bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optical Cellular Micromotion: A New Paradigm to Measure Tumour Cells Invasion in 3D Tumour Environments
Authors: Guo Zhaobin , Yang Chih-Tsung , Chien Chia-Chi , Selth Luke A. , Bagnaninchi Pierre O. , Thierry Benjamin 
Published: August 2021

AbstractMeasuring tumour cell invasiveness through three-dimensional (3D) tissues, particularly at the single cell level, can provide important mechanistic understanding and assist in identifying therapeutic targets of tumour invasion. However, current experimental approaches, including standard in vitro invasion assays, have limited physiological relevance and offer insufficient insight about the vast heterogeneity in tumour cell migration through tissues. To address these issues, here we report on the concept of optical cellular micromotion, where digital holographic microscopy (DHM) is used to map the optical thickness fluctuations at sub-micron scale within single cells. These fluctuations are driven by the dynamic movement of subcellular structures including the cytoskeleton and inherently associated with the biological processes involved in cell invasion within tissues. We experimentally demonstrate that the optical cellular micromotion correlates with tumour cells motility and invasiveness both at the population and single cell levels. In addition, the optical cellular micromotion significantly reduced upon treatment with migrastatic drugs that inhibit tumour cell invasion. These results demonstrate that micromotion measurements can rapidly and non-invasively determine the invasive behaviour of single tumour cells within tissues, yielding a new and powerful tool to assess the efficacy of approaches targeting tumour cell invasiveness.Significance StatementTumour cells invasion through tissues is a key hallmark of malignant tumour progression and its measurement is essential to unraveling biological processes and screening for new approaches targeting cell motility. To address the limitations of current approaches, we demonstrate that sub-micron scale mapping of the dynamic optical thickness fluctuations within single cells, referred to as optical cellular micromotion, correlates with their motility in ECM mimicking gel, both at the population and single cell levels. We anticipate that 3D optical micromotion measurement will provide a powerful new tool to address important biological questions and screen for new approaches targeting tumour cell invasiveness.
Thermosynechococcus switches the direction of phototaxis by a c-di-GMP dependent process with high spatial resolution
Authors: Nakane Daisuke , Enomoto Gen , Wilde Annegret , Nishizaka Takayuki 
Published: August 2021

AbstractMany cyanobacteria, which use light as an energy source via photosynthesis, show directional movement towards or away from a light source. However, the molecular and cell biological mechanisms for switching the direction of movement remain unclear. Here, we visualized type IV pilus-dependent cell movement in the rod-shaped thermophilic cyanobacterium Thermosynechococcus vulcanus using optical microscopy at physiological temperature and light conditions. Positive and negative phototaxis were controlled on a short time scale of 1 min. The cells smoothly moved over solid surfaces towards green light, but the direction was switched to backward movement when we applied additional blue light illumination. The switching was mediated by three photoreceptors, SesA, SesB and SesC, which have cyanobacteriochrome photosensory domains and synthesis/degradation activity of the bacterial second messenger cyclic dimeric GMP (c-di-GMP). Our results suggest that the decision-making process for directional switching in phototaxis involves light-dependent changes in the cellular concentration of c-di-GMP. Furthermore, we reveal that rod-shaped cells can move perpendicular to the light vector, indicating that the polarity can be controlled not only by pole-to-pole regulation but also within-a-pole regulation. This study provides insights into previously undescribed rapid bacterial polarity regulation via second messenger signalling with high spatial resolution.
A promiscuity locus confers Lotus burttii nodulation with rhizobia from five different genera
Authors: Zarrabian Mohammad , Montiel Jesús , Sandal Niels , Jin Haojie , Lin Yen-Yu , Klingl Verena , Marín Macarena , James Euan , Parniske Martin , Stougaard Jens , Andersen Stig U. 
Published: August 2021

