bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personality and the collective: bold homing pigeons occupy higher leadership ranks in flocks
Authors: Sasaki Takao , Mann Richard P. , Warren Katherine N. , Herbert Tristian , Wilson Tara , Biro Dora 
Published: March 2018

While collective movement is ecologically widespread and conveys numerous benefits on individuals, it also poses a coordination problem: who controls the group's movements? The role that animal ‘personalities’ play in this question has recently become a focus of research interest. Although many animal groups have distributed leadership (i.e. multiple individuals influence collective decisions), studies linking personality and leadership have focused predominantly on the group's single most influential individual. In this study, we investigate the relationship between personality and the influence of multiple leaders on collective movement using homing pigeons,Columba livia, a species known to display complex multilevel leadership hierarchies during flock flights. Our results show that more exploratory (i.e. ‘bold’) birds are more likely to occupy higher ranks in the leadership hierarchy and thus have more influence on the direction of collective movement than less exploratory (i.e. ‘shy’) birds during both free flights around their lofts and homing flights from a distant site. Our data also show that bold pigeons fly faster than shy birds during solo flights. We discuss our results in light of theories about the evolution of personality, with specific reference to the adaptive value of heterogeneity in animal groups.This article is part of the theme issue ‘Collective movement ecology’.
UNC-16/JIP3 and UNC-76/FEZ1 limit the density of mitochondria inC. elegansneurons by maintaining the balance of anterograde and retrograde mitochondrial transport
Authors: Sure Guruprasada Reddy , Chatterjee Anusheela , Mishra Nikhil , Sabharwal Vidur , Devireddy Swathi , Awasthi Anjali , Mohan Swetha , Koushika Sandhya P. 
Published: March 2018

AbstractWe investigate the role of axonal transport in regulating neuronal mitochondrial density. We show that the density of mitochondria in the touch receptor neuron (TRN) of adultCaenorhabditis elegansis constant. Mitochondrial density and transport are controlled both by the Kinesin heavy chain and the Dynein-Dynactin complex. However, unlike in other models, the presence of mitochondria inC. elegansTRNs depends on Kinesin light chain as well. Mutants in the threeC. elegans mirogenes do not alter mitochondrial density in the TRNs. Mutants in the Kinesin-1 associated proteins, UNC-16/JIP3 and UNC-76/FEZ1, show increased mitochondrial density and also have elevated levels of both the Kinesin Heavy and Light Chains in neurons. Genetic analyses suggest that, the increased mitochondrial density at the distal end of the neuronal process inunc-16andunc-76depends partly on Dynein. We observe a net anterograde bias in the ratio of anterograde to retrograde mitochondrial flux in the neuronal processes ofunc-16andunc-76, likely due to both increased Kinesin-1 and decreased Dynein in the neuronal processes. Our study shows that UNC-16 and UNC-76 indirectly limit mitochondrial density in the neuronal process maintaining a balance in anterograde and retrograde mitochondrial axonal transport.
Body mass index and mortality in UK Biobank: revised estimates using Mendelian randomization
Authors: Wade Kaitlin H , Carslake David , Sattar Naveed , Smith George Davey , Timpson Nicholas J 
Published: March 2018

AbstractObjectiveObtain estimates of the causal relationship between different levels of body mass index (BMI) and mortality.MethodsMendelian randomization (MR) was conducted using genotypic variation reliably associated with BMI to test the causal effect of increasing BMI on all-cause and cause-specific mortality in participants of White British ancestry in UK Biobank.ResultsMR analyses supported existing evidence for a causal association between higher levels of BMI and greater risk of all-cause mortality (hazard ratio (HR) per 1kg/m2: 1.02; 95% CI: 0.97,1.06) and mortality from cardiovascular diseases (HR: 1.12; 95% CI: 1.02, 1.23), specifically coronary heart disease (HR: 1.19; 95% CI: 1.05, 1.35) and those other than stroke/aortic aneurysm (HR: 1.13; 95% CI: 0.93, 1.38), stomach cancer (HR: 1.30; 95% CI: 0.91, 1.86) and oesophageal cancer (HR: 1.08; 95% CI: 0.84, 1.38), and with decreased risk of lung cancer mortality (HR: 0.97; 95% CI: 0.84, 1.11). Sex-stratified analyses supported a causal role of higher BMI in increasing the risk of mortality from bladder cancer in males and other causes in females, but in decreasing the risk of respiratory disease mortality in males. The characteristic J-shaped observational association between BMI and mortality was visible with MR analyses but with a smaller value of BMI at which mortality risk was lowest and apparently flatter over a larger range of BMI.ConclusionResults support a causal role of higher BMI in increasing the risk of all-cause mortality and mortality from other causes. However, studies with greater numbers of deaths are needed to confirm the current findings.
From de novo to ‘de nono’: most novel protein coding genes identified with phylostratigraphy represent old genes or recent duplicates
Authors: Casola Claudio 
Published: March 2018

