bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of whether published non-Cochrane systematic reviews of nursing follow the review protocols registered in the International Prospective Register of Systematic Reviews (PROSPERO): A comparative study
Authors: Hu Kaiyan , Mei Fan , Gao Qianqian , Zhao Li , Chen Fei , Liu Qinghua , Suo Lingling , Ma Yuxia , Zhang Ting , Zhang Weiyi , Zhao Bing , Ma Bin 
Published: April 2020

AbstractPurposeWe compare published non-Cochrane reviews of nursing with their pre-registered protocols on PROSPERO to quantify the prevalence of differences and the extent to which the differences were explained.MethodsWe searched for protocols and their corresponding reviews in PROSPERO’s nursing group that were “completed and published” from inception to September 8th, 2019. Two authors independently identified differences and classified the difference as none, partial, or complete, and determined if the existed differences had been explained. Frequency (n), percentage (%), median, and inter-quartile ranges were used to analyze the extent of differences and explanations.ResultsWe identified 22 pre-registered protocols and their reviews. All 22 pairs (100%) exhibited differences. Eighteen pairs (82%) showed differences in at least six methodological sections, while 21 pairs (95%) involved completed difference in at least one section. The median number of differences per review was 8.00 (upper quartile = 6.00, lower quartile = 9.75). The differences involved all 13 compared methodology-related sections. Only 5 (3%) of all differences were explained in the systematic reviews.ConclusionsWe observed widespread differences between non-Cochrane reviews of nursing and their protocols recorded in PROSPERO, with relatively few explanations for the changes. Measures including establishing a new item in the reporting guideline of systematic reviews to guide reporting and explaining the reasons for differences between protocols and systematic reviews or even requiring authors to do so at the Journal’s author guideline are recommended to improve transparency.
Specificities of and functional coordination between the two Cas6 maturation endonucleases inAnabaenasp. PCC 7120 assign orphan CRISPR arrays to three groups
Authors: Reimann Viktoria , Ziemann Marcus , Li Hui , Zhu Tao , Behler Juliane , Lu Xuefeng , Hess Wolfgang R. 
Published: April 2020

AbstractThe majority of bacteria and archaea possess an RNA-guided adaptive and inheritable immune system against viruses and other foreign genetic elements that consists of clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins. In most CRISPR-Cas systems, the maturation of CRISPR-derived small RNAs (crRNAs) is essential for functionality. In some bacteria, multiple instances ofcasgene-free (orphan) repeat-spacer arrays exist, while additional instances of arrays that are linked tocasgene cassettes are present elsewhere in the genome.In the cyanobacteriumAnabaenasp. PCC 7120, ten CRISPR-Cas repeat-spacer arrays are present, but only twocasgene cassettes plus a Tn7-associated eleventh array are observed. In this study, we deleted the twocas6genesalr1482(Type III-D) oralr1566(Type I-D) and tested the specificities of the two corresponding enzymes in the resulting mutant strains, as recombinant proteins and in a cell-free transcription-translation system. The results assign the direct repeats (DRs) to three different groups. While Alr1566 is specific for one group, Alr1482 has a higher preference for the DRs of the second group but can also cleave those of the first group. We found that this cross-recognition limits crRNA accumulation for the Type I-D systemin vivo.We also show that the DR of thecasgene-free CRISPR array of cyanophage N-1 is processed by these enzymes, suggesting that it is fully competent in association with host-encoded Cas proteins. The data support a strong tendency for array fragmentation in multicellular cyanobacteria and disfavor other possibilities, such as the nonfunctionality of these orphan repeat-spacer arrays. Our data demonstrate the functional coordination of Cas6 endonucleases with both neighboring and remote repeat-spacer arrays in the CRISPR-Cas system of cyanobacteria.
Syngap1 Dynamically Regulates the Fine-Scale Reorganization of Cortical Circuits in Response to Sensory Experience
Authors: Llamosas Nerea , Vaissiere Thomas , Rojas Camilo , Michaelson Sheldon , Miller Courtney A. , Rumbaugh Gavin 
Published: April 2020

