bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of diarised sleep onset time, period and duration with total and central adiposity in a biethnic sample of young children: the Born in Bradford study
Authors: Collings Paul J , Blackwell Jane E , Pal Elizabeth , Ball Helen L , Wright John 
Published: October 2020

AbstractObjectivesTo investigate associations of sleep timing, period and duration with total and abdominal adiposity in a biethnic sample of children aged 18 and 36 months (m)DesignCross-sectional observational studySettingThe Born in Bradford 1000 study, UKParticipantsChildren aged approximately 18m (n=209; 40.2% South Asian; 59.8% White) and 36m (n=162; 40.7% South Asian; 59.3% White)Primary and secondary outcome measuresParents completed a 3-day sleep diary from which children’s average daily sleep onset time, period and duration were calculated. Weekday to weekend differences in sleep parameters were also derived. As outcomes, indices of total (BMI z-score and sum of 2-skinfolds) and abdominal adiposity (waist circumference) were measured. Adjusted regression was used to quantify associations of sleep parameters with adiposity by age group and ethnicity.ResultsThe average daily sleep onset time was markedly later in South Asian (9:26pm ± 68 mins) than White children (7:41pm ± 48 mins). Later sleep onset was associated with lower BMI z-score and sum of 2-skinfolds in White children aged 18m. In contrast, later sleep onset was associated with higher BMI z-score in South Asian children aged 36m. For weekday to weekend differences, longer sleep duration and later sleep onset on weekends than weekdays were both associated with higher total and abdominal adiposity in South Asian children aged 18m. On the contrary, compared to consistent sleep onset times, going to sleep ≥20 minutes later on weekends than weekdays was associated with lower waist circumference in White children aged 18m.ConclusionsSleep timing is associated with total and central adiposity in young children but associations differ by age group and ethnicity. Sleep onset times and regular sleep schedules may be important for obesity prevention.
The IHAT-GUT iron supplementation trial in rural Gambia: barriers, facilitators, and benefits
Authors: Stelle Isabelle , McDonagh Lorraine K. , Hossain Mohammad Ilias , Kalea Anastasia Z. , Pereira Dora I.A. 
Published: October 2020

ABSTRACTIntroductionIn most sub-Saharan African countries iron deficiency anaemia remains highly prevalent in children and this has not changed in the last 25 years. Supplementation with iron hydroxide adipate tartrate (IHAT) was being investigated in anaemic children in a phase two clinical-trial (termed IHAT-GUT), conducted at the MRC Unit The Gambia at LSHTM (MRCG). This qualitative study aimed to explore the personal perceptions of the trial staff in relation to conducting a clinical trial in such settings in order to highlight the health system specific needs and strengths in the rural, resource-poor setting of the Upper River Region in The Gambia.MethodsIndividual interviews (n=17) were conducted with local trial staff of the IHAT-GUT trial. Data were analysed using inductive thematic analysis.ResultsPotential barriers and facilitators to conducting this clinical trial were identified at the patient, staff, and trial-management levels. Several challenges, such as the rural location and cultural context, were identified but noted as not being long-term inhibitors. Participants believed the facilitators and benefits outnumbered the barriers, and included the impact on education and healthcare, the ambitious and knowledgeable locally recruited staff and the local partnership.ConclusionWhile facilitators and barriers were identified to conducting this clinical trial in a rural, resource poor setting, the overall impact was perceived as beneficial, and this study is a useful example of community involvement and partnership for further health improvement programs. To effectively implement a nutrition intervention, the local health systems and context must be carefully considered through qualitative research beforehand.
Projected HIV and Bacterial STI Incidence Following COVID-Related Sexual Distancing and Clinical Service Interruption
Authors: Jenness Samuel M. , Le Guillou Adrien , Chandra Christina , Mann Laura M. , Sanchez Travis , Westreich Daniel , Marcus Julia L. 
Published: October 2020

