bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative of the Effectiveness of Different Objective Method for Infraclavicular Brachial Plexus Block Success; Which One of Them is A Reliable and Early Indicator?
Authors: Şengel Abdulhakim , Karahan Mahmut Alp , Altay Nuray , Binici Orhan , Pehlivan Veli Fahri , Atlas Ahmet 
Published: June 2021

ABSTRACTBACKGROUNDTraditional methods that evaluate the success of peripheral nerve block have been replaced by methods that allow objective evaluations over time. Multiple objective techniques for peripheral nerve block have been discussed in the literature.OBJECTIVEThis study aims to investigate whether perfusion index (PI), non-invasive tissue hemoglobin monitoring (SpHb), tissue oxygen saturation (StO2), tissue hemoglobin index (THI) and body temperature are reliable and objective methods to evaluate the adequacy of infraclavicular blockage.DESIGNA prospective observational study.SETTINGSingle center, Department of Anesthesiology, Harran University Medical Faculty, Turkey, from February 2019 to December 2019.PATIENTSA total of 100 patients scheduled to undergo forearm surgery.INTERVENTIONUltrasound-guided infraclavicular block (ICB) in 100 patients undergoing forearm surgery.MAIN OUTCOME MEASURESPI, SpHb, StO2, THI and Body Temperature measurements were recorded 5 min before the block procedure, right after the procedure, and until the 25th minute after the procedure at 5-min intervals. These values were compared between the blocked limbs and non-blocked limbs while being statistically compared between the successful and failed block groups.RESULTSAlthough there were significant differences between the groups of blocked extremity and non-blocked extremity in terms of StO2 (P = 0.001), THI (P = 0.001), PI (P = 0.001) and body temperature (P = 0.001), there was no significant difference between these groups in terms of SpHb (P > 0.05). Moreover, a significant difference was detected between the groups of successful block and failed block in terms of StO2 (P = 0.002), PI (P = 0.002) and body temperature (P = 0.005), while there was no significant difference between these groups in terms of THI (P > 0.05) and SpHb (P > 0.05).CONCLUSIONStO2, PI and body temperature measurements are the simple, objective, noninvasive techniques to be used to evaluate success of block procedures. According to The receiver operating characteristic (ROC) analysis, StO2 is the specific parameter with the highest sensitivity among these parameters.TRIAL REGISTRATIONACTRN12621000588897
Minimizing the infected peak utilizing a single lockdown: a technical result regarding equal peaks
Authors: Greene James M. , Sontag Eduardo D. 
Published: June 2021

AbstractDue to the usage of social distancing as a means to control the spread of the novel coronavirus disease COVID-19, there has been a large amount of research into the dynamics of epidemiological models with time-varying transmission rates. Such studies attempt to capture population responses to differing levels of social distancing, and are used for designing policies which both inhibit disease spread but also allow for limited economic activity. One common criterion utilized for the recent pandemic is the peak of the infected population, a measure of the strain placed upon the health care system; protocols which reduce this peak are commonly said to ‘flatten the curve.” In this work, we consider a very specialized distancing mandate, which consists of one period of fixed length of distancing, and addresses the question of optimal initiation time. We prove rigorously that this time is characterized by an equal peaks phenomenon: the optimal protocol will experience a rebound in the infected peak after distancing is relaxed, which is equal in size to the peak when distancing is commenced. In the case of a non-perfect lockdown (i.e. disease transmission is not completely suppressed), explicit formulas for the initiation time cannot be computed, but implicit relations are provided which can be pre-computed given the current state of the epidemic. Expected extensions to more general distancing policies are also hypothesized, which suggest designs for the optimal timing of non-overlapping lockdowns.
Interrogation of genome-wide, experimentally dissected gene regulatory networks reveals mechanisms underlying dynamic cellular state control
Authors: Tan Xiangtian , Worley Jeremy , Turunen Mikko , Wong Kelly , Fernández Ester Calvo , Paull Evan , Jones Sunny , Wang Junqiang , Noh Heeju , Salvatori Beatrice , Chavez Alejandro , Califano Andrea 
Published: June 2021

