bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of spinocerebellar ataxia related variants with myokymia and neuromyotonia in dogs
Authors: Vanhaesebrouck An , Van Poucke Mario , Stee Kimberley , Peelman Luc , Van Ham Luc , Bhatti Sofie F.M. 
Published: November 2022

ABSTRACTBackgroundKCNJ10 and CAPN1 variants have been shown to cause spinocerebellar ataxia (SCA) in Jack Russell, Parson Russell and Fox terriers (JRT, PRT and FT). However, their association with the clinical manifestation of myokymia and neuromyotonia (M/NM), often reported alongside SCA, remains unclear.AimsTo investigate the association between M/NM and SCA-related variants in 34 with SCA and/or M/NM affected dogs (30 JRTs; 1 PRT; 1 Yorkshire terrier, YT; 1 Dachshund; 1 crossbreed).MethodsKCNJ10 XM_038448705.1:c.627C>G (p.(Ile209Met)) and CAPN1 XM_038425033.1:c.344G>A (p.(Cys115Tyr)) variants, and the complete coding sequence (CDS) of KCNA1, KCNA2, KCNA6, KCNJ10 and HINT1, were analysed via Sanger sequencing.ResultsThe KCNJ10 c.627C>G variant was homozygously present in 16 JRTs, 1 Dachshund and 1 crossbreed with SCA and M/NM, and in 9 JRTs with SCA but without M/NM. The CAPN1 c.344G>A variant was homozygously present in 1 PRT with SCA but without M/NM. Both variants were not found in 2 JRTs with SCA but without M/NM, neither in 3 JRTs and 1 YT without SCA but with M/NM. No other causal variants were found in the coding sequence of the investigated candidate genes in these latter 6 dogs.ConclusionsThe KCNJ10 c.627C>G or CAPN1 c.344G>A variant was confirmed to be the causal variant in 28 of the 34 affected dogs (including 1 Dachshund with the KCNJ10 variant). The fact that 10 of these 28 dogs did not suffer from M/NM (all of them suffered from SCA) and that these variants were not found in 4 dogs suffering from M/NM without SCA, suggests that M/NM is caused by another genetic variant or that these patients suffer from an acquired (immune-mediated) syndrome, similar to humans. Another SCA-causing variant is probably also segregating in JRTs (but not in the CDS of the investigated candidate genes), because no causal variant was found in 2 JRTs suffering from SCA without M/NM.
Phosphatidylserine-exposing medium/large extracellular vesicles: potential cancer biomarkers
Authors: Perez Gloria I. , Bernard Matthew P. , Vocelle Daniel , Zarea Ahmed A. , Schneider Doug , Bauzon Maxine , Hermiston Terry , Kanada Masamitsu 
Published: November 2022

AbstractUnder physiological conditions, phosphatidylserine (PS) predominantly localizes to the cytosolic leaflet of the plasma membrane of cells. During apoptosis, PS is exposed on the cell surface and serves as an “eat-me” signal for macrophages to prevent releasing self-immunogenic cellular components from dying cells which could potentially lead to autoimmunity. However, increasing evidence indicates that viable cells can also expose PS on their surface. Interestingly, tumor cell-derived extracellular vesicles (EVs) also externalize PS. Recent studies have proposed PS-exposing EVs as a potential biomarker for the early detection of cancer and other diseases. However, there are confounding results regarding subtypes of PS-positive EVs, and knowledge of PS exposure on the EV surface requires further elucidation. In this study, we enriched small EVs (sEVs) and medium/large EVs (m/lEVs) from conditioned media of breast cancer cells (MDA-MB-231, MDA-MB-468) and non-cancerous cells (keratinocytes, fibroblasts). Since several PS-binding molecules are available to date, we compared recombinant proteins of annexin A5 and the carboxylated glutamic acid domain of Protein S (GlaS), also specific for PS, to detect PS-exposing EVs. Firstly, PS externalization in each EV fraction was analyzed using a bead-based EV assay, which combines EV capture using microbeads and analysis of PS-exposing EVs by flow cytometry. The bulk EV assay showed higher PS externalization in m/lEVs derived from MDA-MB-468 cells but not from MDA-MB-231 cells, while higher binding of GlaS was also observed in m/lEVs from fibroblasts. Second, using single EV flow cytometry, PS externalization was also analyzed on individual sEVs and m/lEVs. Significantly higher PS externalization was detected in m/lEVs (annexin A1+) derived from cancer cells compared to m/lEVs (annexin A1+) from non-cancerous cells. These results emphasize the significance of PS-exposing m/lEVs as an undervalued EV subtype for early cancer detection and provide a better understanding of PS externalization in disease-associated EV subtypes.
ppGpp is Present in and Functions to Regulate Sleep inDrosophila
Authors: Dai Xihuimin , Yang Wei , Zhang Xiaohui , Zhou Enxing , Liu Ying , Wang Tao , Zhang Wenxia , Zhang Xinxiang , Rao Yi 
Published: November 2022

