bluuebunny/crossref_metadata_2025 huggingface dataset:
Disentangling social interactions and environmental drivers in multi-individual wildlife tracking data
Authors: Calabrese Justin M. , Fleming Christen H. , Fagan William F. , Rimmler Martin , Kaczensky Petra , Bewick Sharon , Leimgruber Peter , Mueller Thomas
Published: March 2018

While many animal species exhibit strong conspecific interactions, movement analyses of wildlife tracking datasets still largely focus on single individuals. Multi-individual wildlife tracking studies provide new opportunities to explore how individuals move relative to one another, but such datasets are frequently too sparse for the detailed, acceleration-based analytical methods typically employed in collective motion studies. Here, we address the methodological gap between wildlife tracking data and collective motion by developing a general method for quantifying movement correlation from sparsely sampled data. Unlike most existing techniques for studying the non-independence of individual movements with wildlife tracking data, our approach is derived from an analytically tractable stochastic model of correlated movement. Our approach partitions correlation into a deterministic tendency to move in the same direction termed ‘drift correlation’ and a stochastic component called ‘diffusive correlation’. These components suggest the mechanisms that coordinate movements, with drift correlation indicating external influences, and diffusive correlation pointing to social interactions. We use two case studies to highlight the ability of our approach both to quantify correlated movements in tracking data and to suggest the mechanisms that generate the correlation. First, we use an abrupt change in movement correlation to pinpoint the onset of spring migration in barren-ground caribou. Second, we show how spatial proximity mediates intermittently correlated movements among khulans in the Gobi desert. We conclude by discussing the linkages of our approach to the theory of collective motion.

This article is part of the theme issue 'Collective movement ecology'.
Collective animal navigation and migratory culture: from theoretical models to empirical evidence
Authors: Berdahl Andrew M. , Kao Albert B. , Flack Andrea , Westley Peter A. H. , Codling Edward A. , Couzin Iain D. , Dell Anthony I. , Biro Dora
Published: March 2018

Animals often travel in groups, and their navigational decisions can be influenced by social interactions. Both theory and empirical observations suggest that such collective navigation can result in individuals improving their ability to find their way and could be one of the key benefits of sociality for these species. Here, we provide an overview of the potential mechanisms underlying collective navigation, review the known, and supposed, empirical evidence for such behaviour and highlight interesting directions for future research. We further explore how both social and collective learning during group navigation could lead to the accumulation of knowledge at the population level, resulting in the emergence of migratory culture.

This article is part of the theme issue ‘Collective movement ecology’.
From single steps to mass migration: the problem of scale in the movement ecology of the Serengeti wildebeest
Authors: Torney Colin J. , Hopcraft J. Grant C. , Morrison Thomas A. , Couzin Iain D. , Levin Simon A.
Published: March 2018

A central question in ecology is how to link processes that occur over different scales. The daily interactions of individual organisms ultimately determine community dynamics, population fluctuations and the functioning of entire ecosystems. Observations of these multiscale ecological processes are constrained by various technological, biological or logistical issues, and there are often vast discrepancies between the scale at which observation is possible and the scale of the question of interest. Animal movement is characterized by processes that act over multiple spatial and temporal scales. Second-by-second decisions accumulate to produce annual movement patterns. Individuals influence, and are influenced by, collective movement decisions, which then govern the spatial distribution of populations and the connectivity of meta-populations. While the field of movement ecology is experiencing unprecedented growth in the availability of movement data, there remain challenges in integrating observations with questions of ecological interest. In this article, we present the major challenges of addressing these issues within the context of the Serengeti wildebeest migration, a keystone ecological phenomena that crosses multiple scales of space, time and biological complexity.