AbstractPooled CRISPRi-mediated silencing of >1,000 transcriptional regulators expressed in single colorectal adenocarcinoma cells, followed by single-cell RNA-seq profiling at two timepoints, 1 day and 4 days, allowed reverse engineering the underlying tumor context-specific, causal regulatory network. Furthermore, the availability of experimentally derived, highly multiplexed gene reporter assays for each regulator, as identified by this analysis, allowed accurate assessment of differential protein activity following silencing of each regulator, thus providing proof-of-concept for generating comprehensive, tissue-specific networks of transcriptional and post-translational interactions. Analysis of this causal network allowed elucidation of complex autoregulatory mechanisms that have eluded previous computational approaches and supported systematic elucidation of cooperative mechanisms, where one regulatory protein can modulate the activity of another regulatory protein, as well as transcriptional mimicry, where one regulatory protein can phenocopy others.
A chromosome-level genome sequence of a model chrysanthemum: evolution and reference for hexaploid cultivated chrysanthemum
Authors: Nakano Michiharu , Hirakawa Hideki , Fukai Eigo , Toyoda Atsushi , Kajitani Rei , Minakuchi Yohei , Itoh Takehiko , Higuchi Yohei , Kozuka Toshiaki , Bono Hidemasa , Shirasawa Kenta , Shiraiwa Ippei , Sumitomo Katsuhiko , Hisamatsu Tamotsu , Shibata Michio , Isobe Sachiko , Taniguchi Kenji , Kusaba Makoto 
Published: June 2021

AbstractChrysanthemums are one of the most industrially important cut flowers worldwide. However, their segmental allopolyploidy and self-incompatibility have prevented the application of genetic analysis and modern breeding strategies. We thus developed a model strain, Gojo-0 (Chrysanthemum seticuspe), which is a diploid and self-compatible pure line. Here, we present the 3.05 Gb chromosome-level reference genome sequence, which covered 97% of the C. seticuspe genome. The genome contained more than 80% interspread repeats, of which retrotransposons accounted for 72%. We identified recent segmental duplication and retrotransposon expansion in C. seticuspe, contributing to a relatively large genome size. Furthermore, we identified aretrotransposon, SbdRT, which was enriched in gene-dense genome regions and had experienced a very recent transposition burst. We also demonstrated that the chromosome-level genome sequence facilitates positional cloning in C. seticuspe. The genome sequence obtained here can greatly contribute as a reference for chrysanthemum in front-line breeding including genome editing.
GuideMaker: Software to design CRISPR-Cas guide RNA pools in non-model genomes
Authors: Poudel Ravin , Rodriguez Lidimarie Trujillo , Reisch Christopher R. , Rivers Adam R. 
Published: June 2021

AbstractBackgroundCRISPR-Cas systems have expanded the possibilities for gene editing in bacteria and eukaryotes. There are many excellent tools for designing the CRISPR-Cas guide RNAs for model organisms with standard Cas enzymes. GuideMaker is intended as a fast and easy-to-use design tool for atypical projects with 1) non-standard Cas enzymes, 2) non-model organisms, or 3) projects that need to design a panel of guide RNAs (gRNA) for genome-wide screens.FindingsGuideMaker can rapidly design gRNAs for gene targets across the genome from a degenerate protospacer adjacent motif (PAM) and a GenBank file. The tool applies Hierarchical Navigable Small World (HNSW) graphs to speed up the comparison of guide RNAs. This allows the user to design gRNAs targeting all genes in a typical bacterial genome in about 1-2 minutes.ConclusionsGuidemaker enables the rapid design of genome-wide gRNA for any CRISPR-Cas enzyme in non-model organisms. While GuideMaker is designed with prokaryotic genomes in mind, it can efficiently process smaller eukaryotic genomes as well. GuideMaker is available as command-line software, a stand-alone web application, and a tool in the CyCverse Discovery Environment. All versions are available under a Creative Commons CC0 1.0 Universal Public Domain Dedication.
A centronuclear myopathy-causing mutation in dynamin-2 perturbs the actin-dependent structure of dendritic spines leading to excitatory synaptic defects in a murine model of the disease
Authors: Arriagada-Diaz Jorge , Gómez Bárbara , Prado-Vega Lorena , Mattar-Araos Michelle , Labraña-Allende Marjorie , Hinostroza Fernando , Gajardo Ivana , Guerra-Fernández María José , Bevilacqua Jorge A. , Cárdenas Ana M. , Bitoun Marc , Ardiles Alvaro O. , Gonzalez-Jamett Arlek M. 
Published: June 2021

