bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical correlates of sarcopenia and falls in Parkinson’s disease
Authors: Lima Danielle Pessoa , de Almeida Samuel Brito , de Carvalho Bonfadini Janine , de Luna João Rafael Gomes , de Alencar Madeleine Sales , Pinheiro-Neto Edilberto Barreira , Viana-Júnior Antonio Brazil , Veras Samuel Ranieri Oliveira , Sobreira-Neto Manoel Alves , de Sá Roriz-Filho Jarbas , Braga-Neto Pedro 
Published: December 2019

ABSTRACTBackgroundSarcopenia is a complex and multifactorial geriatric condition seen in several chronic degenerative diseases. This study aimed to screen for sarcopenia and fall risk in a sample of Parkinson’s disease (PD) patients and to investigate demographic and clinical factors associated.MethodsThis is a cross-sectional study. We evaluated 218 PD patients at the Movement Disorders Clinic in Fortaleza, Brazil, and collected clinical data including experiencing falls in the six months prior to their medical visit. Probable sarcopenia diagnosis was confirmed by using a sarcopenia screening tool (SARC-F questionnaire) and the presence of low muscle strength.ResultsOne hundred and twenty-one patients (55.5%) were screened positive for sarcopenia using the SARC-F and 103 (47.4%) met the criteria for probable sarcopenia. Disease duration, modified Hoehn and Yahr stage, Schwab and England Activities of Daily Living Scale score, levodopa equivalent dose, probable sarcopenia and positive SARC-F screening were all associated with experiencing falls in the prior six months. Disease duration, lower quality of life and female gender were independently associated with sarcopenia. Experiencing falls in the prior six months was significantly more frequent among patients screened positive in the SARC-F compared to those screened negative.ConclusionsSarcopenia and PD share common pathways and may affect each other’s prognosis and patients’ quality of life. Since sarcopenia is associated with lower quality of life and increased risk of falls, active case finding, diagnosis and proper management of sarcopenia in PD patients is essential.
Automatic and fast encoding of representational uncertainty underlies probability distortion
Authors: Ren Xiangjuan , Luo Huan , Zhang Hang 
Published: December 2019

AbstractHumans do not have an accurate representation of probability information in the environment but distort it in a surprisingly stereotyped way (“probability distortion”), as shown in a wide range of judgment and decision-making tasks. Many theories hypothesize that humans automatically compensate for the uncertainty inherent in probability information (“representational uncertainty”) and probability distortion is a consequence of uncertainty compensation. Here we examined whether and how the representational uncertainty of probability is quantified in the human brain and its relevance to probability distortion behavior. Human subjects kept tracking the relative frequency of one color of dot in a sequence of dot arrays while their brain activity was recorded by magnetoencephalography (MEG). We found converging evidence from both neural entrainment and time-resolved decoding analysis that a mathematically- derived measure of representational uncertainty is automatically computed in the brain, despite it is not explicitly required by the task. In particular, the encodings of relative frequency and its representational uncertainty respectively occur at latencies of approximately 300 ms and 400 ms. The relative strength of the brain responses to these two quantities correlates with the probability distortion behavior. The automatic and fast encoding of the representational uncertainty provides neural basis for the uncertainty compensation hypothesis of probability distortion. More generally, since representational uncertainty is closely related to confidence estimation, our findings exemplify how confidence might emerge prior to perceptual judgment.
Deciphering the mechanism of inhibition of SERCA1a by sarcolipin using molecular simulations
Authors: Barbot T. , Beswick V. , Montigny C. , Quiniou E. , Jamin N. , Mouawad L. 
Published: December 2019