AbstractThe evolution of novel protein-coding genes from noncoding regions of the genome is one of the most compelling evidence for genetic innovations in nature. One popular approach to identify de novo genes is phylostratigraphy, which consists of determining the approximate time of origin (age) of a gene based on its distribution along a species phylogeny. Several studies have revealed significant flaws in determining the age of genes, including de novo genes, using phylostratigraphy alone. However, the rate of false positives in de novo gene surveys, based on phylostratigraphy, remains unknown. Here, I re-analyze the findings from three studies, two of which identified tens to hundreds of rodent-specific de novo genes adopting a phylostratigraphy-centered approach. Most of the putative de novo genes discovered in these investigations are no longer included in recently updated mouse gene sets. Using a combination of synteny information and sequence similarity searches, I show that about 60% of the remaining 381 putative de novo genes share homology with genes from other vertebrates, originated through gene duplication, and/or share no synteny information with non-rodent mammals. These results led to an estimated rate of ∼12 de novo genes per million year in mouse. Contrary to a previous study (Wilson et al. 2017), I found no evidence supporting the preadaptation hypothesis of de novo gene formation. Nearly half of the de novo genes confirmed in this study are within older genes, indicating that co-option of preexisting regulatory regions and a higher GC content may facilitate the origin of novel genes.
Efficacy and acceptability of non-invasive brain stimulation for the treatment of adult unipolar and bipolar depression: A systematic review and meta-analysis of randomised sham-controlled trials
Authors: Mutz Julian , Edgcumbe Daniel R. , Brunoni Andre R. , Fu Cynthia H.Y. 
Published: March 2018

AbstractWe examined the efficacy and acceptability of non-invasive brain stimulation in adult unipolar and bipolar depression. Randomised sham-controlled trials of transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS) and theta-burst stimulation (TBS), without co-initiation of another treatment, were included. We analysed response, remission and all-cause discontinuation rates, and depression severity scores. Fifty-four studies were included (N = 2,959, mean age = 44.94 years, 61.98% female). Response rates demonstrated efficacy of high-frequency rTMS over the left DLPFC (OR = 3.94, 95% CI [2.52; 6.15]), right-sided low-frequency rTMS (OR = 7.44, 95% CI [2.06; 26.83]) bilateral rTMS (OR = 3.68, 95% CI [1.66; 8.13]), deep TMS (OR = 1.69, 95% CI [1.003; 2.85]), intermittent TBS (OR = 4.70, 95% CI [1.14; 19.38]) and tDCS (OR = 4.32, 95% CI [2.02; 9.29]); but not for continuous TBS, bilateral TBS or synchronised TMS. There were no differences in all-cause discontinuation rates. The strongest evidence was for high-frequency rTMS over the left DLPFC. Intermittent TBS provides an advance in terms of reduced treatment duration. tDCS is a potential treatment for non-resistant depression.
Appraising the causal relevance of DNA methylation for risk of lung cancer
Authors: Battram T , Richmond RC , Baglietto L , Haycock P , Perduca V , Bojesen S , Gaunt TR , Hemani G , Guida F , Carreras-Torres R , Hung R , Amos CI , Freeman JR , Sandanger TM , Nøst TH , Nordestgaard B , Teschendorff AE , Polidoro S , Vineis P , Severi G , Hodge A , Giles G , Grankvist K , Johansson MB , Johansson M , Davey Smith G , Relton CL 
Published: March 2018

