bluuebunny/crossref_metadata_2025_split huggingface dataset:
The turning and barrier course reveals gait parameters for detecting freezing of gait and measuring the efficacy of deep brain stimulation
Authors: O’Day Johanna , Syrkin-Nikolau Judy , Anidi Chioma , Kidzinski Lukasz , Delp Scott , Bronte-Stewart Helen 
Published: June 2019

AbstractFreezing of gait (FOG) is a devastating motor symptom of Parkinson’s disease that leads to falls, reduced mobility, and decreased quality of life. Reliably eliciting FOG has been difficult in the clinical setting, which has limited discovery of pathophysiology and/or documentation of the efficacy of treatments, such as different frequencies of subthalamic deep brain stimulation (STN DBS). In this study we validated an instrumented gait task, the turning and barrier course (TBC), with the international standard FOG questionnaire question 3 (FOG-Q3, r = 0.74,p< 0.001). The TBC is easily assembled and mimics real-life environments that elicit FOG. People with Parkinson’s disease who experience FOG (freezers) spent more time freezing during the TBC compared to during forward walking (p= 0.007). Freezers also exhibited greater arrhythmicity during non-freezing gait when performing the TBC compared to forward walking (p= 0.006); this difference in gait arrhythmicity between tasks was not detected in non-freezers or controls. Freezers’ non-freezing gait was more arrhythmic than that of non-freezers or controls during all walking tasks (p< 0.05). A logistic regression model determined that a combination of gait arrhythmicity, stride time, shank angular range, and asymmetry had the greatest probability of classifying a step as FOG (area under receiver operating characteristic curve = 0.754). Freezers’ percent time freezing and non-freezing gait arrhythmicity decreased, and their shank angular velocity increased in the TBC during both 60 Hz and 140 Hz STN DBS (p< 0.05) to non-freezer values. The TBC is a standardized tool for eliciting FOG and demonstrating the efficacy of 60 Hz and 140 Hz STN DBS for gait impairment and FOG. The TBC revealed gait parameters that differentiated freezers from non-freezers and best predicted FOG; these may serve as relevant control variables for closed loop neurostimulation for FOG in Parkinson’s disease.
Histopathological Study Of Different Organs Of Charles Foster Rats Under The Exposure Of Pueraria tuberosa
Authors: Pandey Harsh , Srivastava Shivani , Kumar Mohan , Tripathi Yamini Bhusan 
Published: June 2019

ABSTRACTThe present study was undertaken to investigate the safe doses of Pueraria tuberosa water extract (PTWE) on different organs. The OECD guidelines 407 of repeated toxicity was followed with respect to the selection of dose and days for different organs. The selected doses of PTWE were 250, 500, 1000 and 2000 mg/kg b wt for 7, 14, 21 and 28 days. Haematoxylin and eosin staining was used to study the morphological alterations in heart, intestine, testis, adrenal gland and spleen. In the present study, no adverse alterations in cardiac fibers of the heart, size and shapes in crypts and villi of intestine, seminiferous tubules and spermatozoa count in testis, three zones of adrenal gland, and spleen were seen in all treated groups of PTWE. There were no adverse morphological alterations found in described organs. The PTWE are safe at 1000 mg/kg b wt. up to 28 days and 2000 mg/ kg b. wt up to 21 days, respectively.
RamaNet: Computational de novo helical protein backbone design using a long short-term memory generative neural network
Authors: Sabban Sari , Markovsky Mikhail 
Published: June 2019

