bluuebunny/crossref_metadata_2025_split huggingface dataset:
20-hydroxyecdysone (20E) signaling regulates amnioserosa morphogenesis during Drosophila dorsal closure: EcR modulates gene expression in a complex with the AP-1 subunit, Jun
Authors: Yoo Byoungjoo , Kim Hae-yoon , Chen Xi , Shen Weiping , Jang Ji Sun , Stein Shaianne N. , Cormier Olga , Pereira Lionel , Shih Claire R. Y. , Krieger Charles , Reed Bruce , Harden Nicholas , Wang Simon J. H. 
Published: July 2021

ABSTRACT
Steroid hormones influence diverse biological processes throughout the animal life cycle, including metabolism, stress resistance, reproduction, and lifespan. In insects, the steroid hormone, 20-hydroxyecdysone (20E), is the central hormone regulator of molting and metamorphosis, and plays roles in tissue morphogenesis. For example, amnioserosa contraction, which is a major driving force in Drosophila dorsal closure (DC), is defective in embryos mutant for 20E biosynthesis. Here, we show that 20E signaling modulates the transcription of several DC participants in the amnioserosa and other dorsal tissues during late embryonic development, including zipper, which encodes for non-muscle myosin. Canonical ecdysone signaling typically involves the binding of Ecdysone receptor (EcR) and Ultraspiracle heterodimers to ecdysone-response elements (EcREs) within the promoters of responsive genes to drive expression. During DC, however, we provide evidence that 20E signaling instead acts in parallel to the JNK cascade via a direct interaction between EcR and the AP-1 transcription factor subunit, Jun, which together binds to genomic regions containing AP-1 binding sites but no EcREs to control gene expression. Our work demonstrates a novel mode of action for 20E signaling in Drosophila that likely functions beyond DC, and may provide further insights into mammalian steroid hormone receptor interactions with AP-1.
Polyploid cardiomyocytes: implications for heart regeneration
Authors: Kirillova Anna , Han Lu , Liu Honghai , Kühn Bernhard 
Published: July 2021

ABSTRACT
Terminally differentiated cells are generally thought to have arrived at their final form and function. Many terminally differentiated cell types are polyploid, i.e. they have multiple copies of the normally diploid genome. Mammalian heart muscle cells, termed cardiomyocytes, are one such example of polyploid cells. Terminally differentiated cardiomyocytes are bi- or multi-nucleated, or have polyploid nuclei. Recent mechanistic studies of polyploid cardiomyocytes indicate that they can limit cellular proliferation and, hence, heart regeneration. In this short Spotlight, we present the mechanisms generating bi- and multi-nucleated cardiomyocytes, and the mechanisms generating polyploid nuclei. Our aim is to develop hypotheses about how these mechanisms might relate to cardiomyocyte proliferation and cardiac regeneration. We also discuss how these new findings could be applied to advance cardiac regeneration research, and how they relate to studies of other polyploid cells, such as cancer cells.
Molecular insight into how γ-TuRC makes microtubules
Authors: Thawani Akanksha , Petry Sabine 
Published: July 2021

ABSTRACT
As one of four filament types, microtubules are a core component of the cytoskeleton and are essential for cell function. Yet how microtubules are nucleated from their building blocks, the αβ-tubulin heterodimer, has remained a fundamental open question since the discovery of tubulin 50 years ago. Recent structural studies have shed light on how γ-tubulin and the γ-tubulin complex proteins (GCPs) GCP2 to GCP6 form the γ-tubulin ring complex (γ-TuRC). In parallel, functional and single-molecule studies have informed on how the γ-TuRC nucleates microtubules in real time, how this process is regulated in the cell and how it compares to other modes of nucleation. Another recent surprise has been the identification of a second essential nucleation factor, which turns out to be the well-characterized microtubule polymerase XMAP215 (also known as CKAP5, a homolog of chTOG, Stu2 and Alp14). This discovery helps to explain why the observed nucleation activity of the γ-TuRC in vitro is relatively low. Taken together, research in recent years has afforded important insight into how microtubules are made in the cell and provides a basis for an exciting era in the cytoskeleton field.
Conserved cholesterol-related activities of Dispatched 1 drive Sonic hedgehog shedding from the cell membrane
Authors: Ehring Kristina , Manikowski Dominique , Goretzko Jonas , Froese Jurij , Gude Fabian , Jakobs Petra , Rescher Ursula , Kirchhefer Uwe , Grobe Kay 
Published: July 2021

