bluuebunny/crossref_metadata_2025 huggingface dataset:
Using features of a Creole language to reconstruct population history and cultural evolution: tracing the English origins of Sranan
Authors: Sherriah André C. , Devonish Hubert , Thomas Ewart A. C. , Creanza Nicole
Published: February 2018

Creole languages are formed in conditions where speakers from distinct languages are brought together without a shared first language, typically under the domination of speakers from one of the languages and particularly in the context of the transatlantic slave trade and European colonialism. One such Creole in Suriname, Sranan, developed around the mid-seventeenth century, primarily out of contact between varieties of English from England, spoken by the dominant group, and multiple West African languages. The vast majority of the basic words in Sranan come from the language of the dominant group, English. Here, we compare linguistic features of modern-day Sranan with those of English as spoken in 313 localities across England. By way of testing proposed hypotheses for the origin of English words in Sranan, we find that 80% of the studied features of Sranan can be explained by similarity to regional dialect features at two distinct input locations within England, a cluster of locations near the port of Bristol and another cluster near Essex in eastern England. Our new hypothesis is supported by the geographical distribution of specific regional dialect features, such as post-vocalic rhoticity and word-initial ‘h’, and by phylogenetic analysis of these features, which shows evidence favouring input from at least two English dialects in the formation of Sranan. In addition to explicating the dialect features most prominent in the
linguistic
evolution of Sranan, our historical analyses also provide supporting evidence for two distinct hypotheses about the likely
geographical
origins of the English speakers whose language was an input to Sranan. The emergence as a likely input to Sranan of the speech forms of a cluster near Bristol is consistent with historical records, indicating that most of the indentured servants going to the Americas between 1654 and 1666 were from Bristol and nearby counties, and that of the cluster near Essex is consistent with documents showing that many of the governors and important planters came from the southeast of England (including London) (Smith 1987
The Genesis of the Creole Languages of Surinam
; Smith 2009 In
The handbook of pidgin and creole studies
, pp. 98–129).

This article is part of the theme issue ‘Bridging cultural gaps: interdisciplinary studies in human cultural evolution’.
Evolutionary demography of age at last birth: integrating approaches from human behavioural ecology and cultural evolution
Authors: Mattison Siobhan , Moya Christina , Reynolds Adam , Towner Mary C.
Published: February 2018

Cultural evolutionary theory and human behavioural ecology offer different, but compatible approaches to understanding human demographic behaviour. For much of their 30 history, these approaches have been deployed in parallel, with few explicit attempts to integrate them empirically. In this paper, we test hypotheses drawn from both approaches to explore how reproductive behaviour responds to cultural changes among Mosuo agriculturalists of China. Specifically, we focus on how age at last birth (ALB) varies in association with temporal shifts in fertility policies, spatial variation and kinship ecologies. We interpret temporal declines in ALB as plausibly consistent with demographic front-loading of reproduction in light of fertility constraints and later ages at last birth in matrilineal populations relative to patrilineal ones as consistent with greater household cooperation for reproductive purposes in the former. We find little evidence suggesting specific transmission pathways for the spread of norms regulating ALB, but emphasize that the rapid pace of change strongly suggests that learning processes were involved in the general decline in ALB over time. The different predictions of models we employ belie their considerable overlap and the potential for a synthetic approach to generate more refined tests of evolutionary hypotheses of demographic behaviour.

This article is part of the theme issue ‘Bridging cultural gaps: interdisciplinary studies in human cultural evolution’.
Divide and conquer: intermediate levels of population fragmentation maximize cultural accumulation
Authors: Derex Maxime , Perreault Charles , Boyd Robert
Published: February 2018

Identifying the determinants of cumulative cultural evolution is a key issue in the interdisciplinary field of cultural evolution. A widely held view is that large and well-connected social networks facilitate cumulative cultural evolution because they promote the spread of useful cultural traits and prevent the loss of cultural knowledge through factors such as drift. This view stems from models that focus on the transmission of cultural information, without considering how new cultural traits actually arise. In this paper, we review the literature from various fields that suggest that, under some circumstances, increased connectedness can decrease cultural diversity and reduce innovation rates. Incorporating this idea into an agent-based model, we explore the effect of population fragmentation on cumulative culture and show that, for a given population size, there exists an intermediate level of population fragmentation that maximizes the rate of cumulative cultural evolution. This result is explained by the fact that fully connected, non-fragmented populations are able to maintain complex cultural traits but produce insufficient variation and so lack the cultural diversity required to produce highly complex cultural traits. Conversely, highly fragmented populations produce a variety of cultural traits but cannot maintain complex ones. In populations with intermediate levels of fragmentation, cultural loss and cultural diversity are balanced in a way that maximizes cultural complexity. Our results suggest that population structure needs to be taken into account when investigating the relationship between demography and cumulative culture.

