bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning from unexpected events in the neocortical microcircuit
Authors: Gillon Colleen J. , Pina Jason E. , Lecoq Jérôme A. , Ahmed Ruweida , Billeh Yazan N. , Caldejon Shiella , Groblewski Peter , Henley Timothy M. , Kato India , Lee Eric , Luviano Jennifer , Mace Kyla , Nayan Chelsea , Nguyen Thuyanh V. , North Kat , Perkins Jed , Seid Sam , Valley Matthew T. , Williford Ali , Bengio Yoshua , Lillicrap Timothy P. , Richards Blake A. , Zylberberg Joel 
Published: January 2021

AbstractScientists have long conjectured that the neocortex learns the structure of the environment in a predictive, hierarchical manner. According to this conjecture, expected, predictable features are differentiated from unexpected ones by comparing bottom-up and top-down streams of information. It is theorized that the neocortex then changes the representation of incoming stimuli, guided by differences in the responses to expected and unexpected events. In line with this conjecture, different responses to expected and unexpected sensory features have been observed in spiking and somatic calcium events. However, it remains unknown whether these unexpected event signals occur in the distal apical dendrites where many top-down signals are received, and whether these signals govern subsequent changes in the brain’s stimulus representations. Here, we show that both somata and distal apical dendrites of cortical pyramidal neurons exhibit distinct unexpected event signals that systematically change over days. These findings were obtained by tracking the responses of individual somata and dendritic branches of layer 2/3 and layer 5 pyramidal neurons over multiple days in primary visual cortex of awake, behaving mice using two-photon calcium imaging. Many neurons in both layers 2/3 and 5 showed large differences between their responses to expected and unexpected events. Interestingly, these responses evolved in opposite directions in the somata and distal apical dendrites. These differences between the somata and distal apical dendrites may be important for hierarchical computation, given that these two compartments tend to receive bottom-up and top-down information, respectively.
Reduction in transfer of micro-organisms between patients and staff using short-sleeved gowns and hand/arm hygiene in Intensive Care during the Covid pandemic: a simulation-based randomised trial
Authors: Vincent Laura , Ibrahim Mudathir , Kitchin Joanne , Pickering Claire , Wilson Jennie , Sorrentino Enrico , Salvagno Claudia , Earl Laurie , Ma Louise , Simpson Kathryn , Baker Rose , McCulloch Peter 
Published: January 2021

ABSTRACTBackgroundCurrent PPE practices in UK intensive care units involve “sessional” gown use. This protects staff, but puts patients at risk of nosocomial infection via PPE gowns. Anecdotal reports of such infections in ITUs during Covid are frequent. We therefore explored the use of short-sleeved gowns with hand and arm hygiene as an alternative to sessional gowns.MethodsITU Staff were invited for simulation suite training in Covid intubation and proning. They were trained in a specific hand and arm washing technique before performing simulated tasks using both standard and modified (short sleeved) PPE. Fluorescent powder was used to simulate micro-organisms, and detected using standardised photos under U/V light. Teams of staff were randomised to use standard or modified PPE first. Individuals were questioned about their feeling of personal safety, comfort and the patient’s safety at 4 intervals.Results68 staff and 17 proning volunteers were studied in 17 sessions. Modified PPE completely prevented staff contamination during Covid intubation, which occurred in 30/67 staff wearing standard PPE (p = 0.0029, McNemar). Conversely, proning volunteers were contaminated by staff in 15/17 sessions with standard PPE and in 1/17 with modified PPE (P = 0.0227 McNemar). Impressions of staff comfort were superior with modified PPE (p< 0.001, t-test); personal safety scored higher with standard PPE, but the difference decreased during the session (p<0.001 start, 0.068 end). Impressions of patient safety were initially similar (p=0.87) but finished strongly in favour of modified PPE (p<0.001).ConclusionsModified PPE using short sleeves and hand/arm cleansing appears superior to standard PPE with sessional gowns in preventing transfer of contamination between staff and patients. A clinical trial of this strategy is merited.
Maternal prenatal anxiety and depression and trajectories of cardiometabolic risk factors across childhood and adolescence: a prospective cohort study
Authors: Matvienko-Sikar Karen , O’ Neill Kate N , Fraser Abigail , Hayes Catherine , Howe Laura D , Huizink Anja C , Kearney Patricia M , Khashan Ali , Redsell Sarah , O’Keeffe Linda M 
Published: January 2021