AbstractLegumes acquire access to atmospheric nitrogen through nitrogen fixation by rhizobia in root nodules. Rhizobia are soil dwelling organisms and there is a tremendous diversity of rhizobial species in different habitats. From the legume perspective, host range is a compromise between the ability to colonize new habitats, where the preferred symbiotic partner may be absent, and guarding against infection by suboptimal nitrogen fixers. Here, we investigate natural variation in rhizobial host range across Lotus species. We find that Lotus burttii is considerably more promiscuous than Lotus japonicus, represented by the Gifu accession, in its interactions with rhizobia. This promiscuity allows Lotus burttii to form nodules with Mesorhizobium, Rhizobium, Sinorhizobium, Bradyrhizobium, and Allorhizobium species that represent five distinct genera. Using recombinant inbred lines, we have mapped the Gifu/burttii promiscuity QTL to the same genetic locus regardless of rhizobial genus, suggesting a general genetic mechanism for host-range expansion. The Gifu/burttii QTL now provides an opportunity for genetic and mechanistic understanding of promiscuous legume-rhizobia interactions.
Development and Characterization of a Weaned Pig Model of Shiga Toxin–Producing E. coli-Induced Gastrointestinal Disease
Authors: Boeckman Justin X. , Sprayberry Sarah , Korn Abby , Suchodolski Jan S. , Paulk Chad , Genovese Kenneth , Rech Raquel R. , Giaretta Paula R. , Blick Anna , Callaway Todd , Gill Jason J. 
Published: August 2021

AbstractPost-weaning enteropathies in swine caused by pathogenic E. coli, such as post-weaning diarrhea (PWD) or edema disease (ED), remain a significant problem for the swine industry. Reduction in the use of antibiotics over concerns of antibiotic resistance and public health concerns, necessitate the evaluation of effective antibiotic alternatives to prevent significant loss of livestock and/or reductions in swine growth performance. For this purpose, an appropriate piglet model of enterotoxigenic E. coli enteropathy is required. In this study, we attempted to induce clinical signs of post-weaning disease in a piglet model using a one-time acute or lower daily chronic dose of a Shiga toxin–producing and enterotoxigenic E. coli strain. The induced disease state was monitored by determining fecal shedding and colonization of the challenge strain, animal growth performance, cytokine levels, fecal calprotectin, histology, fecal metabolomics, and fecal microbiome shifts. The most informative analyses were colonization and shedding of the pathogen, serum cytokines, metabolomics, and targeted metagenomics to determine dysbiosis. Histopathological changes of the gastrointestinal (GI) tract and tight junction leakage as measured by fecal calprotectin concentrations were not observed. Chronic dosing was similar to the acute regimen suggesting that a high dose of pathogen, as used in many studies, may not be necessary. The piglet disease model presented here can be used to evaluate alternative PWD treatment options. Furthermore, this relatively mild disease model presented here may be informative for modeling human chronic gastrointestinal diseases, such as inflammatory bowel disease, which otherwise require invasive procedures for study.ImportancePost-weaning diarrhea remains a significant problem in swine production and appropriate models of pathogenesis are needed to test alternative treatment options. In this study, we present an E. coli induced piglet model for post-weaning diarrhea, and also explore its translational potential as a model for human intestinal inflammation. Our study here presents two firsts to our knowledge. 1) The first simultaneous analysis of the intestinal microbiome and metabolome through fecal sampling of piglets challenged with Shiga toxin–producing E. coli. This is valuable given the limited metabolomics data from swine in various disease states. 2) A comparison of the clinical signs caused by a daily chronic vs one-time dosing regimen of E. coli. This comparison is key as infection by pathogenic E. coli in real-world settings likely occurs from chronic exposure to contaminated food, water, or environment rather than the highly concentrated dose of pathogen that is commonly given in the literature.
Current attitudes towards HIV viral load self-testing: thematic analysis of a consultation with potential end-users
Authors: Gliddon Harriet D , McKendry Rachel A , Gibbs Jo 
Published: August 2021