AbstractDNA methylation changes in peripheral blood have been identified in relation to lung cancer risk. However, the causal nature of these associations remains to be fully elucidated. Meta-analysis of four epigenome-wide association studies (918 cases, 918 controls) revealed differential methylation at 16 CpG sites (FDR < 0.05) in relation to lung cancer risk. A two-sample Mendelian randomization analysis, using genetic instruments for methylation at 14 of the 16 CpG sites, and 29,863 cases and 55,586 controls from the TRICL-ILCCO lung cancer consortium, was performed to appraise the causal role of methylation at these sites on lung cancer. This approach provided little evidence that DNA methylation in peripheral blood at the 14 CpG sites play a causal role in lung cancer development, including for cg05575921AHRR, where methylation is strongly associated with lung cancer risk. Further studies are needed to investigate the causal role played by DNA methylation in lung tissue.
The median and the mode as robust meta-analysis methods in the presence of small study effects
Authors: Hartwig Fernando Pires , Smith George Davey , Schmidt Amand Floriaan , Bowden Jack 
Published: March 2018

AbstractMeta-analyses based on systematic literature reviews are commonly used to obtain a quantitative summary of the available evidence on a given topic. Despite its attractive simplicity, and its established position at the summit of the evidence-based medicine hierarchy, the reliability of any meta-analysis is largely constrained by the quality of its constituent studies. One major limitation is small study effects, whose presence can often easily be detected, but not so easily adjusted for. Here, robust methods of estimation based on the median and mode are proposed as tools to increase the reliability of findings in a meta-analysis. By re-examining data from published meta-analyses, and by conducting a detailed simulation study, we show that these two simple methods offer notable robustness to a range of plausible bias mechanisms, without making any explicit modelling assumptions. In conclusion, when performing a meta-analysis with suspected small study effects, we recommend reporting the mean, median and modal pooled estimates as a simple but informative sensitivity analyses.
Directed, but not random, breast cancer cell migration is faster in the G1 phase of the cell cycle in 2D and 3D environments
Authors: Pourfarhangi Kamyar Esmaeili , de la Hoz Edgar Cardenas , Cohen Andrew R. , Gligorijevic Bojana 
Published: March 2018

AbstractCancer cell migration is essential for the early steps of metastasis, during which cancer cells move through the primary tumor and reach the blood vessels. In vivo, cancer cells are exposed to directional guidance cues, either soluble, such as gradients of growth factors, or insoluble, such as collagen fiber alignment. Depending on the number and strength of such cues, cells will migrate in a random or directed manner. Interestingly, similar cues also stimulate cell proliferation. In this regard, it is not clear whether cell cycle progression affects migration of cancer cells and whether this effect is different in random versus directed migration. In this study, we tested the effect of cell cycle progression on random and directed migration, both in 2D and 3D environments, in the breast carcinoma cell line, FUCCI-MDA-MB-231, using computational image analysis by LEVER. Directed migration in 2D was modeled as chemotaxis along a gradient of soluble EGF inside 10 µm-wide microchannels. In 3D, directed migration was modeled as contact guidance (alignotaxis) along aligned collagen fibers. Time-lapse recordings of cells in 2D and 3D revealed that directed, but not random migration, is cell cycle-dependent. In both 2D and 3D directed migration, cells in the G1 phase of the cell cycle outperformed cells in the G2 phase in terms of migration persistence and instantaneous velocity. These data suggest that in the presence of guidance cues in vivo, breast carcinoma cells in the G1 phase of the cell cycle may be more efficient in reaching vasculature.
Low-Cost Touchscreen Driven Programmable Dual Syringe Pump for Life Science Applications
Authors: Garcia Valentina E. , Liu Jamin , DeRisi Joseph L. 
Published: March 2018

AbstractSyringe pumps are powerful tools able to automate routine laboratory practices that otherwise consume large amounts of manual labor time. Commercially available syringe pumps are expensive, difficult to customize, and often preset for a narrow range of operations. Here, we show how to build a programmable dual syringe pump (PDSP) that overcomes these limitations. The PDSP is driven by a Raspberry Pi paired with a stepper motor controller to allow maximal customization via Python scripting. The entire setup can be controlled by a touchscreen for use without a keyboard or mouse. Furthermore, the PDSP is structured around 3D printed parts, enabling users to change any component for their specific application. We demonstrate one application of the PDSP by using it to generate whole cell lysates using a cell homogenizer in an automated fashion.Specifications table
Structural insights into the conformational plasticity of the full-length trimeric HIV-1 envelope glycoprotein precursor
Authors: Zhang Shijian , Wang Wei Li , Chen Shuobing , Lu Maolin , Go Eden P. , Steinbock Robert T. , Ding Haitao , Desaire Heather , Kappes John C. , Sodroski Joseph , Mao Youdong 
Published: March 2018

