bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Paratonia on Fine and Gross Motor Function in Older Adults With Mild and Moderate Dementia
Authors: Van Deun Bieke , Van Den Noortgate Nele , Van Bladel Anke , Palmans Tanneke , Cambier Dirk 
Published: October 2018

Background:
Dementia is associated with impairment in gait, balance, and fine motor function. Paratonia, a form of hypertonia, is often present in severe dementia. However, little is known about muscle tone in early dementia, and the eventual relation between muscle tone abnormalities and changes in fine and gross motor function.

Methods:
Three groups of participants were included in the study: healthy controls (n=60), participants with mild dementia (MiD) (n=31), and participants with moderate dementia (n=31). Measurements of fine motricity (Purdue pegboard test), balance and gait (Dynaport Hybrid), the presence of paratonia (PAI), and muscle tone measurements (MyotonPRO) were performed.

Results:
Paratonia was present in 42% of participants with MiD and in 58% of participants with moderate dementia. Participants with paratonia had lower Purdue Pegboard scores (P<0.001), lower balance coordination in semitandem stance (P<0.001), lower walking speed at a fast pace (P=0.001), and lower step regularity at normal (P=0.025) and fast (P<0.001) pace.

Conclusions:
Paratonia is already present in participants with MiD and is associated with a decline in both fine and gross motor performance. Early detection of paratonia might be helpful to detect persons at higher risk of motor deterioration and falls.
Crosstalk between RNA Pol II C-Terminal Domain Acetylation and Phosphorylation via RPRD Proteins
Authors: Ali Ibraheem , Ruiz Diego Garrido , Ni Zuyao , Johnson Jeffrey R. , Zhang Heng , Li Pao-Chen , Khalid Mir , Conrad Ryan J. , Guo Xinghua , Min Jinrong , Greenblatt Jack , Jacobson Matthew , Krogan Nevan J. , Ott Melanie 
Published: October 2018

SUMMARYPost-translational modifications of the RNA polymerase II C-terminal domain (CTD) coordinate the transcription cycle. Crosstalk between different modifications is poorly understood. Here, we show how acetylation of lysine residues at position 7 of characteristic heptad repeats (K7ac)—only found in higher eukaryotes—regulates phosphorylation of serines at position 5 (S5p), a conserved mark of polymerases initiating transcription. We identified the regulator of pre-mRNA domain-containing (RPRD) proteins as reader proteins of K7ac. K7ac enhanced CTD peptide binding to the CTD-interacting domain (CID) of RPRD1A and RPRD1B proteins in isothermal calorimetry and molecular modeling experiments. Deacetylase inhibitors increased K7ac- and decreased S5-phosphorylated polymerases, consistent with acetylation-dependent S5 dephosphorylation by an RPRD-associated S5 phosphatase. Consistent with this model, RPRD1B knockdown increased S5p, but enhanced K7ac, indicating RPRD proteins recruit K7 deacetylases, including HDAC1. We also report auto-regulatory crosstalk between K7ac and S5p via RPRD proteins and their interactions with acetyl- and phospho-eraser proteins.
High residual prevalence of vaccine-serotypeStreptococcus pneumoniaecarriage after introduction of a pneumococcal conjugate vaccine in Malawi: a prospective serial cross-sectional study
Authors: Swarthout Todd D. , Fronterre Claudio , Lourenço José , Obolski Uri , Gori Andrea , Bar-Zeev Naor , Everett Dean , Kamng’ona Arox W. , Mwalukomo Thandie S. , Mataya Andrew A. , Mwansambo Charles , Banda Marjory , Gupta Sunetra , Diggle Peter , French Neil , Heyderman Robert S. 
Published: October 2018