This article is part of the theme issue ‘Bridging cultural gaps: interdisciplinary studies in human cultural evolution’.
Missing compared to what? Revisiting heritability, genes and culture
Authors: Feldman Marcus W. , Ramachandran Sohini
Published: February 2018

Standard models for the determination of phenotypes from genes are grounded in simple assumptions that are inherent in the modern evolutionary synthesis (MES), which was developed in the 1930s, 1940s and 1950s. The MES was framed in the context of Mendelian genetic transmission enhanced by the Fisherian view of the way discretely inherited genes determine continuously quantitative phenotypes. The statistical models that are used to estimate and interpret genetic contributions to human phenotypes—including behavioural traits—are constructed within the framework of the MES. Variance analysis constitutes the main tool and is used under this framework to characterize genetic inheritance, and hence determination of phenotypes. In this essay, we show that cultural inheritance, when incorporated into models for the determination of phenotypes, can sharply reduce estimates of the genetic contribution to these phenotypes. Recognition of the importance of non-genetic transmission of many human traits is becoming ever more necessary to prevent regression to the debates of the 1970s and 1980s concerning policies based on genetic determination of complex human phenotypes.

This article is part of the theme issue ‘Bridging cultural gaps: interdisciplinary studies in human cultural evolution’.
Control of Spreading Depression with Electrical Fields
Authors: Whalen Andrew J. , Xiao Ying , Kadji Herve , Dahlem Markus , Gluckman Bruce J. , Schiff Steven J.
Published: February 2018

Spreading depression or depolarization is a large-scale pathological brain phenomenon related to migraine, stroke, hemorrhage and traumatic brain injury. Once initiated, spreading depression propagates across gray matter extruding potassium and other active molecules, collapsing the resting membrane electro-chemical gradient of cells leading to spike inactivation and cellular swelling, and propagates independently of synaptic transmission. We demonstrate the modulation, suppression and prevention of spreading depression utilizing applied transcortical DC electric fields in brain slices, measured with intrinsic optical imaging and potassium dye epifluorescence. We experimentally observe a surface-positive electric field induced forcing of spreading depression propagation to locations in cortex deeper than the unmodulated propagation path, whereby further propagation is confined and arrested even after field termination. The opposite surface-negative electric field polarity produces an increase in propagation velocity and a confinement of the wave to more superficial layers of cortex than the unmodulated propagation path. These field polarities are of opposite sign to the polarity that blocks neuronal spiking and seizures, and are consistent with biophysical models of spreading depression. The results demonstrate the potential feasibility of electrical control and prevention of spreading depression.
Multiple laboratory mouse reference genomes define strain specific haplotypes and novel functional loci
Authors: Lilue Jingtao , Doran Anthony G. , Fiddes Ian T. , Abrudan Monica , Armstrong Joel , Bennett Ruth , Chow William , Collins Joanna , Collins Stephan , Czechanski Anne , Danecek Petr , Diekhans Mark , Dolle Dirk-Dominic , Dunn Matt , Durbin Richard , Earl Dent , Ferguson-Smith Anne , Flicek Paul , Flint Jonathan , Frankish Adam , Fu Beiyuan , Gerstein Mark , Gilbert James , Goodstadt Leo , Harrow Jennifer , Howe Kerstin , Kolmogorov Mikhail , Köenig Stefanie , Lelliott Chris , Loveland Jane , Mathews Clayton E. , Mott Richard , Muir Paul , Navarro Fabio , Odom Duncan , Park Naomi , Pelan Sarah , Phan Son K , Quail Michael , Reinholdt Laura , Romoth Lars , Shirley Lesley , Sisu Cristina , Sjoberg-Herrera Marcela , Stanke Mario , Steward Charles , Thomas Mark , Threadgold Glen , Thybert David , Torrance James , Wong Kim , Wood Jonathan , Yalcin Binnaz , Yang Fengtang , Adams David J. , Paten Benedict , Keane Thomas M.
Published: February 2018

The most commonly employed mammalian model organism is the laboratory mouse. A wide variety of genetically diverse inbred mouse strains, representing distinct physiological states, disease susceptibilities, and biological mechanisms have been developed over the last century. We report full length draft de novo genome assemblies for 16 of the most widely used inbred strains and reveal for the first time extensive strain-specific haplotype variation. We identify and characterise 2,567 regions on the current Genome Reference Consortium mouse reference genome exhibiting the greatest sequence diversity between strains. These regions are enriched for genes involved in defence and immunity, and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. Several immune related loci, some in previously identified QTLs for disease response have novel haplotypes not present in the reference that may explain the phenotype. We used these genomes to improve the mouse reference genome resulting in the completion of 10 new gene structures, and 62 new coding loci were added to the reference genome annotation. Notably this high quality collection of genomes revealed a previously unannotated gene (Efcab3-like) encoding 5,874 amino acids, one of the largest known in the rodent lineage. Interestingly, Efcab3-like−/− mice exhibit severe size anomalies in four regions of the brain suggesting a mechanism of Efcab3-like regulating brain development.
Surprise About Sensory Event Timing Drives Cortical Transients in the Beta Frequency Band
Authors: Meindertsma T. , Kloosterman N.A. , Engel A.K. , Wagenmakers E.J. , Donner T.H.
Published: February 2018