AbstractSERCA1a is an ATPase calcium pump that transports Ca2+from the cytoplasm to the sarco/endoplasmic reticulum lumen. Sarcolipin (SLN), a transmembrane peptide, regulates the activity of SERCA1a by decreasing its Ca2+transport rate, but its mechanism of action is still not well understood. To decipher this mechanism, we have performed normal modes analysis in the all-atom model, with the SERCA1a-SLN complex or the isolated SERCA1a embedded in an explicit membrane. The comparison of the results allowed us to provide an explanation for the action of SLN that is in good agreement with experimental observations. In our analyses, the presence of SLN locally perturbs the TM6 transmembrane helix and as a consequence modifies the position of D800, one of the key metal-chelating residues. Additionally, it reduces the flexibility of the gating residues, V304 and E309 in TM4, at the entrance of the Ca2+binding sites, which would decrease the affinity for Ca2+. Unexpectedly, SLN has also an effect on the ATP binding site more than 35 Å away, due to the straightening of TM5, a long helix considered as the spine of the protein. The straightening of TM5 modifies the structure of the P-N linker that sits above it, and which comprises the351DKTG354conserved motif, resulting in an increase of the distance between ATP and the phosphorylation site. As a consequence, the turn-over rate could be affected. All this gives SERCA1a the propensity to go toward a Ca2+-deprived E2-like state in the presence of SLN and toward a Ca2+high-affinity E1-like state in the absence of SLN, although the SERCA1a-SLN complex was crystallized in an E1-like state. In addition to a general mechanism of inhibition of SERCA1a regulatory peptides, this study also provides an insight in the conformational transition between the E2 and E1 states.Statement of SignificanceThe role of sarco/endoplasmic reticulum calcium ATPase in muscle relaxation is essential. Impairment of its function may result in either cardiac diseases, or myopathies, and also thermogenesis defects. Inhibition of the ATPase by regulatory peptide such as sarcolipin remains unclear. The structure of the ATPase in complex with this peptide was studied by all-atom normal modes analysis, an in silico technique which allows us to decipher the mechanism of inhibition of calcium transport by sarcolipin at a molecular level. Our results open the way to understanding the impact of in vivo misregulation of the ATPase activity by sarcolipin. Development of tools enhancing or preventing interaction between the ATPase and its regulatory peptide could be considered as new therapeutic approaches.
Control of assembly of extra-axonemal structures: the paraflagellar rod of trypanosomes
Authors: Alves Aline A. , Bezerra Maria J. R. , de Souza Wanderley , Vaughan Sue , Cunha-e-Silva Narcisa L. , Sunter Jack D. 
Published: December 2019

AbstractEukaryotic flagella are complex microtubule based organelles and in many organisms there are extra-axonemal structures present, including the outer dense fibres of mammalian sperm and the paraflagellar rod (PFR) of trypanosomes. Flagellum assembly is a complex process occurring across three main compartments, the cytoplasm, the transition fibre-transition zone, and the flagellum. It begins with translation of protein components, followed by their sorting and trafficking into the flagellum, transport to the assembly site and then incorporation. Flagella are formed from over 500 proteins; the principles governing axonemal component assembly are relatively clear. However, the coordination and sites of extra-axonemal structure assembly processes are less clear.We have discovered two cytoplasmic proteins inT. bruceithat are required for PFR formation, PFR assembly factors 1 and 2. Deletion of either PFR-AF1 or PFR-AF2 dramatically disrupted PFR formation and caused a reduction in the amount of major PFR proteins. The presence of cytoplasmic factors required for PFR formation aligns with the concept of processes occurring across multiple compartments to facilitate axoneme assembly and this is likely a common theme for extra-axonemal structure assembly.Summary statementEukaryotic flagella are complex organelles. In many organisms there are extra-axonemal structures including the trypanosome paraflagellar rod. We have discovered two cytoplasmic proteins that are required for paraflagellar rod formation.
To mock or not: a comprehensive comparison of mock IP and DNA input for ChIP-seq
Authors: Xu Jinrui , Kudron Michelle M. , Victorsen Alec , Gao Jiahao , Ammouri Haneen N. , Navarro Fabio C. P. , Gevirtzman Louis , Waterston Robert H. , White Kevin P. , Reinke Valerie , Gerstein Mark 
Published: December 2019