This article is part of the theme issue 'Collective movement ecology'.
Migration in the Anthropocene: how collective navigation, environmental system and taxonomy shape the vulnerability of migratory species
Authors: Hardesty-Moore Molly , Deinet Stefanie , Freeman Robin , Titcomb Georgia C. , Dillon Erin M. , Stears Keenan , Klope Maggie , Bui An , Orr Devyn , Young Hillary S. , Miller-ter Kuile Ana , Hughey Lacey F. , McCauley Douglas J.
Published: March 2018

Recent increases in human disturbance pose significant threats to migratory species using collective movement strategies. Key threats to migrants may differ depending on behavioural traits (e.g. collective navigation), taxonomy and the environmental system (i.e. freshwater, marine or terrestrial) associated with migration. We quantitatively assess how collective navigation, taxonomic membership and environmental system impact species' vulnerability by (i) evaluating population change in migratory and non-migratory bird, mammal and fish species using the Living Planet Database (LPD), (ii) analysing the role of collective navigation and environmental system on migrant extinction risk using International Union for Conservation of Nature (IUCN) classifications and (iii) compiling literature on geographical range change of migratory species. Likelihood of population decrease differed by taxonomic group: migratory birds were more likely to experience annual declines than non-migrants, while mammals displayed the opposite pattern. Within migratory species in IUCN, we observed that collective navigation and environmental system were important predictors of extinction risk for fishes and birds, but not for mammals, which had overall higher extinction risk than other taxa. We found high phylogenetic relatedness among collectively navigating species, which could have obscured its importance in determining extinction risk. Overall, outputs from these analyses can help guide strategic interventions to conserve the most vulnerable migrations.

This article is part of the theme issue ‘Collective movement ecology'.
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’.
Mechanism of activation of the BNLF2a immune evasion gene of Epstein-Barr virus by Zta
Authors: Almohammed Rajaei , Osborn Kay , Ramasubramanyan Sharada , Perez-Fernandez Ijiel Barak Naranjo , Godfrey Anja , Mancini Erika J. , Sinclair Alison J.
Published: March 2018

The human gamma herpes virus Epstein–Barr virus (EBV) exploits multiple routes to evade the cellular immune response. During the EBV lytic replication cycle, viral proteins are expressed that provide excellent targets for recognition by cytotoxic T cells. This is countered by the viral BNLF2a gene. In B cells during latency, where BNLF2a is not expressed, we show that its regulatory region is embedded in repressive chromatin. The expression of BNLF2a mirrors the expression of a viral lytic cycle transcriptional regulator, Zta (BZLF1, EB1, ZEBRA), in B cells and we propose that Zta plays a role in up-regulating BNLF2a. In cells undergoing EBV lytic replication, we identified two distinct regions of interaction of Zta with the chromatin-associated BNLF2a promoter. We identify five potential Zta-response elements (ZREs) in the promoter that are highly conserved between virus isolates. Zta binds to these elements in vitro and activates the expression of the BNLF2a promoter in both epithelial and B cells. We also found redundancy amongst the ZREs. The EBV genome undergoes a biphasic DNA methylation cycle during its infection cycle. One of the ZREs contains an integral CpG motif. We show that this can be DNA methylated during EBV latency and that both Zta binding and promoter activation are enhanced by its methylation. In summary, we find that the BNLF2a promoter is directly targeted by Zta and that DNA methylation within the proximal ZRE aids activation. The implications for regulation of this key viral gene during the reactivation of EBV from latency are discussed.
Combinatorial neural inhibition for stimulus selection across space
Authors: Mahajan Nagaraj R. , Mysore Shreesh P.
Published: March 2018

The ability to select the most salient stimulus among competing ones is essential for animal behavior and operates regardless of the spatial locations that stimuli occupy. Here, we reveal that the brain employs a combinatorially optimized strategy to solve such location-invariant stimulus selection. With experiments in a key inhibitory nucleus in the vertebrate midbrain selection network, called isthmi pars magnocellularis (Imc) in owls, we discovered that the central element is a ‘multilobe’ neuron, which encodes visual locations with multiple firing fields. This multilobed coding of space is necessitated by scarcity of Imc neurons. Although distributed seemingly randomly in space, the locations of these lobes are optimized across the high firing Imc neurons, allowing them to cooperatively suppress stimuli throughout 2D visual space while minimizing metabolic and circuit wiring costs. Our work suggests that combinatorial coding of space by sparse inhibitory neurons may be a general functional module for spatial selection.
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

We 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

Objective

Obtain estimates of the causal relationship between different levels of body mass index (BMI) and mortality.