AbstractThe ability to perform de novo protein design will allow researchers to expand the variety of available proteins. By designing synthetic structures computationally, they can utilise more structures than those available in the Protein Data Bank, design structures that are not found in nature, or direct the design of proteins to acquire a specific desired structure. While some researchers attempt to design proteins from first physical and thermodynamic principals, we decided to attempt to test whether it is possible to perform de novo helical protein design of just the backbone statistically using machine learning by building a model that uses a long short-term memory (LSTM) architecture. The LSTM model used only the ϕ and ψ angles of each residue from an augmented dataset of only helical protein structures. Though the network’s generated backbone structures were not perfect, they were idealised and evaluated post generation where the non-ideal structures were filtered out and the adequate structures kept. The results were successful in developing a logical, rigid, compact, helical protein backbone topology. This paper is a proof of concept that shows it is possible to generate a novel helical backbone topology using an LSTM neural network architecture using only the ϕ and ψ angles as features. The next step is to attempt to use these backbone topologies and sequence design them to form complete protein structures.Author summaryThis research project stemmed from the desire to expand the pool of protein structures that can be used as scaffolds in computational vaccine development, since the number of structures available from the Protein Data Bank was not sufficient to allow for great diversity and increase the probability of grafting a target motif onto a protein scaffold. Since a protein structure’s backbone can be defined by the ϕ and ψ angles of each amino acid in the polypeptide and can effectively translate a protein’s 3D structure into a table of numbers, and since protein structures are not random, this numerical representation of protein structures can be used to train a neural network to mathematically generalise what a protein structure is, and therefore generate new a protein backbone. Instead of using all proteins in the Protein Data Bank a curated dataset was used encompassing protein structures with specific characteristics that will, theoretically, allow them to be evaluated computationally. This paper details how a trained neural network was able to successfully generate helical protein backbones.
Real-time detection of neural oscillation bursts allows behaviourally relevant neurofeedback
Authors: Karvat Golan , Schneider Artur , Alyahyaey Mansour , Steenbergen Florian , Diester Ilka 
Published: June 2019

AbstractNeural oscillations are increasingly interpreted as transient bursts, yet a method to measure these short-lived events in real-time is missing. Here we present a real-time data analysis system, capable to detect short and narrowband bursts, and demonstrate its usefulness for volitional increase of beta-band burst-rate in rats. This neurofeedback-training induced changes in overall oscillatory power, and bursts could be decoded from the movement of the rats, thus enabling future investigation of the role of oscillatory bursts.
Long-term impact of fecal transplantation in healthy volunteers
Authors: Goloshchapov Oleg V , Olekhnovich Evgenii I , Sidorenko Sergey V , Moiseev Ivan S , Kucher Maxim A , Fedorov Dmitry E. , Pavlenko Alexander V , Manolov Alexander I , Gostev Vladimir V , Veselovsky Vladimir A , Klimina Ksenia M , Kostryukova Elena S , Bakin Evgeny A , Shvetcov Alexander N , Gumbatova Elvira D , Klementeva Ruslana V , Shcherbakov Alexander A , Gorchakova Margarita V , Egozcue Juan José , Pawlowsky-Glahn Vera , Suvorova Maria A , Chukhlovin Alexey B , Govorun Vadim M , Ilina Elena N , Afanasyev Boris V 
Published: June 2019

AbstractBackgroundFecal microbiota transplantation (FMT) is now approved for the treatment of refractory recurrent clostridial colitis, but a number of studies are ongoing in inflammatory bowel diseases, i.e., Crohn’s disease, nonspecific ulcerative colitis, and in other autoimmune conditions. In most cases, the effects of FMT are evaluated on patients with initially altered microbiota. The aim of the present study was to evaluate effects of FMT on the gut microbiota composition in healthy volunteers and to track long-term changes.ResultsWe have performed a combined analysis of three healthy volunteers before and after FMT with frozen capsules, followed by evaluation of their general condition, adverse clinical effects, changes of basic laboratory parameters, and several immune markers. Intestinal microbiota samples were evaluated by 16S rRNA gene sequencing (16S seq) and shotgun sequencing (or whole-genome sequencing – WGS). The data analysis demonstrated the profound shift towards the donor microbiota taxonomic composition in all volunteers. Following FMT, all the volunteers exhibited gut colonization with donor gut bacteria, and persistence of this effect for almost ~1 year of observation. Transient changes of immune parameters were consistent with suppression of T-cell cytotoxicity. FMT was well tolerated with mild gastrointestinal adverse events and systemic inflammatory response in one volunteer.ConclusionsThe FMT procedure leads to significant long-term changes of the gut microbiota in healthy volunteers with the shift towards donor microbiota composition, being relatively safe to the recipients without long-term adverse events.
Disrupted information flow in resting-state in adolescents with sports related concussion
Authors: Hristopulos Dionissios T. , Babul Arif , Babul Shazia’Ayn , Brucar Leyla R. , Virji-Babul Naznin 
Published: June 2019

