bluuebunny/crossref_metadata_2025_split huggingface dataset:
The actin-capping protein alpha-adducin is required for T-cell costimulation
Authors: Thauland Timothy J. , Butte Manish J. 
Published: March 2019

AbstractAlpha-adducin (Add1) is a critical component of the actin-spectrin network in erythrocytes, acting to cap the fast-growing, barbed ends of actin filaments, and recruiting spectrin to these junctions. Add1 is highly expressed in T cells, but its role in T-cell activation has not been examined. Using a conditional knockout model, we show that Add1 is necessary for complete activation of CD4+ T cells in response to low levels of antigen but is dispensable for CD8+ T cell activation and response to infection. Surprisingly, costimulatory signals through CD28 were completely abrogated in the absence of Add1. This study is the first to examine the role of actin-capping in T cells, and it reveals a previously unappreciated role for the actin cytoskeleton in regulating costimulation.
Gut microbiota plasticity is correlated with sustained weight loss on a low-carb or low-fat dietary intervention
Authors: Grembi Jessica A , Nguyen Lan H , Haggerty Thomas D , Gardner Christopher D , Holmes Susan P , Parsonnet Julie 
Published: March 2019

AbstractBackgroundObesity is a complex global health challenge. Although both low-carbohydrate (low-carb) and low-fat diets can lead to weight loss, there is typically substantial variability in weight and related outcomes for both diet approaches among obese but otherwise healthy adults. Elucidating individual characteristics that might contribute to sustained weight loss is critical to developing effective dietary intervention strategies. We hypothesized that structural differences in the gut microbiota explained some portion of the weight loss variability among people randomized to either a low-carb or low-fat diet, possibly related to its effects on dietary compliance.ResultsOur study included two staggered cohorts of obese adults enrolled in the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) study - a randomized clinical trial of either a low-fat or low-carb diet. In the discovery cohort (n=66), 161 pre-diet fecal samples were sequenced in addition to 157 samples collected after 10-weeks of dietary intervention. In the validation cohort (n = 56), 106 pre-diet fecal samples were sequenced. Pre-diet taxonomic features, such as the Prevotella/Bacteroides ratio, correlated to weight loss in the discovery cohort were not confirmed in the validation cohort. The most robust finding in the discovery cohort indicated that gut microbiota plasticity was linked to 12-month weight loss in a diet-dependent manner; subjects with higher sustained weight loss on a low-fat diet had higher pre-diet daily plasticity, whereas those most successful on the low-carb diet had greater microbiota plasticity over 10 weeks of dietary intervention. Unfortunately, because sample frequency and timing was quite different in the validation cohort, the relationship between plasticity and weight loss could not be studied in this group.ConclusionsThese findings suggest the potential importance of gut microbiota plasticity in sustained weight loss. We highlight the importance of evaluating kinetic trends and in assessing reproducibility in studies of the gut microbiota.
Molecular signatures of the rediae, cercariae and adult worm stages in the complex life cycles of parasitic flatworms (Psilostomatidae, Trematoda)
Authors: Nesterenko Maksim A. , Starunov Viktor V. , Shchenkov Sergei V. , Maslova Anna R. , Denisova Sofia A. , Granovich Andrey I. , Dobrovolskij Andrey A. , Khalturin Konstantin V. 
Published: March 2019

AbstractTrematodes are one of the most remarkable animals with complex life cycles with several generations. Life histories of a parasitic flatworms include several stages with disparate morphological and physiological characteristics follow each other and infect hosts ranging from mollusks to higher vertebrates. How does one genome regulate the development of various life forms and how many genes are needed to the functioning of each stages? How similar are molecular signatures of life stages in closely related species of parasitic flatworms? Here we present the comparative analysis of transcriptomic signatures of the rediae, cercaria and adult worm stages in two representatives of the family Psilostomatidae (Echinostomata, Trematoda) -Psilotrema simillimumandSphaeridiotrema pseudoglobulus. Our results indicate that the transitions between the stages of the complex life cycle are associated with massive changes in gene expression with thousands of genes being stage-specific. In terms of expression dynamics, the adult worm is the most similar stage betweenPsilotremaandSpaeridiotrema, while expression patterns of genes in the rediae and cercariae stages are much more different. This study provides transcriptomic evidences not only for similarities and differences between life stages of two related species, but also for cryptic species inSphaeridiotrema.
The Work Performed By Biological Motors
Authors: Baker Josh E. 
Published: March 2019