SummaryThe human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer mediates viral entry into cells and is the major target for the host antibody response. In infected cells, the mature Env [(gp120/gp41)3] is produced by cleavage of a trimeric gp160 precursor. Proteolytic cleavage decreases Env conformational flexibility, allowing the mature Env to resist antibody binding to conserved elements. The conformational plasticity of the Env precursor skews the humoral immune response towards the elicitation of ineffectual antibodies, contributing to HIV-1 persistence in the infected host. The structural basis for the plasticity of the Env precursor remains elusive. Here we use cryo-electron microscopy to visualize two coexisting conformational states of the full-length Env precursor at nominal resolutions of 5.5 and 8.0 Å. The State-P2 conformation features a three-helix bundle of the gp41 heptad repeat region in the core, but has disordered membrane-interactive regions. State-P1 trimers lack the three-helix bundle and instead retain ordered transmembrane and membrane-proximal external regions embracing a central cavity. Our structural data shed light on the unusual plasticity of the Env precursor and provide new clues to Env immunogen discovery.
Expansion, retention and loss in the Acyl-CoA Synthetase“Bubblegum”(Acsbg) gene family in vertebrate history
Authors: Lopes-Marques Mónica , Machado André M. , Ruivo Raquel , Fonseca Elza , Carvalho Estela , Castro L. Filipe C. 
Published: March 2018

AbstractFatty acids (FAs) constitute a considerable fraction of all lipid molecules with a fundamental role in numerous physiological processes. In animals, the majority of complex lipid molecules are derived from the transformation of FAs through several biochemical pathways. Yet, for FAs to enroll in these pathways they require an activation step. FA activation is catalyzed by the rate limiting action of Acyl-CoA synthases. Several Acyl-CoA enzyme families have been previously described and classified according to the chain length of FA they process. Here, we address the evolutionary history of the ACSBG gene family which activates, FA with more than 16 carbons. Currently, two different ACSBG gene families,ACSBG1andACSBG2, are recognized in vertebrates. We provide evidence that a wider and unequalACSBGgene repertoire is present in vertebrate lineages. We identify a novelACSBG-likegene lineage which occurs specifically in amphibians, ray finned fish, coelacanths and chondrichthyes namedACSBG3. Also, we show that theACSBG2gene lineage duplicated in the Theria ancestor. Our findings, thus offer a far richer understanding on FA activation in vertebrates and provide key insights into the relevance of comparative and functional analysis to perceive physiological differences, namely those related with lipid metabolic pathways.
A Global Analysis of Mutations Accompanying Microevolution in the Heterozygous Diploid PathogenCandida albicans
Authors: Ene Iuliana V. , Farrer Rhys A. , Hirakawa Matthew P. , Agwamba Kennedy , Cuomo Christina A. , Bennett Richard J. 
Published: March 2018

AbstractCandida albicansis a heterozygous diploid yeast that is a commensal of the human gastrointestinal (GI) tract and a prevalent opportunistic pathogen. Here, whole-genome sequencing was performed on multipleC. albicansisolates passaged in different niches to characterize the complete spectrum of mutations arising during microevolution. We reveal that evolution during short time-scales (<600 generations) is driven by bothde novobase substitutions and short-tract loss of heterozygosity (LOH) events. In contrast, large-scale chromosomal changes are relatively rare, although chromosome 7 trisomies repeatedly emerged during passaging in one GI colonization model. Both strain background and chromosomal features affected mutational patterns, with mutation rates being greatly elevated in regions adjacent to emergent LOH tracts. Mutation rates were also elevated during host infection where genomes showed strong evidence of purifying selection. These results establish the genetic events drivingC. albicansevolution and that this heterozygous diploid is extensively shaped by purifying selection.
Share, but unequally: A mechanism for emergence and maintenance of intratumor heterogeneity
Authors: Li Xin , Thirumalai D. 
Published: March 2018