AbstractBackgroundQuantifying long-term offspring cardiometabolic health risks associated with maternal prenatal anxiety and depression can guide cardiometabolic risk prevention. This study examines associations between maternal prenatal anxiety and depression, and offspring cardiometabolic risk from birth to 18 years.MethodsParticipants were 526-8,606 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Exposures were anxiety (Crown-Crisp Inventory score) and depression (Edinburgh Postnatal Depression Scale score) measured at 18 and 32 weeks gestation. Outcomes were trajectories of offspring body mass index; fat mass; lean mass; pulse rate; glucose, diastolic and systolic blood pressure; triglycerides, high-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol, and insulin from birth/early childhood to 18 years. Exposures were analysed categorically using clinically relevant, cut-offs and continuously to examine associations across the distribution of prenatal anxiety and depression.ResultsWe found no strong evidence of associations between maternal anxiety and depression, and offspring trajectories of any cardiometabolic risk factors, except for small, inconsistent associations with fat mass trajectories that attenuated upon confounder adjustment. For instance, in unadjusted analyses, anxiety at both 18 and 32 weeks was associated with a 1.8% (95% Confidence Interval (CI), 0.29,3.33) higher mean BMI, which spanned the null (difference (95% CI): 0.7% (−0.76,2.13) after adjustment for confounders.ConclusionsThis is the first examination of maternal prenatal anxiety and depression and trajectories of offspring cardiometabolic risk. Our findings suggest that prevention of maternal prenatal anxiety and depression may have limited impact on offspring cardiometabolic health across the first two decades of life.
Nationwide large-scale data of acute lower gastrointestinal bleeding in Japan uncover detailed etiologies and relevant outcomes: CODE BLUE J-Study
Authors: Nagata Naoyoshi , Kobayashi Katsumasa , Yamauchi Atsushi , Yamada Atsuo , Omori Jun , Ikeya Takashi , Aoyama Taiki , Tominaga Naoyuki , Sato Yoshinori , Kishino Takaaki , Ishii Naoki , Sawada Tsunaki , Murata Masaki , Takao Akinari , Mizukami Kazuhiro , Kinjo Ken , Fujimori Shunji , Uotani Takahiro , Fujita Minoru , Sato Hiroki , Suzuki Sho , Narasaka Toshiaki , Hayasaka Junnosuke , Funabiki Tomohiro , Kinjo Yuzuru , Mizuki Akira , Kiyotoki Shu , Mikami Tatsuya , Gushima Ryosuke , Fujii Hiroyuki , Fuyuno Yuta , Gunji Naohiko , Toya Yosuke , Narimatsu Kazuyuki , Manabe Noriaki , Nagaike Koji , Kinjo Tetsu , Sumida Yorinobu , Funakoshi Sadahiro , Kawagishi Kana , Matsuhashi Tamotsu , Komaki Yuga , Miki Kuniko , Watanabe Kazuhiro , Fukuzawa Masakatsu , Itoi Takao , Uemura Naomi , Kawai Takashi , Kaise Mitsuru 
Published: January 2021

AbstractBackgroundThe value of endoscopy for acute lower GI bleeding (ALGIB) remains unclear, given few large cohort studies. We aim to provide detailed clinical data for ALGIB management and to identify patients at risk for adverse outcomes based on endoscopic diagnosis.MethodsWe conducted a multicenter, retrospective cohort study, named CODE BLUE J-Study, in 49 hospitals throughout Japan and studied 10,342 cases admitted for outpatient-onset of acute hematochezia.ResultsCases were mostly elderly, with 29.5% hemodynamic instability and 60.1% comorbidity. 69.1% and 87.7 % of cases underwent CT and colonoscopy, respectively. Diagnostic yield of colonoscopy reached 94.9%, revealing 48 etiologies, most frequently diverticular bleeding. During hospitalization, the endoscopic therapy rate was 32.7%, mostly using clipping and band ligation. IVR and surgery were infrequently performed, for 2.1% and 1.4%. In-hospital rebleeding and death occurred in 15.2% and 0.9%. Diverticular bleeding cases had higher rates of hemodynamic instability, rebleeding, endoscopic therapy, IVR, and transfusion, but lower rates of death and surgery than other etiologies. Small bowel bleeding cases had significantly higher rates of surgery, IVR, and transfusion than other etiologies. Malignancy or upper GIB cases had significantly higher rates of thromboembolism and death than other etiologies. Etiologies that have favorable outcomes were ischemic colitis, infectious colitis, and post-endoscopy bleeding.ConclusionsLarge-scale data of patients with acute hematochezia revealed high proportions of colonoscopy and CT, resulting in high endoscopic therapy rates. We highlight the importance of colonoscopy in detecting accurate bleeding etiologies that stratify patients at high or low risk of adverse outcomes.
Brassinosteroid signaling component SlBES1 promotes tomato fruit softening through transcriptional repression ofPMEU1
Authors: Liu Haoran , Liu Lihong , Liang Dongyi , Zhang Min , Jia Chengguo , Qi Mingfang , Liu Yuanyuan , Shao Zhiyong , Meng Fanliang , Hu Songshen , Li Chuanyou , Wang Qiaomei 
Published: January 2021