ABSTRACT
The Sonic hedgehog (Shh) pathway controls embryonic development and tissue homeostasis after birth. Long-standing questions about this pathway include how the dual-lipidated, firmly plasma membrane-associated Shh ligand is released from producing cells to signal to distant target cells and how the resistance–nodulation–division transporter Dispatched 1 (Disp, also known as Disp1) regulates this process. Here, we show that inactivation of Disp in Shh-expressing human cells impairs proteolytic Shh release from its lipidated terminal peptides, a process called ectodomain shedding. We also show that cholesterol export from Disp-deficient cells is reduced, that these cells contain increased cholesterol amounts in the plasma membrane, and that Shh shedding from Disp-deficient cells is restored by pharmacological membrane cholesterol extraction and by overexpression of transgenic Disp or the structurally related protein Patched 1 (Ptc, also known as Ptch1; a putative cholesterol transporter). These data suggest that Disp can regulate Shh function via controlled cell surface shedding and that membrane cholesterol-related molecular mechanisms shared by Disp and Ptc exercise such sheddase control.
This article has an associated First Person interview with the first author of the paper.
Interactions between developmental and adult acclimation have distinct consequences for heat tolerance and heat stress recovery
Authors: Willot Quentin , Loos Ben , Terblanche John S. 
Published: July 2021

ABSTRACT
Developmental and adult thermal acclimation can have distinct, even opposite, effects on adult heat resistance in ectotherms. Yet, their relative contribution to heat-hardiness of ectotherms remains unclear despite the broad ecological implications thereof. Furthermore, the deterministic relationship between heat knockdown and recovery from heat stress is poorly understood but significant for establishing causal links between climate variability and population dynamics. Here, using Drosophila melanogaster in a full-factorial experimental design, we assessed the heat tolerance of flies in static stress assays, and document how developmental and adult acclimation interact with a distinct pattern to promote survival to heat stress in adults. We show that warmer adult acclimation is the initial factor enhancing survival to constant stressful high temperatures in flies, but also that the interaction between adult and developmental acclimation becomes gradually more important to ensure survival as the stress persists. This provides an important framework revealing the dynamic interplay between these two forms of acclimation that ultimately enhance thermal tolerance as a function of stress duration. Furthermore, by investigating recovery rates post-stress, we also show that the process of heat-hardening and recovery post-heat knockdown are likely to be based on set of (at least partially) divergent mechanisms. This could bear ecological significance as a trade-off may exist between increasing thermal tolerance and maximizing recovery rates post-stress, constraining population responses when exposed to variable and stressful climatic conditions.
Energy Expenditure of a Male and Female Tennis Player during Association of Tennis Professionals/Women’s Tennis Association and Grand Slam Events Measured by Doubly Labeled Water
Authors: ELLIS DANIEL G. , SPEAKMAN JOHN , HAMBLY CATHERINE , MORTON JAMES P. , CLOSE GRAEME L. , LEWINDON DAN , DONOVAN TIMOTHY F. 
Published: July 2021

ABSTRACT
Understanding the total energy expenditure (TEE) for competition and training in sport are vital to ensure suitable nutritional strategies. This study assessed TEE of a world class male and female tennis player during competition at the highest level. Participants: Career high ranking, Female: Women’s Tennis Association top 10; Male: Association of Tennis Professionals top 15.

Methods
Doubly labeled water assessed TEE during a 17-d period analyzed by days 1 to 7 (P1) and 7–17 (P2) which included a Women’s Tennis Association/Association of Tennis Professionals tournament and culminated at the Wimbledon Championships. Daily training and match loads were assessed using a 10-point Borg scale multiplied by time. Match data were provided by video analysis and player tracking technology.

Results
The TEE during P1 for the female player was 3383 kcal·d−1 (63.5 kcal·kg−1) fat-free mass (FFM) with 362 points played over 241 min in three matches covering a distance of 2569 m, with an additional 875 min training. During P2, TEE was 3824 kcal·d−1 (71.7 kcal·kg−1) FFM with 706 points played over 519 min during five matches, covering a distance of 7357 m with an additional 795 min training. The TEE during P1 for the male player was 3712 kcal·d−1 (56.3 kcal·kg−1) FFM with 133 points played over 88 min during one match covering 1125 m, with an additional 795 min training. During P2, TEE was 5520 kcal·d−1 (83.7 kcal·kg−1) FFM with 891 points played over 734 min during five matches, covering 10,043 m, with an additional 350 min training.