AbstractBackgroundHIV viral load (VL) is key to monitoring response to antiretroviral therapy. A number of point-of-care HIV VL tests are in development. These tests could be repurposed for HIV VL self-testing.MethodsWe held a patient and public involvement (PPI) consultation for people living with HIV to explore the prospect of HIV viral load self-testing. We conducted a thematic analysis on the data from this consultation.ResultsKey themes were access, convenience, usability, technical aspects, technology potential, connectivity and confidentiality. Attendees expressed significant appetite for decentralised HIV care, including HIV VL self-testing.ConclusionsThis PPI consultation can help researchers developing HIV viral load self-testing technology to better understand the needs of potential end users. Our findings will help guide the development and implementation of HIV VL self-testing.
Training and Development Needs Assessment in a large NIHR Biomedical Research Centre: A Survey
Authors: Bell Karen , Shah Syed Ghulam Sarwar , Henderson Lorna R. , Kiparoglou Vasiliki 
Published: August 2021

ABSTRACTObjectiveTo assess the training and development needs of researchers and support staff affiliated to the NIHR Oxford Biomedical Research Centre (BRC), one of the largest BRCs in England, and to find out about their past experiences of training.DesignA cross-sectional online questionnaire survey.Setting and ParticipantsA convenience sample of clinicians, nurses, midwives, allied health professionals, researchers and support staff (N=798) affiliated with the NIHR Oxford Biomedical Research Centre.Primary and secondary outcome measuresThe primary outcome measure was the type of training and the secondary outcome measures were the duration, location and timing of training.ResultsThe response rate was 24%. Of 189 respondents, 114 were women (60%) and 75 men (40%). Respondents included research scientists (31%), medical doctors and dentists (17%), nurses and midwives (16%) and research managers and administrators (16%). Seventy-one percent respondents (n=134) reported attending at least one training activity in the last year and the most wanted training was leadership skills (25%), followed by research grant and fellowship writing (18%) and statistical analysis (16%). An ideal length of a training course was half a day (41%), whole day (25%) and 1-2 hours (22%). The most preferred time of the day for training was morning (60%) and afternoon (22%) and the favoured delivery style of training was an interactive workshop (52%), lecture/talk (25%), online (9%) and practical activities (9%). The main barriers to attending training courses were the lack of time (n-18%), work commitments (13%), and childcare responsibilities (6%).ConclusionsTranslational researchers and supporting affiliates want short, easily accessible, interactive training sessions, particularly leadership training skills and grant and fellowship writing. However, practical elements are important too e.g. in a convenient location during the working day. Work commitment is the biggest obstacle in doing training.Strengths and limitations of this studyThis survey was done to develop and revamp the NIHR Oxford BRC’s training programme that met the training and development needs of our researchers and research support staff.Leadership skills, research grant and fellowship writing, statistical analysis were the most wanted training.The lack of time, work commitments, and childcare responsibilities were the main barriers to attending training courses.Our findings have limited generalisability because the study is based on the responses of participants who are affiliated with only one NIHR BRC; hence, these findings could not be generalised to other NIHR BRCs.These findings might inform the training and development programmes in other NIHR BRCs in the country.
Novel Coronavirus Pandemic Impacts Children and Adolescents’ Psychological Well-Being in Heavily Hit Chinese Provinces
Authors: Ma Jing , Ding Jun , Hu Jiawen , Wang Kai , Xiao Shuaijun , Luo Ting , Yu Shuxiang , Liu Chuntao , Xu Yunxuan , Liu Yingxian , Wang Changhong , Guo Suqin , Yang Xiaohua , Song Haidong , Geng Yaoguo , Jin Yu , Chen Huayun , Liu Chunyu 
Published: August 2021

