bluuebunny/crossref_metadata_2025_split huggingface dataset:
NeuroEPO improves cognition in Parkinson’s disease. Preliminary report
Authors: Bringas Vega Maria L. , Shengnan Liu , Leon Yanetsy Rodriguez , Rodriguez Ania Mesa , Fernandez Enrique Casabona , Llano Marite Garcia , Gonzalez Daniel Amaro , Obaya Teresita Rodriguez , Ruiz Leslie Perez , Teste Iliana Sosa , Razzaq Fuleah A. , Jahanshahi Marjan , Ibañez Ivonne Pedroso , Valdes-Sosa Pedro 
Published: February 2022

AbstractBackgroundCognitive impairment is a feature of Parkinson’s Disease (PD) from the early stages, but currently, no treatment for cognitive deficits in PD is available. Erythropoietin (EPO) has been studied for its potential neuroprotective properties in neurologic disorders with a beneficial action on cognition.ObjectiveTo evaluate if NeuroEPO, a new formulation of EPO with low content of sialic acid, improves the cognitive function in PD patients.MethodsA double-blind, randomized, placebo-controlled physician lead trial was conducted. The sample was composed of 26 PD patients (HY stages I-II), where 15 received intranasal NeuroEPO for 5 weeks, and another age and gender-matched 11 patients were randomly assigned to the Placebo. All the samples received 9 months of intensive NeuroEPO treatment during a post-trial. The cognitive functions were assessed using a comprehensive neuropsychological battery before, one week, and 6 months after the first intervention and one week after a 9months post-trial. The effects of NeuroEPO were evaluated using a multivariate linear mixed-effects model using a latent variable for cognition instead of the raw neuropsychological scores.ResultsA significant and direct effect of the Dose of NeuroEPO (p=0.00003) was found on cognitive performance with a strong positive influence of educational level (p=0.0032) and negative impact of age (p=0.0063).ConclusionsThese preliminary results showed a positive effect of NeuroEPO on cognition in PD patients with better benefit for younger and higher educated patients.
Oral health and its association with self-rated health in Colombian community-dwelling older adults
Authors: Venegas-Sanabria Luis Carlos , Moreno-Echeverry María Manuela , Borda Miguel German , Chavarro-Carvajal Diego Andrés , Cano-Gutierrez Carlos Alberto 
Published: February 2022

AbstractObjectiveDetermine the association between different parameters of oral health and the self-rated health (SRH) in Colombian community-dwelling older adults.MethodsThis is a secondary analysis of the SABE-Colombia study performed in 2015. The dependent variable was defined as the SRH status assessed by the question “Compared with other people your age: Do you consider your health status to be: better, equal or worse?” The oral health parameters were edentulism, the GOHAI score and the use of dental prosthesis. Three multivariable logistic regression was performed compared better vs. worse, better vs. equal and equal vs. worse health status, adjusted by socio-demographic variables, comorbidities, and geriatric syndromes.ResultsAfter the exclusion of missing data, 18180 persons were included in the final analysis. 10.6, 37.6 and 51.6% persons reported worse, equal and better SRH, respectively. The worse SRH group had a higher proportion of > 80 years old persons, dependence, cognitive impairment, and depressive symptoms. The presence of edentulism and a low score of GOHAI were more frequent in the worse SHR group. After the multivariable logistic regression, all parameters of oral health status were associated with a worse SRH.ConclusionIn our study, the oral health parameters were associated with self-rated health status. This result supports the inclusion of oral health in comprehensive geriatric assessment.
Empirical Frequency Bound Derivation Reveals Prominent Mid-Frontal Alpha Associated with Neurosensory Dysfunction in Fragile X Syndrome
Authors: Pedapati Ernest V , Sweeney John A. , Schmitt Lauren M. , Ethridge Lauren E. , Miyakoshi Makoto , Liu Rui , Smith Elizabeth , Shaffer Rebecca C. , Wu Steve W. , Gilbert Donald L. , Horn Paul S. , Buckley Aaron , Erickson Craig A. 
Published: February 2022