ABSTRACTSleep is essential for animals, and receives inputs from circadian, homeostasis, and environment, yet the mechanisms of sleep regulation remain elusive. Discovery of molecules in living systems and demonstration of their functional roles are pivotal in furthering our understanding of the molecular basis of biology. Here we report that ppGpp (guanosine-5’-diphosphate, 3’-diphosphate), a molecule that has been detected in prokaryotes for more than five decades, is present inDrosophila, and plays an important role in regulation of sleep and SISL (starvation induced sleep loss). ppGpp is detected in germ-freeDrosophilaand hydrolyzed by an enzyme encoded by themesh1gene inDrosophila. Nighttime sleep and SISL were defected inmesh1mutant flies, and rescued by expression of wildtype Mesh1, but not the enzymatically defective mutant Mesh1E66A. Ectopic expression of RelA, theE. colisynthetase for ppGpp, phenocopiedmesh1knockout mutants, whereas overexpression of Mesh1 resulted in the opposite phenotypes, supporting that ppGpp is both necessary and sufficient in sleep regulation. A chemoconnectomic screen followed by genetic intersection experiments implicate the Dilp2 neurons in thepars intercerebralis(PI) brain region as the site of ppGpp function. Our results have thus supported that ppGpp is present in animals after long lag since its discovery in bacteria, and revealed a physiological role of ppGpp in sleep regulation for the first time.
Exploration of the autonomous replication region and its utilization for expression vectors in cyanobacteria
Authors: Sakamaki Yutaka , Maeda Kaisei , Nimura-Matsune Kaori , Chibazakura Taku , Watanabe Satoru 
Published: November 2022

AbstractDue to their photosynthetic capabilities, cyanobacteria is expected to be an ecologically friendly host for the production of biomaterials. However, compared to other bacteria, there is little information of autonomous replication sequences, and tools for genetic engineering, especially expression vector systems, are limited. In this study, we established an effective screening method, namely AR-seq (Autonomous Replication sequencing), for finding autonomous replication regions in cyanobacteria and utilized the region for constructing expression vector. AR-seq using the genomic library ofSynechocystissp. PCC 6803 revealed that a certain region containing Rep-related protein (here named as Cyanobacterial Rep protein A2: CyRepA2) exhibits high autonomous replication activity in a heterologous host cyanobacterium,Synechococcus elongatusPCC 7942. The reporter assay using GFP showed that the expression vector pYS carrying CyRepA2 can be maintained in a wide range of multiple cyanobacterial species, not onlyS. 6803 andS. 7942, but alsoSynechococcussp. PCC 7002 andAnabaenasp. PCC 7120. InS. 7942, the GFP expression in pYS-based system can be tightly regulated by IPTG, achieving 10-fold higher levels than that of chromosome-based system. Furthermore, pYS can be used together with conventional vector pEX, which was constructed from an endogenous plasmid in5. 7942. The combination of pYS with other vectors is useful for genetic engineering, such as modifying metabolic pathways, and is expected to improve the performance of cyanobacteria as bioproduction chassis.
Human Early Syncytiotrophoblasts Are Highly Susceptible to SARS-CoV-2 Infection
Authors: Ruan Degong , Ye Zi-Wei , Yuan Shuofeng , Li Zhuoxuan , Zhang Weiyu , Ong Chon Phin , Tang Kaiming , Guo Jilong , Xuan Yiyi , Tam Timothy Theodore Ka Ki , Huang Yunying , Zhang Qingqing , Lee Cheuk-Lun , Chiu Philip C.N. , Liu Fang , Jin Dong-Yan , Liu Pentao 
Published: November 2022

