bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proximal arm non-use optimises movement when the shoulder is weak: consequences for stroke patients
Authors: Faity Germain , Mottet Denis , Pla Simon , Froger Jérôme 
Published: October 2020

AbstractMost stroke patients do not use their paretic limb whereas they are able to. The Constraint-Induced Movement Therapy (CIMT) is effective to reverse this non-use behaviour in some patients but is inapplicable or unsuccessful on others. Here, we investigate how much non-use could come from shoulder weakness instead of the behavioural conditioning treated by the CIMT. We asked 26 healthy participants to reach a target while holding a dumbbell. We found that 18/26 participants exhibit proximal arm non-use when loaded and that non-use reduces shoulder torque of final posture. We either found that non-use improves accuracy in a high gravity field. Following optimal control policy, we explain how the non-use could be an adaptative solution when the shoulder is weak. Our results show the need to include muscular strength into cost function used to model human movement. The framework presented here suggests that psychological non-use could be treated effectively with CIMT, while physiological non-use, resulting from shoulder weakness, might respond better to anti-gravity muscles strengthening.
Post-exposure protection of SARS-CoV-2 lethal infected K18-hACE2 transgenic mice by neutralizing human monoclonal antibody
Authors: Rosenfeld Ronit , Noy-Porat Tal , Mechaly Adva , Makdasi Efi , Levy Yinon , Alcalay Ron , Falach Reut , Aftalion Moshe , Epstein Eyal , Gur David , Chitlaru Theodor , Vitner Einat B. , Melamed Sharon , Politi Boaz , Zauberman Ayelet , Lazar Shirley , Beth-Din Adi , Evgy Yentl , Yitzhaki Shmuel , Shapira Shmuel C. , Israely Tomer , Mazor Ohad 
Published: October 2020

AbstractCoronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits high levels of mortality and morbidity and has dramatic consequences on human life, sociality and global economy. Neutralizing antibodies constitute a highly promising approach for treating and preventing infection by this novel pathogen. In the present study, we characterized and further evaluated the recently identified human monoclonal MD65 antibody for its ability to provide protection against a lethal SARS-CoV-2 infection of K18-hACE2 transgenic mice. Eighty percent of the untreated mice succumbed 6-9 days post-infection while administration of the MD65 antibody as late as 3 days after exposure, rescued all infected animals. In addition, the efficiency of the treatment is supported by prevention of morbidity and ablation of the load of infective virions in the lungs of treated animals. The data unprecedentedly demonstrate, the therapeutic value of human monoclonal antibodies as a life-saving treatment of severe COVID-19 infection.
Not so optimal: The evolution of mutual information in potassium voltage-gated channels
Authors: Durán Alejandra , Marzen Sarah 
Published: October 2020

AbstractPotassium voltage-gated (Kv) channels need to detect and respond to rapidly changing ionic concentrations in their environment. With an essential role in regulating electric signaling, they would be expected to be optimal sensors that evolved to predict the ionic concentrations. To explore these assumptions, we use statistical mechanics in conjunction with information theory to model how animal Kv channels respond to changes in potassium concentrations in their environment. By estimating mutual information in representative Kv channel types across a variety of environments, we find two things. First, under a wide variety of environments, there is an optimal gating current that maximizes mutual information between the sensor and the environment. Second, as Kv channels evolved, they have moved towards decreasing mutual information with the environment. This either suggests that Kv channels do not need to act as sensors of their environment or that Kv channels have other functionalities that interfere with their role as sensors of their environment.
Survey, Identification and Evaluation of biodiversity ofSeabuckthorn(Hippophae salicifolia) in hills of Uttarakhand
Authors: Singh Ranjit , Dwivedi S.K. , Bala Madhu 
Published: October 2020