AbstractThe FMR1 gene is inactive in Fragile X syndrome (FXS), resulting in low levels of FMRP and consequent neurochemical, synaptic and local circuit neurophysiological alterations in the fmr1 KO mouse. In FXS patients, electrophysiological studies of have demonstrated a marked reduction in global alpha activity and regional increases in gamma oscillations that have been associated with intellectual disability and sensory hypersensitivity. Since alpha activity is associated with thalamocortical function that has widely distributed modulatory effects on neocortical excitability, insight into alpha physiology may provide insight into systems-level disease mechanisms. Herein, we took a data driven approach to clarify the temporal and spatial properties of alpha and theta activity in participants with FXS. High-resolution resting-state EEG data was collected from participants affected by FXS (n=65) and matched controls (n=70). We used a multivariate technique to empirically classify neural oscillatory bands based on their coherent spatiotemporal patterns. Participants with FXS demonstrated: 1) a redistribution of lower-frequency boundaries indicating a “slower” dominant alpha rhythm, 2) an anteriorization of alpha frequency activity, and 3) a correlation of increased individualized alpha power measurements with auditory neurosensory dysfunction. These findings suggest an important role for alterations in thalamocortical physiology for the well-established neocortical hyper-excitability in FXS, and thus a role for neural systems level disruption to cortical hyperexcitability that has been studied primarily at the local circuit level in mouse model research.
Comparative transcriptomics reveal highly conserved regional programs between porcine and human colonic enteric nervous system
Authors: Li Tao , Morselli Marco , Su Trent , Mulugeta Million , Larauche Muriel , Pellegrini Matteo , Taché Yvette , Yuan Pu-Qing 
Published: February 2022

AbstractThe porcine gut is increasingly regarded as a useful translational model. The enteric nerve system (ENS) in the colon coordinates diverse functions. However, knowledge of the molecular profiling of porcine ENS and its similarity to that of human is limited. We identified the distinct transcriptional programs associated with functional characteristics between inner submucosal and myenteric ganglia (ISG, MG) in porcine proximal and distal colon (p-pC, p-dC) using bulk RNA sequencing (RNA-seq) and single-cell RNA-seq. Comparative transcriptomics of MG in corresponding colonic regions of porcine and human revealed highly conserved programs existing in p-pC and p-dC, which explained >90% of their transcriptomic responses to vagal nerve stimulation (VNS), suggesting that p-pC and p-dC could serve as predictors in translational studies. The conserved programs specific for inflammatory modulation were displayed in porcine with VNS. This study provides a valuable transcriptomic resource for understanding of human colonic functions and neuromodulation using porcine model.
A new paradigm of multiheme cytochrome evolution by grafting and pruning protein modules
Authors: Soares Ricardo , Costa Nazua L. , Paquete Catarina M. , Andreini Claudia , Louro Ricardo O. 
Published: February 2022

AbstractMultiheme cytochromes play key roles in diverse biogeochemical cycles, but understanding the origin and evolution of these proteins is a challenge due to their ancient origin and complex structure. Up until now, the evolution of multiheme cytochromes composed by multiple redox modules in a single polypeptide chain was proposed to occur by gene fusion events. In this context, the pentaheme nitrite reductase NrfA and the tetraheme cytochromec554were previously proposed to be at the origin of the extant octa- and nonaheme cytochromescinvolved in metabolic pathways that contribute to the nitrogen, sulfur and iron biogeochemical cycles by a gene fusion event. Here, we combine structural and character-based phylogenetic analysis with an unbiased root placement method to refine the evolutionary relationships between these multiheme cytochromes. The evidence show that NrfA and cytochromec554belong to different clades, which suggests that these two multiheme cytochromes are products of truncation of ancestral octaheme cytochromes related to extant ONR and MccA, respectively. From our phylogenetic analysis, the last common ancestor is predicted to be an octaheme cytochrome with nitrite reduction ability. Evolution from this octaheme framework led to the great diversity of extant multiheme cytochromes analised here by pruning and grafting of protein modules and hemes. By shedding light into the evolution of multiheme cytochromes that intervene in different biogeochemical cycles, this work contributes to our understanding about the interplay between biology and geochemistry across large time scales in the history of Earth.
Resource requirements for ecotoxicity testing: A comparison of traditional and new approach methods
Authors: Mittal Krittika , Crump Doug , Head Jessica A. , Hecker Markus , Hickey Gordon , Maguire Steve , Hogan Natacha , Xia Jianguo , Basu Niladri 
Published: February 2022

