family firms. Our results show that the level of social identification varies among family CEOs.Theoretical/Academic ImplicationsOur findings indicate that differences in social identification among individual family executives are an important factor in CEO compensation in family firms. This factor has been overlooked in the literature, which has instead focused on the explanatory power of faultlines between family versus non‐family firms or family versus non‐family executives in family firms.Practitioner/Policy ImplicationsPractitioners may value our finding that socio‐psychological dynamics influence strategic decision‐making in family firms, such as setting the compensation of the family CEO. In particular, practitioners should be aware of each family CEO's level of identification and should not assume that all family members equally socially identify with the family firm.