SUMMARYThe ongoing and devastating pandemic of coronavirus disease 2019 (COVID-19) has led to a global public health crisis. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can potentially pose a serious risk to maternal and neonatal health. Cases of abnormal pregnancy and vertical transmission of SARS-CoV-2 from mother to foetus have been reported but no firm conclusions are drawn. Trophoblasts are the major constituents of the placenta to protect and nourish the developing foetus. However, directin vivoinvestigation of trophoblast’s susceptibility to SARS-CoV-2 and of COVID-19 and pregnancy is challenging. Here we report that human early syncytiotrophoblasts (eSTBs) are highly susceptible to SARS-CoV-2 infection in an angiotensin-converting enzyme 2 (ACE2)-dependent manner. From human expanded potential stem cells (hEPSCs), we derivedbona fidetrophoblast stem cells (TSCs) that resembled those originated from the blastocyst and the placenta in generating functional syncytiotrophoblasts (STBs) and extravillus trophoblasts (EVTs) and in low expression of HLA-A/B and amniotic epithelial (AME) cell signature. The EPSC-TSCs and their derivative trophoblasts including trophoblast organoids could be infected by SARS-CoV-2. Remarkably, eSTBs expressed high levels of ACE2 and produced substantially higher amounts of virion than Vero E6 cells which are widely used in SARS-CoV-2 research and vaccine production. These findings provide experimental evidence for the clinical observations that opportunistic SARS-CoV-2 infection during pregnancy can occur. At low concentrations, two well characterized antivirals, remdesivir and GC376, effectively eliminated infection of eSTBs by SARS-CoV-2 and middle east respiratory syndrome-related coronavirus (MERS-CoV), and rescued their developmental arrest caused by the virus infection. Several human cell lines have been used in coronavirus research. However, they suffer from genetic and/or innate immune defects and have some of the long-standing technical challenges such as cell transfection and genetic manipulation. In contrast, hEPSCs are normal human stem cells that are robust in culture, genetically stable and permit efficient gene-editing. They can produce and supply large amounts of physiologically relevant normal and genome-edited human cells such as eSTBs for isolation, propagation and production of coronaviruses for basic research, antivirus drug tests and safety evaluation.
Addressable and adaptable intercellular communication via DNA messaging
Authors: Marken John P. , Murray Richard M. 
Published: November 2022

AbstractEngineered consortia are a major research focus for synthetic biologists because they can implement sophisticated behaviors inaccessible to single-strain systems. However, this functional capacity is constrained by their constituent strains’ ability to engage in complex communication. DNA messaging, by enabling information-rich channel-decoupled communication, is a promising candidate architecture for implementing complex communication. But its major advantage, its messages’ dynamic mutability, is still unexplored. We develop a framework for addressable and adaptable DNA messaging that leverages all three of these advantages and implement it in a plasmid conjugation-based communication channel. Our system can bias the transfer of messages to targeted receiver strains by 100-to 1000-fold, and their recipient lists can be dynamically updatedin situto control the flow of information through the population. This work lays the foundation for future developments that further utilize the unique advantages of DNA messaging to engineer previously-inaccessible levels of complexity into biological systems.
Fragment Linker Prediction Using Deep Encoder-Decoder Network for PROTAC Drug Design
Authors: Kao Chien-Ting , Lin Chieh-Te , Chou Cheng-Li , Lin Chu-Chung 
Published: November 2022