ABSTRACTToxicity testing is under transformation as it aims to harness the potential of New Approach Methods (NAMs) as alternative test methods that may be less resource intensive (i.e., fewer animals, cheaper costs, quicker assays) than traditional approaches while also providing more data and information. While many stakeholders are of the opinion that this unfolding transformation holds significant promise as a more efficient and ethical way forward, few studies have compared the resources required for NAMs versus those needed for traditional animal-based toxicity tests, particularly in the field of ecotoxicology. The objective was to compare resources needed for traditional animal-based ecotoxicity tests versus alternative tests using emergent NAMs. From a bibliometric review, we estimate that traditional tests for a single chemical cost $118,000 USD, require 135 animals, and take 8 weeks. In comparison, alternative tests cost $2,600, require 20 animals (or none), and take up to 4 weeks to test 16 (to potentially hundreds of) chemicals. Based on our analysis we conclude that NAMs in ecotoxicology can be more advantageous than traditional methods in terms of resources required (i.e., monetary costs, number of animals needed, and testing times). We note, however, that the evidence underpinning these conclusions is relatively sparse. Moving forward, groups developing and applying NAMs should provide more detailed accounts of the resources required. In addition, there is also a need for carefully designed case studies that demonstrate the domain of applicability of NAMs (and make comparisons to traditional tests) to ultimately build confidence among the user community.
Scrub encroachment promotes biodiversity in wetland restoration under eutrophic conditions
Authors: Brunbjerg Ane Kirstine , Fløjgaard Camilla , Frøslev Tobias Guldberg , Andersen Dagmar Kappel , Bruun Hans Henrik , Dalby Lars , Goldberg Irina , Lehmann Louise Juhl , Moeslund Jesper Erenskjold , Ejrnæs Rasmus 
Published: February 2022

AbstractWetlands are important habitats, often threatened by drainage, eutrophication and suppression of ungulate grazing. In many countries, considerable resources are spent combatting scrub encroachment. Here, we hypothesize that encroachment may benefit biodiversity – especially under eutrophic conditions where asymmetric competition among plants compromises conservation targets.We studied the effects of scrub cover, nutrient levels and soil moisture on richness of vascular plants, bryophytes, soil fungi and microbes in open and overgrown wetlands. We also tested the effect of encroachment, eutrophication and soil moisture on indicators of conservation value (red-listed species, indicator species and uniqueness).Plant and bryophyte species richness peaked at low soil fertility, whereas soil fertility promoted soil microbes. Soil fungi responded negatively to increasing soil moisture. Lidar-derived variables reflecting degree of scrub cover had predominantly positive effects on species richness measures.Conservation value indicators had a negative relationship to soil fertility and a positive to encroachment. For plant indicator species, the negative effect of high nutrient levels was offset by encroachment, supporting our hypothesis of competitive release under shade. The positive effect of soil moisture on indicator species was strong in open habitats only.Nutrient poor mires and meadows host many rare species and require conservation management by grazing and natural hydrology. On former arable lands, where restoration of infertile conditions is unfeasible, we recommend rewilding with opportunities for encroachment towards semi-open willow scrub and swamp forest, with the prospect of high species richness in bryophytes, fungi and soil microbes and competitive release in the herb layer.
Comparing algorithms for assessing upper limb use with inertial measurement units
Authors: Subash Tanya , David Ann , ReetaJanetSurekha StephenSukumaran , Gayathri Sankaralingam , Samuelkamaleshkumar Selvaraj , Magimairaj Henry Prakash , Malesevic Nebojsa , Antfolk Christian , Varadhan SKM , Melendez-Calderon Alejandro , Balasubramanian Sivakumar 
Published: February 2022

