bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-selected step length asymmetry is not explained by energy cost minimization in individuals with chronic stroke
Authors: Nguyen Thu M. , Jackson Rachel W. , Aucie Yashar , de Kam Digna , Collins Steven H. , Torres-Oviedo Gelsy 
Published: December 2019

AbstractBackgroundAsymmetric gait post-stroke is associated with decreased mobility, yet individuals with chronic stroke often self-select an asymmetric gait despite being capable of walking more symmetrically. The purpose of this study was to test whether self-selected asymmetry could be explained by energy cost minimization. We hypothesized that short-term deviations from self-selected asymmetry would result in increased metabolic energy consumption, despite being associated with long-term rehabilitation benefits. Other studies have found no difference in metabolic rate across different levels of enforced asymmetry among individuals with chronic stroke, but used methods that left some uncertainty to be resolved.MethodsIn this study, ten individuals with chronic stroke walked on a treadmill at participant-specific speeds while voluntarily modulating step length asymmetry. We included only participants with significant self-selected asymmetry who were able to significantly alter asymmetry using visual biofeedback. Conditions included targeting zero asymmetry, self-selected asymmetry, and double the self-selected asymmetry. Participants were trained with the biofeedback system in one session, and data were collected in three subsequent sessions with repeated measures. Self-selected asymmetry was consistent across sessions. A similar protocol was conducted among unimpaired participants.ResultsParticipants with chronic stroke substantially altered step length asymmetry using biofeedback, but this did not affect metabolic rate (ANOVA, p = 0.8). In unimpaired participants, self-selected step length asymmetry was close to zero and corresponded to the lowest energy cost (ANOVA, p = 6e-4). While the symmetry of unimpaired gait may be the result of energy cost minimization, self-selected step length asymmetry in individuals with chronic stroke cannot be explained by a similar least-effort drive.ConclusionsInterventions that encourage changes in step length asymmetry by manipulating metabolic energy consumption may be effective because these therapies would not have to overcome a metabolic penalty for altering asymmetry.
Targeting dual signaling pathways in concert with immune checkpoints for the treatment of pancreatic cancer
Authors: Knudsen Erik S , Kumarasamy Vishnu , Chung Sejin , Vail Paris , Tzetzo Stephanie , Ruiz Amanda , Seshadri Mukund , Abrams Scott I , Wang Jianmin , Witkiewicz Agnieszka K 
Published: December 2019

ABSTRACTPancreatic cancer harbors a poor prognosis due to the lack of effective systemic therapies. Here we interrogated means to target key effector pathways down-stream from KRAS. We found that combination treatment with MEK and CDK4/6 inhibitors was effective across a broad range of PDX models in delaying tumor progression. These effects were associated with stable cell cycle arrest, as well as the induction of multiple genes associated with interferon response and antigen presentation in an RB-dependent fashion. Using single cell sequencing and complementary approaches, we found that the combination of CDK4/6 and MEK inhibition had a significant impact on increasing T-cell infiltration and altering myeloid populations, while potently cooperating with immune checkpoint inhibitors. Together, these data indicate that there are canonical and non-canonical features of CDK4/6 and MEK inhibition that impact on the tumor and host that can contribute to durable control for tumors in combination with immune checkpoint inhibitor therapy.
Co-transcriptional folding of a bio-orthogonal fluorescent scaffolded RNA origami
Authors: Torelli Emanuela , Kozyra Jerzy W. , Shirt-Ediss Ben , Piantanida Luca , Voïtchovsky Kislon , Krasnogor Natalio 
Published: December 2019

ABSTRACTThe scaffolded origami technique has provided an attractive tool for engineering nucleic acid nanostructures. This paper demonstrates scaffolded RNA origami folding in vitro in which all components are transcribed simultaneously in a single-pot reaction. Double-stranded DNA sequences are transcribed by T7 RNA polymerase into scaffold and staple strands able to correctly fold in high yield into the nanoribbon. Synthesis is successfully confirmed by atomic force microscopy and the unpurified transcription reaction mixture is analyzed by an in gel-imaging assay where the transcribed RNA nanoribbons are able to capture the specific dye through the reconstituted split Broccoli aptamer showing a clear green fluorescent band. Finally, we simulate the RNA origami in silico using the nucleotide-level coarse-grained model oxRNA to investigate the thermodynamic stability of the assembled nanostructure in isothermal conditions over a period of time.Our work suggests that the scaffolded origami technique is a valid, and potentially more powerful, assembly alternative to the single-stranded origami technique for future in vivo applications.Abstract Figure
Heme uptake inLactobacillus sakeievidenced by a new ECF-like transport system
Authors: Verplaetse Emilie , André-Leroux Gwenaëlle , Duhutrel Philippe , Coeuret Gwendoline , Chaillou Stéphane , Nielsen-Leroux Christina , Champomier-Vergès Marie-Christine 
Published: December 2019