ABSTRACTChildren and youth are at a greater risk of concussions than adults, and once injured, take longer to recover. A key feature of concussion is a diffuse increase in functional connectivity; yet it remains unclear how changes in functional connectivity relate to the patterns of information flow within resting state networks following concussion and how these relate to brain function. We applied a data-driven measure of directed effective brain connectivity to compare the patterns of information flow in healthy adolescents and adolescents with subacute concussion during the resting state condition. Data from 32 healthy adolescents (mean age =16 years) and 24 concussed adolescents (mean age = 13.8 years) with subacute concussion (< 3 months post injury) took part in the study. Five minutes of resting state data EEG were collected while participants sat quietly with their eyes closed. We applied the Kleeman-Liang information flow rate to measure the transfer of information between the EEG time series of each individual at different source locations, and therefore between different brain regions. Based on the ensemble means of the magnitude of normalized information flow rate, our analysis shows that information flow in the healthy adolescents is characterized by a predominantly (L) lateralized pattern with bidirectional information flow between frontal regions, between frontal and central/temporal regions and between parietal and occipital regions. In contrast, adolescents with concussion show distinct differences in information flow marked by a more symmetrical pattern with connections evenly distributed across the entire brain, increased information flow in the posterior regions of the brain and the emergence of bidirectional, inter-hemispheric connections between the left and right temporal regions of the brain. We also find that the statistical distribution of the normalized information flow rates in each group (control and concussed) is significantly different. Our results are the first to describe altered patterns of information flow in adolescents with concussion as well as differences in the statistical distribution of information flow rate. We hypothesize that the observed changes in information flow in the concussed group are a consequence of the brain injury and indicate functional reorganization of resting state networks.
Corruption of the Pearson correlation coefficient by measurement error: estimation, bias, and correction under different error models
Authors: Saccenti Edoardo , Hendriks Margriet H. W. B. , Smilde Age K. 
Published: June 2019

ABSTRACTCorrelation coefficients are abundantly used in the life sciences. Their use can be limited to simple exploratory analysis or to construct association networks for visualization but they are also basic ingredients for sophisticated multivariate data analysis methods. It is therefore important to have reliable estimates for correlation coefficients. In modern life sciences, comprehensive measurement techniques are used to measure metabolites, proteins, gene-expressions and other types of data. All these measurement techniques have errors. Whereas in the old days, with simple measurements, the errors were also simple, that is not the case anymore. Errors are heterogeneous, non-constant and not independent. This hampers the quality of the estimated correlation coefficients seriously. We will discuss the different types of errors as present in modern comprehensive life science data and show with theory, simulations and real-life data how these affect the correlation coefficients. We will briefly discuss ways to improve the estimation of such coefficients.
Structural basis of p62/SQSTM1 helical filaments, their presence in p62 bodies and role in cargo recognition in the cell
Authors: Jakobi Arjen J. , Huber Stefan T. , Mortensen Simon A. , Schultz Sebastian W. , Palara Anthimi , Kuhm Tanja , Shrestha Birendra Kumar , Lamark Trond , Hagen Wim J.H. , Wilmanns Matthias , Johansen Terje , Brech Andreas , Sachse Carsten 
Published: June 2019

