bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis-rcs-data: Open-source toolbox for the ingestion, time-alignment, and visualization of sense and stimulation data from the Medtronic Summit RC+S system
Authors: Sellers Kristin K , Gilron Ro’ee , Anso Juan , Louie Kenneth H , Shirvalkar Prasad R , Chang Edward F , Little Simon J , Starr Philip A. 
Published: June 2021

AbstractClosed-loop neurostimulation is a promising therapy being tested and clinically implemented in a growing number of neurological and psychiatric indications. This therapy is enabled by chronically implanted, bidirectional devices including the Medtronic Summit RC+S system. In order to successfully optimize therapy for patients implanted with these devices, analyses must be conducted offline on the recorded neural data, in order to inform optimal sense and stimulation parameters. The file format, volume, and complexity of raw data from these device necessitate conversion, parsing, and time reconstruction ahead of time-frequency analyses and modeling common to standard neuroscientific analyses. Here, we provide an open-source toolbox written in Matlab which takes raw files from the Summit RC+S and transforms these data into a standardized format amenable to conventional analyses. Furthermore, we provide a plotting tool which can aid in the visualization of multiple data streams and sense, stimulation, and therapy settings. Finally, we describe an analysis module which replicates RC+S on-board power computations, functionality which can accelerate biomarker discovery. This toolbox aims to accelerate the research and clinical advances made possible by longitudinal neural recordings and adaptive neurostimulation in people with neurological and psychiatric illnesses.
Small Molecule Stabilization of PINK-1/PINK1 Improves Neurodegenerative Disease
Authors: Tjahjono Elissa , Pei Jingqi , Revtovich Alexey V. , Liu Terri-Jeanne E. , Swadi Alisha , Kirienko Natalia V. 
Published: June 2021

AbstractMacroautophagic recycling of dysfunctional mitochondria, known as mitophagy, is essential for mitochondrial homeostasis and cell viability. Accumulation of defective mitochondria and impaired mitophagy have been widely implicated in many neurodegenerative diseases, and loss-of-function mutations of two regulators of mitophagy, PINK1 and Parkin, are amongst the most common causes of recessive Parkinson’s disease. Activation of mitophagy via pharmacological treatments may be a feasible approach for combating neurodegeneration. In this effort, we screened ∼45,000 small molecules for the ability to activate mitophagy. A high-throughput, whole-organism, phenotypic screen was conducted by monitoring stabilization of PINK-1/PINK1, a key event in mitophagy activation, in a Caenorhabditis elegans strain carrying a Ppink-1::PINK-1::GFP reporter. We obtained eight hits that induced mitophagy, as evidenced by increased mitochondrial fragmentation and autophagosome formation. Several of the compounds also reduced ATP production, oxygen consumption, mitochondrial mass, and/or mitochondrial membrane potential. Importantly, we found that treatment with two compounds, which we named PS83 and PS106 (more commonly known as sertraline) reduced neurodegenerative disease phenotypes (including delayed paralysis in a C. elegans Alzheimer’s model) in a PINK-1/PINK1-dependent manner. This report presents a promising step toward the identification of compounds that will stimulate mitochondrial turnover.
The interaction of enteric bacterial effectors with the host engulfment pathway control innate immune responses
Authors: Sayed Ibrahim M , Ibeawuchi Stella-Rita , Lie Dominique , Anandachar Mahitha Shree , Pranadinata Rama , Raffatellu Manuela , Das Soumita 
Published: June 2021