AbstractLactobacillus sakeiis a non-pathogenic lactic acid bacterium and a natural inhabitant of meat ecosystems. Although red meat is a heme-rich environment,L. sakeidoes not need iron or heme for growth, while possessing a heme-dependent catalase. Iron incorporation intoL. sakeifrom myoglobin and hemoglobin was formerly shown by microscopy and theL. sakeigenome reveals a complete equipment for iron and heme transport. Here, we report the characterization of a five-gene cluster (lsa1836-1840) encoding a putative metal iron ABC transporter. Interestingly, this cluster, together with a heme dependent catalase gene, is also conserved in other species from the meat ecosystem. Our bioinformatic analyses revealed that the locus might refer to a complete machinery of an Energy Coupling Factor (ECF) transport system. We quantifiedin vitrothe intracellular heme in wild-type (WT) and in our Δlsa1836-1840deletion mutant using an intracellular heme sensor and ICP-Mass spectrometry for quantifying incorporated57Fe heme. We showed that in the WTL. sakei, heme accumulation occurs fast and massively in the presence of hemin, while the deletion mutant was impaired in heme uptake; this ability was restored byin transcomplementation. Our results establish the main role of theL. sakeiLsa1836-1840 ECF-like system in heme uptake. This research outcome shed new light on other possible functions of ECF-like systems.ImportanceLactobacillus sakeiis a non-pathogenic bacterial species exhibiting high fitness in heme rich environments such as meat products, although it does not need iron nor heme for growth. Heme capture and utilization capacities are often associated with pathogenic species and are considered as virulence-associated factors in the infected hosts. For these reasons, iron acquisition systems have been deeply studied in such species, while for non-pathogenic bacteria the information is scarce. Genomic data revealed that several putative iron transporters are present in the genome of the lactic acid bacteriumL. sakei.In this study, we demonstrate that one of them, is an ECF-like ABC transporter with a functional role in heme transport. Such evidence has not yet been brought for an ECF, therefore our study reveals a new class of heme transport system.
Growth and mortality of the oak processionary moth,Thaumetopoea processioneaL., on two oak species: direct and trait-mediated effects of host and neighbour species identity
Authors: Damestoy Thomas , Moreira Xoaquín , Jactel Hervé , Valdes-Correcher Elena , Plomion Christophe , Castagneyrol Bastien 
Published: December 2019

AbstractThe presence of heterospecific neighbours can affect damage caused by pest insects on focal plants. However, how plant neighbours influence herbivore performance is poorly understood. We tested the independent and interactive effects of tree species identity and tree neighbour type (conspecific vs. heterospecific) on the performance of a major oak pest, the oak processionary moth larvae (OPM,Thaumetopoea processionea) fed onQuercus roburandQ. petraea. We performed a factorial greenhouse experiment in which we grew two oak saplings per pot, either from the same species or from both species. We quantified growth and mortality of OPM larvae, leaf phenolic compounds, C:N ratio and bud phenology. OPM larvae performed significantly better onQ. petraeathan onQ. robur, regardless of plant neighbour type. Phenolic compounds and C:N, but not phenology, differed between oak species and neighbour species identity. Only bud phenology had a significant effect on OPM performance, which was better when young larvae had access to recently unfolded leaves, regardless of oak species and neighbour identity. Although oak neighbour identity altered the expression of leaf traits, this effect had no measurable consequences on OPM performance. However, further studies should consider the effect of oak species neighbour on OPM preferences for eitherQ. roburorQ. petraea, in pure and mixed stands, before translating current results into recommendations for forest management.Author ContributionTD and BC conceived the study and acquired the data. TD performed experiment and analysed the data. EV, TD and XM performed the chemical analyses. TD and BC drafted the first version of the manuscript and all authors wrote the final version of the manuscript.TD, BC conceived and designed research. TD performed experiment and analysed data. EV, TD, XM performed the chemical analyses. TD, BC wrote the manuscript. All authors read and approved the manuscript.AM and DB conceived and designed research. AM and BB conducted experiments. GR contributed new reagents or analytical tools. AM, BB and GR analysed data. AM wrote the manuscript. All authors read and approved the manuscript.
Central deficiency of norepinephrine synthesis and norepinephrinergic neurotransmission contributes to seizure-induced respiratory arrest
Authors: Shen Yue , Ma HaiXiang , Lu Han , Zhao HaiTing , Sun Jianliang , Cheng Yuan , Shen Yi , Zhou Yu Dong , Zhang HongHai 
Published: December 2019