Conclusions
This novel data positions elite tennis, played at the highest level, as a highly energetic demanding sport, highlighting that nutritional strategies should ensure sufficient energy availability during competition schedules.
Motor Competence and Health-related Fitness of School-Age Children: A Two-Year Latent Transition Analysis
Authors: JAAKKOLA TIMO , YLI-PIIPARI SAMI , HUHTINIEMI MIKKO , SALIN KASPER , HAKONEN HARTO , GRÅSTÉN ARTO 
Published: July 2021

ABSTRACT

Purpose
The aims of this study were twofold: 1) to identify latent physical performance profiles of motor competence (MC) and cardiorespiratory (CF) and muscular fitness (MF) among school-age children and 2) explore transition probabilities in physical performance profiles over a 2-yr period.

Methods
The present sample comprised 1148 (583 girls, 565 boys) elementary school students (baseline M
age = 11.27 ± 0.32), and data were collected annually (equal intervals) over a period of 2 yr which resulted in a total of three measurements. The measures used were the throwing–catching combination test, 5-leaps and two-legged jumps from side-to-side test (MC), 20-meter shuttle run test (CF), and curl-up and push-up tests (MF). Latent transition analysis was used to identify and track physical performance profiles derived from the measurements of MC, CF, and MF scores.

Results
The key findings were: 1) three physical performance profiles were identified: (a) low (28% of the sample; lowest level in each category), (b) moderate (43% of the sample; higher MC, CF, and MF than low), (c) high (29% of the sample; highest MF); 2) the number of physical performance profiles and probability to belong to a given profile were stable across time; 3) the highest transition probability was found in the high group, where some students had transitioned to the moderate group at T2; and 4) girls were most likely to belong to the low group.

Conclusions
Results demonstrated that children’s physical performance profiles are stable from late childhood to early adolescence. This study suggests that the early elementary school years are essential for the development of children’s MC and health-related fitness.
Four-Second Power Cycling Training Increases Maximal Anaerobic Power, Peak Oxygen Consumption, and Total Blood Volume
Authors: SATIROGLU REMZI , LALANDE SOPHIE , HONG SUNGMO , NAGEL MERCEDES J. , COYLE EDWARD F. 
Published: July 2021

ABSTRACT

Introduction
High-intensity interval training is an effective tool to improve cardiovascular fitness and maximal anaerobic power. Different methods of high-intensity interval training have been studied but the effects of repeated maximal effort cycling with very short exercise time (i.e., 4 s) and short recovery time (15–30 s) might suit individuals with limited time to exercise.

Purpose
We examined the effects of training at near maximal anaerobic power during cycling (PC) on maximal anaerobic power, peak oxygen consumption (V˙O2peak), and total blood volume in 11 young healthy individuals (age: 21.3 ± 0.5 yr) (six men, five women).

Methods
Participants trained three times a week for 8 wk performing a PC program consisting of 30 bouts of 4 s at an all-out intensity (i.e., 2 min of exercise per session). The cardiovascular stress progressively increased over the weeks by decreasing the recovery time between sprints (30–24 s to 15 s), and thus, total session time decreased from 17 to <10 min.

Results
Power cycling elicited a 13.2% increase in V˙O2peak (Pre: 2.86 ± 0.18 L·min−1, Post: 3.24 ± 0.21 L·min−1; P = 0.003) and a 7.6% increase in total blood volume (Pre: 5139 ± 199 mL, Post: 5529 ± 342 mL; P < 0.05). Concurrently, maximal anaerobic power increased by 17.2% (Pre: 860 ± 53 W, Post: 1,009 ± 71 W; P < 0.001).

Conclusions
A PC training program employing 30 bouts of 4 s duration for a total of 2 min of exercise, resulting in a total session time of less than 10 min in the last weeks, is effective for improving total blood volume, V˙O2peak and maximal anaerobic power in young healthy individuals over 8 wk. These observations require reconsideration of the minimal amount of exercise needed to significantly increase both maximal aerobic and anaerobic power.
Development of Children’s Actual and Perceived Motor Competence, Cardiorespiratory Fitness, Physical Activity, and BMI
Authors: KOLUNSARKA IIRIS , GRÅSTEN ARTO , HUHTINIEMI MIKKO , JAAKKOLA TIMO 
Published: July 2021

ABSTRACT

Purpose
To examine synergistic associations between developmental trajectories of motor competence, perceived motor competence, cardiorespiratory fitness, moderate-to-vigorous physical activity (MVPA), and body mass index (BMI) from late childhood to adolescence.