AbstractExperience induces complex, neuron-specific changes in population activity within sensory cortex circuits. However, the mechanisms that enable neuron-specific changes within cortical populations remain unclear. To explore the idea that synapse strengthening is involved, we studied fine-scale cortical plasticity inSyngap1mice, a neurodevelopmental disorder model useful for linking synapse biology to circuit functions. Repeated functional imaging of the same L2/3 somatosensory cortex neurons during single whisker experience revealed thatSyngap1selectively regulated the plasticity of a low-active, or “silent”, neuronal subpopulation.Syngap1also regulated spike-timing-dependent synaptic potentiation and experience-mediatedin vivosynapse bouton formation, but not synaptic depression or bouton elimination in L2/3. Adult re-expression ofSyngap1restored plasticity of “silent” neurons, demonstrating that this gene controls dynamic cellular processes required for population-specific changes to cortical circuits during experience. These findings suggest that abnormal experience-dependent redistribution of cortical population activity may contribute to the etiology of neurodevelopmental disorders.
A spatiotemporal translatome of mouse tissue development
Authors: Wang Hongwei , Wang Yan , Yang Jiaqi , Tang Nan , Li Huihui , Xie Mingzhe , Xie Zhi 
Published: April 2020

AbstractThe precise regulation of gene expression in mammalian tissues during development results in their functional specification. Although previous transcriptomic and proteomic analyses have provided great biological insights into tissue-specific gene expression and the physiological relevance of these tissues in development, our understanding of translational regulation in developing tissues is lacking. In this study, we performed a spatiotemporally resolved translatome analysis of six mouse tissues at the embryonic and adult stages to quantify the effects of translational regulation and identify new translational components. We quantified the spatial and temporal divergences of gene expression and detected specific changes in gene expression and pathways underlying these divergences. We further showed that dynamic translational control can be achieved by modulating the translational efficiency, which resulted in the enhancement of tissue specificity during development. We also discovered thousands of actively translated upstream open reading frames (ORFs) that exhibited spatiotemporal patterns and demonstrated their regulatory roles in translational regulation. Furthermore, we identified known and novel micropeptides encoded by small ORFs from long noncoding RNAs that are functionally relevant to tissue development. Our data and analyses facilitate a better understanding of the complexity of translational regulation across tissue and developmental spectra and serve as a useful resource of the mouse translatome.
Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances learning of cue-reward contingency
Authors: Crouse Richard B. , Kim Kristen , Batchelor Hannah M. , Kamaletdinova Rufina , Chan Justin , Rajebhosale Prithviraj , Pittenger Steven T. , Role Lorna W. , Talmage David A. , Jing Miao , Li Yulong , Gao Xiao-Bing , Mineur Yann S. , Picciotto Marina R. 
Published: April 2020

AbstractThe basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and principal neuron activity in mice during cue-reward learning using a fluorescent ACh sensor and calcium indicators. We found that ACh levels and activity of nucleus basalis of Meynert (NBM) cholinergic terminals in the BLA (NBM-BLA) increased sharply in response to reward-related events and shifted as mice learned the tone-reward contingency. BLA principal neuron activity followed reward retrieval and moved to the reward-predictive tone after task acquisition. Optical stimulation of cholinergic NBM-BLA terminal fibers during cue-reward learning led to more rapid learning of the cue-reward contingency. These results indicate that BLA ACh signaling carries important information about salient events in cue-reward learning and provides a framework for understanding how ACh signaling contributes to shaping BLA responses to emotional stimuli.
High-level stimulus template modulates neuronal response at the earlier processing stages
Authors: Maksimenko Vladimir , Kuc Alexander , Frolov Nikita , Kurkin Semen , Hramov Alexander 
Published: April 2020

