bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteoarthritis pain. Recent advances and controversies
Authors: Schaible Hans-Georg 
Published: February 2018

Purpose of review
Osteoarthritis is one of the most frequent causes of chronic pain. Because there is no causal treatment of osteoarthritis, sufficient pain control is of uppermost importance but often not met. The review reports recent advances and controversies in our understanding of osteoarthritis pain and its treatment.

Recent findings
Osteoarthritis pain is determined by processes at different levels. An important local factor of pain generation in the joint is inflammation such as synovitis, and neuropathic components of osteoarthritis pain are being discussed. Neuroplastic changes in the nociceptive system such as peripheral and central sensitization facilitate pain processing. Osteoarthritis pain may also be aggravated by general factors such as metabolic changes and diabetes mellitus, genetic and psychological factors. The review will also address mediators involved in osteoarthritis pain and treatment options.

Summary
Recent research is increasing our understanding of osteoarthritis pain by elucidating local factors in the joint which cause pain, by showing neuroplastic changes in the nociceptive system and by addressing the significance of general factors in pain such as metabolic changes. The weight of such factors may determine the pain pattern in individual patients.
Keep Your Eyes Wide Open: On Visual- and Vision-Related Measurements to Better Understand Multiple Sclerosis Pathophysiology
Authors: Backner Yael , Levin Netta 
Published: February 2018

Background:Multiple sclerosis (MS), a demyelinating disease of the central nervous system, is multifaceted. It manifests as acute episodes as well as an accumulative chronic disability; myelin involvement as well as axonal damage; local as well as global effects; and disease load elements as well as compensatory mechanisms. The visual system, with its clear structural organization and relatively direct reflection of damage, may serve as an appropriate model to study MS.Methods:In recent years, we have witnessed a blossoming in the field of visual measures in MS. Because it is impossible to cover all different aspects of these measures, we chose to focus on several hot topics in MS literature and shed light on them through studies conducted in the visual system.Results:We argue that numerous methods can be used to study axonal and demyelinating aspects of the disease. Although optical coherence tomography and static visual functions better reflect the axonal aspects of the disease, conduction velocity as measured by visual-evoked potential latencies and dynamic visual function mirrors myelin levels. We also posit that the classic disease load parameters cannot be the only means by which we assess a patient's condition. Novel imaging methods such as diffusion tensor imaging and functional magnetic resonance imaging can be used to assess the global effects of local damage on neighboring white matter and compensatory abilities of the brain.Conclusions:There have been great advances in therapeutic research in MS. However, the stratification of patients according to their prognosis and predictive outcomes in response to treatment is still in its infancy. The many facets of MS make it difficult to piece all the data together into one cohesive conclusion for the individual patient. The visual system, with our ability to assess both structure and function, offers a promising opportunity to study both pathophysiologic mechanisms and novel therapies.
Disinhibited Blink Reflex Recovery Is Related to Lateral Trunk Flexion in Parkinson Disease
Authors: Sugiyama Takashi , Mochizuki Hitoshi , Hara Yoshine , Miyamoto Miyuki , Nakazato Yuki , Taniguchi Akitoshi , Ishii Nobuyuki , Shiomi Kazutaka , Nakazato Masamitsu 
Published: February 2018

Purpose:
Lateral trunk flexion is often observed in patients with Parkinson disease (PD) and causes poor quality of life. Asymmetrical function of the basal ganglia is believed to be the main cause of lateral trunk flexion, and dysfunction of the basal ganglia facilitates the blink reflex by disinhibiting the spinal trigeminal nucleus. Our aim was to investigate whether a disinhibited blink reflex recovery curve (BRrc) was associated with lateral trunk flexion in PD patients.

Methods:
We enrolled 21 PD patients, including 11 with marked lateral trunk flexion (F-PD) and 10 with normal posture (N-PD), and 10 normal controls. Blink reflex recovery curves at interstimulus intervals of 200, 300, and 500 ms were compared between F-PD, N-PD, and normal controls.

Results:
The BRrc in F-PD patients was more disinhibited than in N-PD patients and controls, and this disinhibition was asymmetrical.

Conclusions:
The asymmetrically disinhibited BRrc in F-PD patients was associated with lateral trunk flexion. This is the first neurophysiological study of patients with PD with abnormal posture. Examination of the BRrc may permit early detection of asymmetrical basal ganglia dysfunction that can eventually cause lateral trunk flexion.
High-magnitude innovators as keystone individuals in the evolution of culture
Authors: Arbilly Michal 
Published: February 2018

Borrowing from the concept of keystone species in ecological food webs, a recent focus in the field of animal behaviour has been keystone individuals: individuals whose impact on population dynamics is disproportionally larger than their frequency in the population. In populations evolving culture, such may be the role of high-magnitude innovators: individuals whose innovations are a major departure from the population's existing behavioural repertoire. Their effect on cultural evolution is twofold: they produce innovations that constitute a ‘cultural leap' and, once copied, their innovations may induce further innovations by conspecifics (socially induced innovations) as they explore the new behaviour themselves. I use computer simulations to study the coevolution of independent innovations, socially induced innovations and innovation magnitude, and show that while socially induced innovation is assumed here to be less costly than independent innovation, it does not readily evolve. When it evolves, it may in some conditions select against independent innovation and lower its frequency, despite it requiring independent innovation in order to operate; at the same time, however, it leads to much faster cultural evolution. These results confirm the role of high-magnitude innovators as keystones, and suggest a novel explanation for the low frequency of independent innovation.
This article is part of the theme issue ‘Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.
Assessing the relative impact of historical divergence and inter-group transmission on cultural patterns: a method from evolutionary ecology
Authors: von Cramon-Taubadel Noreen , Lycett Stephen J. 
Published: February 2018

In the study of cultural evolution, observed among-group affinity patterns reflect the effects of processes such as mutation (e.g. innovation and copying error), between-group interaction (culture flow), drift and selection. As in biology, cultural affinity patterns are often spatially correlated, making it difficult to distinguish between the opposing geographically mediated forces of divergence and interaction, which cause groups to become more distinct or similar over time, respectively. Analogous difficulties are faced by evolutionary biologists examining the relationship between biological affinity and geography, particularly at lower taxonomic levels where the potential for gene flow between lineages is greatest. Tree models are generally used to assess the fit between affinity patterns and models of historical divergence. However, factors driving lineage divergence are often spatially mediated, resulting in tree models that are themselves geographically structured. Here, we showcase a simple method drawn from evolutionary ecology for assessing the relative impact of both geographically mediated processes simultaneously. We illustrate the method using global human craniometric diversity and material culture from the northern coast of New Guinea as example case studies. This method can be employed to quantify the relative importance of history (divergence) and geographically mediated between-group interaction (culture flow) in explaining observed cultural affinity patterns.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

AbstractSpreading 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

AbstractThe 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

AbstractLearning 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 statementThe 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

AbstractWhile 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.Contactall 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

ABSTRACTGenomic 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.