Learning the statistical structure of the environment is crucial for adaptive behavior. Humans and non-human decision-makers seem to track such structure through a process of probabilistic inference, which enables predictions about behaviorally relevant events. Deviations from such predictions cause surprise, which in turn helps improve inference. Surprise about the timing of behaviorally relevant sensory events drives phasic responses of neuromodulatory brainstem systems, which project to the cerebral cortex. Here, we developed a computational model-based magnetoencephalography (MEG) approach for mapping the resulting cortical transients across space, time, and frequency, in the human brain (N=28, 17 female). We used a Bayesian ideal observer model to learn the statistics of the timing of changes in a simple visual detection task. This model yielded quantitative trial-by-trial estimates of temporal surprise. The model-based surprise variable predicted trial-by trial variations in reaction time more strongly than the externally observable interval timings alone. Trial-by-trial variations in surprise were negatively correlated with the power of cortical population activity measured with MEG. This surprise-related power suppression occurred transiently around the behavioral response, specifically in the beta frequency band. It peaked in parietal and prefrontal cortices, remote from the motor cortical suppression of beta power related to overt report (button press) of change detection. Our results indicate that surprise about sensory event timing transiently suppresses ongoing beta-band oscillations in association cortex. This transient suppression of frontal beta-band oscillations might reflect an active reset triggered by surprise, and is in line with the idea that beta-oscillations help maintain cognitive sets.

Significance statement

The brain continuously tracks the statistical structure of the environment to anticipate behaviorally relevant events. Deviations from such predictions cause surprise, which in turn drives neural activity in subcortical brain regions that project to the cerebral cortex. We used magnetoencephalography in humans to map out surprise-related modulations of cortical population activity across space, time, and frequency. Surprise was elicited by variable timing of visual stimulus changes requiring a behavioral response. Surprise was quantified by means of an ideal observer model. Surprise predicted behavior as well as a transient suppression of beta frequency band oscillations in frontal cortical regions. Our results are in line with conceptual accounts that have linked neural oscillations in the beta-band to the maintenance of cognitive sets.
PTMscape: an open source tool to predict generic post-translational modifications and map hotspots of modification crosstalk
Authors: Li Ginny X.H. , Vogel Christine , Choi Hyungwon
Published: February 2018

While tandem mass spectrometry can now detect post-translational modifications (PTM) at the proteome scale, reported modification sites are often incomplete and include false positives. Computational approaches can complement these datasets by additional predictions, but most available tools are tailored for single modifications and each tool uses different features for prediction. We developed an R package called PTMscape which predicts modifications sites across the proteome based on a unified and comprehensive set of descriptors of the physico-chemical microenvironment of modified sites, with additional downstream analysis modules to test enrichment of individual or pairs of modifications in functional protein regions. PTMscape is generic in the ability to process any major modifications, such as phosphorylation and ubiquitination, while achieving the sensitivity and specificity comparable to single-PTM methods and outperforming other multi-PTM tools. Maintaining generalizability of the framework, we expanded proteome-wide coverage of five major modifications affecting different residues by prediction and performed combinatorial analysis for spatial co-occurrence of pairs of those modifications. This analysis revealed potential modification hotspots and crosstalk among multiple PTMs in key protein domains such as histone, protein kinase, and RNA recognition motifs, spanning various biological processes such as RNA processing, DNA damage response, signal transduction, and regulation of cell cycle. These results provide a proteome-scale analysis of crosstalk among major PTMs and can be easily extended to other modifications.

Contact

all correspondence should be addressed tohwchoi@nus.edu.sg.
A Comprehensive Overview of Genomic Imprinting in Breast & Its Deregulation in Cancer
Authors: Goovaerts Tine , Steyaert Sandra , Vandenbussche Chari A , Galle Jeroen , Thas Olivier , Criekinge Wim Van , Meyer Tim De
Published: February 2018

Genomic imprinting, the parent-of-origin specific monoallelic expression of genes, plays an important role in growth and development. Loss of imprinting of individual genes has been found in varying cancers, yet data-analytical challenges have impeded systematic studies so far. We developed a mixture distribution model to detect monoallelically expressed loci in a genome-wide manner without the need for genotyping data, and applied the methodology on TCGA breast tissue RNA-seq data. We identified 35 putatively imprinted genes in healthy breast. In breast cancer however, HM13 was featured by significant loss of imprinting and expression upregulation, which could be linked to DNA demethylation. Other imprinted genes (25 out of 35) demonstrated consistent expression downregulation in breast cancer, which often correlated with loss of imprinting. A breast imprinted gene network, deregulated in cancer, might hence be present. In summary, our novel methodology highlights the massive deregulation of imprinting in breast cancer.
Single Session Real-time fMRI Neurofeedback has a Lasting Impact on Cognitive Behavioral Therapy Strategies
Authors: MacDuffie Katherine E. , MacInnes Jeff , Dickerson Kathryn C. , Eddington Kari M. , Strauman Timothy J. , Adcock R. Alison
Published: February 2018