ABSTRACTExtensive studies were carried out during 2017-2019 to evaluate theHippophae salicifolia(Seabuckthorn) biodiversity in Uttarakhand for their physico-chemical/biochemical parameters of ripe fruits like acidity (1.78-3.01 %), pH (2.15-2.87), Vitamin ‘C’ (271-494mg/100g), Total soluble solids (5.1-9.8) etc. Variation was also observed in fruit color (light yellow, yellow, light yellow orange, orange and orange red), fruit size (length 6.29-8.77mm, width 4.80-7.59mm), Juice (44.23-76.18%), Pomace (8.01-28.30%) and seed (6.8-21.1%). On the basis of above parameters, promising morphotypes were identified and conserved at field gene bank at DIBER field station, Auli (Joshimath) 3142m AMSL.
Proteomic and transcriptomic analysis ofMicroviridaeφXI74 infection reveals broad up-regulation of host membrane damage and heat shock responses
Authors: Wright Bradley W , Logel Dominic Y , Mirzai Mehdi , Pascovici Dana , Molloy Mark P , Jaschke Paul R 
Published: October 2020

ABSTRACTMeasuring host-bacteriophage dynamics is an important approach to understanding bacterial survival functions and responses to infection. The modelMicroviridaebacteriophage φX174 is endemic to the human gut and has been studied for over seventy years but the host response to infection has never been investigated in detail. To address this gap in our understanding of this important interaction within our microbiome we have measured hostEscherichia coliC proteomic and transcriptomic response to φX174 infection. We used mass spectrometry and RNA-seq to identify and quantify all 11 φX174 proteins and over 1,700E. coliproteins, enabling us to comprehensively map host pathways involved in φX174 infection. Most notably, we see significant host responses centered on membrane damage and remodeling, cellular chaperone and translocon activity, and lipoprotein processing, which we speculate is due to the peptidoglycan-disruptive effects of the φX174 lysis protein E on MraY activity. We also observe the massive upregulation of small heat-shock proteins IbpA/B, along with other heat shock pathway chaperones, and speculate on how the specific characteristics of holdase protein activity may be beneficial for viral infections. Together, this study enables us to begin to understand the proteomic and transcriptomic host responses ofE. colitoMicroviridaeinfections and contributes insights to the activities of this important model phage.IMPORTANCEA major part of the healthy human gut microbiome are theMicroviridaebacteriophage, exemplified by the model φX174 phage. Although much has been learned from studying φX174 over the last half century, until this work, theE. colihost response to infection has never been investigated in detail. We reveal the proteomic and transcriptomic pathways differentially regulated during the φX174 infection cycle, and uncover the details of a coordinated cellular response to membrane damage that results in increased lipoprotein processing and membrane trafficking, likely due to the phage antibiotic-like lysis protein. We also reveal that small heat shock proteins IbpA/B are massively upregulated during infection and that these holdase chaperones are highly conserved across the domains of life, indicating that reliance on them is likely widespread across viruses.
Natural Cystatin C fragments inhibit GPR15-mediated HIV and SIV infection without interfering with GPR15L signaling
Authors: Hayn Manuel , Blötz Andrea , Rodríguez Armando , Vidal Solange , Preising Nico , Ständker Ludger , Wiese Sebastian , Stürzel Christina M. , Harms Mirja , Groß Rüdiger , Jung Christoph , Kiene Miriam , Hahn Beatrice H. , Jacob Timo , Pöhlmann Stefan , Forssmann Wolf-Georg , Münch Jan , Sparrer Konstantin M. J. , Seuwen Klaus , Kirchhoff Frank 
Published: October 2020

SUMMARYGPR15 is a G protein-coupled receptor proposed to play a role in mucosal immunity that also serves as entry cofactor for HIV and SIV. To discover novel endogenous GPR15 ligands, we screened a hemofiltrate-derived peptide library for inhibitors of GPR15-mediated SIV infection. Our approach identified a C-terminal fragment of Cystatin C (CysC95-146) that specifically inhibits GPR15-dependent HIV-1, HIV-2 and SIV infection. In contrast, GPR15L, the chemokine ligand of GPR15, failed to inhibit virus infection. We found that Cystatin C fragments preventing GPR15-mediated viral entry do not interfere with GPR15L signaling and are generated by proteases activated at sites of inflammation. The antiretroviral activity of CysC95-146 was confirmed in primary CD4+ T cells and is conserved in simian hosts of SIV infection. Thus, we identified a potent endogenous inhibitor of GPR15-mediated HIV and SIV infection that does not interfere with the physiological function of this G protein-coupled receptor.
Positive outcomes of COVID-19 research-related gender policy changes
Authors: Witteman Holly O. , Haverfield Jenna , Tannenbaum Cara 
Published: October 2020