AbstractThere is ample evidence that the brain matches sensory information with internal templates, but the details of this mechanism remain unknown. Here we consider the processing of repeatedly presented ambiguous stimuli with high ambiguity (HA) and low ambiguity (LA) and analyze how the processing depends on the ambiguity of the previous stimulus. On the behavioral level, we report a faster response to the HA stimulus after HA stimuli and a faster response to the LA stimulus after LA stimuli. The EEG analysis reveals that when HA stimulus follows LA stimuli, the neuronal activity in the sensory areas attenuates at the early processing stage but enhances during the latter stages. It evidences the hierarchical processing organization where low levels process the stimulus details, and high levels represent its interpretation. It also confirms that on low levels, HA and LA stimuli processing is similar due to their similar morphology. Therefore, the brain uses the LA stimulus template on the low levels to reduce the demands when processing the HA stimulus details. When LA stimulus follows HA stimuli, the attenuated response in the sensory regions accompanies high response in the frontal cortex. Namely, we observe highθpower in the medial frontal cortex and highβpower in the right inferior frontal cortex. It shows activation of the top-down cognitive control functions detecting the mismatch between the LA stimulus and the HA stimulus template and transfer this template to the low processing levels.Significance statementThe brain attenuates its response to repeatedly presented similar stimuli. When an ambiguous visual stimulus follows unambiguous stimuli with the same morphology, the neuronal response in sensory areas decreases at the early processing stage but enhances during the latter stages. It evidences hierarchical processing organization where low levels process the details, and high levels represent the interpretation. It also confirms that the brain uses templates on different levels to reduce the processing demands. When an unambiguous stimulus follows ambiguous stimuli, a low response in the sensory regions accompanies high response in the frontal cortex. It manifests activation of the top-down mechanisms to detect the mismatch between an unambiguous stimulus and an ambiguous template and transfer this template to low levels.
An aptamer-based magnetic flow cytometer using matched filtering
Authors: Huang Chih-Cheng , Ray Partha , Chan Matthew , Zhou Xiahan , Hall Drew A. 
Published: April 2020

AbstractFacing unprecedented population-ageing, the management of noncommunicable diseases (NCDs) urgently needs a point-of-care (PoC) testing infrastructure. Magnetic flow cytometers are one such solution for rapid cancer cellular detection in a PoC setting. In this work, we report a giant magnetoresistive spin-valve (GMR SV) biosensor array with a multi-stripe sensor geometry and matched filtering to improve detection accuracy without compromising throughput. The carefully designed sensor geometry generates a characteristic signature when cells labeled with magnetic nanoparticles (MNPs) pass by thus enabling multi-parametric measurement like optical flow cytometers (FCMs). Enumeration and multi-parametric information were successfully measured across two decades of throughput. 10-µm polymer microspheres were used as a biomimetic model where MNPs and MNP-decorated polymer conjugates were flown over the GMR SV sensor array and detected with a signal-to-noise ratio (SNR) as low as 2.5 dB due to the processing gain afforded by the matched filtering. The performance was compared against optical observation, exhibiting a 92% detection efficiency. The system achieved a 95% counting accuracy for biomimetic models and 98% for aptamer-based pancreatic cancer cell detection. This system demonstrates the ability to perform reliable PoC diagnostics towards the benefit for NCD control plans.
The FDA- approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells
Authors: Rothan Hussin A. , Stone Shannon , Natekar Janhavi , Kumari Pratima , Arora Komal , Kumar Mukesh 
Published: April 2020