AbstractDynamin-2 is a large GTP-ase, member of the dynamin superfamily, that regulates membrane remodeling and cytoskeleton dynamics. In the mammalian nervous system dynamin-2 modulates synaptic vesicle (SV)-recycling at the nerve terminals and receptor-trafficking to and from postsynaptic densities (PSDs). Mutations in dynamin-2 cause autosomal dominant centronuclear myopathy (CNM), a congenital neuromuscular disorder characterized by progressive weakness and atrophy of distal skeletal muscles. Cognitive defects have also been reported in dynamin-2-linked CNM patients suggesting a concomitant impairment of the central nervous system. Here we addressed the mechanisms that lead to cognitive defects in dynamin-2-linked CNM using a knock-in mouse model that harbors the p.R465W mutation in dynamin-2, the most common causing CNM. Our results show that these mice exhibit reduced capability to learn and acquire spatial and recognition memory, impaired long-term potentiation of the excitatory synaptic strength and perturbed dendritic spine morphology, which seem to be associated with actin defects. Together, these data reveal for the first time that structural and functional synaptic defects underlie cognitive defects in the CNM context. In addition our results contribute to the still scarce knowledge about the importance of dynamin-2 at central synapses.
THERAPEUTIC EFFECTS OF HYPOXIC AND PRO-INFLAMMATORY PRIMING OF MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES IN INFLAMMATORY ARTHRITIS
Authors: Kay Alasdair G. , Treadwell Kane , Roach Paul , Morgan Rebecca , Lodge Rhys , Hyland Mairead , Piccinini Anna M. , Forsyth Nicholas , Kehoe Oksana 
Published: June 2021

AbstractNovel biological therapies have revolutionised the management of Rheumatoid Arthritis (RA) but no cure currently exists. Mesenchymal stem cells (MSCs) immunomodulate inflammatory responses through paracrine signalling, including via secretion of extracellular vesicles (EVs) in the cell secretome. We evaluated the therapeutic potential of MSCs-derived small EVs in an antigen-induced model of arthritis (AIA).EVs isolated from MSCs cultured normoxically (21% O2, 5% CO2), hypoxically (2% O2, 5% CO2) or with a pro-inflammatory cytokine cocktail were applied into the AIA model. Disease pathology was assessed post-arthritis induction through swelling and histopathological analysis of synovial joint structure. Activated CD4+ T cells from healthy mice were cultured with EVs or MSCs to assess deactivation capabilities prior to application of standard EVs in vivo to assess T cell polarisation within the immune response to AIA.All EVs treatments reduced knee-joint swelling whilst only normoxic and pro-inflammatory primed EVs improved histopathological outcomes. In vitro culture with EVs did not achieve T cell deactivation. Polarisation towards CD4+ helper cells expressing IL17a (Th17) was reduced when normoxic and hypoxic EV treatments were applied in vitro. Normoxic EVs applied into the AIA model reduced Th17 polarisation and improved Th17:Treg homeostatic balance.Priming of MSCs in EV production can be applied to alter the therapeutic efficacy however normoxic EVs present the optimal strategy for broad therapeutic benefit. The varied outcomes observed in MSCs priming may promote EVs optimised for therapies targeted for specific therapeutic priorities. EVs present an effective novel technology with potential for cell-free therapeutic translation.
Epigenetic Regulation of Nuclear Lamina-Associated Heterochromatin by HAT1 and the Acetylation of Newly Synthesized Histones
Authors: Popova Liudmila V. , Nagarajan Prabakaran , Lovejoy Callie M. , Sunkel Benjamin D. , Gardner Miranda L. , Wang Meng , Freitas Michael A. , Stanton Benjamin Z. , Parthun Mark R. 
Published: June 2021