SummaryObjectiveSudden unexpected death in epilepsy (SUDEP) is the leading cause of mortality in patients in patients with intractable epilepsy. However, the pathogenesis of SUDEP seems to be poorly understood. Our previous findings showed that the incidence of seizure-induced respiratory arrest (S-IRA) was markedly reduced by atomoxetine in a murine SUDEP model. Because the central NE α-1 receptor (NEα-1R) plays a vital role in regulating respiratory function, we hypothesized that the suppression of S-IRA by atomoxetine was mediated by NE/NEα-1R interactions that can be reversed by NEα-1R antagonism.MethodsWe examined whether atomoxetine-mediated suppression of S-IRA evoked by either acoustic stimulation or pentylenetetrazole (PTZ) in DBA/1 mice can be reversed by intraperitoneal (IP) and intracerebroventricular (ICV) administration of prazosin, a selective antagonist of NEα-1R. The content and activity of tyrosine hydroxylase (TH), a rate-limiting enzyme for NE synthesis, in the lower brainstem was measured by ELISA. Electroencephalograms (EEG) were obtained by using the PTZ-evoked SUDEP model.ResultsAtomoxetine-mediated suppression of S-IRA evoked by either acoustic stimulation or PTZ was significantly reversed by low doses of IP and ICV prazosin. Neither repetitive acoustic stimulation nor S-IRA reduced TH levels in lower brainstem. However, the enzyme activity of TH levels in lower brainstem was significantly increased by mechanical ventilation with DBA/1 mice ,which makes dead DBA/1 mice suffered from S-IRA and SUDEP recover. EEG data showed that although the protective effect of atomoxetine was reversed by prazosin, neither drug affected EEG activity.SignificanceThese data suggest that deficient synthesis of NE and norepinephrinergic neurotransmission contributes to S-IRA and that the NEα-1R is a potential therapeutic target for the prevention of SUDEP.
LARGE MICROBIOTA SURVEY REVEALS HOW THE MICROBIAL ECOLOGY OF COOKED HAM IS SHAPED BY DIFFERENT PROCESSING STEPS
Authors: Zagdoun Marine , Coeuret Gwendoline , N’Dione Méry , Champomier-Vergès Marie-Christine , Chaillou Stéphane 
Published: December 2019

ABSTRACTThe production of cooked ham involves numerous steps shaping the microbial communities of the final product, with consequences on spoilage metabolites production. To identify the main factors driving the ecology of ham and its spoilage, we designed a study encompassing five variables related to ham production: type of storage during meat transportation, churning speed, drain-off time, slicing line and O2packaging permeability. We obtained about 200 samples from the same facility and we characterizedi)their microbiota based ongyrBamplicon sequencingii) their production of spoilage-related metabolites based on E-Nose analysis and enzymatic assays. The slicing was the most critical step, shaping two general types of microbiota according to the slicing line: one dominated byCarnobacterium divergensand another one dominated byLeuconostoc carnosumandSerratia proteamaculans. Regarding metabolites production,L. carnosumwas associated to D-lactic acid, ethanol and acetic acid production, whereasSerratia proteamaculanswas associated to acetic acid production. This last species prevailed with highly O2-permeable packaging. Within a given slicing line, we observed campaign-based variations, withLactobacillus sakei,Leuconostoc mesenteroidesandCarnobacterium maltaromaticumprevalent in summer.L. sakeiwas associated with L-lactic acid production andC. maltaromaticumwith formic and acetic acid productions.
Finding valuable bioactive components from Jerusalem artichoke (Helianthus tuberosusL.) leaf protein concentrate in a green biorefinery concept
Authors: Kaszás László , Alshaal Tarek , El-Ramady Hassan , Kovács Zoltán , Koroknai Judit , Elhawat Nevien , Nagy Éva , Cziáky Zoltán , Fári Miklós , Domokos-Szabolcsy Éva 
Published: December 2019