ABSTRACTChromatin immunoprecipitation (IP) followed by sequencing (ChIP-seq) is the gold standard to detect genome-wide DNA-protein binding. The binding sites of transcription factors facilitate many biological studies. Of emerging concern is the abundance of spurious sites in ChIP-seq, which are mainly caused by uneven genomic sonication and nonspecific interactions between chromatin and antibody. A “mock” IP is designed to correct for both factors, whereas a DNA input control corrects only for uneven sonication. However, a mock IP is more susceptible to technical noise than a DNA input, and empirically, these two controls perform similarly for ChIP-seq. Therefore, DNA input is currently being used almost exclusively. With a large dataset, we demonstrate that using a DNA input control results in a definable set of spurious sites, and their abundance is tightly associated with the intrinsic properties of the ChIP-seq sample. For example, compared to human cell lines, samples such as human tissues and whole worm and fly have more accessible genomes, and thus have more spurious sites. The large and varying abundance of spurious sites may impede comparative studies across multiple samples. In contrast, using a mock IP as control substantially removes these spurious sites, resulting in high-quality binding sites and facilitating their comparability across samples. Although outperformed by mock IP, DNA input is still informative and has unique advantages. Therefore, we have developed a method to use both controls in combination to further improve binding site detection.
Association of Sonic Hedgehog with the extracellular matrix requires its zinc-coordination fold
Authors: Jägers Carina , Roelink Henk 
Published: December 2019

AbstractSonic Hedgehog (Shh) has a catalytic cleft characteristic for zinc metallopeptidases and has significant sequence similarities with some bacterial peptidoglycan metallopeptidases defining a subgroup within the M15A family that, besides having the characteristic zinc coordination domain, can bind two calcium ions. Extracellular matrix (ECM) components in animals include heparan-sulfate proteoglycans, which are analogs of bacterial peptidoglycan and thus potentially involved in the extracellular distribution of Shh. We found that the zinc-coordination fold of Shh is required for its association with ECM as well as for non-cell autonomous signaling. Association with the ECM requires the presence of at least 0.1 μM zinc and is prevented by mutations affecting critical conserved catalytical residues as well as extracellular calcium. Our results demonstrate that the zinc-coordination fold is required for ECM-association and suggest that the putative intrinsic peptidase activity of Shh is required for non-cell autonomous signaling.
Adaptive shifts in gene regulation underlie a developmental delay in thermogenesis in high-altitude deer mice
Authors: Velotta Jonathan P. , Robertson Cayleih E. , Schweizer Rena M. , McClelland Grant B. , Cheviron Zachary A. 
Published: December 2019

AbstractAerobic performance is tied to fitness as it influences an animal’s ability to find food, escape predators, or survive extreme conditions. At high altitude, where low O2availability and persistent cold prevail, maximum metabolic heat production (thermogenesis) is an aerobic performance trait that is intimately linked to survival. Understanding how thermogenesis evolves to enhance survival at high altitude will yield insight into the links between physiology, performance, and fitness. Recent work in deer mice (Peromyscus maniculatus) has shown that adult mice native to high-altitude have higher thermogenic capacities under hypoxia compared to lowland conspecifics, but developing high-altitude pups delay the onset of thermogenesis. This suggests that natural selection on thermogenic capacity varies across life stages. To determine the mechanistic cause of this ontogenetic delay, we analyzed the transcriptomes of thermo-effector organs – brown adipose tissue and skeletal muscle – in developing deer mice native to low- and high-altitude. We demonstrate that the developmental delay in thermogenesis is associated with adaptive shifts in the expression of genes involved in nervous system development, fuel/O2supply, and oxidative metabolism gene pathways. Our results demonstrate that selection has modified the developmental trajectory of the thermoregulatory system at high altitude and has done so by acting on the regulatory systems that control the maturation of thermo-effector tissues. We suggest that the cold and hypoxic conditions of high altitude may force a resource allocation trade-off, whereby limited energy is allocated to developmental processes such as growth, versus active thermogenesis during early development.
Xi rhythms: decoding neural oscillations to create full-brain high-resolution spectra parametric mapping
Authors: Hu Shiang , Valdes-Sosa Pedro A. 
Published: December 2019