ABSTRACTBackgroundThe global COVID-19 pandemic has the potential to indirectly impact the transmission dynamics and prevention of HIV and other sexually transmitted infections (STI). Studies have already documented reductions in sexual activity (“sexual distancing”) and interruptions in HIV/STI services, but it is unknown what combined impact these two forces will have on longer-term HIV/STI epidemic trajectories.MethodsWe adapted a network-based model of co-circulating HIV, gonorrhea, and chlamydia for a population of men who have sex with men (MSM) in the Atlanta area. Model scenarios varied the timing, overlap, and relative extent of COVID-related sexual distancing in casual and one-time partnership networks and service interruption within four service categories (HIV screening, HIV PrEP, HIV ART, and STI treatment).ResultsA 50% relative decrease in sexual partnerships and interruption of all clinical services, both lasting 18 months, would generally offset each other for HIV (total 5-year population impact for Atlanta MSM: −227 cases), but have net protective effect for STIs (−23,800 cases). Greater relative reductions and longer durations of service interruption would increase HIV and STI incidence, while greater relative reductions and longer durations of sexual distancing would decrease incidence of both. If distancing lasted only 3 months but service interruption lasted 18 months, the total 5-year population impact would be an additional 890 HIV cases and 57,500 STI cases.ConclusionsThe counterbalancing impact of sexual distancing and clinical service interruption depends on the infection and the extent and durability of these COVID-related changes. If sexual behavior rebounds while service interruption persists, we project an excess of hundreds of HIV cases and thousands of STI cases just among Atlanta MSM over the next 5 years. Immediate action to limit the impact of service interruptions is needed to address the indirect effects of the global COVID pandemic on the HIV/STI epidemic.
The NK Landscape as a Versatile Benchmark for Machine Learning Driven Protein Engineering
Authors: Mater Adam C. , Sandhu Mahakaran , Jackson Colin 
Published: October 2020

AbstractMachine learning (ML) has the potential to revolutionize protein engineering. However, the field currently lacks standardized and rigorous evaluation benchmarks for sequence-fitness prediction, which makes accurate evaluation of the performance of different architectures difficult. Here we propose a unifying framework for ML-driven sequence-fitness prediction. Using simulated (theNKmodel) and empirical sequence landscapes, we define four key performance metrics: interpolation within the training domain, extrapolation outside the training domain, robustness to sparse training data, and ability to cope with epistasis/ruggedness. We show that architectural differences between algorithms consistently affect performance against these metrics across both experimental and theoretical landscapes. Moreover, landscape ruggedness is revealed to be the greatest determinant of the accuracy of sequence-fitness prediction. We hope that this benchmarking method and the code that accompanies it will enable robust evaluation and comparison of novel architectures in this emerging field and assist in the adoption of ML for protein engineering.
A comparative transcriptional landscape of two castor cultivars obtained by single-molecule sequencing comparative analysis
Authors: Zhou Wei , Zhou Yaxing , Zhu Guoli , Wang Yun , He Zhibiao , Shi Zhensheng 
Published: October 2020

AbstractBackground and ObjectivesCastor (Ricinus communisL.) is an important non-edible oilseed crop. Lm type female strains and normal amphiprotic strains are important castor cultivars, and are mainly different in inflorescence structures and leaf shapes. To better understand the mechanisums underling these differences at the molecular level, we performed comparative transcriptional analysis.Materials and MethodsFull-length transcriptome sequencing and short-read RNA sequencing were employed.ResultsA total of 76,068 and 44,223 non-redundant transcripts were obtained from high-quality transcripts of Lm type female strains and normal amphiprotic strains, respectively. In Lm female strain and normal amphiprotic strains 51,613 and 20,152 alternative splicing events were found, respectively. There were 13,239 transcription factors identified from the full-length transcriptomes. Comparative analysis showed great different gene expression of common and unique transcription factors between the two cultivars. Meanwhile, functional analysis of isoform was conducted. Full-length sequences were used as a reference genome, and short-read RNA sequencing analysis was performed to conduct differential gene analysis. Furthermore, the function of DEGs were performed to annotation analysis.ConclusionsThe results revealed considerable difference and expression diversity between two cultivars, well beyond what was reported in previous studies, likely reflecting the differences in architecture between these two cultivars.HighlightUsing the full-length transcriptome sequencing technology, we performed comparative analysis of transcription factors of two castor cultivars, analyzed alternative splicing events, and identified their lncRNAs.
Changes in the plasmodesma structure and permeability at the bundle sheath and mesophyll interface during the maize C4 leaf development
Authors: Gao Peng , Du Baijuan , Li Pinghua , Kang Byung-Ho 
Published: October 2020