SUMMARYIntratumor heterogeneity (ITH), referring to coexistence of different cell subpopulations in a single tumor, has been a major puzzle in cancer research for almost half a century. The lack of understanding of the underlying mechanism of ITH hinders progress in developing effective therapies for cancers. Based on the findings in a recent quantitative experiment on pancreatic cancer we developed a general evolutionary model, accounting for interactions between different cell populations through paracrine or juxtacrine factors. We show that the emergence of a stable heterogeneous state in a tumor requires an unequal allocation of paracrine growth factors (“public goods”) between cells that produce them and those that merely consume them. Our model provides a quantitative explanation of recentin vitroexperimental studies in pancreatic cancer in which insulin growth factor (IGF-II) plays the role of public goods. The calculated phase diagrams as a function of exogenous resources and fraction of growth factor producing cells show ITH persists only in a narrow range of concentration of exogenous IGF-II. Remarkably, maintenance of ITH requires cooperation among tumor cell subpopulations in harsh conditions, specified by lack of exogenous IGF-II, whereas surplus exogenous IGF-II elicits competition. The theory also quantitatively accounts for measuredin vivotumor growth in glioblastoma multiforme (GBM). The predictions for GBM tumor growth as a function of the fraction of tumor cells are amenable to experimental tests. The mechanism for ITH also provides hints for devising efficacious therapies.
Microstructural properties of the vertical occipital fasciculus explain the variability in human stereoacuity
Authors: Oishi Hiroki , Takemura Hiromasa , Aoki Shuntaro C. , Fujita Ichiro , Amano Kaoru 
Published: March 2018

AbstractStereopsis is a fundamental visual function that has been studied extensively. However, it is not clear why depth discrimination (stereoacuity) varies more significantly among people than other modalities. Previous studies reported the involvement of both dorsal and ventral visual areas in stereopsis, implying that not only neural computations in cortical areas but also the anatomical properties of white matter tracts connecting those areas can impact stereopsis and stereoacuity. Here, we studied how human stereoacuity relates to white matter properties by combining psychophysics, diffusion MRI (dMRI), and quantitative MRI (qMRI). We performed a psychophysical experiment to measure stereoacuity, and in the same participants we analyzed the microstructural properties of visual white matter tracts based on two independent measurements, dMRI (fractional anisotropy, FA) and qMRI (macromolecular tissue volume; MTV). Microstructural properties along the right vertical occipital fasciculus (VOF), a major tract connecting dorsal and ventral visual areas, were highly correlated with measures of stereoacuity. This result was consistent for both FA and MTV, suggesting that the structural-behavioral relationship reflects differences in neural tissue density, rather than differences in the morphological configuration of fibers. fMRI confirmed that binocular disparity stimuli activated the dorsal and ventral visual regions near VOF endpoints. No other occipital tracts explained the variance in stereoacuity. In addition, the VOF properties were not associated with differences in performance on a different psychophysical task (contrast detection). These series of experiments suggest that stereoscopic depth discrimination performance is, at least in part, constrained by dorso-ventral communication through the VOF.
Dynamic and Structural Modeling of the Specificity in Protein-DNA Interactions Guided by Binding Assay and Structure Data
Authors: Tan Cheng , Takada Shoji 
Published: March 2018

ABSTRACTHow transcription factors (TFs) recognize their DNA sequences is often investigated complementarily by high-throughput protein binding assays and by structural biology experiments. The former quantifies the specificity of TF binding sites for numerous DNA sequences, often represented as the position-weight-matrix (PWM). The latter provides mechanistic insights into the interactions via the protein-DNA complex structures. However, these two types of data are not readily integrated. Here, we propose and test a new modeling method that incorporates the PWM with complex structure data. Based on pre-tuned coarse-grained models for proteins and DNAs, we model the specific protein-DNA interactions, PWMcos, in terms of an orientation-dependent potential function, which enables us to perform molecular dynamics simulations at unprecedentedly large scales. We show that the PWMcos model reproduces subtle specificity in the protein-DNA recognition. During the target search in genomic sequences, TF moves on highly rugged landscapes and occasionally flips on DNA depending on the sequence. The TATA-binding protein exhibits two remarkably distinct binding modes, of which frequencies differ between TATA-containing and TATA-less promoters. The PWMcos is general and can be applied to any protein-DNA interactions given their PWMs and complex structure data are available.