To benefit from cognitive behavioral therapy (CBT), individuals must not only learn new skills but also strategically implement them outside the session. Here, we tested a novel technique for personalizing CBT skills and facilitating their generalization to daily life. We hypothesized that showing participants the impact of specific CBT strategies on their own brain function using real-time functional magnetic imaging (rt-fMRI) neurofeedback would increase their metacognitive awareness, help them identify effective strategies, and motivate real-world use. In a within-subjects design, participants who had completed a clinical trial of a standardized course of CBT created a personal repertoire of negative autobiographical stimuli and mood regulation strategies. From each participant’s repertoire, a set of experimental and control strategies were identified; only experimental strategies were practiced in the scanner. During the rt-fMRI neurofeedback session, participants used negative stimuli and strategies from their repertoire to manipulate activation in the anterior cingulate cortex, a region implicated in emotional distress. The primary outcome measures were changes in participant ratings of strategy difficulty, efficacy, and frequency of use. As predicted, ratings for unscanned control strategies were stable across observations, whereas ratings for experimental strategies changed after neurofeedback. At follow-up one month after the session, efficacy and frequency ratings for scanned strategies were predicted by neurofeedback during the rt-fMRI session. These results suggest that rt-fMRI neurofeedback created a salient and durable learning experience for patients, extending beyond the clinic to guide and motivate CBT skill use weeks later. This metacognitive approach to neurofeedback offers a promising model for increasing clinical benefits from cognitive-behavioral therapy by personalizing skills and facilitating generalization.
Structure of Zip2:Spo16, a conserved XPF:ERCC1-like complex critical for meiotic crossover formation
Authors: Arora Kanika , Corbett Kevin D.
Published: February 2018

In eukaryotic meiosis, generation of haploid gametes depends on the formation of inter-homolog crossovers, which enable the pairing, physical linkage, and eventual segregation of homologs in the meiosis I division. A class of conserved meiosis-specific proteins, collectively termed ZMMs, are required for formation and spatial control of crossovers throughout eukaryotes. Here, we show that threeS. cerevisiaeZMM proteins – Zip2, Zip4, and Spo16 – interact with one another and form a DNA-binding complex critical for crossover formation and control. We determined the crystal structure of a Zip2:Spo16 subcomplex, revealing a heterodimer structurally related to the XPF:ERCC1 endonuclease complex. Zip2:Spo16 lacks an endonuclease active site, but binds specific DNA structures found in early meiotic recombination intermediates. Mutations in multiple DNA-binding surfaces on the Zip2:Spo16 complex severely compromise DNA binding, supporting a model in which the complex’s central and HhH domains cooperate to bind DNA. Overall, our data support a model in which the Zip2:Zip4:Spo16 complex binds and stabilizes early meiotic recombination intermediates, then coordinates additional factors to promote crossover formation and license downstream events including synaptonemal complex assembly.
Selection dynamics in transient compartmentalization
Authors: Blokhuis Alex , Lacoste David , Nghe Philippe , Peliti Luca
Published: February 2018

Transient compartments have been recently shown to be able to maintain functional replicators in the context of prebiotic studies. Motivated by this experiment, we show that a broad class of selection dynamics is able to achieve this goal. We identify two key parameters, the relative amplification of non-active replicators (parasites) and the size of compartments. Since the basic ingredients of our model are the competition between a host and its parasite, and the diversity generated by small size compartments, our results are relevant to various phage-bacteria or virus-host ecology problems.

PACS numbers: 05.40.-a, 87.14.G-, 87.23.Kg
Presenilin-mediated cleavage of APP regulates synaptotagmin-7 and presynaptic plasticity
Authors: Barthet Gaël , Jordà-Siquier Tomàs , Rumi-Masante Julie , Bernadou Fanny , Müller Ulrike , Mulle Christophe
Published: February 2018

Presenilin (PS), the catalytic subunit of γ-secretase and its main substrate the amyloid precursor protein (APP) are mutated in a large majority of patients with familial Alzheimer disease. PS and APP interact with proteins of the neurotransmitter release machinery but the functional consequences of these interactions are unknown. Here we report that genetic deletion of presynaptic PS markedly decreases the axonal expression of the Ca2+sensor synaptotagmin-7 (Syt7), and impairs synaptic facilitation and replenishment of release-competent synaptic vesicles. These properties are fully restored by presynaptic re-expression of Syt7. The regulation of Syt7 expression occurs post-transcriptionally and depends on γ-secretase activity. In the combined absence of both APP and PS1, the loss of Syt7 is prevented, indicating that the action of γ-secretase on presynaptic mechanisms depends on its substrate APP. The molecular mechanism involves the substrate of PS, APP-βCterminal (APP-βCTF), which interacts with Syt7 and accumulates in synaptic terminals under conditions of pharmacological or genetic inhibition of γ-secretase. These results reveal a role of PS in presynaptic mechanisms through regulation of Syt7 by APP-dependent cleavage, and highlight aberrant synaptic vesicle processing as a possible new pathway in AD.
GEMC1 and CCNO are required for efferent duct development and male fertility
Authors: Terré Berta , Lewis Michael , Gil-Gómez Gabriel , Stracker Travis H.
Published: February 2018