AbstractPlasmodesmata are intercellular channels that facilitate molecular diffusion between neighboring plant cells. The development and functions of plasmodesmata are controlled by multiple intra- and intercellular signaling pathways. Plasmodesmata are critical for dual-cell C4 photosynthesis in maize because plasmodesmata at the mesophyll and bundle sheath interface mediate exchange of CO2-carrying organic acids. We examined developmental profiles of plasmodesmata and chloroplasts in the maize leaf from young cells in the base to mature cell in the tip using microscopy approaches. Young mesophyll and bundle sheath cells in the leaf base had proplastids, and their plasmodesmata were simple, devoid of cytoplasmic sleeves. In maturing cells where Kranz anatomy and dimorphic chloroplasts were evident, we observed extensive remodeling of plasmodesmata that included acquisition of an electron-dense ring on the mesophyll side and cytoplasmic sleeves on the bundle sheath side. Interestingly, the changes in plasmodesmata involved a drop in symplastic dye mobility and suberin accumulation in the cell wall, implying a more stringent mesophyll-bundle sheath transport. We compared kinetics of the plasmodesmata and the cell wall modification in wildtype leaves with leaves fromppdk and dct2mutants with defective C4 pathways. Plasmodesmata development, symplastic transport inhibition, and cell wall suberization were accelerated in the mutant lines, probably due to the aberrant C4 cycle. Transcriptomic analyses of the mutants confirmed the expedited changes in the cell wall. Our results suggest that a regulatory machinery at the mesophyll-bundle sheath boundary suppresses erroneous flux of C4 metabolites in the maize leaf.Significance StatementPlasmodesmata in the maize Kranz anatomy mediate the exchange of organic acids between mesophyll and bundle sheath. Since solute diffusion through plasmodesmata is governed by solute concentration gradients, a balanced distribution of C4 metabolites is critical for concentration of CO2in the bundle sheath. Plasmodesmata bridging the mesophyll and bundle sheath cytoplasm have a cylindrical cavity, which can facilitate molecular movements, and a valve-like attachment. Construction of the sophisticated plasmodesmata was linked to C4 photosynthesis, and plasmodesmata assembly finished more rapidly in maize mutants with defective C4 pathways than in wild-type plants. These results suggest that the specialized plasmodesmata contribute to controlled transport of C4 metabolites.
REEP4 is recruited to the inner nuclear membrane by ELYS and promotes nuclear pore complex formation
Authors: Golchoubian Banafsheh , Brunner Andreas , Bragulat-Teixidor Helena , Akarlar Busra A. , Ozlu Nurhan , Schlaitz Anne-Lore 
Published: October 2020

AbstractNuclear pore complexes (NPCs) are channels within the nuclear envelope that mediate nucleocytoplasmic transport. NPCs assemble either into the closed nuclear envelope during interphase or concomitantly with nuclear envelope reformation during anaphase. Both, interphase and post-mitotic NPC biogenesis require local deformation of membrane. Yet, the factors that control proper membrane remodeling for post-mitotic NPC assembly are unknown. Here, we report that the reticulon homology domain-protein REEP4 localizes not only to high-curvature membrane of the cytoplasmic endoplasmic reticulum (ER) but also to the inner nuclear membrane (INM). We show that REEP4 is recruited to the INM by the NPC biogenesis factor ELYS and promotes NPC assembly. REEP4 contributes mainly to anaphase NPC assembly, suggesting that REEP4 has an unexpected role in coordinating nuclear envelope reformation with post-mitotic NPC biogenesis.
Subunit epsilon ofE. coliF1FoATP synthase attenuates enzyme activity by modulating central stalk flexibility
Authors: Sobti Meghna , Walshe James L. , Zeng Yi C. , Ishmukhametov Robert , Stewart Alastair G. 
Published: October 2020