AbstractMolecular motors are enzymes that perform work (F · x) when they move along a track a distance x against a constant force F. This work is performed through intermediate chemical steps in a motor’s ATPase reaction cycle, each step having a free energy change associated with it that is a sum of chemical, Δµchem, and mechanical, Δµext, potentials. Defining Δµext is fundamental to our understanding of how molecular motors work, yet after decades of study the definition of Δµext remains disputed. Some postulate that Δµext is a function of both F and x, while others assume that Δµext is a function of neither F nor x, and still others argue that Δµext is a function of F but not x. Here we evaluate these models and conclude that only the latter – a mechanochemical model proposed by A.V. Hill in the 1930’s – describes molecular motor mechanochemistry.
A candidate causal variant underlying both enhanced cognitive performance and increased risk of bipolar disorder
Authors: Shen Susan Q. , Kim-Han Jeong Sook , Cheng Lin , Xu Duo , Gokcumen Omer , Hughes Andrew E.O. , Myers Connie A. , Corbo Joseph C. 
Published: March 2019

ABSTRACTBipolar disorder is a highly heritable mental illness, but the relevant genetic variants and molecular mechanisms are largely unknown. Recent GWASs have identified an intergenic region associated with both cognitive performance and bipolar disorder. This region contains dozens of putative fetal brain-specific enhancers and is located ∼0.7 Mb upstream of the neuronal transcription factor POU3F2. We identified a candidate causal variant, rs77910749, that falls within a highly conserved putative enhancer, LC1. This human-specific variant is a single-base deletion in a PAX6 binding site and is predicted to be functional. We hypothesized that rs77910749 alters LC1 activity and hence POU3F2 expression during neurodevelopment. Indeed, transgenic reporter mice demonstrated LC1 activity in the developing cerebral cortex and amygdala. Furthermore, ex vivo reporter assays in embryonic mouse brain and human iPSC-derived cerebral organoids revealed increased enhancer activity conferred by the variant. To probe the in vivo function of LC1, we deleted the orthologous mouse region, which resulted in amygdala-specific changes in Pou3f2 expression. Lastly, ‘humanized’ rs77910749 knock-in mice displayed behavioral defects in sensory gating, an amygdala-dependent endophenotype seen in patients with bipolar disorder. Our study suggests a molecular mechanism underlying the long-speculated link between enhanced cognitive performance and neuropsychiatric disease.
Proteomic Analysis ofPlasmodiumMerosomes: The Link Between Liver and Blood Stages in Malaria
Authors: Shears Melanie J , Nirujogi Raja Sekhar , Swearingen Kristian E , Renuse Santosh , Mishra Satish , Reddy Panga Jaipal , Moritz Robert L , Pandey Akhilesh , Sinnis Photini 
Published: March 2019

SummaryThe pre-erythrocytic liver stage of the malaria parasite, comprising sporozoites and the liver stages into which they develop, remains one of the least understood parts of the lifecycle, in part owing to the low numbers of parasites. Nonetheless, it is recognized as an important target for anti-malarial drugs and vaccines. Here we provide the first proteomic analysis of merosomes, which define the final phase of the liver stage and are responsible for initiating the blood stage of infection. We identify a total of 1879 parasite proteins, and a core set of 1188 proteins quantitatively detected in every biological replicate, providing an extensive picture of the protein repertoire of this stage. This unique dataset will allow us to explore key questions about the biology of merosomes and hepatic merozoites.HighlightsFirst proteome of the merosome stage of malaria parasitesQuantitative detection of 1188 parasite proteins across 3 biological replicatesComparison to blood stage proteomes identifies shared and unique proteinsDiscovery of cleaved PEXEL motifs highlights liver stage protein exportIn BriefThe merosome stage that links malaria liver and blood stage infection is poorly understood. Here we provide the first proteome of this life cycle stage using thePlasmodium bergheirodent malaria model.Graphical Abstract
The RNA encoding the microtubule-associated protein tau has extensive structure that affects its biology
Authors: Chen Jonathan L. , Moss Walter N. , Spencer Adam , Zhang Peiyuan , Childs-Disney Jessica L. , Disney Matthew D. 
Published: March 2019