GEMC1 is a Geminin family protein that triggers the E2F4/5-mediated transcriptional activation of target genes, including many required for multiciliogenesis, such as Mcidas, FoxJ1 and Ccno. Male mice lacking either Gemc1 or Ccno were found to be infertile, but the origin of this defect has remained unclear. Here we show that mice lacking either Gemc1 or Ccno showed a nearly empty seminiferous tubule phenotype. While both genes were expressed in the testes, much higher levels were observed in the efferent ducts that mobilize sperm to the epididymis. We found that both GEMC1 and CCNO were required for the generation of multiciliated cells in the efferent ducts but that they differentially affect activation of FoxJ1 and Tp73. These data indicate that defective efferent duct development, rather than defects in testes development, are likely the primary origin of male infertility observed in the absence of GEMC1 and CCNO and this could extend to Reduced Generation of Multiple Motile Cilia patients with MCIDAS and CCNO mutations.

Summary statement

We demonstrate that male mice lacking GEMC1 or CCNO are infertile due to defects in the formation of the efferent ducts.
Bioelectric-calcineurin signaling module regulates allometric growth and size of the zebrafish fin
Authors: Daane Jacob M , Lanni Jennifer , Rothenberg Ina , Seebohm Guiscard , Higdon Charles W , Johnson Stephen L , Harris Matthew P
Published: February 2018

The establishment of relative size of organs and structures is paramount for attaining final form and function of an organism. Importantly, variation in the proportions of structures frequently underlies adaptive change in morphology in evolution and maybe a common mechanism underlying selection. However, the mechanism by which growth is integrated within tissues during development to achieve proper proportionality is poorly understood. We have shown that signaling by potassium channels mediates coordinated size regulation in zebrafish fins. Recently, calcineurin inhibitors were shown to elicit changes in zebrafish fin allometry as well. Here, we identify the potassium channelkcnk5bas a key player in integrating calcineurin’s growth effects, in part through regulation of the cytoplasmic C-terminus of the channel. We propose that the interaction between Kcnk5b and calcineurin acts as a signaling node to regulate allometric growth. Importantly, we find that this regulation is epistatic to inherent mechanisms instructing overall size as inhibition of calcineurin is able to bypass genetic instruction of size as seen insofand wild-type fins, however, it is not sufficient to re-specify positional memory of size of the fin. These findings integrate classic signaling mediators such as calcineurin with ion channel function in the regulation of size and proportion during growth.
Neuregulin-1 exerts molecular control over axolotl lung regeneration through ErbB family receptors
Authors: Jensen Tyler B , Giunta Peter , Schulz Natalie Grace , Kyeremateng Yaa , Wong Hilary , Adesina Adeleso , Monaghan James R
Published: February 2018

The induction of new lung tissue after disease or trauma has the potential to save lives and transform patient outcomes. Ambystoma mexicanum, the axolotl salamander, is a classic model organism used to study vertebrate regeneration, primarily after limb amputation. While it is hypothesized that axolotls regenerate all of their tissues, exploration of lung regeneration has not been performed until now. Proliferation after lung injury was observed to be a global response, suggesting that regeneration utilizes a compensatory mechanism, in contrast to limb regeneration’s epimorphic response. ErbB signaling is crucial for the proliferative response during lung regeneration, likely through the ErbB2:ErbB4 receptor heterodimer. ErbB4 mRNA was found to be highly upregulated at both one and three weeks post amputation. Neuregulin-1p (NRG1) can induce proliferation in the lung and likely exerts molecular control over lung regeneration. Inhibition of ErbB2 was sufficient to both block regeneration and the proliferative response observed after NRG1 treatment.
Identification of transcriptional signatures for cell types from single-cell RNA-Seq
Authors: Ntranos Vasilis , Yi Lynn , Melsted Páll , Pachter Lior
Published: February 2018

Single-cell RNA-Seq makes it possible to characterize the transcriptomes of cell types and identify their transcriptional signatures via differential analysis. We present a fast and accurate method for discriminating cell types that takes advantage of the large numbers of cells that are assayed. When applied to transcript compatibility counts obtained via pseudoalignment, our approach provides a quantification-free analysis of 3’ single-cell RNA-Seq that can identify previously undetectable marker genes.
Modulation of neuronal resilience during aging by Hsp70/Hsp90/STI1 chaperone system
Authors: Lackie Rachel E. , Razzaq Abdul R. , Farhan Sali M.K. , Moshitzky Gilli , Beraldo Flavio H. , Lopes Marilene H. , Maciejewski Andrzej , Gros Robert , Fan Jue , Choy Wing-Yiu , Greenberg David S. , Martins Vilma R. , Duennwald Martin L. , Soreq Hermona , Prado Vania F. , Prado Marco A.M.
Published: February 2018