ABSTRACTBackgroundThere are concerns that pneumococcal conjugate vaccines (PCV) in sub-Saharan Africa sub-optimally interrupt vaccine-serotype (VT) carriage and transmission, thus limiting vaccine-induced direct and indirect protection. We assessed carriage in vaccinated children and unvaccinated populations targeted for indirect protection, between 4 and 7 years after Malawi’s November 2011 introduction of PCV13 using a 3+0 schedule.MethodsWe conducted sequential prospective nasopharyngeal carriage surveys between 2015 and 2018 among healthy PCV-vaccinated and PCV-unvaccinated children, and HIV-infected adults. VT and NVT carriage risk by age was analysed by non-linear regression.ResultsAmong PCV-vaccinated children, there was a 24% relative reduction in carriage, from a mean 21.1% to 16.1%; 45% reduction among older PCV-unvaccinated children, from 27.5% to 15.2%; 41.4% reduction among adults, from 15.2% to 8.9%. Using carriage data from children 3.6 to 10 years of age, VT carriage probability declined with age, with a similar prevalence half-life among PCV-vaccinated (3.34 years) and PCV-unvaccinated (3.26 years) children.ConclusionCompared to high-income settings, the 3+0 schedule in Malawi has led to a sub-optimal reduction in pneumococcal carriage prevalence. This is likely due to recolonisation of vaccinated children with waning vaccine-induced immunity, resulting in insufficient indirect protection of unvaccinated populations. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns is required.
Protein aggregation capture on microparticles enables multi-purpose proteomics sample preparation
Authors: Batth Tanveer S. , Tollenaere Maxim A.X. , Rüther Patrick L. , Gonzalez-Franquesa Alba , Prabhakar Bhargav S. , Bekker-Jensen Simon , Deshmukh Atul S. , Olsen Jesper V. 
Published: October 2018

ABSTRACTUniversal proteomics sample preparation is challenging due to the high heterogeneity of biological samples. Here we describe a novel mechanism that exploits the inherent instability of denatured proteins for non-specific immobilization on microparticles by protein aggregation capture. To demonstrate the general applicability of this mechanism, we analyzed phosphoproteomes, tissue proteomes, and interaction proteomes as well as dilute secretomes. The findings presents a practical, sensitive and cost-effective proteomics sample preparation method.
Elevated expression of LGR5 and WNT signalling factors in neuroblastoma cells with acquired drug resistance
Authors: Myssina Svetlana , Clark-Corrigall John , Michaelis Martin , Cinatl Jindrich , Ahmed Shafiq U. , Carr-Wilkinson Jane 
Published: October 2018

AbstractNeuroblastoma (NB) is the most common paediatric solid cancer with high fatality, relapses and acquired resistance to drug therapy. The clinical challenge NB poses requires new therapeutic approaches to improve survival rates.The WNT signalling pathway is crucial in embryonic development but has also been reported to be dysregulated in glioblastoma, ovarian, breast and colorectal cancer. LGR5 is a receptor which potentiates the WNT/β-catenin signalling pathway, hence contributing to cancer stem cell proliferation and self-renewal. LGR5 has been reported to promote both development and survival of colorectal cancer and glioblastomas.Our previous study illustrated that LGR5 is associated with aggressiveness in NB cell lines established at different stages of treatment. Following these findings, we investigated whether LGR5 is involved in acquired drug resistance via the WNT pathway in NB cell lines.Cell lines in this study have an acquired drug resistance to vincristine (VCR) or doxorubicin (DOX).In this study, we showed LGR5-LRP6 cooperation with enhanced expression of both proteins in SHSY5YrVCR, IMR32rDOX, IMR5rVCR and IMR5rDOX NB cell lines compared to paired parental cells. We also found elevated expression of β-catenin in cell lines with acquired drug resistance is indicative of β-catenin-dependent WNT signalling.This study warrants further investigation into the role of the WNT signalling pathway in acquired drug resistance.
An Accessible Continuous-Culture Turbidostat for Pooled Analysis of Complex Libraries
Authors: McGeachy Anna M. , Meacham Zuriah A. , Ingolia Nicholas T. 
Published: October 2018