Methods
In this 3-yr follow-up study, motor competence, perceived motor competence, cardiorespiratory fitness, MVPA, and BMI were assessed in 1167 Finnish school-age children (girls = 583, boys = 565; M
age = 11.27 ± 0.33). Moderate-to-vigorous physical activity was measured using hip-mounted accelerometers. Developmental trajectories were analyzed using latent growth curve modeling.

Results
The development of motor competence, cardiorespiratory fitness, and BMI was positive over time, whereas the development of perceived motor competence and physical activity was negative. The development of BMI was inversely associated with the development of cardiorespiratory fitness and physical activity.

Conclusions
In the transition from late childhood to adolescence, motor competence, cardiorespiratory fitness, and BMI increased, and perceived motor competence and physical activity decreased. However, individual variance in the developmental trajectories was significant. Moreover, children with a greater increase in BMI showed a greater decrease in cardiorespiratory fitness and physical activity from late childhood to adolescence.
Generalized Equations for Predicting Percent Body Fat from Anthropometric Measures Using a Criterion Five-Compartment Model
Authors: CICONE ZACKARY S. , NICKERSON BRETT S. , CHOI YOUN-JENG , HOLMES CLIFTON J. , HORNIKEL BJOERN , FEDEWA MICHAEL V. , ESCO MICHAEL R. 
Published: July 2021

ABSTRACT

Introduction
Anthropometric-based equations are used to estimate percent body fat (%BF) when laboratory methods are impractical or not available. However, because these equations are often derived from two-compartment models, they are prone to error because of the assumptions regarding fat-free mass composition. The purpose of this study was to develop a new anthropometric-based equation for the prediction of %BF, using a five-compartment (5C) model as the criterion measure.

Methods
A sample of healthy adults (52.2% female; age, 18 to 69 yr; body mass index, 15.7 to 49.5 kg·m−2) completed hydrostatic weighing, dual-energy x-ray absorptiometry, and bioimpedance spectroscopy measurements for calculation of 5C %BF (%BF5C), as well as skinfolds and circumferences. %BF5C was regressed on anthropometric measures using hierarchical variable selection in a random sample of subjects (n = 279). The resulting equation was cross-validated in the remaining participants (n = 78). New model performance was also compared with several common anthropometric-based equations.

Results
The new equation [%BFNew = 6.083 + (0.143 × SSnew) − (12.058 × sex) − (0.150 × age) − (0.233 × body mass index) + (0.256 × waist) + (0.162 × sex × age)] explained a significant proportion of variance in %BF5C (R2
= 0.775, SEE = 4.0%). Predictors included sum of skinfolds (SSnew, midaxillary, triceps, and thigh) and waist circumference. The new equation cross-validated well against %BF5C when compared with other existing equations, producing a large intraclass correlation coefficient (0.90), small mean bias and limits of agreement (0.4% ± 8.6%), and small measures of error (SEE = 2.5%).

Conclusions
%BFNew improved on previous anthropometric-based equations, providing better overall agreement and less error in %BF estimation. The equation described in this study may provide an accurate estimate of %BF5C in healthy adults when measurement is not practical.
Classification of small ruminant lentivirus subtype A2, subgroups 1 and 2 based on whole genome comparisons and complex recombination patterns
Authors: Dickey Aaron M. , Smith Timothy P. L. , Clawson Michael L. , Heaton Michael P. , Workman Aspen M. 
Published: July 2021