AbstractBackgroundHost engulfment protein ELMO1 generates intestinal inflammation following internalization of enteric bacteria. In Shigella, bacterial effector IpgB1 interacts with ELMO1 and promotes bacterial invasion. IpgB1 belongs to the WxxxE effector family, a motif found in several effector of enteric pathogens. Here, we have studied the role of WxxxE effectors, with emphasis on Salmonella SifA and whether it interacts with ELMO1 to regulate inflammation.MethodologyIn-silico-analysis of WxxxE effectors was performed using BLAST search and Clustal W program. The interaction of ELMO1 with SifA was assessed by GST pulldown assay and co-immunoprecipitation. ELMO1 knock-out mice, and ELMO1-depleted murine macrophage J774 cell lines were challenged with WT and SifA mutant Salmonella. Bacterial effectors containing the WxxxE motif were transfected in WT and ELMO1-depleted J774 cells to assess the inflammatory cytokines.ResultsELMO1 generates differential pro-inflammatory cytokines between pathogenic and non-pathogenic bacteria. WxxxE motif is present in pathogens and in the TIR domain of host proteins. The C-terminal part of ELMO1 interacts with SifA where WxxxE motif is important for interaction. ELMO1-SifA interaction affects the bacterial colonization, dissemination, and inflammatory cytokines in vivo. Moreover, ELMO1-SifA interaction increases TNF-α and IL-6 production from the macrophage cell line and is associated with enhanced Rac1 activity. ELMO1 also interacts with WxxxE effectors IpgB1, IpgB2, and Map, and induces inflammation after challenge with microbe or microbial ligand.ConclusionELMO1 generates a differential response through interaction with the WxxxE motif which is absent in commensals. ELMO1-WxxxE interaction plays a role in bacterial pathogenesis and induction of inflammatory response.HighlightsELMO1 generates a differential immune response between enteric pathogens and commensals.Enteric bacterial effectors containing WxxxE signature motif interact with ELMO1.The WxxxE effector of Salmonella SifA interacts with the C-terminal part of ELMO1.ELMO1-SifA interaction increases the inflammatory response in vivo and in vitro.
A dopamine-dependent decrease in dorsomedial striatum direct pathway neuronal activity is required for learned motor coordination
Authors: Cataldi Stefano , Lacefield Clay , Shashaank N , Kumar Gautam , Sulzer David 
Published: June 2021

AbstractIt has been suggested that the dorsomedial striatum (DMS) facilitates the early stages of motor learning for goal-directed actions, whereas at later stages, control is transferred to the dorsolateral striatum (DLS), which enables the motor actions to become a skill or habit. It is unknown whether these striatal regions are simultaneously active while expertise is acquired during skill learning. To address this question, we developed the “treadmill training task” to track changes in mouse locomotor coordination during practice at running that simultaneously provides a means to measure local neuronal activity using photometry. We analyzed body position and paw movement to evaluate changes in motor coordination over practice sessions on the treadmill using DeepLabCut and custom-built code. By correlating improvements in motor coordination during training with simultaneous neuronal calcium activity in the striatum, we found that DMS direct pathway neurons exhibited decreased activity as the mouse gains proficiency at running. In contrast, direct pathway activity in the DLS was similar throughout training and did not correlate with learned skill proficiency. Pharmacological blockade of D1 dopamine receptors in these subregions during task performance confirmed that dopamine neurotransmission in the DMS direct pathway activity is necessary for efficient motor coordination learning, while dopamine signalling in the DLS is important for both coordination learning and maintenance of the acquired skill. These results provide new tools to measure changes in fine motor skills during simultaneous recordings of brain activity, revealing fundamental features of the neuronal substrates of motor learning.
An estimation of the absolute number of axons indicates that human cortical areas are sparsely connected
Authors: Rosen Burke Q. , Halgren Eric 
Published: June 2021

AbstractThe tracts between cortical areas are conceived as playing a central role in cortical information processing, but their actual numbers have never been determined in humans. Here we estimate the absolute number of axons linking cortical areas from a whole-cortex diffusion-MRI (dMRI) connectome, calibrated using the histologically-measured callosal fiber density. Median connectivity is estimated as ~6200 axons between cortical areas within-hemisphere and ~1300 axons inter-hemispherically, with axons connecting functionally-related areas surprisingly sparse. For example, we estimate that <5% of the axons in the trunk of the arcuate and superior longitudinal fasciculi connect Wernicke’s and Broca’s areas. These results suggest that detailed information is transmitted between cortical areas either via linkage of the dense local connections or via rare, extraordinarily privileged long-range connections.
A personalized anti-cancer vaccine for melanoma based on an approved vaccine against measles, mumps, and rubella
Authors: Ylösmäki Erkko , Fusciello Manlio , Uoti Arttu , Feola Sara , Martins Beatriz , Aalto Karri , Hamdan Firas , Ciaro Jacopo , Viitala Tapani , Cerullo Vincenzo 
Published: June 2021