ABSTRACTF1FoATP synthase functions as a biological rotary generator that makes a major contribution to cellular energy production. Proton flow through the Fomotor generates rotation of the central stalk, inducing conformational changes in the F1motor that catalyzes ATP production via flexible coupling. Here we present a range of cryo-EM structures ofE. coliATP synthase in different rotational and inhibited states observed following a 45 second incubation with 10 mM MgATP. The structures generated describe multiple changes that occur following addition of MgATP, with the inhibitory C-terminal domain of subunit ε (εCTD) disassociating from the central stalk to adopt a condensed “down” conformation. The transition to the εCTD down state increases the torsional flexibility of the central stalk allowing its foot to rotate by ∼50°, with further flexing in the peripheral stalk enabling thec-ring to rotate by two sub-steps in the Fomotor. Truncation mutants lacking the second helix of the εCTD suggest that central stalk rotational flexibility is important for F1FoATP synthase function. Overall this study identifies the potential role played by torsional flexing within the rotor and how this could be influenced by the ε subunit.
Novel Chlamydiae andAmoebophilusendosymbionts are prevalent in wild isolates of the model social amoebaDictyostelium discoideum
Authors: Haselkorn Tamara S. , Jimenez Daniela , Bashir Usman , Sallinger Eleni , Queller David C. , Strassmann Joan E. , DiSalvo Susanne 
Published: October 2020

SummaryAmoebae interact with bacteria in diverse and multifaceted ways. Amoeba predation can serve as a selective pressure for the development of bacterial virulence traits. Bacteria may also adapt to life inside amoebae, resulting in symbiotic relationships (pathogenic or mutualistic). Indeed, particular lineages of obligate bacterial endosymbionts have been found in different amoebae. Here, we screened an extensive collection ofDictyostelium discoideumwild isolates for the presence of such bacterial symbionts using PCR primers that identify these endosymbionts. This is the first report of obligate symbionts in this highly-studied amoeba species. They are surprisingly common, identified in 42% of screened isolates (N=730). Members of the Chlamydiae phylum are particularly prevalent, occurring in 27% of the host strains. They are novel and phylogenetically distinct. We also foundAmoebophilussymbionts in 8% of screened isolates (N=730). Antibiotic-cured amoebae behave similarly to their endosymbiont-infected counterparts, suggesting that endosymbionts do not significantly impact host fitness, at least in the laboratory. We found several natural isolates were co-infected with multiple endosymbionts, with no obvious fitness effects of co-infection under laboratory conditions. The high prevalence and novelty of amoeba endosymbiont clades in the model organismD. discoideumopens the door to future research on the significance and mechanisms of amoeba-symbiont interactions.
TheGiardia lambliaribosome structure reveals divergence in translation and quality control pathways
Authors: Eiler Daniel R. , Wimberly Brian T. , Bilodeau Danielle Y. , Rissland Olivia S. , Kieft Jeffrey S. 
Published: October 2020

ABSTRACTGiardia lambliais a human pathogen of worldwide importance with limited treatment options. Its unusual molecular biology presents targets for new therapies and the opportunity to explore the fundamental features of important biological mechanisms. We determined the structure of theG. lamblia80S ribosome by cryoelectron microscopy, revealing how it combines eukaryotic and bacterial features. The structure reveals regions that are rapidly evolving, including depletion of A and U bases from its rRNA. Specific features of theG. lambliaribosome suggest it is less prone to stall on problematic peptide sequences, and that the organism uses altered ribosome quality control pathways compared to other eukaryotes. Examination of translation initiation factor binding sites suggests these interactions are conserved despite a divergent initiation mechanism. This work defines key new questions regarding ribosome-centric biological pathways inG. lambliaand motivates new experiments to explore potential targetable mechanisms.
Social relationships among captive male pygmy slow lorises (Nycticebus pygmaeus): Is forming male same-sex pairs a feasible management strategy?
Authors: Yamanashi Yumi , Nemoto Kei , Alejandro Josue 
Published: October 2020