AbstractNeural oscillations excitability shape sensory, motor, and cognitive processes of the brain operation. To quantify the spectrum of brain magnetic and electrical recordings has become the main methodology to study neural oscillations. However, there is still lacking a valid approach, although the literatures on the spectrum decomposition is vast. In this work, we fit the neural spectrum by means of the Expectation Maximization algorithm, where the E step turns into a Winner filtering to separate multiple components and the M step is to fit each component by minimizing the smoothness penalized Whittle likelihood and shape-restricted regression, say, monotonicity, that is able to fit the diverse shape of each component. The decomposition allows characterizing the oscillation amplitude, resonance frequency, bandwidth, skewness, kurtosis, and slope of each component. This approach is termed as ‘Xi rhythms’, with Xi and rhythms standing for the background activity and multiple peaks. We apply it to: 1) multinational EEG database consisting of 535 subjects to create the quantitative spectrum norms (QSN); 2) large sample intracranial EEG (iEEG) dataset to infer the oscillations from recorded region to unrecorded areas within one subject and over inter-individuals and create the full brain high resolution statistical spectra parametric mapping. The statistical spectrum parameter mapping of iEEG promisingly provides an atlas and creates a norm for neural oscillations and quantitative electrophysiology study which can gain us more insightful understanding to brain dynamics, cognitive process and mental disorders.
Dose–response relationship between physical activity and mortality in adults with noncommunicable diseases: A systematic review and meta-analysis of cohort studies
Authors: Geidl Wolfgang , Schlesinger Sabrina , Mino Eriselda , Miranda Lorena , Pfeifer Klaus 
Published: December 2019

ABSTRACTObjectiveTo investigate the relationship between post-diagnosis physical activity and mortality in patients with selected noncommunicable diseases, including breast cancer, lung cancer, type 2 diabetes (T2D), ischemic heart disease (IHD), chronic obstructive pulmonary disease (COPD), stroke, osteoarthritis, low back pain and major depressive disorders.DesignSystematic review and dose–response meta-analysis.Data sourcesPubMed, Scopus and the Web of Science were searched systematically for English publications from the inception of the platforms until August 2018. Additionally, the search was updated in August 2019.Eligibility criteriaProspective observational studies examining the relationship between at least three physical activity categories and all-cause mortality or disease-specific mortality as the primary outcome.ResultsIn total, 28 studies were included: 12 for breast cancer, 6 for T2D, 8 for IHD and 2 for COPD. The linear meta-analysis revealed that each 10 metabolic equivalent tasks (MET) h increase of physical activity per week was associated with a 22% lower mortality rate in breast cancer patients (Hazard Ratio [HR], 0.78; 95% CI: 0.71, 0.86), 12% in IHD patients (HR, 0.88; 95% CI: 0.83, 0.93), 30% in COPD patients (HR, 0.70; 95% CI: 0.45, 1.09) and 4% in T2D patients (HR, 0.96; 95% CI: 0.93, 0.99). The non-linear meta-analysis showed a regressive association with no threshold for the beneficial effect of physical activity on mortality.ConclusionHigher levels of post-diagnosis physical activity are associated with lower mortality rates in breast cancer, T2D, IHD and COPD patients, with evidence of a no-threshold and non-linear dose–response pattern.SUMMARY BOXExisting findings- Higher levels of physical activity are associated with a clear reduction in all-cause mortality in the general population.- In the general population, the shape of the dose–response curve between levels of physical activity and reduced mortality rates is characterized by a regressive, non-linear effect.New findings- Higher levels of post-diagnosis physical activity are associated with a clear reduction in all-cause mortality in adults with breast cancer, T2D, IHD and COPD.- The shape of the indication-specific dose–response curves between post-diagnosis physical activity and mortality are characterized by a regressive, non-linear association with (1) no threshold for the beneficial effect, (2) pronounced reductions of mortality for lower levels of physical activity compared to those who are physically inactive and (3) no harmful effects at higher levels of physical activity.
Dopamine manipulations modulate paranoid social inferences in healthy people
Authors: Barnby J.M. , Bell V. , Deeley Q. , Mehta M.A. 
Published: December 2019