AbstractDuring S phase, eukaryotic cells must faithfully duplicate both the sequence of the genome and the regulatory information found in the epigenome. A central component of the epigenome is the pattern of histone post-translational modifications that play a critical role in the formation of specific chromatin states. During DNA replication, parental nucleosomes are disrupted and re-deposited on the nascent DNA near their original location to preserve the spatial memory of the epigenetic modifications. Newly synthesized histones must also be incorporated into the nascent chromatin to maintain nucleosome density. Transfer of modification patterns from parental histones to new histones is a fundamental step in epigenetic inheritance. Whether new histones play an active or passive role in epigenetic inheritance is unknown. Here we report that HAT1, which acetylates lysines 5 and 12 of newly synthesized histone H4 during replication-coupled chromatin assembly, regulates the epigenetic inheritance of chromatin states. HAT1 regulates the accessibility of large domains of heterochromatin termed HAT1-dependent Accessibility Domains (HADs). HADs are mega base-scale domains that comprise ~10% of the mouse genome. HAT1 functions as a global negative regulator of H3 K9me2/3 and HADs correspond to the regions of the genome that display HAT1-dependent increases in H3 K9me3 peak density. HADs display a high degree of overlap with a subset of Lamin-Associated Domains (LADs). HAT1 is required to maintain nuclear structure and integrity. These results indicate that HAT1 and the acetylation of newly synthesized histones are critical regulators of the epigenetic inheritance of heterochromatin and suggest a new mechanism for the epigenetic regulation of nuclear lamina-heterochromatin interactions.
Plant lipid metabolism in susceptible and tolerant soybean (Glycine max) cultivars in response to Phytophthora sojae colonization and infection
Authors: Adigun Oludoyin Adeseun , Pham Thu Huong , Grapov Dmitry , Nadeem Muhammad , Jewell Linda Elizabeth , Cheema Mumtaz , Galagedara Lakshman , Thomas Raymond 
Published: June 2021

AbstractSoybean is one of the most cultivated crops globally and a staple food for much of the world’s population. The annual global crop losses due to infection by the Phytophthora sojae are currently estimated at approximately $2B USD, yet we have limited understanding of the role of lipid metabolism in the adaptative strategies used to limit infection and crop loss. We employed a multi-modal lipidomics approach to investigate how soybean cultivars remodel their lipid metabolism to successfully limit infection by Phytophthora sojae. Both the tolerant and susceptible soybean cultivars showed alterations in lipid metabolism in response to Phytophthora sojae infection. Relative to non-inoculated controls, induced accumulation of stigmasterol was observed in the susceptible cultivar whereas, induced accumulation of phospholipids and glycerolipids occurred in tolerant soybean cultivar. We have generated a comprehensive metabolic map of susceptible and tolerant soybean root and stem lipid metabolism to identify lipid modulators of host immune or tolerance response to Phytophthora sojae infection and identified potential pathways and unique lipid biomarkers like TG(15:0/22:0/22:5), TG(10:0/10:0/10:0), TG(10:0/10:0/14:0), DG(18:3/18:3), DG(16:0/18:3) and DG(24:0/18:2) as possible targets for the development of future plant protection solutions.
Neural Correlates of Value-Driven Spatial Attention
Authors: Liao Ming-Ray , Kim Andy J. , Anderson Brian A. 
Published: June 2021

ABSTRACTReward learning has been shown to habitually guide spatial attention to regions of a scene. However, the neural mechanisms that support this bias in spatial orienting are unknown. In the present study, participants learned to orient to a particular quadrant of a scene (high-value quadrant) to maximize monetary gains. This learning was scene-specific, with the high-value quadrant varying across different scenes. During a subsequent test phase, participants were faster at identifying a target if it appeared in the high-value quadrant (valid), and initial saccades were more likely to be made to the high-value quadrant. fMRI analyses during the test phase revealed learning-dependent priority signals in the bilateral caudate tail and superior colliculus, frontal eye field, substantia nigra, and insula, paralleling findings concerning feature-based value-driven attention. In addition, ventral regions typically associated with scene selective and spatial information processing, including the hippocampus, parahippocampal gyrus, and temporo-occipital cortex, were also implicated. Taken together, our findings offer new insights into the neural architecture subserving value-driven attention, both extending our understanding of nodes in the attention network previously implicated in feature-based value-driven attention and identifying a ventral network of brain regions implicated in reward’s influence on scene-dependent spatial orienting.
Optogenetic suppression of corticogeniculate feedback in anesthetized ferrets is overridden by visual stimulation
Authors: Zhu S. , Hasse J.M. , Briggs F. 
Published: June 2021