ABSTRACTTauopathies are neurodegenerative diseases that affect millions of people worldwide including those with Alzheimer’s disease. While many efforts have focused on understanding the role of tau protein in neurodegeneration, there has been little done to systematically analyze and study the structures within tau’s encoding RNA and their connection to disease pathology. Knowledge of RNA structure can provide insights into disease mechanisms and how to affect protein production for therapeutic benefit. Using computational methods based on thermodynamic stability and evolutionary conservation, we identified structures throughout the tau pre-mRNA, especially at exon-intron junctions and within the 5′ and 3′ untranslated regions (UTRs). In particular, structures were identified at twenty exon-intron junctions. The 5′ UTR contains one structured region, which lies within a known internal ribosome entry site. The 3′ UTR contains eight structured regions, including one that contains a polyadenylation signal. A series of functional experiments were carried out to assess the effects of mutations associated with mis-regulation of alternative splicing of exon 10 and to identify regions of the 3′ UTR that contain cis-regulatory elements. These studies defined novel structural regions within the mRNA that affect stability and pre-mRNA splicing and may lead to new therapeutic targets for treating tau-associated diseases.
Morphine analgesia and μ opioid receptor signaling require programed death protein 1
Authors: Wang Zilong , Jiang Changyu , He Qianru , Matsuda Megumi , Han Qingjian , Wang Kaiyuan , Bang Sangsu , Ji Ru-Rong 
Published: March 2019

SummaryOpioids such as morphine produce analgesia via mu opioid receptor (MOR), but opioid receptor signaling is not fully understood. Here we report that morphine analgesia and MOR signaling require neuronal Programmed cell death protein-1 (PD-1). We found that morphine-induced antinociception following systemic or intrathecal injection was compromised in Pd1-/- mice. Morphine analgesia was also abrogated in wild-type mice after treatment with Nivolumab, a clinically used anti-PD-1 monoclonal antibody. Morphine produced analgesia by suppressing calcium currents in DRG neurons and excitatory synaptic transmission in spinal cord neurons, but strikingly, both actions were impaired by PD-1 blockade. In a mouse model of bone cancer, the antinociceptive action of systemic morphine was compromised in Pd1-/- mice. Finally, PD-L1 and morphine produce synergistic analgesia. Our findings demonstrate that PD-1 also acts as a neuro checkpoint inhibitor and mediates opioid-induced analgesia and MOR signaling in neurons.
Ancestral range reconstruction of remote oceanic island species of Plantago (Plantaginaceae) reveals differing scales and modes of dispersal
Authors: Iwanycki Ahlstrand N. , Verstraete B. , Hassemer G. , Dunbar‐Co S. , Hoggard R. , Meudt H. M. , Rønsted N. 
Published: March 2019

AbstractAimThe aim of this study was to resolve the phylogenetic placement of island taxa, reconstruct ancestral origins and resolve competing hypotheses of dispersal patterns and biogeographical histories for oceanic island endemic taxa within subgenus Plantago (Plantaginaceae).LocationJuan Fernández Islands, the Auckland Islands, Lord Howe Island, New Amsterdam Island, New Zealand, Tasmania, Falkland Islands, Rapa Iti and the Hawaiian Islands.TaxonIsland endemics within Plantago (Plantaginaceae), a globally distributed taxonomic group comprising approximately 250 species.MethodsWe use Bayesian phylogenetic and divergence time analyses and historical biogeographical analysis of molecular sequence data to infer the ancestral origins of the oceanic island species in Plantago.ResultsTaxa within subgenus Plantago form clades based on geographic proximities and challenge previous phylogenetic relationships and classification based on morphology. We infer that biogeographic histories of oceanic island taxa from multiple islands were shaped by dispersal at different scales and possibly by different types of birds. The highly remote Hawaiian Islands and Rapa Iti were colonized from North American taxa in a pattern corresponding to known migration routes of large marine birds, rather than from New Zealand as previously hypothesized. The island endemics of Juan Fernández, the Falkland Islands, Lord Howe, Auckland Islands and New Zealand are found to have sources in the nearest continental areas. The analyses confirm recent speciation within subgenus Plantago – which is particularly heightened in island lineages in Hawaii and Rapa Iti – but show slightly older divergence times than previous molecular dating studies.Main conclusionsUsing molecular data to infer ancestral ranges for plants with uncertain taxonomic relationships can greatly improve our understanding of biogeographical histories and help elucidate origins, dispersal modes and routes in widespread lineages with complex distribution patterns such as Plantago. We improve understanding of important floristic exchange areas between continents and islands as a result of long‐distance dispersal. We infer that a combination of both stepping stone dispersal and extreme long‐distance dispersal can shape insular floras, and that multiple floristic areas can be the sources of closely related island taxa. However, despite the successful dispersal of Plantago, radiation in island archipelagos is generally limited suggesting specific traits may limit diversification.
How does 6 months of active bike commuting or leisure-time exercise affect insulin sensitivity, cardiorespiratory fitness and intra-abdominal fat? A randomised controlled trial in individuals with overweight and obesity
Authors: Blond Martin Bæk , Rosenkilde Mads , Gram Anne Sofie , Tindborg Marie , Christensen Anders Nymark , Quist Jonas Salling , Stallknecht Bente Merete 
Published: March 2019