ABSTRACTWe present an accessible, robust continuous-culture turbidostat system that enables biologists to generate and phenotypically analyze highly complex libraries in yeast and bacteria. Our system has many applications in genomics and systems biology; here, we demonstrate three of these uses. We first measure how the growth rate of budding yeast responds to limiting nitrogen at steady state and in a dynamically varying environment. We also demonstrate the direct selection of a diverse, genome-scale protein fusion library in liquid culture. Finally, we perform a comprehensive mutational analysis of the essential gene RPL28 in budding yeast, mapping sequence constraints on its wild-type function and delineating the binding site of the drug cycloheximide through resistance mutations. Our system can be constructed and operated with no specialized skills or equipment and applied to study genome-wide mutant pools and diverse libraries of sequence variants under well-defined growth conditions.
The Swiss Primary Ciliary Dyskinesia registry: objectives, methods and first results
Authors: Myrofora Goutaki , Marc Eich , Halbeisen Florian S. , Juerg Barben , Carmen Casaulta , Christian Clarenbach , Hafen Gaudenz , Philipp Latzin , Nicolas Regamey , Romain Lazor , Stefan Tschanz , Maura Zanolari , Elisabeth Maurer , Claudia Kuehni E. ,   Swiss PCD Registry (CH-PCD) Working Group
Published: October 2018

AbstractPrimary Ciliary Dyskinesia (PCD) is a rare hereditary, multi-organ disease caused by defects in ciliary structure and function. It results in a wide range of clinical manifestations, most commonly in the upper and lower airways. Central data collection in national and international registries is essential to studying the epidemiology of rare diseases and filling in gaps in knowledge of diseases such as PCD. For this reason, the Swiss Primary Ciliary Dyskinesia Registry (CH-PCD) was founded in 2013 as a collaborative project between epidemiologists and adult and paediatric pulmonologists.The registry records patients of any age, suffering from PCD, who are treated and resident in Switzerland. It collects information from patients identified through physicians, diagnostic facilities, and patient organisations. The registry dataset contains data on diagnostic evaluations, lung function, microbiology and imaging, symptoms, treatments, and hospitalizations.By May 2018, CH-PCD has contacted 566 physicians of different specialties and identified 134 patients with PCD. At present this number represents an overall 1 in 63,000 prevalence of people diagnosed with PCD in Switzerland. Prevalence differs by age and region; it is highest in children and adults younger than 30 years, and in Espace Mittelland. The median age of patients in the registry is 25 years (range 5-73), and 49 patients have a definite PCD diagnosis based on recent international guidelines. Data from CH-PCD are contributed to international collaborative studies and the registry facilitates patient identification for nested studies.CH-PCD has proven to be a valuable research tool that already has highlighted weaknesses in PCD clinical practice in Switzerland. Development of centralised diagnostic and management centres and adherence to international guidelines are needed to improve diagnosis and management—particularly for adult PCD patients.
The CRUNCH model does not account for load-dependent changes in visuospatial working memory in older adults: Evidence for the file-drawer problem in neuroimaging
Authors: Jamadar Sharna D 
Published: October 2018

AbstractNumerous neuroimaging studies have shown that older adults tend to activate the brain to a greater extent than younger adults during the performance of a task. This is typically interpreted as evidence for cognitive compensation. The Compensation-Related Utilisation of Neural Circuits Hypothesis (CRUNCH) model is a highly influential model of compensation, and states that increased functional magnetic resonance imaging (fMRI) activity in older adults compared to younger adults should reverse at higher levels of task difficulty. We tested the CRUNCH model using a visuospatial working memory paradigm, and found that fMRI activity in older vs. younger adults was in the opposite direction to that predicted by the model. Given that the CRUNCH model is the predominant model of compensation, this result was surprising. We followed up our results with a systematic review of the CRUNCH in healthy ageing literature using p-curve analysis. We find evidence for selective reporting, or the ‘file-drawer’ problem, in the cognitive compensation literature. Further experimental work is required to validate the CRUNCH model in cognitive ageing.AbbreviationsCRUNCH: compensation-related utilisation of neural circuits hypothesis; fMRI: functional magnetic resonance imagingHighlights-CRUNCH is the leading model of cognitive compensation in ageing-We find fMRI activity in old vs. young adults in opposite direction predicted by CRUNCH-We report quantitative evidence of selective reporting in CRUNCH literature
Sparse Coding with a Somato-Dendritic Rule
Authors: Drix Damien , Hafner Verena V. , Schmuker Michael 
Published: October 2018