AbstractThe feedforward projection from the retina shapes the spatial receptive field properties of neurons in the dorsal lateral geniculate nucleus of the thalamus (LGN). Corticogeniculate feedback from the visual cortex appears to exert a more subtle, modulatory influence on LGN responses. Studies involving manipulations of corticogeniculate feedback have yielded inconsistent findings, but the reasons for these inconsistencies are not known. To examine the functional contributions of corticogeniculate feedback, and to resolve past inconsistencies, we examined the effects of selective optogenetic suppression of corticogeniculate neurons in anesthetized ferrets. In particular, we examined the responses of LGN and V1 neurons during optogenetic suppression of corticogeniculate feedback in the presence and absence of visual stimulation and across conditions in which the frequency of LED illumination varied. Optogenetic suppression of corticogeniculate feedback decreased activity among LGN neurons in the absence of visual stimulation, dispelling the notion that anesthesia causes a floor effect. In contrast, suppressing corticogeniculate feedback did not affect the visual responses of LGN neurons, suggesting that feedforward visual stimulus drive overrides weak corticogeniculate influence. Optogenetic effects on LGN and V1 neuronal responses depended on the frequency of LED illumination, with higher frequency illumination inducing slow oscillations in V1, dis-inhibiting V1 neurons locally, and producing more suppression among LGN neurons. These results demonstrate that corticogeniculate influence depends on stimulation parameters including visual stimulus conditions and frequency of inactivation. Furthermore, weak corticogeniculate influence is overridden by strong feedforward visual stimulus drive – this attribute is the most likely source of inconsistencies in past studies.Significance StatementAlthough corticogeniculate synapses onto thalamic neurons far outnumber those coming from the retina, the function of corticogeniculate feedback in vision has remained a stubborn puzzle. Prior studies of corticogeniculate feedback have yielded inconsistent findings, but the source for these inconsistencies is unknown. We utilized selective optogenetic suppression of corticogeniculate feedback to examine its effects on thalamic neuronal responses and to resolve sources of prior inconsistencies. We found that suppression of corticogeniculate feedback reduced thalamic responses, but only in the absence of visual input. This suggests that the major source of inconsistencies across prior studies is the fact that weak corticogeniculate influence is overcome by strong feedforward visual stimulus drive.
Are microbes growing on flowers evil? Effects of old flower microbes on fruit set in a wild ginger with one-day flowers, Alpinia japonica (Zingiberaceae)
Authors: Elvira Nuria Jiménez , Ushio Masayuki , Sakai Shoko 
Published: June 2021

AbstractFlowers are colonized and inhabited by diverse microbes. Plants rapidly replace flowers with short lifespan, and old flowers senesce. This may contribute to avoiding adverse effects of the microbes. In this study, we investigate if the flower microbial community on old flowers impedes fruit and seed production in a wild ginger with one-day flowers. We inoculated newly opened flowers with old flower microbes, and monitored the effects on fruit and seed set. We also assessed prokaryotic communities on the flowers using amplicon sequencing. We found six bacterial amplicon sequence variants (ASVs) whose proportions were increased on the inoculated flowers. These ASVs were also found on flower buds and flowers that were bagged by net or paper during anthesis, suggesting that they had been present in small numbers prior to flowering. Fruit set was negatively associated with the proportions of these ASVs, while seed set was not. The results suggest that old flowers harbor microbial communities different from those at anthesis, and that the microbes abundant on old flowers negatively affect plant reproduction. Though the short lifespan of flowers has gotten little attention, it might be an essential defense mechanism to cope with antagonistic microbes that rapidly proliferate on the flowers.
MICRA-Net: MICRoscopy Analysis Neural Network to solve detection, classification, and segmentation from a single simple auxiliary task
Authors: Bilodeau Anthony , Delmas Constantin V.L. , Parent Martin , De Koninck Paul , Durand Audrey , Lavoie-Cardinal Flavie 
Published: June 2021

AbstractHigh throughput quantitative analysis of microscopy images presents a challenge due to the complexity of the image content and the difficulty to retrieve precisely annotated datasets. In this paper we introduce a weakly-supervised MICRoscopy Analysis neural network (MICRA-Net) that can be trained on a simple main classification task using image-level annotations to solve multiple the more complex auxiliary semantic segmentation task and other associated tasks such as detection or enumeration. MICRA-Net relies on the latent information embedded within a trained model to achieve performances similar to state-of-the-art architectures when no precisely annotated dataset is available. This learnt information is extracted from the network using gradient class activation maps, which are combined to generate detailed feature maps of the biological structures of interest. We demonstrate how MICRA-Net significantly alleviates the Expert annotation process on various microscopy datasets and can be used for high-throughput quantitative analysis of microscopy images.