AbstractCommon vaccines for infectious diseases have been repurposed as cancer immunotherapies. Intratumoural administration of these repurposed vaccines can induce immune cell infiltration into the treated tumour. Here, we have used an approved trivalent live attenuated measles, mumps, and rubella (MMR) vaccine in our previously developed PeptiENV anti-cancer vaccine platform. Intratumoural administration of this novel MMR-containing PeptiENV anti-cancer vaccine significantly increased both intratumoural as well as systemic tumour-specific T cell responses. In addition, PeptiENV therapy, in combination with immune checkpoint inhibitor therapy, significantly improved tumour growth control and survival as well as increased the number of mice responsive to immune checkpoint inhibitor therapy.
Differential ampicillin/ceftriaxone susceptibility among diverse Enterococcus faecalis from infective endocarditis
Authors: Westbrook Kevin J. , Chilambi Gayatri Shankar , Nordstrom Hayley R. , Iovleva Alina , Shah Niyati H. , Jones Chelsea E. , Kline Ellen G. , Doi Yohei , Shields Ryan K. , Van Tyne Daria 
Published: June 2021

AbstractEnterococcus faecalis is a leading cause of infective endocarditis (IE), especially among older patients with comorbidities. Here we investigated the genomic diversity and antimicrobial susceptibility of 33 contemporary E. faecalis isolates from definite or probable IE cases at the University of Pittsburgh Medical Center (UPMC) between 2018 and 2020. Isolates belonging to two multi-locus sequence types (STs), ST6 and ST179, were isolated from nearly 40% of IE patients. Both of these dominant STs carried known beta-lactam resistance-associated mutations affecting the low-affinity penicillin-binding protein 4 (PBP4). We assessed the ability of ampicillin and ceftriaxone (AC) both alone and in combination to inhibit genetically diverse E. faecalis IE isolates in checkerboard synergy assays and an in vitro one-compartment pharmacokinetic-pharmacodynamic (PK-PD) model of AC treatment. ST6 isolates as well as an isolate with a mutation in the PP2C-type protein phosphatase IreP had higher ceftriaxone MICs compared to other isolates, and showed diminished in vitro synergy of AC. Additionally, both ST6 and ST179 isolates exhibited regrowth after 48 hours of humanized exposures to AC. Overall, we found evidence for diminished in vitro AC activity among E. faecalis IE isolates with PBP4 and IreP mutations. This study highlights the need to evaluate alternate antibiotic combinations in clinical practice against diverse contemporary E. faecalis IE isolates.
Aberrant hippocampal transmission and behavior in mice with a stargazin mutation linked to intellectual disability
Authors: Caldeira GL , Inácio AS , Beltrão N , Barreto CAV , Rodrigues MV , Rondão T , Macedo R , Gouveia RP , Edfawy M , Guedes J , Cruz B , Louros SR , Moreira IS , Peça J , Carvalho AL 
Published: June 2021

ABSTRACTMutations linked to neurodevelopmental disorders, such as intellectual disability (ID), are frequently found in genes that encode for proteins of the excitatory synapse. Transmembrane AMPA receptor regulatory proteins (TARPs) are AMPA receptor auxiliary proteins that regulate crucial aspects of receptor function. Here, we investigate an ID-associated mutant form of the TARP family member stargazin. Molecular dynamics analyses showed that the stargazin V143L variant weakens the overall interface of the AMPAR:stargazin complex and hinders the stability of the complex. Knock-in mice for the V143L stargazin mutation manifest cognitive and social deficits and hippocampal synaptic transmission defects. In the hippocampus of stargazin V143L mice, CA1 neurons show impaired spine maturation in basal dendrites, and synaptic ultrastructural alterations. These data demonstrate a causal role for mutated stargazin in the pathogenesis of ID and highlight its role in the development and function of hippocampal synapses.
In depth analysis of Cyprus-specific mutations of SARS-CoV-2 strains using computational approaches
Authors: Oulas Anastasis , Richter Jan , Zanti Maria , Tomazou Marios , Michailidou Kyriaki , Christodoulou Kyproula , Christodoulou Christina , Spyrou George M. 
Published: June 2021