ABSTRACTFirmness is one of the most important factors that affect postharvest properties of tomato fruit. However, the regulatory mechanism underlying firmness formation in tomato fruit is poorly understood. Here, we report a novel role of SlBES1, a transcriptional factor (TF) mediating brassinosteroid (BR) signaling, in tomato fruit softening. We first found that SlBES1 promotes fruit softening during tomato fruit ripening and postharvest storage. RNA-seq analysis suggested thatPMEU1, which encodes a pectin de-methylesterification protein, might participate in SlBES1-mediated fruit softening. Biochemical and immunofluorescence assays inSlBES1transgenic fruits indicated that SlBES1 inhibitedPMEU1-related pectin de-methylesterification. Further molecular and genetic evidence verified that SlBES1 directly binds to the E-box in the promoter ofPMEU1to repress its expression, leading to the softening of the tomato fruits. Loss-of-functionSlBES1mutant generated by CRISPR/cas9 showed firmer fruits and longer shelf life during postharvest storage without the color, size and nutritional quality alteration. Collectively, our results indicated the potential of manipulatingSlBES1to regulate fruit firmness via transcriptional inhibition ofPMEU1without negative consequence on visual and nutrition quality.
Loss of Cysteine Rich domain was critical for evolution of heterodimerization in Toll proteins
Authors: Ranga Poonam , Sawanth Suresh Kumar , Mrinal Nirotpal 
Published: January 2021

AbstractToll proteins play roles in immunity/development which have largely remained conserved. However, there are differences in Toll biology as mammalian TLRs recognise pathogen associated molecular patterns (PAMPs) but not their invertebrate homologues. The reason for the same is not known. One critical molecular difference is absence of Cysteine Rich Domain (CRD) in vertebrate Tolls and their presence in invertebrates. Interestingly, in Drosophila, all Toll proteins have CRD except Toll9. This provided us the appropriate model to investigate significance of loss of CRD in Toll evolution. CRDs nudge protein dimerization by forming disulphide bonds hence we asked if they did same in Drosophila Toll-proteins. We tested if, Toll-1(which forms homodimer) can heterodimerize with Toll-9. We found that wildtype Toll-1 didn’t interact with Toll9 however; when CRD of Toll1 was deleted/mutated it formed heterodimer with Toll9. This indicates that presence of CRD limits Toll proteins to form homodimer and thus its loss was a critical event which pushed Toll proteins towards heterodimerization. We further show that Drosophila Toll9 can directly bind dsRNA, a PAMP. Interestingly, dsRNA affinity for toll-9 monomer was twice as that for the dimer, which can be attributed to CRD loss. Thus, we show that loss of CRD was a major step in Toll evolution as it resulted in functional diversity and was a first step towards heterodimer formation. Therefore, we propose that CRD loss was under positive selection and also that heterodimerization of Toll-proteins is an evolved property.One line summaryLoss of Cysteine Rich Domain in Drosophila Toll9 and recognition of dsRNA.
Immunoengineered Nanobead System for the Isolation and Detection of Circulating Tumor Cells
Authors: Zhang Pengfei , Draz Mohamed S. , Xiong Anwen , Yan Wannian , Han Huanxing , Chen Wansheng 
Published: January 2021

AbstractHighly efficient capture and detection of circulating tumor cells (CTCs) remain elusive mainly because of their extremely low concentration in the peripheral blood of patients. Herein, we present an approach for the simultaneous capturing, isolation, and detection of CTCs using an immuno-fluorescent magnetic nanobead system (iFMNS) coated with a monoclonal anti-EpCAM antibody. The developed antibody nanobead system allows magnetic isolation and fluorescent-based quantification of CTCs. The expression of EpCAM on the surface of captured CTCs could be directly visualized without additional immune-fluorescent labeling. Our approach is shown to result in a 70 - 95% capture efficiency of CTCs, and 95% of the captured cells remain viable. Using our approach, the isolated cells could be directly used for culture, reverse transcription-polymerase chain reaction (RT-PCR), and immunocytochemistry (ICC) identification. We applied iFMNS for testing CTCs in peripheral blood samples from a lung cancer patient, which suggested that this approach would be a promising tool for CTCs enrichment and detection in one step.
Evaluation of the effects of SARS-CoV-2 genetic mutations on diagnostic RT-PCR assays
Authors: Nakabayashi Takeru , Kawasaki Yuki , Murashima Koichiro , Omi Kazuya , Yuhara Satoshi 
Published: January 2021