AbstractsIn light of the novel coronavirus’s (COVID-19’s) threat to public health worldwide, we sought to elucidate COVID-19’s impacts on the mental health of children and adolescents in China. Through online self-report questionnaires, we aimed to discover the psychological effects of the pandemic and its associated risk factors for developing mental health symptoms in young people.We disseminated a mental health survey through online social media, WeChat, and QQ in the five Chinese provinces with the most confirmed cases of COVID-19 during the late stage of the country-wide lockdown. We used a self-made questionnaire that queried children and adolescents aged 6 to 18 on demographic information, psychological status, and other lifestyle and COVID-related variables.A total of 17,740 children and adolescents with valid survey data participated in the study. 10,022 (56.5%), 11,611 (65.5%), 10,697 (60.3%), 6,868 (38.7%), and 6,225 (35.1%) participants presented, respectively, more depressive, anxious, compulsive, inattentive, and sleep-related problems compared to before the outbreak of COVID-19. High school students reported a greater change in depression and anxiety than did middle school and primary school students. Despite the fact that very few children (0.1%) or their family members (0.1%) contracted the virus in this study, the psychological impact of the pandemic was clearly profound. Fathers’ anxiety appeared to have the strongest influence on a children’s psychological symptoms, explaining about 33% of variation in the child’s overall symptoms. Other factors only explained less than 2% of the variance in symptoms once parents’ anxiety was accounted for.The spread of COVID-19 significantly influenced the psychological state of children and adolescents. It is clear that children and adolescents, particularly older adolescents, need mental health support during the pandemic. The risk factors we uncovered suggest that reducing fathers’ anxiety is particularly critical to addressing young people’s mental health disorders in this time.
Physical Activity Moderates Inflammatory Gene Expression in Rheumatoid Arthritis
Authors: Patterson Sarah L. , Sun Shenghuan , Rychkov Dmitry , Katz Patricia , Tsitsiklis Alexandra , Nakamura Mary C. , Serpa Paula Hayakawa , Langelier Charles R , Sirota Marina 
Published: August 2021

AbstractBackgroundWhile general population studies have shown associations between greater physical activity and lower inflammatory markers, effects of physical activity on inflammatory pathways in rheumatoid arthritis (RA) remain unknown. We aimed to determine whether physical activity independently associates with differential expression of inflammatory genes in RA.MethodsData derived from an observational RA cohort. Physical activity was measured with the GT9X ActiGraph Link device. RNA extraction from peripheral blood, sequencing library preparation and transcriptomic analyses were performed using established methods. Genes differentially expressed in the most versus least physically active groups (top versus bottom activity tertiles) were identified using DESeq2 after adjusting for sex, age, race/ethnicity, and disease activity. Ingenuity Pathway Analysis (IPA) was employed to identify canonical biological pathways and upstream regulating cytokines associated with physical activity.Results35 participants were enrolled (mean age 56±12 years; 91% female; race/ethnicity 31% white, 9% African American, 9% Asian, 40% Hispanic). 767 genes were differentially expressed (padj<0.1) between high versus low activity groups. The high activity group exhibited downregulation of innate and adaptive immune signaling pathways, including CD40, STAT3, TREM-1, IL-17a, IL-8, toll-like receptor and interferon signaling. Upstream cytokine analysis demonstrated inhibition of TNF-alpha and interferon among individuals in the most active group.ConclusionIn a racially diverse RA cohort, patients who were more physically active had lower expression of immune signaling pathways implicated in RA pathogenesis, even after adjusting for disease activity, suggesting a potential protective effect of physical activity in RA.
Balancing growth amidst salinity stress – lifestyle perspectives from the extremophyte model Schrenkiella parvula
Authors: Tran Kieu-Nga , Pantha Pramod , Wang Guannan , Kumar Narender , Wijesinghege Chathura , Oh Dong-Ha , Duppen Nick , Li Hongfei , Hong Hyewon , Johnson John C. , Kelt Ross , Matherne Megan G. , Clement Ashley , Tran David , Crain Colt , Adhikari Prava , Zhang Yanxia , Foroozani Maryam , Sessa Guido , Larkin John C. , Smith Aaron P. , Longstreth David , Finnegan Patrick , Testerink Christa , Barak Simon , Dassanayake Maheshi 
Published: August 2021