SummarySARS-COV-2 has recently emerged as a new public health threat. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. Treatment of cells with auranofin resulted in a 95% reduction in the viral RNA at 48 hours after infection. Auranofin treatment dramatically reduced the expression of SARS-COV-2-induced cytokines in human cells. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, anti-inflammatory and anti-ROS properties. Auranofin has a well-known toxicity profile and is considered safe for human use.
Forkhead box O1-mediated ubiquitination suppresses RIG-I-mediated antiviral immune responses via its DNA binding domain
Authors: Liu Wei , Yue Yanlei , Zhang Wenwen , Ma Zhenling , Yao Wen , Li Tao , Xu Jun , Li Wenqing , Sun Lei , Liu Wenjun , Yang Guoqing 
Published: April 2020

StatementThe authors have withdrawn our manuscript whilst we perform additional experiments to test some of our conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Spatio-temporal mapping of mechanical force generated by macrophages during FcγR-dependent phagocytosis reveals adaptation to target stiffness
Authors: Rougerie Pablo , Cox Dianne 
Published: April 2020

ABSTRACTMacrophage phagocytosis is a strikingly flexible process central to pathogen clearance and is an attractive target for the development of anti-cancer immunotherapies. To harness the adaptability of phagocytosis, we must understand how macrophages can successfully deform their plasma membrane. While the signaling pathways and the molecular motors responsible for this deformation have been studied for many years, we only have limited insight into the mechanics that drive the formation of the phagocytic cup. Using Traction Force Microscopy (TFM), we have been able to characterize the spatio-temporal dynamics of mechanical forces generated in the course of FcγR-dependent frustrated phagocytosis and we determined whether this was affected by the stiffness of the potential phagocytic targets. We observed that frustrated phagocytosis is an atypical form of spreading where the cell deformation rate is unaffected by the substrate stiffness. Interestingly, the cell initially extends without forces being recorded then switches to a mode of pseudopod extension involving spatially organized force transmission. Importantly we demonstrate that macrophages adapt to the substrate stiffness primarily through a modulation of the magnitude of mechanical stress exerted, and not through modification of the mechanical stress kinetics or distribution. Altogether, we suggest that macrophage phagocytosis exhibits a clear resilience to variations of the phagocytic target stiffness and this is favored by an adaptation of their mechanical response.
Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers
Authors: Petrany Michael J , Swoboda Casey O , Sun Chengyi , Chetal Kashish , Chen Xiaoting , Weirauch Matthew T. , Salomonis Nathan , Millay Douglas P 
Published: April 2020

AbstractWhile the majority of cells contain a single nucleus, cell types such as trophoblasts, osteoclasts, and skeletal myofibers require multinucleation. One advantage of multinucleation can be the assignment of distinct functions to different nuclei, but comprehensive interrogation of transcriptional heterogeneity within multinucleated tissues has been challenging due to the presence of a shared cytoplasm. Here, we utilized single-nucleus RNA-sequencing (snRNA-seq) to determine the extent of transcriptional diversity within multinucleated skeletal myofibers. Nuclei from mouse skeletal muscle were profiled across the lifespan, which revealed the emergence of distinct myonuclear populations in postnatal development and their reactivation in aging muscle. Our datasets also provided a platform for discovery of novel genes associated with rare specialized regions of the muscle cell, including markers of the myotendinous junction and functionally validated factors expressed at the neuromuscular junction. These findings reveal that myonuclei within syncytial muscle fibers possess distinct transcriptional profiles that regulate muscle biology.
Extracellular adenosine signaling reverses the age-driven decline in the ability of neutrophils to killS. pneumoniae
Authors: Bhalla Manmeet , Simmons Shaunna R. , Abamonte Alexsandra , Herring Sydney E. , Roggensack Sara E. , Bou Ghanem Elsa N. 
Published: April 2020