AbstractThis study aims to characterize SARS-CoV-2 mutations which are primarily prevalent in the Cypriot population. Moreover, using computational approaches, we assess whether these mutations are associated with changes in viral virulence. We utilize genetic data from 144 sequences of SARS-CoV-2 strains from the Cypriot population obtained between March 2020 and January 2021, as well as all data available from GISAID. We combine this with countries’ regional information, such as deaths and cases per million, as well as COVID-19-related public health austerity measure response times. Initial indications of selective advantage of Cyprus-specific mutations are obtained by mutation tracking analysis. This entails calculating specific mutation frequencies within the Cypriot population and comparing these with their prevalence world-wide throughout the course of the pandemic. We further make use of linear regression models to extrapolate additional information that may be missed through standard statistical analysis. We report a single mutation found in the ORF1ab gene (S6059F) that appears to be significantly enriched within the Cypriot population. We further analyse this mutation using regression models to investigate possible associations with increased deaths and cases per million. Moreover, protein structure prediction tools show that the mutation infers a conformational change to the protein that significantly alters its structure when compared to the reference protein. Investigating Cyprus-specific mutations for SARS-CoV-2 can not only lead to important findings from which to battle the pandemic on a national level, but also provide insights into viral virulence worldwide.
Cognitive functions and underlying parameters of human brain physiology are associated with chronotype
Authors: Salehinejad Mohammad Ali , Wischnewski Miles , Ghanavati Elham , Mosayebi-Samani Mohsen , Kuo Min-Fang , Nitsche Michael A. 
Published: June 2021

AbstractCircadian rhythms have natural relative variations among humans known as chronotype. Chronotype or being a morning or evening person, has a specific physiological, behavioural, and also genetic manifestation. Whether and how chronotype modulates human brain physiology and cognition is, however, not well understood. Here we examine how cortical excitability, neuroplasticity, and cognition are associated with chronotype in early and late chronotype individuals. We monitor motor cortical excitability, brain stimulation-induced neuroplasticity, and examine motor learning and cognitive functions at circadian-preferred and non-preferred times of day in 32 individuals. Motor learning and cognitive performance (working memory, and attention) along with their electrophysiological components are significantly enhanced at the circadian-preferred, compared to the non-preferred time. This outperformance is associated with enhanced cortical excitability (prominent cortical facilitation, diminished cortical inhibition), and long-term potentiation/depression-like plasticity. Our data show convergent findings of chronotype can modulate human brain functions from basic physiological mechanisms to behaviour and higher cognitive functions.
Bacterioplankton Diversity and Distribution in Relation to Phytoplankton Community Structure in the Ross Sea surface waters
Authors: Cordone Angelina , D’Errico Giuseppe , Magliulo Maria , Bolinesi Francesco , Selci Matteo , Basili Marco , de Marco Rocco , Saggiomo Maria , Rivaro Paola , Giovannelli Donato , Mangoni Olga 
Published: June 2021