AbstractThe various existing measures to quantify upper limb use from wrist-worn inertial measurement units (IMU) can be grouped into three categories: (a) Thresholded activity counting, (b) Gross movement score and (c) machine learning. While machine learning algorithms are a promising approach to detect upper limb use, there is currently no knowledge of the information used by these methods, and the data-related factors that influence their performance. A comparison of existing methods was carried out using data from a previous study which was collected from 10 unimpaired and 5 hemiparetic subjects, with annotation to identify periods of functional and non-functional upper limb use. Intra-subject random forest machine learning measures were found to classify upper limb use more accurately than other measures. The random forest measure uses information about the orientation and the amount of movement of the forearm to detect upper limb use. The types of movements and the proportion of functional data included in training/testing set influences the performance of machine learning measures. This study presents the first step towards understanding and optimizing machine learning methods for upper limb use assessment using wearable sensors.
A novel missense mutation in the proprotein convertase gene furinb causes hepatic cystogenesis during liver development in zebrafish
Authors: Ellis Jillian L. , Evason Kimberley J. , Zhang Changwen , Fourman Makenzie N. , Liu Jiandong , Ninov Nikolay , Delous Marion , Vanhollebeke Benoit , Fiddes Ian , Otis Jessica P. , Houvras Yariv , Farber Steven A. , Xu Xiaolei , Lin Xueying , Stainier Didier Y.R. , Yin Chunyue 
Published: February 2022

AbstractHepatic cysts are fluid-filled lesions in the liver that are estimated to occur in 5% of the population. They may cause hepatomegaly and abdominal pain. Progression to secondary fibrosis, cirrhosis, or cholangiocarcinoma can lead to morbidity and mortality. Previous studies of patients and rodent models have associated hepatic cyst formation with increased proliferation and fluid secretion in cholangiocytes, which are partially due to impaired primary cilia. Congenital hepatic cysts are thought to originate from faulty bile duct development, but the underlying mechanisms are not fully understood. In a forward genetic screen, we identified a zebrafish mutant that develops hepatic cysts during larval stages. Cyst formation in these mutants is not due to changes in biliary cell proliferation, bile secretion, or impairment of primary cilia. Instead, time-lapse live imaging data showed that the mutant biliary cells failed to form interconnecting bile ducts because of defects in motility and protrusive activity. Accordingly, immunostaining revealed an excessive and disorganized actin and microtubule cytoskeleton in the mutant biliary cells. By whole-genome sequencing, we determined that the cystic phenotype in the mutant was caused by a missense mutation in the furinb gene which encodes a proprotein convertase. The mutation alters Furinb localization and causes endoplasmic reticulum (ER) stress. The cystic phenotype could be suppressed by treatment with the ER stress inhibitor 4-phenylbutyric acid and exacerbated by treatment with the ER stress inducer tunicamycin. The mutant livers also exhibited increased mTOR signaling and treatment with the mTOR inhibitor rapamycin partially blocked cyst formation by reducing ER stress. Our study has established a novel vertebrate model for studying hepatic cystogenesis and illustrated the role of ER stress in the disease pathogenesis.
Identification of HIV-Reservoir Cells with Reduced Susceptibility to Antibody-Dependent Immune Response
Authors: Astorga-Gamaza Antonio , Grau-Expósito Judith , Burgos Joaquín , Navarro Jordi , Curran Adrià , Planas Bibiana , Suanzes Paula , Falcó Vicenç , Genescà Meritxell , Buzon Maria J. 
Published: February 2022

AbstractHIV establishes a persistent infection in heterogeneous cell reservoirs, which can be maintained by different mechanisms including cellular proliferation, and represent the main obstacle to curing the infection. The expression of the Fcγ receptor CD32 has been identified as a marker of the active cell reservoirs in people on antiretroviral therapy, but if its expression has any role in conferring advantage for viral persistence is unknown. Here, we report that HIV-infected cells expressing CD32 have reduced susceptibility to natural killer (NK) antibody-dependent cell cytotoxicity (ADCC) by a mechanism compatible with the suboptimal binding of HIV-specific antibodies. Infected CD32 cells have increased proliferative capacity in the presence of immune complexes, and are more resistant to strategies directed to potentiate NK function. Remarkably, reactivation of the latent reservoir from antiretroviral-treated people living with HIV increases the pool of infected CD32 cells, which are largely resistant to the ADCC immune mechanism. Thus, we report the existence of reservoir cells that evade part of the NK immune response through the expression of CD32.Graphical Abstract
Active exploration of a novel environment drives the activation of the hippocampus-amygdala complex of domestic chicks
Authors: Morandi-Raikova Anastasia , Mayer Uwe 
Published: February 2022