AbstractDrug discovery and development pipeline is a prolonged and complex process and remains challenging for both computational methods and medicinal chemists. Deep learning has shed light on various fields and achieved tremendous success in designing novel molecules in the pharmaceutical industry. We utilize state-of-the-art techniques to propose a deep neural network for rapid designing and generating meaningful drug-like Proteolysis-Targeting Chimeras (PROTACs) analogs. Our method, AIMLinker, takes the structural information from the corresponding fragments and generates linkers to incorporate them. In this model, we integrate filters for excluding non-druggable structures guided by protein-protein complexes while retaining molecules with potent chemical properties. The novel PROTACs subsequently pass through molecular docking, taking root-mean-square deviation (RMSD), the change of Gibbs free energy (ΔGbinding), and relative Gibbs free energy (ΔΔGbinding) as the measurement criteria for testing the robustness and feasibility of the model. The generated novel PROTACs molecules possess similar structural information with superior binding affinity to the binding pockets in comparison to existing CRBN-dBET6-BRD4 ternary complexes. We demonstrate the effectiveness of AIMLinker having the power to design compounds for PROTACs molecules with better chemical properties.
Target of Rapamycin Complex 2 modulates development through Hedgehog/Patched signaling inC. elegans
Authors: Emans Sinclair W. , Yerevanian Armen , Ahsan Fasih M. , Zhou Yifei , Cedillo Lucydalila , Soukas Alexander A. 
Published: November 2022

ABSTRACTBoth Hedgehog (Hh) signaling and target of rapamycin complex 2 (TORC2) are central, evolutionarily conserved pathways that regulate development and metabolism. InC. elegans, loss of essential TORC2 component RICTOR (rict-1) causes delayed development, shortened lifespan, reduced brood, small size, and increased fat. Here we report that knockdown of Hedgehog-related morphogengrd-1and its Patched-related receptorptr-11rescues delayed development in TORC2 loss of function mutants, indicating an unexpected role forgrd-1/ptr-11in slowing developmental rate downstream of nutrient sensing pathways. Further, we implicate chronic stress transcription factorpqm-1as a key transcriptional effector ofgrd-1/ptr-11in slowing whole-organism growth. We propose that the TORC2/grd-1/ptr-11/pqm-1signaling relay acts as a critical executor of growth to slow development whenC. elegansencounters unfavorable growth conditions.Summary statementDevelopmental rate inC. elegansis dramatically slowed in animals deficient in nutrient-sensitive target of rapamycin complex 2 signaling and slowing is effected by increased activity of a previously uncharacterized Hh-r/Ptr signaling relay.
Impact of the COVID-19 pandemic on children and adolescents: determinants and association with quality of life and mental health – A cross-sectional study
Authors: Richard Viviane , Dumont Roxane , Lorthe Elsa , Loizeau Andrea , Baysson Hélène , Zaballa María-Eugenia , Pennacchio Francesco , Barbe Rémy P. , Posfay-Barbe Klara M. , Guessous Idris , Stringhini Silvia ,   SEROCoV-KIDS study group
Published: November 2022

ABSTRACTBackgroundThe medium-term impact of the COVID-19 pandemic on the wellbeing of children and adolescents remains unclear. More than two years into the pandemic, we aimed to quantify the frequency and determinants of having been severely impacted by the COVID-19 pandemic and estimate its impact on health-related quality of life (HRQoL) and mental health.MethodsData was drawn from a population-based cohort of children and adolescents, recruited between December 2021 and June 2022, in Geneva, Switzerland. We measured the impact of the pandemic via the Coronavirus impact scale, which assesses the multidimensional impact of the pandemic at the child and family level through parent’s report. A score higher than one standard deviation above the mean was deemed a severe impact. Parents additionally reported about their offspring HRQoL and mental health with validated scales. Determinants of having been severely impacted were assessed with logistic models, as were the associations between having experienced a severe impact and poor HRQoL or mental health.ResultsOut of 2101 participants aged 2-17, 12.7% had experienced a severe pandemic impact. Having a lasting health condition, a pandemic-related worsening of lifestyle habits or an unfavorable family environment were associated with having been severely impacted by the pandemic. Participants who had experienced a severe pandemic impact were more likely to present poor HRQoL (aOR=3.1; 95%CI: 2.3-4.4) and poor mental health (aOR=3.9; 95%CI: 2.5-6.2).ConclusionsThe COVID-19 pandemic may have persistent consequences on the wellbeing of children and adolescents, especially among those with health and family vulnerabilities.
An examination of the effects of financial and process innovation on the sustainability of businesses under the influence of entrepreneurial leadership: a research in energy companies
Authors: Sonmez Cakir Fatma , Adiguzel Zafer 
Published: November 2022