AbstractAltered dopamine transmission is thought to influence the formation of persecutory delusions. However, despite extensive evidence from clinical studies there is little experimental evidence on how modulating the dopamine system changes social attributions related to paranoia, and the salience of beliefs more generally. 27 healthy male participants received 150mg L-DOPA, 3mg haloperidol, or placebo in a double blind, randomised, placebo-controlled study, over three within-subject sessions. Participants completed a multi-round Dictator Game modified to measure social attributions, and a measure of belief salience spanning themes of politics, religion, science, morality, and the paranormal. We preregistered predictions that altering dopamine function would affect i) attributions of harmful intent and ii) salience of paranormal beliefs. As predicted, haloperidol reduced attributions of harmful intent across all conditions compared to placebo. L-DOPA reduced attributions of harmful intent in fair conditions compared to placebo. Unexpectedly, haloperidol increased attributions of self-interest for opponents’ decisions. There was no change in belief salience within any theme. These results could not be explained by scepticism or subjective mood. Our findings demonstrate the selective involvement of dopamine in social inferences related to paranoia in healthy individuals.
Exploring prokaryotic transcription, operon structures, rRNA maturation and modifications using Nanopore-based native RNA sequencing
Authors: Grünberger Felix , Knüppel Robert , Jüttner Michael , Fenk Martin , Borst Andreas , Reichelt Robert , Hausner Winfried , Soppa Jörg , Ferreira-Cerca Sébastien , Grohmann Dina 
Published: December 2019

AbstractThe prokaryotic transcriptome is shaped by transcriptional and posttranscriptional events that define the characteristics of an RNA, including transcript boundaries, the base modification status, and processing pathways to yield mature RNAs. Currently, a combination of several specialised short-read sequencing approaches and additional biochemical experiments are required to describe all transcriptomic features. In this study, we present native RNA sequencing of bacterial (E. coli) and archaeal (H. volcanii, P. furiosus) transcriptomes employing the Oxford Nanopore sequencing technology. Based on this approach, we could address multiple transcriptomic characteristics simultaneously with single-molecule resolution. Taking advantage of long RNA reads provided by the Nanopore platform, we could (re-)annotate large transcriptional units and boundaries. Our analysis of transcription termination sites suggests that diverse termination mechanisms are in place in archaea. Moreover, we shed additional light on the poorly understood rRNA processing pathway in Archaea. One of the key features of native RNA sequencing is that RNA modifications are retained. We could confirm this ability by analysing the well-known KsgA-dependent methylation sites and mapping of N4-acetylcytosines modifications in rRNAs. Notably, we were able to follow the relative timely order of the installation of these modifications in the rRNA processing pathway.
ADAMDEC1 maintains a novel growth factor signaling loop in cancer stem cells
Authors: Hale James S. , Jimenez-Pascual Ana , Kordowski Anja , Pugh Jamie , Rao Shilpa , Silver Daniel J. , Alban Tyler , Watson Defne Bayik , Chen Rui , McIntyre Thomas M. , Colombo Giorgio , Taraboletti Giulia , Holmberg Karl O. , Forsberg-Nilsson Karin , Lathia Justin D. , Siebzehnrubl Florian A. 
Published: December 2019

AbstractGlioblastomas (GBM) are lethal brain tumors where poor outcome is attributed to cellular heterogeneity, therapeutic resistance, and a highly infiltrative nature. These characteristics are preferentially linked to GBM cancer stem cells (GSCs), but how GSCs maintain their stemness is incompletely understood and the subject of intense investigation. Here, we identify a novel signaling loop that induces and maintains GSCs. This loop consists of an atypical metalloproteinase, a disintegrin and metalloproteinase domain-like protein decysin 1 (ADAMDEC1), secreted by GSCs. ADAMDEC1 rapidly solubilizes fibroblast growth factor-2 (FGF2) to stimulate FGF receptor 1 (FGFR1) expressed on GSCs. This signaling axis induces upregulation of Zinc finger E-box-binding homeobox 1 (ZEB1) that regulates ADAMDEC1 expression, creating a positive feedback loop. Genetic or pharmacological targeting of components of this axis attenuates self-renewal and tumor growth. These findings reveal a new signaling axis for GSC maintenance and highlight ADAMDEC1 and FGFR1 as potential therapeutic targets in GBM.Statement of SignificanceCancer stem cells (CSC) drive tumor growth in many cancers including glioblastoma. We identified a novel sheddase, a disintegrin and metalloproteinase domain-like protein decysin 1, that initiates a fibroblast growth factor autocrine loop to promote stemness in CSCs. This loop can be targeted to reduce glioblastoma growth.