AbstractJerusalem artichoke is widely known for its inulin-enriched tubers. Recently the opportunity has been arisen to involve the whole plant in biorefinery concept due to its high lignocellulose biomass and tuber production. This paper focuses on the repeatedly harvestable green biomass of Jerusalem artichoke. Ultra-High Performance Liquid Chromatography-Electrospray Ionization/Mass Spectrometry (UHPLC-ESI-MS) was applied to identify the phytochemicals in Jerusalem artichoke leaf protein concentrate (JAPC) thermally extracted from green biomass of three clones, i.e., Alba, Fuseau and Kalevala. Amino acid and fatty acid profiles as well as yield of JAPC were also analyzed. The UHPLC-ESI-MS analyses showed that no toxic phytochemicals were identified in JAPC. The results revealed, also, that JAPC is not only essential-amino acids-rich but also contains substantial amounts of polyunsaturated fatty acids (66-68%) such as linolenic and linoleic acids. Linolenic acid represented 39-43% of total lipid content; moreover, the ratio between ω-6 and ω-3 essential fatty acids in JAPC was ∼0.6: 1. Using UHPLC-ESI-MS, the following hydroxylated methoxyflavones were for the first time identified in JAPC, i.e., dimethoxy-tetrahydroxyflavone, dihydroxy-methoxyflavone, hymenoxin and nevadensin. These compounds are medically important since they are referred to as anti-cancer, anti-inflammatory and antioxidants. Also, liquiritigenin - estrogenic-like compound - was identified in JAPC alongside the following terpenes, i,e., loliolide and dihydroactinidiolide. However, no remarkable differences of phytochemicals, fatty acids and amino acids composition were seen among Jerusalem artichoke clones. The green biomass of tested clones ranged between 5 to 5.6 kg m-2and JAPC yield varied from 28.6 to 31.2 g DM kg-1green biomass with total protein content, on average, of 33.3%. According to our knowledge, this paper is the first scientific report highlighting bioactive substances in JAPC such as PUFA phytochemicals. These results clearly prove that JAPC is a valuable product which can direct towards human and animal nutrition as well as it can serve as basic material for different industrial purposes.
Calcium-stimulated disassembly of focal adhesions mediated by an ORP3/IQSec1 complex
Authors: D’Souza RS , Lim JY , Turgut A , Servage K , Zhang J , Orth K , Sosale NG , Lazzara MJ , Allegood JC , Casanova JE 
Published: December 2019

AbstractCoordinated assembly and disassembly of integrin-mediated focal adhesions (FAs) is essential for cell migration. Many studies have shown that FA disassembly requires Ca2+influx, however our understanding of this process remains incomplete. Here we show that Ca2+influx via STIM1/Orai1 calcium channels, which cluster near FAs, leads to activation of the GTPase Arf5 via the Ca2+-activated GEF IQSec1, and that both IQSec1 and Arf5 activation are essential for adhesion disassembly. We further show that IQSec1 forms a complex with the lipid transfer protein ORP3, and that Ca2+influx triggers PKC-dependent translocation of this complex to ER/plasma membrane contact sites adjacent to FAs. In addition to allosterically activating IQSec1, ORP3 also extracts PI4P from the PM, in exchange for phosphatidylcholine. ORP3-mediated lipid exchange is also important for FA turnover. Together, these findings identify a new pathway that links calcium influx to FA turnover during cell migration.
Genome-wide analysis of DNA uptake across the outer membrane of naturally competentHaemophilus influenzae
Authors: Mora Marcelo , Mell Joshua Chang , Ehrlich Garth D. , Ehrlich Rachel L. , Redfield Rosemary J. 
Published: December 2019