AbstractLittle is known about the social behavior of pygmy slow lorises, in particular, the social relationships of same-sex individuals have rarely been investigated. The Slow Loris Conservation Center was built at the Japan Monkey Center to enhance the welfare of confiscated slow lorises, promote their conservation, improve public education and perform scientific research on the species. In the course of improving housing conditions, several same-sex pairs of pygmy slow lorises were formed. We monitored their behaviors and fecal glucocorticoid metabolite (FGM) levels to understand whether male same-sex pairings could be a feasible management strategy. The subjects were 10 male and 6 female lorises for comparison, all of whom were over five years old. We successfully formed five pairs of male lorises after eight formation attempts. Male pairs initially showed some aggressive behaviors; however, the rate decreased approximately 10 days after introduction. All of the male pairs eventually exhibited extensive affiliative social behaviors, including allogrooming and social play, during the dark (active) phase, and sleep site sharing during the light (inactive) phase. The rate of sleep site sharing during the light phase was higher than expected, suggesting that the pairs preferred to stay near each other. There was no evidence of increased stress after a long period of male–male social housing. Female same-sex pairs and male-female pairs demonstrated a high level of affiliative behaviors right after introduction. These results highlight the flexibility and high sociability of this species and indicate that such same-sex pairings are a feasible option for their social management.
Polyamines Mediate Folding of Primordial Hyper-Acidic Helical Proteins
Authors: Despotović Dragana , Longo Liam M. , Aharon Einav , Kahana Amit , Scherf Tali , Gruic-Sovulj Ita , Tawfik Dan S. 
Published: October 2020

AbstractPolyamines are known to mediate diverse biological processes, and specifically to bind and stabilize compact conformations of nucleic acids, acting as chemical chaperones that promote folding by offsetting the repulsive negative charges of the phosphodiester backbone. However, whether and how polyamines modulate the structure and function of proteins remains unclear. Further, early proteins are thought to have been highly acidic, like nucleic acids, due to a scarcity of basic amino acids in the prebiotic context. Perhaps polyamines, the abiotic synthesis of which is simple, could have served as chemical chaperones for such primordial proteins? We replaced all lysines of an ancestral 60-residue helix-bundle protein to glutamate, resulting in a disordered protein with 21 glutamates in total. Polyamines efficiently induce folding of this hyper-acidic protein at sub-millimolar concentrations, and their potency scaled with the number of amine groups. Compared to cations, polyamines were several orders of magnitude more potent than Na+, while Mg2+and Ca2+had an effect similar to a di-amine, inducing folding at approximately seawater concentrations. We propose that (i) polyamines and dications may have had a role in promoting folding of early proteins devoid of basic residues, and that (ii) coil-helix transitions could be the basis of polyamine regulation in contemporary proteins.
Regulation of kinase activity by combined action of juxtamembrane and C-terminal regions of receptors
Authors: Lin Chi-Chuan , Wieteska Lukasz , Poncet-Montange Guillaume , Suen Kin M. , Arold Stefan T. , Ahmed Zamal , Ladbury John E. 
Published: October 2020

AbstractDespite the kinetically-favorable, ATP-rich intracellular environment, the mechanism by which receptor tyrosine kinases (RTKs) repress activation prior to extracellular stimulation is poorly understood. RTKs are activated through a precise sequence of phosphorylation reactions starting with a tyrosine on the activation loop (A-loop) of the intracellular kinase domain (KD). This forms an essential mono-phosphorylated ‘active intermediate’ state on the path to further phosphorylation of the receptor. We show that this state is subjected to stringent control imposed by the peripheral juxtamembrane (JM) and C-terminal tail (CT) regions. This entails interplay between the intermolecular interaction between JM with KD, which stabilizes the asymmetric active KD dimer, and the opposing intramolecular binding of CT to KD. A further control step is provided by the previously unobserved direct binding between JM and CT. Mutations in JM and CT sites that perturb regulation are found in numerous pathologies, revealing novel sites for potential pharmaceutical intervention.