bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternating dynamics oforiC, SMC and MksBEF in segregation ofPseudomonas aeruginosachromosome
Authors: Zhao Hang , Bhowmik Bijit , Rybenkov Valentin V. 
Published: May 2020

AbstractCondensins are essential for global chromosome organization in diverse bacteria. Atypically,Pseudomonas aeruginosaencodes condensins from two superfamilies, SMC-ScpAB and MksBEF. We report that the two proteins play specialized roles in chromosome packing and segregation and are synthetically lethal with ParB. Inactivation of SMC or MksB asymmetrically affected global chromosome layout, its timing of segregation and sometimes triggered a chromosomal inversion. Localization pattern was also unique to each protein. SMC clusters colocalized withoriCthroughout cell cycle except shortly after origin duplication, whereas MksB clusters emerged at cell quarters shortly prior tooriCduplication and stayed there even after cell division. Relocation of the proteins was abrupt and coordinated withoriCdynamic. These data reveal that the two condensins asymmetrically play dual roles in chromosome maintenance by organizing it and mediating its segregation. Furthermore, the choreography of condensins andoriCrelocations suggest an elegant mechanism for the birth and maturation of chromosomes.ImportanceMechanisms that define the chromosome as a structural entity remain unknown. A key element in this process are condensins, which globally organize chromosomes and contribute to their segregation. This study characterized condensin and chromosome dynamics inPseudomonas aeruginosa, which harbors condensins from two major protein superfamilies, SMC and MksBEF. The study revealed that both proteins asymmetrically play a dual role in chromosome maintenance by spatially organizing the chromosomes and guiding their segregation but can substitute for each other in some activities. The timing of chromosome, SMC and MksBEF relocation was highly ordered and interdependent revealing causative relationships in the process. Moreover, MksBEF was found to produce clusters at the site of chromosome replication that survived cell division and remained in place until chromosome replication was complete. Overall, these data delineate the functions of condensins from the SMC MksBEF superfamilies, reveal the existence of a chromosome organizing center and suggest a mechanism that might explain the biogenesis of chromosomes.
Modeling Human Peripheral Myelin Fully from Pluripotent Stem Cells and Immune-mediated NeuropathyIn Vitrousing ZIKA Virus
Authors: Mirakhori Fahimeh , Qin Cheng-Feng , Xu Zhiheng 
Published: May 2020

SummaryThe generation ofin vitromodel of human peripheral myelin development and associated disease from human pluripotent stem cells (hPSCs) has been a challenge so far. In addition, the underlying mechanism for ZIKA virus (ZIKV) infection incurred Guillain-Barré syndrome (GBS) remains unexplored due to the lack of a suitable model. Here, we report thede novogeneration of a human peripheral myelination model with competent Schwann cells (SCs). Those human SCs generated from hPSCs via compound screening were capable of forming compact myelin bothin vitroandin vivo. We found ZIKV infection caused GBS-like eventsin vitroincluding myelin sheath degeneration, as well as dysregulated transcriptional profile including the activated cell death pathways and cytokine production. These effects could be partially reversed by several pharmacological inhibitors. Our model therefore provides a new and robust tool for studying the pathogenic mechanisms and developing of therapeutic strategies for related neuropathies.
Comorbid chronic pain and depression: Shared risk factors and differential antidepressant effectiveness
Authors: Roughan William H. , Campos Adrián I. , García-Marín Luis M. , Cuéllar-Partida Gabriel , Lupton Michelle K. , Hickie Ian B. , Medland Sarah E. , Wray Naomi R. , Byrne Enda M. , Ngo Trung Thanh , Martin Nicholas G. , Rentería Miguel E. 
Published: May 2020

ABSTRACTThe bidirectional relationship between depression and chronic pain is well recognized, but their clinical management remains challenging. Here we characterize the shared risk factors and outcomes for their comorbidity in the Australian Genetics of Depression cohort study (N=13,839). Participants completed online questionnaires about chronic pain, psychiatric symptoms, comorbidities, treatment response and general health. Logistic regression models were used to examine the relationship between chronic pain and clinical and demographic factors. Cumulative linked logistic regressions assessed the effect of chronic pain on treatment response for ten different antidepressants. Chronic pain was associated with an increased risk of depression (OR=1.86 [1.37–2.54]), recent suicide attempt (OR=1.88[1.14–3.09]), higher use of tobacco (OR=1.05 [1.02–1.09]) and misuse of painkillers (e.g., opioids; OR=1.31 [1.06–1.62]). Participants with comorbid chronic pain and depression reported fewer functional benefits from antidepressant use and lower benefits from sertraline (OR=0.75[0.68–0.83]), escitalopram (OR=0.75[0.67–0.85]) and venlafaxine (OR=0.78[0.68–0.88]) when compared to participants without chronic pain. Furthermore, participants taking sertraline (OR=0.45[0.30–0.67]), escitalopram (OR=0.45[0.27–0.74]) and citalopram (OR=0.32[0.15–0.67]) specifically for chronic pain (among other indications) reported lower benefits compared to other participants taking these same medications but not for chronic pain. These findings reveal novel insights into the complex relationship between chronic pain and depression. Treatment response analyses indicate differential effectiveness between particular antidepressants and poorer functional outcomes for these comorbid conditions. Further examination is warranted in targeted interventional clinical trials, which also include neuroimaging genetics and pharmacogenomics protocols. This work will advance the delineation of disease risk indicators and novel aetiological pathways for therapeutic intervention in comorbid pain and depression as well as other psychiatric comorbidities.
Shank2 expression identifies a subpopulation of glycinergic interneurons involved in nociception and altered in an autism mouse model
Authors: Heuvel Florian olde , Alami Najwa Ouali , Wilhelm Hanna , Deshpande Dhruva , Khatamsaz Elmira , Catanese Alberto , Woelfle Sarah , Schön Michael , Jain Sanjay , Grabrucker Stefanie , Ludolph Albert C. , Verpelli Chiara , Michaelis Jens , Boeckers Tobias M. , Roselli Francesco 
Published: May 2020