Chaperone networks are dysregulated with aging and neurodegenerative disease, but whether compromised Hsp70/Hsp90 chaperone function directly contributes to neuronal degeneration is unknown. Stress-inducible phosphoprotein-1 (STI1; STIP1; HOP) is a co-chaperone that simultaneously interacts with Hsp70 and Hsp90, but whose functionin vivoremains poorly understood. To investigate the requirement of STI1-mediated regulation of the chaperone machinery in aging we combined analysis of a mouse line with a hypomorphicStip1allele, with a neuronal cell line lacking STI1 and in-depth analyses of chaperone genes in human datasets. Loss of STI1 function severely disturbed the Hsp70/Hsp90 machineryin vivo, and all client proteins tested and a subset of cochaperones presented decreased levels. Importantly, mice expressing a hypomorphic STI1 allele showed spontaneous age-dependent hippocampal neurodegeneration, with consequent spatial memory deficits. STI1 is a critical node for the chaperone network and it can contribute to age-dependent hippocampal neurodegeneration.
SeqOthello: Query over RNA-seq experiments at scale
Authors: Yu Ye , Liu Jinpeng , Liu Xinan , Zhang Yi , Magner Eamonn , Qian Chen , Liu Jinze
Published: February 2018

We present SeqOthello, an ultra-fast and memory-efficient indexing structure to support arbitrary sequence query against large collections of RNA-seq experiments. SeqOthello requires only five minutes to conduct a global survey of 11,658 fusion events against 10,113 TCGA Pan-Cancer RNA-seq datasets on a standard computer with 19.1 GB memory space. The query recovers 92.7% of tier-1 fusions curated by TCGA Fusion Gene Database and further reveals 270 novel fusion occurrences, all of which present as tumor-specific. The entire index is only 76 GB, achieving a 700:1 compression ratio relative to the original sequencing data and making it extremely portable. This is the first sequence search index constructed on the scale of TCGA data. By providing a reference-free, alignment-free, and parameter-free sequence search system, SeqOthello will enable large-scale integrative studies using sequence-level data, an undertaking not previously practicable for many individual labs. SeqOthello is currently available at https://github.com/LiuBioinfo/SeqOthello.
Cortical networks for encoding near and far space in the non-human primate
Authors: Cléry Justine , Guipponi Olivier , Odouard Soline , Wardak Claire , Hamed Suliann Ben
Published: February 2018

While extra-personal space is often erroneously considered as a unique entity, early neuropsychological studies report a dissociation between near and far space processing both in humans and in monkeys. Here, we use functional MRI in a naturalistic 3D environment to describe the non-human primate near and far space cortical networks. We describe the co-occurrence of two extended functional networks respectively dedicated to near and far space processing. Specifically, far space processing involves occipital, temporal, parietal, posterior cingulate as well as orbitofrontal regions not activated by near space, possibly subserving the processing of the shape and identity of objects. In contrast, near space processing involves temporal, parietal and prefrontal regions not activated by far space, possibly subserving the preparation of an arm/hand mediated action in this proximal space. Interestingly, this network also involves somatosensory regions, suggesting a cross-modal anticipation of touch by a nearby object. Last, we also describe cortical regions that process both far and near space with a preference for one or the other. This suggests a continuous encoding of relative distance to the body, in the form of a far-to-near gradient. We propose that these cortical gradients in space representation subserve the physically delineable peripersonal spaces described in numerous psychology and psychophysics studies.

Highlights

Near space processing involves temporal, parietal and prefrontal regions.

Far space activates occipital, temporal, parietal, cingulate & orbitofrontal areas.

Most regions process both far & near space, with a preference for one or the other.

Far-to-near gradient may subserve behavioral changes in peripersonal space size.
The evolution of ogres: cannibalistic growth in giant phagotrophs
Authors: Bloomfield Gareth
Published: February 2018

Eukaryotes span a very large size range, with macroscopic species most often formel in multicellular lifecycle stages, but sometimes as very large single cells containing many nuclei. The Mycetozoa are a group of amoebae that form macroscopic fruiting structures. However the structures formel by the two major mycetozoan groups are not homologous to each other. Here, it is proposel that the large size of mycetozoans frst arose after selection for cannibalistic feeling by zygotes. In one group, Myxogastria, these zygotes became omnivorous plasmolia; in Dictyostelia the evolution of aggregative multicellularity enablel zygotes to attract anl consume surrounling conspecifc cells. The cannibalism occurring in these protists strongly resembles the transfer of nutrients into metazoan oocytes. If oogamy evolvel early in holozoans, it is possible that aggregative multicellularity centrel on oocytes coull have precelel anl given rise to the clonal multicellularity of crown metazoa.
Brain responses to different types of salience in antipsychotic naïve first episode psychosis: An fMRI study
Authors: Knolle Franziska , Ermakova Anna O , Justicia Azucena , Fletcher Paul C , Bunzeck Nico , Düzel Emrah , Murray Graham K
Published: February 2018