Methods

Mendelian 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.

Results

MR 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.

Conclusion

Results 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

The 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

We 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

DNA 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

Meta-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

Cancer 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

Syringe 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

The 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

Abstract

Fatty 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

Candida 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

Intratumor 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

Stereopsis 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

How 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.
Systematic studies of all PIH proteins in zebrafish reveal their distinct roles in axonemal dynein assembly
Authors: Yamaguchi Hiroshi , Oda Toshiyuki , Kikkawa Masahide , Takeda Hiroyuki
Published: March 2018

Construction of motile cilia/flagella requires cytoplasmic preassembly of axonemal dyneins before transport into cilia. Axonemal dyneins have various subtypes, but the roles of each dynein subtype and their assembly processes remain elusive in vertebrates. The PIH protein family, consisting of four members, has been implicated in the assembly of different dynein subtypes, although evidence for this idea is sparse. Here, we established zebrafish mutants of all four PIH-protein genes:pih1d1,pih1d2,ktu, andtwister, and analyzed the structures of axonemal dyneins in mutant spermatozoa by cryo-electron tomography. Mutations caused the loss of specific dynein subtypes, which was correlated with abnormal sperm motility. We also found organ-specific compositions of dynein subtypes, which could explain the severe motility defects of mutant Kupffer’s vesicle cilia. Our data demonstrate that all vertebrate PIH proteins are differently required for cilia/flagella motions and the assembly of axonemal dyneins, assigning specific dynein subtypes to each PIH protein.
Conformational dynamics of Light-Harvesting Complex II in a native membrane environment
Authors: Azadi-Chegeni F. , Ward M.E. , Perin G. , Simionato D. , Morosinotto T. , Baldus M. , Pandit A.
Published: March 2018

Photosynthetic light-harvesting complexes of higher plants, moss and green algae can undergo dynamic conformational transitions, which have been correlated to their ability to adapt to fluctuations in the light environment. Herein, we demonstrate the application of solid-state NMR spectroscopy on native, heterogeneous thylakoid membranes of Chlamydomonas reinhardtii (Cr) and on Cr Light-Harvesting Complex II (LHCII) in thylakoid lipid bilayers to detect LHCII conformational dynamics in its native membrane environment. We show that membrane-reconstituted LHCII contains selective sites that undergo fast, large-amplitude motions, including the phytol tails of two chlorophylls. Protein plasticity is also observed in the N-terminal stromal loop and in protein fragments facing the lumen, involving sites that stabilize the xanthophyll-cycle carotenoid violaxanthin and the two luteins. The results report on the intrinsic flexibility of LHCII pigment-protein complexes in a membrane environment, revealing putative sites for conformational switching. In thylakoid membranes, fast dynamics of protein and pigment sites is significantly reduced, which suggests that in their native organelle membranes, LHCII complexes are locked in specific conformational states.

STATEMENT OF SIGNIFICANCE

Photosynthetic Light-Harvesting Complexes undergo dynamic conformational transitions that regulate the capacity of the light-harvesting antenna. We demonstrate the application of solid-state (ss)NMR spectroscopy to investigate the structural dynamics of LHCII, the most abundant LHC complex of plants and algae, in native membranes. Selective dynamic protein and pigment residues are identified that are putative sites for a conformational switch.
Precision weighting of cortical unsigned prediction errors is mediated by dopamine and benefits learning
Authors: Haarsma J. , Fletcher P.C. , Ziauddeen H. , Spencer T.J. , Diederen K.M.J. , Murray G.K.
Published: March 2018