ObjectivesTo evaluate effects of active bike commuting or leisure-time exercise of two intensities on peripheral insulin sensitivity (primary outcome), cardiorespiratory fitness and intra-abdominal adipose tissue mass (secondary outcomes).Methods188 physically inactive, healthy women and men (20-45 years) with overweight or class 1 obesity were recruited. In the 6-month trial, 130 participants were randomised to either: no intervention (CON), active commuting (BIKE) or leisure-time exercise of moderate (MOD, 50% VO2peak) or vigorous (VIG, 70% VO2peak) intensity. 100 completed follow-up testing. Exercise prescription was 5 days/week with a weekly exercise energy expenditure of 1600 kcal for women and 2100 kcal for men. Testing was performed at baseline, 3 months and 6 months.ResultsPeripheral insulin sensitivity (ml/min/pmol insulin/L) increased (improved) by 24% (95% CI 6% to 46%, p=0.01) in VIG compared with CON at 3 months. Peripheral insulin sensitivity increased (improved) by 20% in BIKE (95% CI 1% to 43%, p=0.04) and 26% in VIG (95% CI 7% to 47%, p<0.01) compared with CON at 6 months. Cardiorespiratory fitness increased in all exercise groups compared with CON at 6 months; but the increase was higher in those that undertook vigorous exercise than those who did moderate exercise. Intra-abdominal adipose tissue mass diminished across all exercise groups in comparison to CON at 6 months.ConclusionsActive bike commuting improved cardiometabolic health; as did leisure-time exercise. Leisure-time exercise of vigorous intensity conferred more rapid effects on peripheral insulin sensitivity as well as additional effects on cardiorespiratory fitness than did moderate intensity exercise.Trial registrationNCT01962259
Does the withdrawal time affect adenoma detection in non-screening colonoscopies?
Authors: Al-Rifaie Ammar , El-Feki Mohammed , Al-Talib Ismaeel , Abdulwahid Maysam , Hopper Andrew , Thoufeeq Mo 
Published: March 2019

AimsThere are no studies looking at the relationship between colonoscopy withdrawal time (CWT) and adenoma detection rate (ADR) in non-screening patients. Our aim is to explore the relationship between CWT and ADR, particularly in the proximal colon where colonoscopy is shown to be less protective for the development of cancers.MethodsThis is a retrospective study during November 2015 to December 2016 of non-screening colonoscopies done at a large teaching hospital. Incomplete and therapeutic procedures were excluded. The 39 endoscopists included were 15 gastroenterologists, 10 colorectal surgeons and 14 trainee colonoscopists. CWT was calculated by reviewing caecal intubation and rectal retroflexion images.Results783 colonoscopies were included, with mean patient age of 58.51 years (SD 15.5). The mean ADR was 21.45% in the study. The CWT could be calculated for 62.83% of the cases (n=492). 80% (393) of colonoscopies had CWT of ≥6 min. Mean CWT was 9.15 min (SD 4.4). The ADR positively correlated with longer CWT (r=0.31, p=0.0001). The ADR was significantly higher when CWT was ≥8 min compared with CWT <6 min or CWT of 6–8 min (p=0.0001). More polyps were detected in the proximal colon when CWT ≥8 min (p=0.078). Mean CWT of gastroenterologists was 9.8 min (SD 4.5), similar to the trainee group (10.3 min, SD 3.8), while mean CWT for colorectal surgeons was 5.7 min (SD 3.2). The ADR for gastroenterologists was 25.9% versus 17.5% for colorectal surgeons and 17.8% for trainees.ConclusionsThere is a moderately strong positive correlation between longer CWT and ADR in non-screening colonoscopies. CWT can differ between different endoscopists. Meticulous colonoscopy withdrawal may improve polyp detection in the proximal colon.
Optimal management adaptive of two crossroads by genetic algorithm
Authors: Merbah Amal , Makrizi Abdelilah 
Published: March 2019