AbstractIn birds, like in mammals, the hippocampus critically mediates spatial navigation through the formation of a spatial map. This study investigates the impact of active exploration of a novel environment on the hippocampus of young domestic chicks, during formation of a new spatial map. Chicks that were free to actively explore the novel environment exhibited a significantly higher neural activation (measured by c-Fos expression), compared to those that passively observed the novel environment from a restricted area. The difference was limited to the anterior and the dorsolateral parts of the intermediate hippocampus. Furthermore, the nucleus taeniae of the amygdala showed a higher c-Fos expression in the active exploration group than the passive observation group. In both brain regions, brain activation correlated with the number of locations that chicks visited during the test. This suggest that the increase of c-Fos expression in the hippocampus is related to increased firing rates of spatially coding neurons. Furthermore, our study indicates a functional linkage of the hippocampus and nucleus taeniae of the amygdala in processing spatial information. Overall, with the present study, we confirm that, in birds like in mammals, exploration of novel environments activates hippocampus, which is likely related to the formation of new spatial representations.Summary statementActive exploration of a novel environment induces stronger activation of hippocampus and taeniae of domestic chicks than pure visual, passive exploration from a restricted area.
Bimodal breeding phenology in the Parsley Frog Pelodytes punctatus as a bet-hedging strategy in an unpredictable environment despite strong priority effects
Authors: Jourdan-Pineau Hélène , Crochet Pierre-André , David Patrice 
Published: February 2022

AbstractWhen environmental conditions are unpredictable, expressing alternative phenotypes spreads the risk of failure, a mixed strategy called bet-hedging. In the southern part of its range, the Parsley Frog Pelodytes punctatus breeds both in autumn and in spring. Our aim was to study the breeding phenology and reproductive success associated with the use of those two seasonal niches to understand how this breeding strategy can be maintained. Field surveys revealed that breeding phenology was typically bimodal with a higher breeding effort in autumn. More importantly, in spring, the survival rate of offspring was severely reduced by the presence of autumn tadpoles, indicating a clear priority effect. However, the autumn cohort often failed to survive over winter, in which case spring cohorts were often successful. Based on those results, we constructed a model in which females can allocate a variable portion of eggs to each season and added a priority effect. We conclude that the existence of the two breeding seasons may indeed constitute a bet-hedging strategy.
Human HspB1, HspB3, HspB5 and HspB8: Shaping these Disease Factors during Vertebrate Evolution
Authors: Benndorf Rainer , Velazquez Ryan , Zehr Jordan D. , Pond Sergei Kosakovsky , Martin Jody L. , Lucaci Alexander G. 
Published: February 2022

AbstractSmall heat shock proteins (sHSPs) emerged early in evolution and occur in all domains of life and nearly in all species, including humans. Mutations in four sHSPs (HspB1, HspB3, HspB5, HspB8) are associated with neuromuscular disorders. The aim of this study is to investigate the evolutionary forces shaping these sHSPs during vertebrate evolution. We performed comparative evolutionary analyses on a set of orthologous sHSP sequences, based on the ratio of non-synonymous: synonymous substitution rates for each codon. We found that these sHSPs had been historically exposed to different degrees of purifying selection, decreasing in this order: HspB8 > HspB1, HspB5 > HspB3. Within each sHSP, regions with different degrees of purifying selection can be discerned, resulting in characteristic selective pressure profiles. The conserved α-crystallin domains were exposed to the most stringent purifying selection compared to the flanking regions, supporting a ‘dimorphic pattern’ of evolution. Thus, during vertebrate evolution the different sequence partitions were exposed to different and measurable degrees of selective pressures. Among the disease-associated mutations, most are missense mutations primarily in HspB1 and to a minor extent in the other sHSPs. Our data provide an explanation for this disparate incidence. Contrary to the expectation, most missense mutations cause dominant disease phenotypes. Theoretical considerations support a connection between the historic exposure of these sHSP genes to a high degree of purifying selection and the unusual prevalence of genetic dominance of the associated disease phenotypes. Our study puts the genetics of inheritable sHSP-borne diseases into the context of vertebrate evolution.