PurposeCompanies must implement sustainability measures in order to survive due to the relationship between financial, social and environmental performances. These elements must be integrated into the business in a complementary manner in this regard. As a result, this study aims to investigate the effects of entrepreneurial leadership on sustainability, as well as financial and process innovation.Design/methodology/approachWithin the scope of the research, a survey was conducted with 295 white-collar employees working in energy companies. SPSS 25, the LISREL program, and SOBEL analysis were used to determine the relationships between the variables.FindingsIn the research, financial innovation perceptions and process innovation activities have a positive effect on business sustainability and entrepreneurial leadership. As both an independent and a mediating variable, entrepreneurial leadership has a positive impact on business sustainability.Research limitations/implicationsCompanies engaged in renewable energy production, operating in the Marmara region, constitute the sample mass. For this reason, it would be more accurate to evaluate the results obtained in this research only for companies producing renewable energy.Practical implicationsIt is concluded that energy companies should prioritize financial and process innovations and that entrepreneurial leadership is required to ensure the sector's long-term viability.Originality/valueThis paper is an innovative study in terms of the scope and content of the research as data are collected and analyzed from companies that produce renewable energy.
Potential impacts of climate extremes on snow under global warming conditions in the Mongolian Plateau
Authors: Li Chunlan , Xu Xinwu , Du Hongyu , Du Debin , Leal Filho Walter , Wang Jun , Bao Gang , Ji Xiaowen , Yin Shan , Bao Yuhai , Azadi Hossein 
Published: November 2022

Purpose
The paper aims to investigate the possible changes in mean temperature in the Mongolian Plateau associated with the 1.5 and 2°C global warming targets and how snow changes in the Mongolian Plateau when the mean global warming is well below 2°C or limited to 1.5°C.

Design/methodology/approach
In total, 30 model simulations of consecutive temperature and precipitation days from Coupled Model Inter-comparison Project Phase 5 (CMIP5) are assessed in comparison with the 111 meteorological monitoring stations from 1961–2005. Multi-model ensemble and model relative error were used to evaluate the performance of CMIP5 models. Slope and the Mann–Kendall test were used to analyze the magnitude of the trends and evaluate the significance of trends of snow depth (SD) from 1981 to 2014 in the Mongolian Plateau.

Findings
Some models perform well, even better than the majority (80%) of the models over the Mongolian Plateau, particularly HadGEM2-CC, CMCC-CM, BNU-ESM and GFDL-ESM2M, which simulate best in consecutive dry days (CDD), consecutive wet days (CWD), cold spell duration indicator (CSDI) and warm spell duration indicator (WSDI), respectively. Emphasis zones of WSDI on SD were deeply analysed in the 1.5 and 2 °C global warming period above pre-industrial conditions, because it alone has a significant negative relation with SD among the four indices. It is warmer than before in the Mongolian Plateau, particularly in the southern part of the Mongolian Plateau, indicating less SD.

Originality/value
Providing climate extremes and SD data sets with different spatial-temporal scales over the Mongolian Plateau. Zoning SD potential risk areas and proposing adaptations to promote regional sustainable development.
What are you looking at? Visual attention during the co-created cellar door experience: customer and staff perspectives from Australian experiences
Authors: d’Ament Genevieve , Saliba Anthony John , Nayeem Tahmid 
Published: November 2022

Purpose
The prevalence of visually splendid multi-million-dollar cellar doors (CDs) builds an assumption that bricks and mortar create the co-created cellar door experience (CDE). This study aims to determine what attracts the visual attention of staff and customers during a CDE at three visual designs of CD: lively, stylised and simple.

Design/methodology/approach
A total of 23 customers and five staff consented to record their CDEs using TobiiPro2 glasses with 35 recordings providing 993 min for analysis with Tobii Pro Lab. Twenty-five areas of interest were used to calculate fixation and visit metrics.

Findings
The most attended elements of a co-created CDE were staff and faces. Attention is less influenced by the design of CD, whereas staff significantly influence attention.

Research limitations/implications
The findings are valuable to the industry as they highlight the importance of human resources to a winery business, an increasingly casualised workforce. Future research could focus on staffing needs, including training and performance during experience delivery, with the expectation of increasing profitability.

Originality/value
To the best of the authors’ knowledge, this study is the first to analyse objective recordings of staff and customer visual attention during their experience.