AbstractCortical neurons are silent most of the time. This sparse activity is energy efficient, and the resulting neural code has favourable properties for associative learning. Most neural models of sparse coding use some form of homeostasis to ensure that each neuron fires infrequently. But homeostatic plasticity acting on a fast timescale may not be biologically plausible, and could lead to catastrophic forgetting in embodied agents that learn continuously. We set out to explore whether inhibitory plasticity could play that role instead, regulating both the population sparseness and the average firing rates. We put the idea to the test in a hybrid network where rate-based dendritic compartments integrate the feedforward input, while spiking somas compete through recurrent inhibition. A somato-dendritic learning rule allows somatic inhibition to modulate nonlinear Hebbian learning in the dendrites. Trained on MNIST digits and natural images, the network discovers independent components that form a sparse encoding of the input and support linear decoding. These findings con-firm that intrinsic plasticity is not strictly required for regulating sparseness: inhibitory plasticity can have the same effect, although that mechanism comes with its own stability-plasticity dilemma. Going beyond point neuron models, the network illustrates how a learning rule can make use of dendrites and compartmentalised inputs; it also suggests a functional interpretation for clustered somatic inhibition in cortical neurons.
HERV-K HML-2 transcription in diverse cancers is related with cancer stem cell and epithelial-mesenchymal transition markers
Authors: Lin Audrey T. , Santander Cindy G. , Nascimento Fabricia F. , Marchi Emanuele , Karamitros Timokratis , Katzourakis Aris , Magiorkinis Gkikas 
Published: October 2018

AbstractEndogenous retroviruses (ERVs) are remnants of ancient retroviral infections that make up 8% of the human genome. Although these elements are mostly fragmented and inactive, many proviruses belonging to the HERV-K (HML-2) family, the youngest lineage in the human genome, have intact open reading frames, some encoding for accessory genes called np9 and rec that interact with oncogenic pathways. Many studies have established that ERVs are transiently expressed in both stem cells and cancer, resulting in aberrant self-renewal and uncontrolled proliferation. np9 and rec expression are significantly correlated with a range of cancer stem cell (CSC) and epithelial to mesenchymal transition (EMT) biomarkers, including cellular receptors, transcription factors, and histone modifiers. Surprisingly, these ERV genes are negatively correlated with genes known to promote pluripotency in embryonic stem cell lines, such as Oct4. These results indicate that HERV-K (HML-2) is part of the transcriptional landscape responsible for cancer cells undergoing the phenotypic switch that characterises EMT. The discovery of np9 and rec’s correlation with CSC and EMT biomarkers suggest a yet undescribed role affecting the transitional CSC-like state in EMT and the shift towards cancer malignancy.ImportanceIn this study, we find that human endogenous retrovirus HERV-K (HML-2)-encoded genes np9 and rec are correlated with the expression of many biomarkers associated with cancer stem cells (CSC) and epithelial-mesenchymal transition (EMT). There has been a significant effort to develop novel treatments targeting CSC and EMT-specific signalling pathways and cell surface markers. This research describes HERV-K (HML-2) as interacting or being part of the regulatory network that make up reversible cell state switching in EMT. Our findings suggest these specific HERVs may be good candidate biomarkers in identifying the transitional CSC-like states that are present during the progression of EMT and cancer metastasis.
Different macroevolutionary routes to becoming a biodiversity hotspot
Authors: Igea J. , Tanentzap A. J. 
Published: October 2018

AbstractWhy is species diversity so unevenly distributed across different regions on Earth? Regional differences in biodiversity may stem from differences in rates of speciation and dispersal and colonization times, but these hypotheses have rarely been tested simultaneously at a global scale. Here we uncovered the routes that generated hotpots of mammal and bird biodiversity by analyzing the tempo and mode of diversification and dispersal within major biogeographic realms. Hotspots in tropical realms had higher rates of speciation whereas those in temperate realms received more immigrant species from their surrounding regions. We also found that hotspots had higher spatial complexity and energy availability, providing a link between the environment and macroevolutionary history. Our study highlights how assessing differences in macroevolutionary history can help to explain why biodiversity varies so much worldwide.
Spontaneous intake and long-term effects of essential oils after a negative postnatal experience in chicks
Authors: Guilloteau Laurence A. , Collin Anne , Koch Alexia , Leterrier Christine 
Published: October 2018