AbstractSchrenkiella parvula, a leading extremophyte model in Brassicaceae, can grow and complete its life cycle under multiple environmental stresses, including high salinity. While foundational genomic resources have been created for S. parvula, a comprehensive physiological or structural characterization of its salt stress responses is absent. We aimed to identify the influential traits that lead to stress-resilient growth of this species. We examined salt-induced changes in the physiology and anatomy of S. parvula throughout its lifecycle across multiple tissues. We found that S. parvula maintains or even exhibits enhanced growth during various developmental stages at salt stress levels known to inhibit growth in Arabidopsis and most crops. The resilient growth of S. parvula was associated with key traits that synergistically allow continued primary root growth, expansion of xylem vessels across the root-shoot continuum, and a high capacity to maintain tissue water levels by developing larger and thicker leaves while facilitating continued photosynthesis during salt stress. These traits at the vegetative phase were followed by a successful transition to the reproductive phase via early flowering, development of larger siliques, and production of viable seeds during salt stress. Additionally, the success of self-fertilization during early flowering stages was dependent on salt-induced filament elongation in flowers that aborted in the absence of salt. Our results suggest that the maintenance of leaf water status and enhancement of selfing in early flowers to ensure reproductive success, are among the most influential traits that contribute to the extremophyte lifestyle of S. parvula in its natural habitat.One sentence summarySchrenkiella parvula salt-resilient growth is facilitated by uncompromised primary root growth, expansion of xylem vessels, maintenance of leaf water status and photosynthesis, and early flowering.
The thymic microenvironment gradually modulates the phenotype of thymus-homing peripheral conventional dendritic cells
Authors: Herppich Susanne , Beckstette Michael , Huehn Jochen 
Published: August 2021

AbstractThymic conventional dendritic cells (t-DCs) are crucial for the development of T cells. A substantial fraction of t-DCs originates extrathymically and migrates to the thymus. Here, these cells contribute to key processes of central tolerance like the clonal deletion of self-reactive thymocytes and the generation of regulatory T (Treg) cells. So far, it is only incompletely understood which impact the thymic microenvironment has on thymus-homing conventional DCs (cDCs), which phenotypic changes occur after the entry of peripheral cDCs into the thymus and which functional properties these modulated cells acquire. In the present study, we mimicked the thymus-homing of peripheral cDCs by introducing ex vivo isolated splenic cDCs (sp-DCs) into re-aggregated thymic organ cultures (RTOCs). Already after two days of culture, the transcriptomic profile of sp-DCs was modulated and had acquired certain key signatures of t-DCs. The regulated genes included immunomodulatory cytokines and chemokines as well as co-stimulatory molecules. After four days of culture, sp-DCs appeared to have at least partially acquired the peculiar Treg cell-inducing capacity characteristic of t-DCs. Taken together, our findings indicate that peripheral cDCs possess a high degree of plasticity enabling them to quickly adapt to the thymus-specific microenvironment. We further provide indirect evidence that thymus-specific properties such as the efficient induction of Treg cells under homeostatic conditions can be partially transferred to thymus-homing peripheral cDC subsets.
Long-Read Sequencing of the Zebrafish Genome Reorganizes Genomic Architecture
Authors: Chernyavskaya Yelena , Zhang Xiaofei , Liu Jinze , Blackburn Jessica S. 
Published: August 2021

AbstractNanopore sequencing technology has revolutionized the field of genome biology with its ability to generate extra-long reads that can resolve regions of the genome that were previously inaccessible to short-read sequencing platforms. Although long-read sequencing has been used to resolve several vertebrate genomes, a nanopore-based zebrafish assembly has not yet been released. Over 50% of the zebrafish genome consists of difficult to map, highly repetitive, low complexity elements that pose inherent problems for short-read sequencers and assemblers. We used nanopore sequencing to improve upon and resolve the issues plaguing the current zebrafish reference assembly (GRCz11). Our long-read assembly improved the current resolution of the reference genome by identifying 1,697 novel insertions and deletions over 1Kb in length and placing 106 previously unlocalized scaffolds. We also discovered additional sites of retrotransposon integration previously unreported in GRCz11 and observed their expression in adult zebrafish under physiologic conditions, implying they have active mobility in the zebrafish genome and contribute to the ever-changing genomic landscape.