SummaryThe elderly are susceptible to serious infections byStreptococcus pneumoniae(pneumococcus), which calls for a better understanding of the pathways driving the decline in host defense in aging. We previously found that extracellular adenosine (EAD) shaped polymorphonuclear cell (PMN) responses, which are crucial for controlling infection. EAD is produced by CD39 and CD73, and signals via A1, A2A, A2B and A3 receptors. The objective of this study was to explore the age-driven changes in the EAD pathway and its impact on PMN function. We found in comparison to young mice, PMNs from old mice expressed significantly less CD73, but similar levels of CD39 and adenosine receptors. PMNs from old mice failed to efficiently kill pneumococciex vivo; however, supplementation with adenosine rescued this defect. Importantly, transfer of PMNs expressing CD73 from young mice reversed the susceptibility of old mice to pneumococcal infection. To identify which adenosine receptor(s) is involved, we used specific agonists and inhibitors. We found that A1 receptor signaling was crucial for PMN function as inhibition or genetic ablation of A1 impaired the ability of PMNs from young mice to kill pneumococci. Importantly, activation of A1 receptors rescued the age-associated defect in PMN function. In exploring mechanisms, we found that PMNs from old mice failed to efficiently kill engulfed pneumococci and that A1 receptor controlled intracellular killing. In summary, targeting the EAD pathway reverses the age-driven decline in PMN antimicrobial function, which has serious implications in combating infections.
Oleic acid Induces Tissue Resident FoxP3 Regulatory T cell Lineage Stability and Suppressive Functions
Authors: Pompura Saige L. , Wagner Allon , Kitz Alexandra , LaPerche Jacob , Yosef Nir , Dominguez-Villar Margarita , Hafler David A. 
Published: April 2020

ABSTRACTFoxP3 positive regulatory T cells (Tregs) rely on fatty acid β-oxidation (FAO)-driven OXPHOS for differentiation and function. Recent data have demonstrated a role for Tregsin the maintenance of tissue homeostasis with tissue-resident Tregspossessing tissue-specific transcriptomes. However, specific signals that establish these tissue-resident Tregsprograms are largely unknown. As Tregsmetabolically rely on FAO, and considering the lipid-rich environments of tissues, we hypothesized that environmental lipids drive Treghomeostasis. Using human adipose tissue as a model for tissue residency, we identify oleic acid as the most prevalent free fatty acid in human adipose tissue. Mechanistically, oleic acid amplifies TregFAO-driven OXPHOS metabolism, creating a positive feedback mechanism that induces the expression of Foxp3 and enhances phosphorylation of STAT5, which acts to stabilize the Treglineage and increase suppressive function. Comparing the transcriptomic program induced by oleic acid to that of the pro-inflammatory arachidonic acid, we find that Tregssorted from peripheral blood and adipose of healthy donors transcriptomically resemble the oleic acidin vitrotreated Tregs, whereas Tregsobtained from the adipose tissue of relapsing-remitting MS patients more closely resemble an arachidonic acid profile. Finally, we find that oleic acid concentrations are reduced in the fat tissue of MS patients, and exposure of dysfunctional MS Tregsto oleic acid restores defects in their suppressive function. These data demonstrate the importance of fatty acids in regulating tissue inflammatory signals.
Expanding the space of protein geometries by computational design ofde novofold families
Authors: Pan Xingjie , Thompson Michael , Zhang Yang , Liu Lin , Fraser James S. , Kelly Mark J. S. , Kortemme Tanja 
Published: April 2020

AbstractNaturally occurring proteins use a limited set of fold topologies, but vary the precise geometries of structural elements to create distinct shapes optimal for function. Here we present a computational design method termed LUCS that mimics nature’s ability to create families of proteins with the same overall fold but precisely tunable geometries. Through near-exhaustive sampling of loop-helix-loop elements, LUCS generates highly diverse geometries encompassing those found in nature but also surpassing known structure space. Biophysical characterization shows that 17 (38%) out of 45 tested LUCS designs were well folded, including 16 with designed non-native geometries. Four experimentally solved structures closely match the designs. LUCS greatly expands the designable structure space and provides a new paradigm for designing proteins with tunable geometries customizable for novel functions.One Sentence SummaryA computational method to systematically sample loop-helix-loop geometries expands the structure space of designer proteins.