The predictive coding framework construes the brain as performing a specific form of hierarchical Bayesian inference. In this framework the precision of cortical unsigned prediction error (surprise) signals is proposed to play a key role in learning and decision-making, and to be controlled by dopamine. To test this hypothesis, we re-analysed an existing data-set from healthy individuals who received a dopamine agonist, antagonist or placebo and who performed an associative learning task under different levels of outcome precision. Computational reinforcement-learning modelling of behaviour provided support for precision-weighting of unsigned prediction errors. Functional MRI revealed coding of unsigned prediction errors relative to their precision in bilateral superior frontal gyri and dorsal anterior cingulate. Cortical precision-weighting was (i) perturbed by the dopamine antagonist sulpiride, and (ii) associated with task performance. These findings have important implications for understanding the role of dopamine in reinforcement learning and predictive coding in health and illness.
Enteral Activation of WR-2721 Mediates Radioprotection and Improved Survival from Lethal Fractionated Radiation
Authors: Molkentine Jessica M. , Fujimoto Tara N. , Horvath Thomas D. , Grossberg Aaron J. , Deorukhkar Amit , Samuel Errol L.G. , Chan Wai Kin , Lorenzi Philip L. , Dantzer Robert , Tour James M. , Mason Kathryn A. , Taniguchi Cullen M.
Published: March 2018

Unresectable pancreatic cancer is almost universally lethal because chemotherapy and radiation cannot completely stop the growth of the cancer. The major problem with using radiation to approximate surgery in unresectable disease is that the radiation dose required to ablate pancreatic cancer exceeds the tolerance of the nearby duodenum. WR-2721, also known as amifostine, is a well-known radioprotector, but has significant clinical toxicities when given systemically. WR-2721 is a prodrug and is converted to its active metabolite, WR-1065, by alkaline phosphatases in normal tissues. The small intestine is highly enriched in these activating enzymes, and thus we reasoned that oral administration of WR-2721 just before radiation would result in localized production of the radioprotective WR-1065 in the small intestine, providing protective benefits without the significant systemic side effects. Here, we show that oral WR-2721 is as effective as intraperitoneal WR-2721 in promoting survival of intestinal crypt clonogens after morbid irradiation. Furthermore, oral WR-2721 confers full radioprotection and survival after lethal upper abdominal irradiation of 12.5Gy x 5 fractions (total of 62.5Gy, D2EQ=140.6Gy), which would likely ablate pancreatic cancer. We find that the efficacy of oral WR-2721 stems from its selective accumulation in the intestine, but not in tumors or other normal tissues, as determined by in vivo mass spectrometry analysis. Thus, we demonstrate that oral WR-2721 is a well-tolerated, and quantitatively selective, radioprotector of the intestinal tract that is capable of enabling clinically relevant ablative doses of radiation to the upper abdomen without unacceptable gastrointestinal toxicity.
Transposable elements are important contributors to standing variation in gene expression inCapsella grandiflora
Authors: Uzunović Jasmina , Josephs Emily B. , Stinchcombe John R. , Wright Stephen I.
Published: March 2018

Transposable elements (TEs) make up a significant portion of eukaryotic genomes, and thus are important drivers of genome evolution. However, the evolutionary forces controlling TE copy number and the extent to which TEs affect phenotypic variation on a genome-wide scale are still unclear. We characterised TE insertion polymorphism and its effects on gene expression in 124 whole genome sequences from a single population ofCapsella grandiflora. The frequency of insertions was negatively correlated with distance to genes, as well as density of conserved non-coding elements, suggesting that the negative effects of TEs on gene regulation are important in limiting their abundance. Rare TE variants strongly influence gene expression variation, predominantly through downregulation. In contrast, rare single nucleotide polymorphisms (SNPs) contribute equally to up- and down-regulation, but have a weaker effect. Taken together, these results imply that TEs are a significant contributor to gene expression variation and can be more likely than rare SNPs to cause extreme changes in gene expression.

Author Summary

Transposable elements (TEs), mobile DNA elements with the ability to excise from the genome and reinsert in new locations, are important components of genomic diversity. Due to their abundance and mobility, TEs play an influential role in genomic evolution, often deleterious. Here we show that TEs in a population of the plantCapsella grandifloraare most deleterious when they insert in genic and regulatory regions. We find that TEs indeed are associated with unusual levels of gene expression, predominantly decreased expression.