AbstractThe COVID-19 pandemic has exposed and exacerbated gender biases in science, technology, engineering, mathematics, and medicine. Accumulating evidence suggests that female scientists’ productivity dropped during the initial lockdown period. With more time being spent on caregiving responsibilities, women may be struggling to collaborate on grant applications and launch new experiments. Scientists with disabilities or who belong to Indigenous nations or communities of color may have less time to devote to research due to health, family, or community needs. Collateral damage in this situation, the appropriate integration of sex, gender, and other identity characteristics in research content may also suffer. Sex and gender are better attended to when female scientists form part of the research team. Research funding agencies have a role to play in mitigating these effects by putting in place gender equity policies that support all applicants and ensure research quality. Accordingly, a national health research funder implemented gender policy changes that included extending deadlines and factoring sex and gender into COVID-19 grant requirements. Following these changes, the funder received more applications from female scientists, awarded a greater proportion of grants to female compared to male scientists, and received and funded more grant applications that considered sex and gender in the content of COVID-19 research. Whether or not these strategies will be sufficient in the long-term to prevent widening of the gender gap in science, technology, engineering, mathematics and medicine requires continued monitoring and oversight. Further work is urgently required to mitigate inequities associated with identity characteristics beyond gender.
Di(2-ethylhexyl) adipate (DEHA), A NEW HOPE! A sustainable and promising process for the plasticisers industry
Authors: Acciaretti Federico , Pasquale Andrea 
Published: October 2020

AbstractPlasticisers are commonly incorporated in plastic materials in order to improve their physico-chemicals properties. In particular, Poly-(vinyl chloride) (PVC) is a polymer which has excellent plasticiser compatibility characteristics. The demand for plasticized-PVC is steadily increasing and its synthesis need to be more sustainable, considering the interest in developing a circular economy in the next years. In order to achieve these goals, a bio-based process to synthesize di(2-ethylhexyl) adipate (DEHA), a widely used plasticiser, could be an interesting approach. The most important starting material for the process is adipic acid, but its synthesis from petrochemical sources is not sustainable. An alternative is using waste materials as substrates for fermentation in a totally green process. Among many strategies, the reverse adipate degradation pathway (RADP) inE. coliseems to be the most interesting one, considering the highest titer of 68 g/L and the yield of 93.1%. The next step is the enzyme-catalysed esterification of adipic acid and 2-ethylhexanol to produce DEHA, using an immobilized lipase fromCandida antarctica. Applying a solvent-free system under vacuum condition is convenient as it guarantees a conversion to DEHA of 100 mol%.
An interplay of population size and environmental heterogeneity explains why fitness costs are rare
Authors: Chavhan Yashraj , Malusare Sarthak , Dey Sutirth 
Published: October 2020

AbstractTheoretical models of ecological specialization commonly assume that adaptation to one environment leads to fitness reductions (costs) in others. However, empirical studies often fail to detect such costs. We addressed this conundrum using experimental evolution withEscherichia coliin several homogeneous and heterogeneous environments at multiple population sizes. We found that in heterogeneous environments, smaller populations paid significant costs, but larger ones avoided them altogether. Contrastingly, in homogeneous environments, larger populations paid more costs than the smaller ones. Overall, large population sizes and heterogeneous environments led to cost avoidance when present together but not on their own. Whole-genome whole-population sequencing revealed that the enrichment of multiple mutations within the same lineage (and not subdivision into multiple distinct specialist subpopulations) was the mechanism of cost avoidance. Since the conditions revealed by our study for avoiding costs are widespread, it explains why the costs expected in theory are rarely detected in experiments.
The association between pain-induced autonomic reactivity and descending pain control is mediated by the periaqueductal grey
Authors: Makovac Elena , Venezia Alessandra , Hohenschurz-Schmidt David , Dipasquale Ottavia , Jackson Jade B , Medina Sonia , O’Daly Owen , Williams Steve CR , McMahon Stephen B , Howard Matthew A 
Published: October 2020