AbstractPrimary productivity in the Ross Sea region is characterized by intense phytoplankton blooms whose temporal and spatial distribution are driven by changes in environmental conditions as well as interactions with the bacterioplankton community. Exchange of exudates, metabolism by-products and cofactors between the phytoplankton and the bacterioplankton communities drive a series of complex interactions affecting the micronutrient availability and co-limitation, as well as nutrient uptakes in Antarctic waters. Yet, the number of studies reporting the simultaneous diversity of the phytoplankton and bacterioplankton in Antarctic waters are limited. Here we report data on the bacterial diversity in relation to phytoplankton community in the surface waters of the Ross Sea during the austral summer 2017. Our results show partially overlapping bacterioplankton communities between the stations located in the Terra Nova Bay coastal waters and the Ross Sea open waters, suggesting that the two communities are subjected to different drivers. We show that the rate of diversity change between the two locations is influenced by both abiotic (salinity and the nitrogen to phosphorus ratio) and biotic (phytoplankton community structure) factors. Our data provides new insight into the coexistence of the bacterioplankton and phytoplankton in Antarctic waters.
The expression of virulence increases outer-membrane permeability and sensitivity to envelope stress in Salmonella Typhimurium
Authors: Sobota Malgorzata , Ramirez Pilar Natalia Rodilla , Cambré Alexander , Haas Tiphaine , Cornillet Delphine , Rocker Andrea , Aertsen Abram , Diard Médéric 
Published: June 2021

AbstractEnvironmental cues modulate the expression of virulence in bacterial pathogens. However, while cues that upregulate virulence are often intuitive and mechanistically well understood, this is less so for cues that downregulate virulence. In this study, we noticed that upregulation of the HilD virulence regulon in Salmonella Typhimurium (S.Tm) sensitized cells to membrane stress mediated by cholate, Tris/EDTA or heat. Further monitoring of membrane status and stress resistance of S.Tm cells in relation to virulence expression, revealed that co-expressed virulence factors embedded in the envelope (including the Type Three Secretion System 1 and the flagella) increased permeability, and stress sensitivity of the membrane. Importantly, pretreating the bacteria by sublethal stress inhibited virulence expression and restored stress resistance. As such, these results demonstrate a trade-off between virulence and stress resistance, which explains the downregulation of virulence expression in response to harsh environments in S.Tm.
Gut bacterial aggregates as living gels
Authors: Schlomann Brandon H. , Parthasarathy Raghuveer 
Published: June 2021

AbstractThe spatial organization of gut microbiota influences both microbial abundances and host-microbe interactions, but the underlying rules relating bacterial dynamics to large-scale structure remain unclear. To this end we studied experimentally and theoretically the formation of three-dimensional bacterial clusters, a key parameter controlling susceptibility to intestinal transport and access to the epithelium. Inspired by models of structure formation in soft materials, we sought to understand how the distribution of gut bacterial cluster sizes emerges from bacterial-scale kinetics. Analyzing imaging-derived data on cluster sizes for eight different bacterial strains in the larval zebrafish gut, we find a common family of size distributions that decay approximately as power laws with exponents close to −2, becoming shallower for large clusters in a strain-dependent manner. We show that this type of distribution arises naturally from a Yule-Simons-type process in which bacteria grow within clusters and can escape from them, coupled to an aggregation process that tends to condense the system toward a single massive cluster, reminiscent of gel formation. Together, these results point to the existence of general, biophysical principles governing the spatial organization of the gut microbiome that may be useful for inferring fast-timescale dynamics that are experimentally inaccessible.
Computation of dimensional variations on the structural analysis of multi-cell aircraft box beams with python scripting
Authors: Yavuz Hande 
Published: June 2021

Purpose
Python codes are developed for the versatile structural analysis on a 3 spar multi-cell box beam by means of idealization approach.

Design/methodology/approach
Shear flow distribution, stiffener loads, location of shear center and location of geometric center are computed via numpy module. Data visualization is performed by using Matplotlib module.

Findings
Python scripts are developed for the structural analysis of multi-cell box beams in lieu of long hand solutions. In-house developed python codes are made available to be used with finite element analysis for verification purposes.

Originality/value
The use of python scripts for the structural analysis provides prompt visualization, especially once dimensional variations are concerned in the frame of aircraft structural design. The developed python scripts would serve as a practical tool that is widely applicable to various multi-cell wing boxes for stiffness purposes. This would be further extended to the structural integrity problems to cover the effect of gaps and/or cut-outs in shear flow distribution in box-beams.