Furthermore, this effect is stronger than the association of single nucleotide polymorphisms with gene expression variation, highlighting the importance of TE contribution to the maintenance of expression variation.
Evolution dynamics of digital HR system at Pak Elektron Ltd (PEL)
Authors: Naz Shumaila , Khan Shabnam
Published: March 2018

Subject area

Human resource management and organizational change.

Study level/applicability

Students on an introductory course on Human Resource Management or a specialization course of HRM such as change management and organizational development. This case study can be taught at the MBA level.

Case overview

This case study can serve as the base for understanding and identifying the various characteristics that relate to revolutionizing HR functions with the help of digitalization. It can also be elaborated further to include the challenges that a company has to face after it decides to establish IT software based on operations. This case is an evolutionary story of a large-scale Pakistani company, Pak Electron Ltd. (PEL) which has been in operation for almost 60 years. The top management decided to move from a traditional administrative system towards setting up an HR department for the first time. The case states the salient features of the traditional administrative system, issues faced by the company in the setup of a new HR system and digital HR system along with the employees’ views and perceptions on these systems.

Expected learning outcomes

Students are expected to learn the following: the various characteristics of a paper-file based traditional administrative system; the various features of an IT-based modern HR system; the decision background and basis for making the switch to the new contemporary HR system; and the reaction of employees against changes in organizational systems.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS: 6: Human Resource Management.
ComProCom: a revised model of occupational competence
Authors: Lester Stan , Koniotaki Anna , Religa Jolanta
Published: March 2018

Purpose

The purpose of this paper is to describe a revised approach describing occupational competence, with particular reference to its application in two European countries at the level of specific occupational fields and in relation to the models used in national vocational education and training (VET) systems.

Design/methodology/approach

An Erasmus+ project involved partners in five countries developing and trialling competence standards, following principles developed from approaches that have recently emerged in some British self-governing professions.

Findings

The model used in the project avoids the narrowness that was characteristic of earlier British approaches to occupational competence. It provides a template that can be used for articulating the essentials of practice, including in emerging fields and those that cut across professions and occupations. It is also flexible enough to provide underpinnings for different types of VET system without making assumptions about the way that economies, labour markets and education systems are organised.

Practical implications

A number of factors are outlined that improve the applicability of practice-based competence descriptions, including starting from occupational fields rather than job roles, focussing on the ethos and core activities of the field, and using concise and precise descriptions that are not limited to specific roles and contexts.

Originality/value

A tested, practice-based model of competence is put forward that can be applied at the level of broad professional or occupational fields, is neutral in respect of national labour markets and educational systems, and offers a means of developing a common “language” of competence at a European level.
One of the family? Familial and professional relationships between migrant live-in caregivers and their employers
Authors: Salami Bukola , Meherali Salima
Published: March 2018

Purpose

Many families in the developed world hire live-in caregivers to meet their childcare and elder care needs. Given the spatial arrangements – i.e., that the caregiver lives with her employer – relationships between employers and live-in caregivers can develop into family-like relationships. The purpose of this paper is to draw on data from two Canadian studies to examine the relationships between migrant live-in caregivers and their employers.

Design/methodology/approach

The first study focused on the live-in caregivers in Canada. Semi-structured interviews were conducted with 15 Filipina nurses who migrated to Canada through the Live-in Caregiver Program. The second study was a pilot descriptive study that included interviews of recruiter groups and employers of live-in caregivers. Data were thematically analyzed, aided by NVivo software.

Findings

The studies indicate that some live-in caregivers prefer to be treated as one of the family, while others prefer to have a strictly professional employer/employee relationship. Their employers are similarly divided. The authors identify reciprocity and respect as important ingredients for healthy relationships between live-in caregivers and their employers. Without these key ingredients, relationships between employers and live-in caregivers can be exploitative, especially given the unequal power inherent in the relationship.

Research limitations/implications

Further studies are needed to better understand how these relationships evolve over time and in space.

Practical implications

There is a need to create policies to further prevent exploitation of live-in caregivers within an unfavorable employee or familial relationship.

Originality/value

This study provides useful insight into the development of knowledge on relationships between live-in caregivers and employers.