SUMMARYThe genomes of naturally competent Pasteurellaceae and Neisseriaceae have many short uptake sequences (USS), which allow them to distinguish self-DNA from foreign DNA. To fully characterize this preference we developed genome-wide maps of DNA uptake using both a sequence-based computational model and genomic DNA that had been sequenced after uptake by and recovery from competentHaemophilus influenzaecells. When DNA fragments were shorter than the average USS spacing of ~1000 bp, sharp peaks of uptake were centered at USS and separated by valleys with 1000-fold lower uptake. Long DNA fragments (1.5-17 kb) gave much less variation, with 90% of positions having uptake within two-fold of the mean. All detectable uptake biases arose from sequences that fit the USS uptake motif. Simulated competition predicted that, in its respiratory tract environment,H. influenzaewill efficiently take up its own DNA even when human DNA is present in 100-fold excess.
Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity- and neurotransmission-related proteins in young recipients
Authors: D’Amato Alfonsina , Di Cesare-Mannelli Lorenzo , Lucarini Elena , Man Angela L. , Le Gall Gwenaelle , Branca Jacopo J. V. , Ghelardini Carla , Amedei Amedeo , Bertelli Eugenio , Regoli Mari , Pacini Alessandra , Luciani Giulia , Gallina Pasquale , Altera Annalisa , Narbad Arjan , Gulisano Massimo , Hoyles Lesley , Vauzour David , Nicoletti Claudio 
Published: December 2019

AbstractBackgroundThe gut-brain axis and the intestinal microbiota are emerging as key players in health and disease. Shifts in intestinal microbiota composition affect a variety of systems, however, evidence of their direct impact on cognitive functions is still lacking. We tested whether faecal microbiota transplant (FMT) from aged donor mice into young adult recipients affected the hippocampus, an area of the central nervous system (CNS) known to be affected by the ageing process, and related functions.Methods and FindingsYoung adult mice were transplanted with the microbiota from either aged or age-matched donor mice. Following transplantation, characterization of the microbiotas and metabolomics profiles along with a battery of cognitive and behavioural tests were performed. Label-free quantitative proteomics was employed to monitor protein expression in the hippocampus of the recipients. Gut permeability, levels of circulating cytokines and expression of markers of microglia cells were also assessed. FMT from aged donors led to impaired spatial learning and memory in young adult recipients, whereas anxiety, explorative behaviour and locomotor activity remained unaffected. This was paralleled by altered expression of proteins involved in synaptic plasticity and neurotransmission in the hippocampus. Also, a strong reduction of bacteria associated with short-chain fatty acids (SCFAs) production (Lachnospiraceae, Faecalibaculum, and Ruminococcaceae) and disorders of the CNS (Prevotellaceae and Ruminococcaceae) was observed. Finally, microglia cells of the hippocampus fimbria, acquired an ageing-like phenotype, while gut permeability and levels of circulating cytokines remained unaffected.ConclusionsThese results demonstrate a direct effect of the age-associated shifts of the microbiota on protein expression and key functions of the central nervous system. Furthermore, these results additionally highlight the paramount importance of the gut-brain axis in ageing and provide a strong rationale to devise therapies aiming to restore a young-like microbiota to improve cognitive functions in the elderly.
The effect of flow on swimming bacteria controls the initial colonization of curved surfaces
Authors: Secchi Eleonora , Vitale Alessandra , Miño Gastón L. , Kantsler Vasily , Eberl Leo , Rusconi Roberto , Stocker Roman 
Published: December 2019

AbstractThe colonization of solid surfaces by bacteria is a widespread phenomenon with major consequences on environmental processes, biotechnology and human health. While much is known about the molecular mechanisms of surface colonization, the influence of the physical environment remains poorly understood. Here we show that the magnitude and location of colonization of non-planar surfaces by motile bacteria is largely controlled by the local flow conditions. Using microfluidic experiments with Pseudomonas aeruginosa and Escherichia coli, we demonstrate that the velocity gradients created by a curved surface drive preferential attachment to specific regions of the collecting surface, namely the leeward side of cylinders and immediately downstream of apexes on corrugated surfaces, locations that are in stark contrast to where non-motile cells attach. The preferential attachment location depends on the local hydrodynamic conditions and, as revealed by a mathematical model benchmarked on the observations, on cell morphology and swimming traits, while it is independent of the physicochemical properties of the surface. The interplay between imposed flow and bacterial motility further affects the overall attachment rate, increasing it by up to two orders of magnitude compared to the non-motile case at moderate flow velocities of up to twenty times the bacterial swimming speed. These results highlight the importance of fluid flow on the magnitude and location of bacterial colonization of surfaces and provide a mechanistic model to predict colonization in flow for a wide range of applications, from infection biology to bioremediation and biofouling.