Abnormal salience processing has been suggested to contribute to the formation of positive psychotic symptoms in schizophrenia and related conditions. Previous research utilising reward learning or anticipation paradigms has demonstrated cortical and subcortical abnormalities in people with psychosis, specifically in the prefrontal cortex, the dopaminergic midbrain and the striatum. In these paradigms, reward prediction errors attribute motivational salience to stimuli. However, little is known about possible abnormalities across different forms of salience processing in psychosis patients, and whether any such abnormalities involve the dopaminergic midbrain. The aim of our study was, therefore, to investigate possible alterations in psychosis in neural activity in response to various forms of salience: novelty, negative emotion, targetness (task-driven salience) and rareness/deviance. We studied 14 antipsychotic naïve participants with first episode psychosis, and 37 healthy volunteers. During fMRI scanning, participants performed a visual oddball task containing these four forms of salience. Psychosis patients showed abnormally reduced signalling in the substantia nigra/ventral tegmental area (SN/VTA) for novelty, negative emotional salience and targetness; reduced striatal and occipital (lingual gyrus) signalling to novelty and negative emotional salience, reduced signalling in the amygdala, anterior cingulate cortex and parahippocamal gyrus to negative emotional salience, and reduced cerebellar signalling to novelty and negative emotional salience. Our results indicate alterations of several forms of salience processing in patients with psychosis in the midbrain SN/VTA, with additional subcortical and cortical regions also showing alterations in salience signalling, the exact pattern of alterations depending on the form of salience in question.
Cognitive Changes associated with Alzheimer’s disease in Down syndrome
Authors: Firth Nicholas C. , Startin Carla M. , Hithersay Rosalyn , Hamburg Sarah , Wijeratne Peter A. , Mok Kin Y. , Hardy John , Alexander Daniel C. ,   The LonDownS Consortium, Strydom André
Published: February 2018

Objective

Individuals with Down syndrome (DS) have an extremely high genetic risk for Alzheimer’s disease (AD) however the course of cognitive decline associated with progression to dementia is ill-defined. Data-driven methods can estimate long-term trends from cross-sectional data while adjusting for variability in baseline ability, which complicates dementia assessment in those with DS.

Methods

We applied an event-based model to cognitive test data and informant-rated questionnaire data from 283 adults with DS (the largest study of cognitive functioning in DS to date) to estimate the sequence of cognitive decline and individuals’ disease stage.

Results

Decline in tests of memory, sustained attention / motor coordination, and verbal fluency occurred early, demonstrating that AD in DS follows a similar pattern of change to other forms of AD. Later decline was found for informant measures. Using the resulting staging model, we showed that adults with a clinical diagnosis of dementia and those with APOE 3:4 or 4:4 genotype were significantly more likely to be staged later, suggesting the model is valid.

Interpretation

Our results identify tests of memory and sustained attention may be particularly useful measures to track decline in the preclinical/prodromal stages of AD in DS whereas informant-measures may be useful in later stages (i.e. during conversion to dementia, or post-diagnosis). These results have implications for the selection of outcome measures of treatment trials to delay or prevent cognitive decline due to AD in DS. As clinical diagnoses are generally made late into AD progression, early assessment is essential.
Frequency and power of human alpha oscillations drift systematically with time-on-task
Authors: Benwell Christopher S.Y. , London Raquel E. , Tagliabue Chiara F. , Veniero Domenica , Gross Joachim , Keitel Christian , Thut Gregor
Published: February 2018

Oscillatory neural activity is a fundamental characteristic of the mammalian brain spanning multiple levels of spatial and temporal scale. Current theories of neural oscillations and analysis techniques employed to investigate their functional significance are based on an often implicit assumption: In the absence of experimental manipulation, the spectral content of any given EEG- or MEG-recorded neural oscillator remains approximately stationary over the course of a typical experimental session (~1 hour), spontaneously fluctuating only around its dominant frequency. Here, we examined this assumption for ongoing neural oscillations in the alpha-band (8:13 Hz). We found that alpha peak frequency systematically decreased over time, while alpha-power increased. Intriguingly, these systematic changes showed partial independence of each other: Statistical source separation (independent component analysis) revealed that while some alpha components displayed concomitant power increases and peak frequency decreases, other components showed either unique power increases or frequency decreases. Interestingly, we also found these components to differ in frequency. Components that showed mixed frequency/power changes oscillated primarily in the lower alpha-band (~8-10Hz), while components with unique changes oscillated primarily in the higher alpha-band (~9-13Hz). Our findings provide novel clues on the time-varying intrinsic properties of large-scale neural networks as measured by M/EEG, with implications for the analysis and interpretation of studies that aim at identifying functionally relevant oscillatory networks or at driving them through external stimulation.
Threshold regulation and stochasticity from the MecA/ClpCP proteolytic system inStreptococcus mutanscompetence
Authors: Son M. , Kaspar J. , Ahn S.J. , Burne R.A. , Hagen S.J.
Published: February 2018