Background: Small ruminant lentiviruses (SRLVs) cause a multisystemic chronic wasting disease in sheep across much of the world. SRLV subtype A2 is prevalent in North America and further classified into multiple subgroups based on variation in the group antigens gene (gag) and envelope (env) genes. In sheep, the ovine transmembrane protein 154 (TMEM154) gene is associated with SRLV susceptibility. Ewes with at least one copy of TMEM154 encoding a full-length protein with glutamate at position 35 (E35; haplotypes 2 and 3), are highly susceptible to SRLV infection while ewes with any combination of TMEM154 haplotypes which encodes lysine (K35; haplotype 1), or truncated proteins (haplotypes 4 and 6) are several times less so. A2 subgroups 1 and 2 are associated with host TMEM154 genotypes; subgroup 1 with the K35/K35 genotype and subgroup 2 with the E35/E35 genotype. Methods: Sequence variation within and among full-length assemblies of SRLV subtype A2 subgroups 1 and 2 was analyzed to identify genome-scale recombination patterns and subgroup-specific variants. Results: Consensus viral genomes were assembled from 23 infected sheep, including animals of assorted TMEM154 genotypes comprised of haplotypes 1, 2, or 3. Viral genome analysis identified viral subgroups 1 and 2 among the samples, and revealed additional sub-structure within subgroup 2 based on models predicting complex patterns of recombination between the two subgroups in several genomes. Animals with evidence of dual subgroup infection also possessed the most diverse quasi-species and the most highly recombined consensus genomes. After accounting for recombination, 413 subgroup diagnostic single nucleotide polymorphisms (SNPs) were identified. Conclusions: The viral subgroup framework developed to classify SRLV consensus genomes along a continuum of recombination suggests that animals with the TMEM154 E35/K35 genotype may represent a reservoir for producing viral genomes representing recombination between A2 subgroups 1 and 2.
The imperative to find the courage to redesign the biomedical research enterprise
Authors: Bielekova Bibiana , Brownlee Shannon 
Published: July 2021

Medical research aims to improve health for everyone. While its advances are undeniable, the pace and cost of the progress are not optimal. For example, independent analyses concluded that at least half of the published biomedical research findings are irreproducible, and most scientific papers are never read or cited. This paper examines biomedical research holistically, as a system of incentives that shape the behavior of scientists, administrators, publishers, and funders, and are detrimental to medical progress. We identify opportunities to change and improve those incentives by altering the way research output is disseminated and evaluated, and recommend transparent, data-driven measures of methodological rigor, reproducibility, and societal value of scientific discoveries. Embracing these opportunities would maximize our investments in biomedical research and optimize its value to human health, while simultaneously increasing freedom, creativity, and satisfaction of the scientific workforce.
What are the most important unanswered research questions on rapid review methodology? A James Lind Alliance research methodology Priority Setting Partnership: the Priority III study protocol
Authors: Beecher Claire , Toomey Elaine , Maeso Beccy , Whiting Caroline , Stewart Derek C. , Worrall Andrew , Elliott Jim , Smith Maureen , Tierney Theresa , Blackwood Bronagh , Maguire Teresa , Kampman Melissa , Ling Benny , Gravel Christopher , Gill Catherine , Healy Patricia , Houghton Catherine , Booth Andrew , Garritty Chantelle , Thomas James , Tricco Andrea C. , Burke Nikita N. , Keenan Ciara , Westmore Matthew , Devane Declan 
Published: July 2021

Background: The value of rapid reviews in informing health care decisions is more evident since the onset of the coronavirus disease 2019 (COVID-19) pandemic. While systematic reviews can be completed rapidly, rapid reviews are usually a type of evidence synthesis in which components of the systematic review process may be simplified or omitted to produce information more efficiently within constraints of time, expertise, funding or any combination thereof. There is an absence of high-quality evidence underpinning some decisions about how we plan, do and share rapid reviews. We will conduct a modified James Lind Alliance Priority Setting Partnership to determine the top 10 unanswered research questions about how we plan, do and share rapid reviews in collaboration with patients, public, reviewers, researchers, clinicians, policymakers and funders. Methods: An international steering group consisting of key stakeholder perspectives (patients, the public, reviewers, researchers, clinicians, policymakers and funders) will facilitate broad reach, recruitment and participation across stakeholder groups. An initial online survey will identify stakeholders’ perceptions of research uncertainties about how we plan, do and share rapid reviews. Responses will be categorised to generate a long list of questions. The list will be checked against systematic reviews published within the past three years to identify if the question is unanswered. A second online stakeholder survey will rank the long list in order of priority. Finally, a virtual consensus workshop of key stakeholders will agree on the top 10 unanswered questions. Discussion: Research prioritisation is an important means for minimising research waste and ensuring that research resources are targeted towards answering the most important questions. Identifying the top 10 rapid review methodology research priorities will help target research to improve how we plan, do and share rapid reviews and ultimately enhance the use of high-quality synthesised evidence to inform health care policy and practice.