Abstractp62/SQSTM1 is an autophagy receptor and signaling adaptor with an N-terminal PB1 domain that forms the scaffold of phase-separated p62 bodies in the cell. The molecular determinants that govern PB1 domain filament formation in vitro remain to be determined and the role of p62 filaments inside the cell is currently unclear. We determined four high-resolution cryo-EM structures of different human and Arabidopsis PB1 domain assemblies and observed a filamentous ultrastructure of phase-separated p62/SQSTM1 bodies using correlative cellular EM. We show that oligomerization or polymerization, driven by a double arginine finger in the PB1 domain, is a general requirement for lysosomal targeting of p62. Furthermore, the filamentous assembly state of p62 is required for autophagosomal processing of the p62-specific cargo KEAP1. Our results show that using such mechanisms, p62 filaments can be critical for cargo recognition and are an integral part of phase separated p62 bodies.
Salience-weighted agreement feature hierarchy modulates language comprehension
Authors: Muralikrishnan R. , Idrissi Ali 
Published: June 2019

AbstractThe brain establishes relations between elements of an unfolding sentence in order to incrementally build a representation of who is doing what based on various linguistic cues. Many languages systematically mark the verb and/or its arguments to imply the manner in which they are related. A common mechanism to this end is subject-verb agreement, whereby the marking on the verb covaries with one or more of the features such as person, number and gender of the subject argument in a sentence. The cross-linguistic variability of these features would suggest that they may modulate language comprehension differentially based on their relative weightings in a given language. To test this, we investigated the processing of subject-verb agreement in simple intransitive Arabic sentences in a visual event-related brain potential (ERP) study. Specifically, we examined the differences, if any, that ensue in the processing of person, number and gender features during online comprehension, employing sentences in which the verb either showed full agreement with the subject noun (singular or plural) or did not agree in one of the features. ERP responses were measured at the post-nominal verb. Results showed a biphasic negativity−late-positivity effect when the verb did not agree with its subject noun in one of the features, in line with similar findings from other languages. Crucially however, the biphasic effect for agreement violations was systematically graded based on the feature that was violated, which is a novel finding in view of results from other languages. Furthermore, this graded effect was qualitatively different for singular and plural subjects based on the differing salience of the features for each subject-type. These results suggest that agreement features, varying in their salience due to their language-specific weightings, differentially modulate language comprehension. We postulate a Salience-weighted Feature Hierarchy based on our findings and argue that this parsimoniously accounts for the diversity of existing cross-linguistic neurophysiological results on verb agreement processing.
Geometrical constraints greatly hinder formin mDia1 activity
Authors: Suzuki Emiko L. , Guichard Bérengère , Romet-Lemonne Guillaume , Jégou Antoine 
Published: June 2019

AbstractFormins are one of the central players in the assembly of most actin networks in cells. The sensitivity of these processive molecular machines to mechanical tension is now well established. However, how the activity of formins is affected by geometrical constraints related to network architecture, such as filament crosslinking and formin spatial confinement, remains largely unknown. Combining microfluidics and micropatterning, we reconstituted in vitro mDia1 formin-elongated filament bundles induced by fascin, with different geometrical constraints on the formins, and measured the impact of these constraints on formin elongation rates and processivity. When filaments are not bundled, formins can be anchored to static or fluid surfaces, by either end of the proteins, without affecting their activity. We show that filament bundling by fascin reduces both unanchored formin elongation rate and processivity. Strikingly, when filaments elongated by surface-anchored formins are cross-linked together, formin elongation rate immediately decreases and processivity is reduced, up to 24-fold, depending on the cumulative impact of formin rotational and translational freedoms. Our results reveal an unexpected crosstalk between the constraints at the filament and the formin levels. We anticipate that in cells, the molecular details of formin anchoring to the plasma membrane, strongly modulate formin activity at actin filament barbed ends.
A young age of subspecific divergence in the desert locustSchistocerca gregaria, inferred by ABC Random Forest
Authors: Chapuis Marie-Pierre , Raynal Louis , Plantamp Christophe , Meynard Christine N. , Blondin Laurence , Marin Jean-Michel , Estoup Arnaud 
Published: June 2019