Many bacterial species use the MecA/ClpCP proteolytic system to block entry into genetic competence. InStreptococcus mutans, MecA/ClpCP degrades ComX (also called SigX), an alternative sigma factor for thecomYoperon and other late competence genes. Although the mechanism of MecA/ClpCP has been studied in multipleStreptococcusspecies, its role within noisy competence pathways is poorly understood.S. mutanscompetence can be triggered by two different peptides, CSP and XIP, but it is not known whether MecA/ClpCP acts similarly for both stimuli, how it affects competence heterogeneity, and how its regulation is overcome. We have studied the effect of MecA/ClpCP on the activation ofcomYin individualS. mutanscells. Our data show that MecA/ClpCP is active under both XIP and CSP stimulation, that it provides threshold control ofcomY, and that it adds noise incomYexpression. Our data agree quantitatively with a model in which MecA/ClpCP prevents adventitious entry into competence by sequestering or intercepting low levels of ComX. Competence is permitted when ComX levels exceed a threshold, but cell-to-cell heterogeneity in MecA levels creates variability in that threshold. Therefore MecA/ClpCP provides a stochastic switch, located downstream of the already noisycomX, that enhances phenotypic diversity.
Inflation versus filling-in: why we feel we see more than we actually do in peripheral vision
Authors: Odegaard Brian , Chang Min Yu , Lau Hakwan , Cheung Sing-Hang
Published: February 2018

Do we perceive fine details in the visual periphery? Here, we propose that phenomenology in the visual periphery can be characterized by an inflated sense of perceptual capacity, as observers overestimate the quality of their perceptual inputs. Distinct from the well-known perceptual phenomenon of “filling-in” where perceptual content is generated or completed endogenously, inflation can be characterized by incorrect introspection at the subjective level. The perceptual content itself may be absent or weak (i.e., not necessarily filled-in), and yet such content is mistakenly regarded by the system as rich. Behaviorally, this can be reflected by metacognitive deficits in the degree to which confidence judgments track task accuracy, and decisional biases for observers to think particular items are present, even when they are not. In two experiments using paradigms which exploit unique attributes of peripheral vision (crowding and summary statistics), we provide evidence that both types of deficits are present in peripheral vision, as observers’ reports are marked by overconfidence in discrimination judgments and high numbers of false alarms in detection judgments. We discuss potential mechanisms which may be the cause of inflation and propose future experiments to further explore this unique sensory phenomenon.
High-Speed Imaging of Paw Withdrawal Reflex to Objectively Assess Pain State in Mice
Authors: Abdus-Saboor Ishmail , Fried Nathan T. , Lay Mark , Dong Peter , Burdge Justin , Lu Ming , Ma Minghong , Dong Xinzhong , Ding Long , Luo Wenqin
Published: February 2018

Rodents are often used for studying chronic pain mechanisms and developing new pain therapeutics, but objectively determining the animal’s pain state is a major challenge. To improve the precision of using reflexive withdrawal behaviors for interpreting the mouse pain state, we adopted high-speed videography to capture sub-second movement features of mice upon hind paw stimulation. We identified several parameters that are significantly different between behaviors evoked by innocuous and noxious stimuli, and combined them to map the mouse pain state through statistical modeling and machine learning. To test the utility of this approach, we determined the pain state triggered by von Frey hairs (VFHs) and optogenetic activation of two nociceptor populations. Our method reliably assesses the “pain-like” probability for each mouse paw withdrawal reflex under all scenarios, highlighting the improved precision of using this high resolution behavior-centered composite methodology to determine the mouse pain state from reflexive withdrawal assays.
Tumour purity as a prognostic factor in colon cancer
Authors: Mao Yihao , Feng Qingyang , Zheng Peng , Yang Liangliang , Liu Tianyu , Xu Yuqiu , Zhu Dexiang , Chang Wenju , Ji Meiling , Tu Yongjiu , Ren Li , Wei Ye , He Guodong , Xu Jianmin
Published: February 2018

Tumour purity is defined as the proportion of cancer cells in the tumour tissue. The impact of tumour purity on colon cancer (CC) prognosis, genetic profile and microenvironment has not been thoroughly accessed. Therefore, clinical and transcriptomic data from three public datasets, GSE17536/17537, GSE39582, and TCGA were retrospectively collected (n = 1248). Tumour purity of each sample was inferred by a computational method based on transcriptomic data. Stage III and MMR-deficient (dMMR) CC patients showed a significantly lower tumour purity. Low purity CC conferred worse survival and tumour purity was identified as an independent prognostic factor. Moreover, high tumour purity CC patients benefited more from adjuvant chemotherapy. Subsequent genomic analysis found that the mutation burden was negatively associated with tumour purity with only APC and KRAS significantly more mutated in high purity CC. However, no somatic copy number alteration event was correlated with tumour purity. Furthermore, immune-related pathways and immunotherapy-associated markers (PD-1, PD-L1, CTLA-4, LAG-3, and TIM-3) were highly enriched in low purity samples. Notably, the relative proportion of M2 macrophages and neutrophils, which indicated worse survival in CC, was negatively associated with tumour purity. Therefore, tumour purity exhibited potential value for CC prognostic stratification as well as adjuvant chemotherapy benefit prediction. The relative worse survival in low purity CC may attribute to higher mutation frequency in key pathways and purity related microenvironmental changing.

Low purity colon cancer patients conferred worse survival and benefited less from adjuvant chemotherapy. The mutation burden was negatively associated with tumour purity. Low purity samples exhibited intense immune phenotype with more M2 macrophages and neutrophils infiltration.