This paper addresses the issue of managing the traffic flow at traffic-light controlled junctions adopting a mixed, nonlinear programming model. More precisely, we adopt an adaptive, acyclic control system based on the genetic algorithm (GA), a system that allows to accurately decide in real time on the light switching pattern that minimizes the traffic waiting time. Equally importantly, the inherent crossroads constraints, namely, the security of their users and the structure thereof, also referred to as the antagonism principle, are considered in the proceeding of this method. The implementation of this model on two crossroads significantly decreases the waiting time and regulates the traffic flow. Therefore, the adaptive control system based on the GA proves efficient compared to the nonadaptive system.
Influence of the vent pipe diameter on the discharge capacity of a circuit vent building drainage system
Authors: Guan Yuxi , Fang Zheng , Tang Zhi , Yuan Jianping 
Published: March 2019

Experiments on different vent pipe diameters (nominal diameters of 100, 75 and 50 mm; DN100, DN75 and DN50, respectively) in a full-scale circuit vent building drainage system were conducted in a 60 -m high structure, and the wastewater discharge capacities as a function of vent pipe diameter were measured. Critical pipe pressures, water seal losses of sanitary fixtures and air flow rates were measured. The ultimate pressure values in pipes on lower floors were larger than those in pipes on higher floors using DN100 and DN75, which was opposite to the results with DN50. A positive correlation between the ultimate pressure values and floor heights, as well as between ultimate pressure values and water seal losses, was found for DN100 and DN75. The maximum discharge flow of the three systems using DN100, DN75 and DN50 vent pipes was 17.0 L/s, 14.0 L/s and 7.5 L/s, respectively. Nevertheless, in China, the maximum wastewater discharge capacity in a circuit vent system adopting a DN100 vent pipe connected to a DN100 drainage stack in tall residential buildings is 11.5 L/s according to the Code for Design of Building Water Supply and Drainage. Thus, the vent pipe diameter DN75 can fully meet the design requirements of drainage systems for high rise buildings in China. The engineering cost associated with material expenses for building drainage systems can be minimised by optimising the size of vent pipe based on required capacity rather than using a single size universally. Practical application: The engineering cost associated with material expenses for building drainage systems can be minimised by optimising the size of vent pipe based on required capacity rather than using a single size universally.
Application of neural network to building environmental prediction and control
Authors: Li Ruocheng , Zhang Xiangpeng , Liu Le , Li Yifan , Xu Qingyang 
Published: March 2019

Energy conservation, environmental protection, and intelligence are topics of interest in intelligent buildings. However, the energy requirement of various electrical equipment in intelligent buildings increases energy consumption. This study presents a neural network-based prediction and control system for the regulation of building environmental parameters. Neural network-based soft sensing technology can detect building environmental parameters through few sensors. The proposed system control algorithm can realize the adaptive adjustment of environmental parameters by using a neural network proportional–integral–derivative controller. Zigbee wireless communication is adopted as the information transmission medium to realize the environmental parameter measurement and network control. The soft sensing technique combined with Zigbee communication technology can effectively reduce energy consumption. The central control system analyzes the data coming from the network and regulates the environmental parameter through lifting temperature, ventilation, and switching curtains by using the neural network proportional–integral–derivative algorithm. The regulation of environmental parameters reduces unnecessary energy consumption. Finally, the effectiveness of the system is verified through simulations. Practical applications: This work reports an energy saving scheme. The building communication system constructed by ZigBee can reduce energy consumption and can be easily expanded. The soft sensing technique based on artificial neural network can predict temperatures by using few sensors. The neural network proportional–integral–derivative control algorithm has good performance in the regulation of environmental parameters for a time-varying system. Building energy consumption can be reduced by conducting these measures.