AbstractThere is a strict interaction between the autonomic nervous system (ANS) and pain, which might involve descending pain modulatory mechanisms. The periaqueductal grey (PAG) is involved both in descending pain modulation and ANS, but its role in mediating this relationship has not yet been explored.Here, we sought to determine brain regions mediating ANS and descending pain control associations. 30 participants underwent Conditioned Pain Modulation (CPM) assessments, in which they rated painful pressure stimuli applied to their thumbnail, either alone or with a painful cold contralateral stimulation. Differences in pain ratings between ‘pressure-only’ and ‘pressure+cold’ stimuli provided a measure of descending pain control. In 18 of the 30 participants, structural scans and two functional MRI assessments, one pain-free and one during cold-pain, were acquired. Heart Rate Variability (HRV) was simultaneously recorded.Low frequency HRV (LF-HRV) and the CPM score were negatively correlated; individuals with higher LF-HRV during pain reported reductions in pain during CPM. PAG-frontal medial cortex (FMC) and PAG-rostral ventro-medial medulla (RVM) functional connectivity correlated negatively with the CPM. Importantly, PAG-FMC functional connectivity mediated the strength of HRV-CPM association. CPM response magnitude was also negatively associated with PAG and positively associated with FMC grey matter volumes.Our multi-modal approach, using behavioral, physiological and MRI measures, provides important new evidence of interactions between ANS and descending pain mechanisms. ANS dysregulation and dysfunctional descending pain modulation are characteristics of chronic pain. We suggest that further investigation of body-brain interactions in chronic pain patients may catalyse the development of new treatments.
LINE-1 retrotransposons facilitate horizontal gene transfer into poxviruses
Authors: Julhasur Rahman M. , Haller Sherry L. , Stoian Ana M. M. , Li Jie , Brennan Greg , Rothenburg Stefan 
Published: October 2020

AbstractThere is ample phylogenetic evidence that many critical virus functions, like immune evasion, evolved by the acquisition of genes from their hosts through horizontal gene transfer (HGT). However, the lack of an experimental system has prevented a mechanistic understanding of this process. We developed a model to elucidate the mechanisms of HGT into vaccinia virus, the prototypic poxvirus. All identified gene capture events showed signatures of long interspersed nuclear element-1 (LINE-1)-mediated retrotransposition, including spliced-out introns, polyadenylated tails and target site duplications. In one case, the acquired gene integrated together with a polyadenylated host U2 small nuclear RNA. Integrations occurred across the genome, in some cases knocking out essential viral genes. These essential gene knockouts were rescued through a process of complementation by the parent virus followed by non-homologous recombination during serial passaging to generate a single competent virus. This work links multiple evolutionary mechanisms into one adaptive cascade and identifies host retrotransposons as major drivers for virus evolution.
Resveratrol reduces COMPopathy in mice through activation of autophagy
Authors: Hecht Jacqueline T. , Coustry Francoise , Veerisetty Alka C. , Hossain Mohammad G. , Posey Karen L. 
Published: October 2020

AbstractMisfolding mutations in cartilage oligomeric matrix protein (COMP) cause it to be retained within in ER of chondrocytes, stimulating a multitude of damaging cellular responses including ER stress, inflammation and oxidative stress which ultimately culminates in the death of growth plate chondrocytes and pseudoachondroplasia (PSACH). Previously, we demonstrated that an antioxidant, resveratrol, substantially reduces the intracellular accumulation of mutant COMP, dampens cellular stress and lowers the level of growth plate chondrocyte death. In addition, we showed that resveratrol reduces mTORC1 (mammalian target of rapamycin complex 1) signaling, suggesting a potential mechanism. In this work, we investigate the role of autophagy in treatment of COMPopathies. In cultured chondrocytes expressing wild type or mutant COMP (MT-COMP), resveratrol significantly increased the number of large LC3 vesicles, directly demonstrating that resveratrol stimulated autophagy is an important component of the resveratrol-driven mechanism responsible for the degradation of mutant COMP. Moreover, pharmacological inhibitors of autophagy suppressed degradation of MT-COMP in our established mouse model of PSACH. In contrast, blockage of the proteasome did not substantially alter resveratrol clearance of mutant COMP from growth plate chondrocytes. Mechanistically, resveratrol increased SIRT1 and PP2A expression and reduced MID1 expression and activation of pAKT and mTORC1 signaling in growth plate chondrocytes, allowing clearance of mutant COMP by autophagy. Importantly, we show that optimal reduction in growth plate pathology, including decreased mutant COMP retention, decreased mTORC1 signaling and restoration of chondrocyte proliferation was attained when treatment was initiated between birth to one week of age in MT-COMP mice, translating to birth to approximately 2 years of age in PSACH children. These results clearly demonstrate that resveratrol stimulates clearance of mutant COMP by an autophagy-centric mechanism.
In vivotwo-photon imaging and parasympathetic neuromodulation of pancreatic microvascular dynamics in rats
Authors: Canzano Joseph S. , Subramanian Narayan , Castro Rebeca , Siddiqi Abdurahman , Oweiss Karim G. 
Published: October 2020