AbstractThe postnatal period is critical for broiler chicks as they are exposed to, possibly stressful, environmental changes in the hatchery and during transportation to the rearing houses. The ability of broiler chicks to spontaneously drink essential oils (EO) to mitigate the effects of a negative postnatal experience was tested. Chicks were either immediately placed in the rearing facility (C group), or subjected to a 24h-delay period before their placement (D group), mimicking the possible transportation delay in commercial conditions.In experiment 1, each group had access to either water only or to water and one EO (cardamom, marjoram or verbena) from D1 to D13. The verbena EO intake was higher in the D group than in the C group from D1 to D6 and the cardamom EO intake was lower in the D group than in the C group from D6 to D13.In experiment 2, half of the groups had access to water only and the other half was offered water and the 3 EO simultaneously. The EO were not differently chosen by chicks between D and C groups except a lower cardamom EO intake was observed in the D group than in the C group from D6 to D12. The delayed placement of the D group reduced chicken growth until 34 days of age and temporarily increased the feed conversion ratio, but did not affect their welfare or the prevalence of health disorders. The EO intake did not allow the chicks in the D group to overcome the growth reduction, but did overcome the reduction in Pectoralis major muscle yield. In conclusion, chicks are able to make spontaneous choices regarding EO intake according to their postnatal experience when EO are presented individually, but in our experimental design, they were not when EO were simultaneously presented. The EO intake only partially mitigated the decrease in chicken performance after the negative postnatal experience.
Cingulate dependent social risk assessment in rats
Authors: Han Yingying , Bruls Rune , Thomas Rajat Mani , Pentaraki Vasiliki , Jelinek Naomi , Heinemans Mirjam , Bassez Iege , Verschooren Sam , Pruis Illanah , Lierde Thijs Van , Carrillo Nathaly , Gazzola Valeria , Carrillo Maria , Keysers Christian 
Published: October 2018

AbstractSocial transmission of distress has been conceived of as a one-way phenomenon in which an observer catches the emotions of another. Here we use a paradigm in which an observer rat witnesses another receive electro-shocks. Bayesian model comparison and Granger causality argue against this one-way vision in favor of bidirectional information transfer: how the observer reacts to the demonstrator’s distress influences the behavior of the demonstrator. Intriguingly, this was true to a similar extent across highly familiar and entirely unfamiliar rats. Injecting muscimol in the anterior cingulate of observers reduced freezing in the observers and in the demonstrators receiving the shocks. That rats share the distress of unfamiliar strains is at odds with evolutionary thinking that empathy should be biased towards close individuals. Using simulations, we support the complementary notion that distress transmission could be selected to more efficiently detect dangers in a group.
Impact of mutation rate and selection at linked sites on fine-scale DNA variation across the homininae genome
Authors: Castellano David , Eyre-Walker Adam , Munch Kasper 
Published: October 2018

AbstractDNA diversity varies across the genome of many species. Variation in diversity across a genome might arise for one of three reasons; regional variation in the mutation rate, selection and biased gene conversion. We show that both non-coding and non-synonymous diversity are correlated to a measure of the mutation rate, the recombination rate and the density of conserved sequences in 50KB windows across the genomes of humans and non-human homininae. We show these patterns persist even when we restrict our analysis to GC-conservative mutations, demonstrating that the patterns are not driven by biased gene conversion. The positive correlation between diversity and our measure of the mutation rate seems to be largely a direct consequence of regions with higher mutation rates having more diversity. However, the positive correlation with recombination rate and the negative correlation with the density of conserved sequences suggests that selection at linked sites affect levels of diversity. This is supported by the observation that the ratio of the number of non-synonymous to non-coding polymorphisms is negatively correlated to a measure of the effective population size across the genome. Furthermore, we find evidence that these genomic variables are better predictors of non-coding diversity in large homininae populations than in small populations, after accounting for statistical power. This is consistent with genetic drift decreasing the impact of selection at linked sites in small populations. In conclusion, our comparative analyses describe for the first time how recombination rate, gene density, mutation rate and genetic drift interact to produce the patterns of DNA diversity that we observe along and between homininae genomes.