AbstractDating population divergence within species from molecular data and relating such dating to climatic and biogeographic changes is not trivial. Yet it can help formulating evolutionary hypotheses regarding local adaptation and future responses to changing environments. Key issues include statistical selection of a demographic and historical scenario among a set of possible scenarios, and estimation of the parameter(s) of interest under the chosen scenario. Such inferences greatly benefit from new statistical approaches including approximate Bayesian computation - Random Forest (ABC-RF), the latter providing reliable inference at a low computational cost, with the possibility to take into account prior knowledge on both biogeographical history and genetic markers. Here, we used ABC-RF, including independent information on evolutionary rate and pattern at microsatellite markers, to decipher the evolutionary history of the African arid-adapted pest locust,Schistocerca gregaria. We found that the evolutionary processes that have shaped the present geographical distribution of the species in two disjoint northern and southern regions of Africa were recent, dating back 2.6 Ky (90% CI: 0.9 – 6.6 Ky). ABC-RF inferences also supported a southern colonization of Africa from a low number of founders of northern origin. The inferred divergence history is better explained by the peculiar biology ofS. gregaria, which involves a density-dependent swarming phase with some exceptional spectacular migrations, rather than a continuous colonization resulting from the continental expansion of open vegetation habitats during more ancient Quaternary glacial climatic episodes.
TrkB-expressing paraventricular hypothalamic neurons suppress appetite through multiple neurocircuits
Authors: An Juan Ji , Kinney Clint E. , Liao Guey-Ying , Kremer Eric J. , Xu Baoji 
Published: June 2019

ABSTRACTThe TrkB receptor is critical for the control of energy balance, as mutations in its gene (NTRK2) lead to hyperphagia and severe obesity in humans and mice. The main neural substrate mediating the appetite-suppressing activity of TrkB, however, remains unknown. Here, we demonstrate that selective Ntrk2 deletion within the paraventricular hypothalamus (PVH) leads to severe hyperphagic obesity. Furthermore, chemogenetic activation or inhibition of TrkB-expressing PVH (PVHTrkB) neurons suppresses or increases food intake, respectively. PVHTrkB neurons project to multiple brain regions, including the ventromedial hypothalamus (VMH) and the lateral parabrachial nucleus (LPBN). We found that PVHTrkB neurons projecting to LPBN are distinct from those projecting to VMH, yet Ntrk2 deletion in PVH neurons projecting to either VMH or LPBN results in hyperphagia and obesity. Therefore, TrkB signaling is a key regulator of a previously uncharacterized and heterogenous neuronal population within the PVH that impinges upon multiple circuits to govern appetite.
Preferential phosphatidylinositol 5-phosphate binding contributes to a destabilization of the VHS domain structure of Tom1
Authors: Xiong Wen , Tang Tuo-Xian , Littleton Evan , Karcini Arba , Lazar Iulia M. , Capelluto Daniel G. S. 
Published: June 2019

AbstractTom1 transports endosomal ubiquitinated proteins that are targeted for degradation in the lysosomal pathway. Infection of eukaryotic cells byShigella flexneriboosts oxygen consumption and promotes the synthesis of phosphatidylinositol-5-phosphate [PtdIns5P], which triggers Tom1 translocation to signaling endosomes. Removing Tom1 from its cargo trafficking function hinders protein degradation in the host and, simultaneously, enables bacterial survival. Tom1 preferentially binds PtdIns5Pviaits VHS domain, but the effects of a reducing environment as well as PtdIns5P on the domain structure and function are unknown. Thermal denaturation studies demonstrate that, under reducing conditions, the monomeric Tom1 VHS domain switches from a three-state to a two-state transition behavior. PtdIns5P reduced thermostability, interhelical contacts, and conformational compaction of Tom1 VHS, suggesting that the phosphoinositide destabilizes the protein domain. Destabilization of Tom1 VHS structure was also observed with other phospholipids. Isothermal calorimetry data analysis indicates that, unlike ubiquitin, Tom1 VHS endothermically binds to PtdIns5P through two noncooperative binding sites, with its acyl chains playing a relevant role in the interaction. Altogether, these findings provide mechanistic insights about the recognition of PtdIns5P by the VHS domain that may explain how Tom1, when in a different VHS domain conformational state, interacts with downstream effectors underS. flexneriinfection.