AbstractSeveral mutant strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are emerging. Mismatch(es) in primer/probe binding regions would decrease the detection sensitivity of the PCR test, thereby affecting the results of clinical testing. In this study, we conducted an in silico survey on SARS-CoV-2 sequence variability within the binding regions of primer/probe published by the Japan National Institute of Infectious Diseases (NIID) and Centers for Disease Control and Prevention (CDC). In silico analysis revealed the presence of mutations in the primer/probe binding regions. We performed RT-PCR assays using synthetic RNAs containing the mutations and showed that some mutations significantly decreased the detection sensitivity of the RT-PCR assays.Our results highlight the importance of genomic monitoring of SARS-CoV-2 and evaluating the effects of mismatches on PCR testing sensitivity.
Individuality, as well as genotype, affects characteristics and temporal consistency of courtship songs in male mice
Authors: Melotti Luca , Siestrup Sophie , Peng Maja , Vitali Valerio , Dowling Daniel , Sachser Norbert , Kaiser Sylvia , Richter S. Helene 
Published: January 2021

ABSTRACTCourtship songs in mice have been investigated to understand the mechanisms and ecological relevance of vocal communication. There is evidence that courtship song characteristics vary between different genotypes, but little is known on whether individuals, even within the same genotype, differ from each other in the composition, complexity, and temporal consistency of their songs. In a first study, we aimed to systematically identify song features typical of different genotypes, by assessing the composition and complexity (i.e., entropy) of the syllabic sequences of male laboratory mice from four different strains(Mus musculusf.domestica:C57BL/6J, BALB/c, DBA/2 and B6D2F1). Mice were individually presented with a swab containing fresh female urine for 5 minutes to elicit courtship songs. The four strains differed not only in the composition but also in the complexity of their syllabic sequences. In a second study, we investigated within-strain individual differences in temporal consistency and recurring motifs (i.e., identical sets of syllables that are repeated within a song), using BALB/c and DBA/2 mice. The same procedure as in the first study was followed, but in addition testing was repeated weekly over three weeks. Both strains showed some level of individual temporal consistency; BALB/c in the overall amount of emitted vocalisations and DBA/2 in the expression of specific syllable types. However, hierarchical cluster analysis revealed remarkable individual variability in how consistent song characteristics were over time. Furthermore, recurring motifs were expressed at varying levels depending on the individual. Taken together, not only genotype but also individuality can affect variability in courtship songs in mice, suggesting the existence of different courtship strategies (e.g., higher song consistency to facilitate individual identification) related to varying levels of behavioural plasticity.HIGHLIGHTSCourtship songs in mice can serve as a model to study vocal communicationWe explore how genotype and individuality affect courtship songs’ characteristicsGenotypes differ in composition and also in complexity of syllabic sequencesWe find remarkable individual variability in how consistent songs are over timeResults suggest the existence of variation in male courting behaviour
Evolution of phenotypic variance in response to a novel hot environment
Authors: Lai Wei-Yun , Schlötterer Christian 
Published: January 2021

AbstractShifts in trait means are widely considered as evidence for adaptive responses, but the impact on phenotypic variance remains largely unexplored. Classic quantitative genetics provides a theoretical framework to predict how selection on phenotypic mean affects the variance. In addition to this indirect effect, it is also possible that the variance of the trait is the direct target of selection, but experimentally characterized cases are rare. Here, we studied gene expression variance ofDrosophila simulansmales before and after 100 generations of adaptation to a novel hot laboratory environment. In each of the two independently evolved populations, the variance of 125 and 97 genes was significantly reduced. We propose that the drastic loss in environmental complexity from nature to the lab may have triggered selection for reduced variance. Our observation that selection could drive changes in the variance of gene expression could have important implications for studies of adaptation processes in natural and experimental populations.
SARS-CoV-2 infection of circulating immune cells is not responsible for virus dissemination in severe COVID-19 patients
Authors: Rosin Nicole L. , Jaffer Arzina , Sinha Sarthak , Mulloy Rory P. , Robinson Carolyn , Labit Elodie , Almeida Luiz G. , Dufour Antoine , Corcoran Jennifer A. , Yipp Bryan , Biernaskie Jeff 
Published: January 2021