AbstractThe pancreas has long been known to be densely innervated with parasympathetic, sympathetic, and visceral afferent fibers that are believed to exert significant influence on local endocrine activity and vascular function. Yet the extent to which these interactions depend on neurovascular dynamics in the normal and pathological states remain largely unknown. Herein we describe a new method for high resolution functional imaging of the rat pancreasin vivo. The method comprises a number of elements: a stability-optimized preparation in dorsal recumbency immobilizing several square centimeters of intact pancreas for upright fluorescent imaging while leaving access for concurrent manipulation of abdominal nerves, a full-frame two-photon imaging protocol and analysis pipeline supporting high-throughput (100+) monitoring of islet and acinar microvessel diameter dynamics simultaneously, and a first adaptation of random-access linescan imaging to the pancreas capable of tracking internal blood flow speeds up to 5 mm/s at 20 Hz across multiple microvessels. These methods were then deployed in concert to characterize the capacity of parasympathetic fibers to modulate pancreatic microvascular dynamics with compartment specificity. Electrical stimulation was repeatedly applied to the abdominal vagal trunks at various current magnitudes while imaging islet and acinar microvascular populations in the pancreas. Vagal stimulation consistently elicited increases in both islet and acinar capillary population motility in a current-dependent manner, with only acinar responsive vessels trending toward dilation. Further, we found vagal stimulation to profoundly and reversibly disrupt all traces of fast-wave vasomotor oscillation across a lobular arteriole-venule pair, and this was associated with a significant increase in average flow speed. Together, these findings add to mounting evidence that vagal projections exert tangible reversible influence on pancreatic microvascular activity and underscore the potential for new neuromodulation-based strategies to address diabetes, pancreatitis, or other diseases of the pancreas under autonomic nervous influence.
Physiological and ecological warnings that Dodder pose an exigent threat to farmlands in Eastern Africa
Authors: Masanga Joel , Mwangi Beatrice Njoki , Kibet Willy , Sagero Philip , Wamalwa Mark , Oduor Richard , Ngugi Mathew , Alakonya Amos , Ojola Patroba , Bellis Emily S. , Runo Steven 
Published: October 2020

AbstractInvasive holoparasitic plants of the genusCuscuta(dodder) threaten Africa’s ecosystems, due to their rapid spread and attack on various host plant species. MostCuscutaspecies cannot photosynthesize, hence rely on host plants for nourishment. After attachment through a peg-like organ called a haustorium, the parasites deprive hosts of water and nutrients leading to their death. Despite their rapid spread in Africa, dodders have attracted limited research attention, although data on their taxonomy, host range and epidemiology are critical for their management. Here, we combine taxonomy and phylogenetics to reveal presence of field dodder (Cuscuta campestris) andC. kilimanjari(both either naturalized or endemic to East Africa), and for the first time in continental Africa, presence of the giant dodder (C. reflexa) a south Asian species. These parasites have a wide host range, parasitizing species across 13 angiosperm orders. Evaluating the possibility ofC. reflexato expand this host range to tea, coffee, and mango, crops of economic importance to Africa, revealed successful parasitism, following haustorial formation and vascular bundle connections in all three crops. However, only mango mounted a successful post-attachment resistance response. Furthermore, species distribution models predicted high habitat suitability for all threeCuscutaspecies across major tea- and coffee-growing regions of Eastern Africa, suggesting an imminent risk to these crops. Our findings provide relevant insights into a little-understood threat to biodiversity and economic wellbeing in Eastern Africa, and providing critical information to guide development of management strategies to avert their spread.Sentence SummaryMicroscopy and habitat suitability modeling provide an early warning that dodder’s invasion in Eastern Africa poses a threat to important cash crops