SummaryIn late 2019 a novel coronavirus (SARS-CoV-2) emerged, and has since caused a global pandemic. Understanding the pathogenesis of COVID-19 disease is necessary to inform development of therapeutics, and management of infected patients. Using scRNAseq of blood drawn from SARS-CoV-2 patients, we asked whether SARS-CoV-2 may exploit immune cells as a ‘Trojan Horse’ to disseminate and access multiple organ systems. Our data suggests that circulating cells are not actively infected with SARS-CoV-2, and do not appear to be a source of viral dissemination.
NF-kB c-Rel is dispensable for the development but is required for the cytotoxic function of NK cells
Authors: Vicioso Y , Zhang K , Ramakrishnan Parameswaran , Parameswaran Reshmi 
Published: January 2021

AbstractNatural Killer (NK) cells are cytotoxic lymphocytes critical to the innate immune system. We found that germline deficiency of NF-kB c-Rel results in a marked decrease in cytotoxic function of NK cells, both in vitro and in vivo, with no significant differences in the stages of NK cell development. We found that c-Rel binds to the promoters of perforin and granzyme B, two key proteins required for NK cytotoxicity, and controls their transactivation. We generated a NK cell specific c-Rel conditional knockout to study NK cell intrinsic role of c-Rel and found that both global and conditional c-Rel deficiency leads to decreased perforin and granzyme B expression and thereby cytotoxic function. We also confirmed the role of c-Rel in perforin and granzyme B expression in human NK cells. c-Rel reconstitution rescued perforin and granzyme B expressions in c-Rel deficient NK cells and restored their cytotoxic function. Our results show a previously unknown role of c-Rel in transcriptional regulation of perforin and granzyme B expressions and control of NK cell cytotoxic function.
Dihydroartemisinin attenuated the symptoms of mice model of systemic lupus erythematosus by restoring the Treg/Th17 balance
Authors: Chen Yan , Tao Tingjun , Wang Weiliang , Yang Botao , Cha Xushan 
Published: January 2021

AbstractThe Treg/Th17 imbalance is associated with the development of systemic lupus erythematosus (SLE). Dihydroartemisinin (DHA), a semi‐synthetic derivative of artemisinin, is isolated from the traditional Chinese herb Artemisia annuaArtemisia annua L. This study aims to evaluate the effects of DHA alone or in combination with prednisone in immunodeficiency of SLE. In vivo, the therapeutical effect of DHA alone or in combination with prednisone was assessed in the pristane‐induced SLE mouse model. Then, the level of serum antibodies, creatinine (Cre), blood urea nitrogen (BUN), urine protein, kidney histopathology, interleukin (IL)‐17, IL‐6, transforming growth factor (TGF)‐β, the expression of RORγt and Foxp3, the percentages of Treg and Th17 in peripheral blood and spleen were assayed. In vitro, the mouse spleen lymphocytes were separated and treated with DHA alone or DHA in combination with prednisone. Then the percentages of Treg and Th17, the concentration of IL‐17, IL‐6, TGF‐β, and the expression of RORγt and Foxp3 were assayed. It was shown that DHA alone or in combination with prednisone treatment significantly alleviated the manifestations of pristane‐induced SLE mice, suppressed inflammation and restored the Treg/Th17 balance. DHA alone or in combination with prednisone significantly inhibited Th17 cell differentiation while induced Treg cell differentiation in vitro. DHA alone or in combination with prednisone also reduced the transcription of RORγt and increased Foxp3 in lymphocytes, as well as IL‐17 and TGF‐β levels. Our data indicated that DHA can produce synergistic effect with prednisone to attenuate the symptoms of SLE by restoring Treg/Th17 balance.
Embedding Impact in Research: Addressing the Interactional Production of Workplace Activities
Authors: vom Lehn Dirk , Heath Christian 
Published: January 2021

AbstractAs scholars both in the UK and we discuss a distinctive approach to developing impact that rests upon close cooperation between academics and practitioners from the outset of a particular project. The approach draws upon ethnomethodology and conversation analysis and addresses the social and interactional foundations of work and organization, an approach that increasingly uses video‐recordings of everyday activities augmented by field studies. We discuss examples drawn from our own research, projects concerned with such matters as eye tests, auctions of fine art and urban transport, and seek to show that developing impact in cooperation with practitioners does not necessitate compromising the academic contribution of research.