AbstractPatients suffering from Autism Spectrum Disorders (ASD) experience disturbed nociception in form of either hyposensitivity to pain or hypersensitivity and allodynia. We have determined that Shank2-KO mice, which recapitulate the genetic and behavioural disturbances of ASD, display increased sensitivity to formalin pain and thermal, but not mechanical allodynia. We demonstrate that high levels of Shank2 expression identifies a subpopulation of neurons in murine and human dorsal spinal cord, composed mainly by glycinergic interneurons and that loss of Shank2 causes the decrease in NMDAR in excitatory synapses on these inhibitory interneurons. In fact, in the subacute phase of the formalin test, glycinergic interneurons are strongly activated in WT mice but not in Shank2-KO mice. As consequence, nociception projection neurons in lamina I are activated in larger numbers in Shank2-KO mice. Our findings prove that Shank2 expression identifies a new subset of inhibitory interneurons involved in reducing the transmission of nociceptive stimuli and whose unchecked activation is associated with pain hypersensitivity. Thus, we provide evidence that dysfunction of spinal cord pain processing circuits may underlie the nociceptive phenotypes in ASD patients and mouse models.
Hidden genomic features of an invasive malaria vector,Anopheles stephensi
Authors: Chakraborty Mahul , Ramaiah Arunachalam , Adolfi Adriana , Halas Paige , Kaduskar Bhagyashree , Ngo Luna Thanh , Jayaprasad Suvratha , Paul Kiran , Whadgar Saurabh , Srinivasan Subhashini , Subramani Suresh , Bier Ethan , James Anthony A. , Emerson J.J. 
Published: May 2020

AbstractBackgroundThe mosquitoAnopheles stephensiis a vector of urban malaria in Asia that recently invaded Africa. Studying the genetic basis of vectorial capacity and engineering genetic interventions are both impeded by limitations of a vector’s genome assembly. The existing assemblies ofAn. stephensiare draft-quality and contain thousands of sequence gaps, potentially missing genetic elements important for its biology and evolution.ResultsTo access previously intractable genomic regions, we generated a reference-grade genome assembly and full transcript annotations that achieve a new standard for reference genomes of disease vectors. Here, we report novel species-specific transposable element families and insertions in functional genetic elements, demonstrating the widespread role of TEs in genome evolution and phenotypic variation. We discovered 29 previously hidden members of insecticide resistance genes, uncovering new candidate genetic elements for the widespread insecticide resistance observed inAn. stephensi. We identified 2.4 Mb of the Y-chromosome and seven new male-linked gene candidates, representing the most extensive coverage of the Y-chromosome in any mosquito. By tracking full length mRNA for >15 days following blood feeding, we discover distinct roles of previously uncharacterized genes in blood metabolism and female reproduction. The Y-linked heterochromatin landscape reveals extensive accumulation of long-terminal repeat retrotransposons throughout the evolution and degeneration of this chromosome. Finally, we identify a novel Y-linked putative transcription factor that is expressed constitutively through male development and adulthood, suggesting an important role throughout male development.ConclusionCollectively, these results and resources underscore the significance of previously hidden genomic elements in the biology of malaria mosquitoes and will accelerate development of genetic control strategies of malaria transmission.
Structural visualization of septum formation inStaphylococcus warneriusing atomic force microscopy
Authors: Su Hai-Nan , Li Kang , Yuan Xiao-Xue , Zhang Meng-Yao , Liu Si-Min , Chen Xiu-Lan , Liu Lu-Ning , Zhang Yu-Zhong 
Published: May 2020

ABSTRACTCell division ofStaphylococcusadopts a “popping” mechanism that mediates extremely rapid separation of the septum. Elucidating the structure of the septum is crucial for understanding this exceptional bacterial cell division mechanism. Here, the septum structure ofStaphylococcus warneriis extensively characterized using high-speed time-lapse confocal microscopy, atomic force microscopy, and electron microscopy. The cells ofS. warneridivide in a fast “popping” manner on a millisecond timescale. Our results show that the septum is composed of two separable layers, providing a structural basis for the ultrafast daughter cell separation. The septum is formed progressively toward the center with non-uniform thickness of the septal disk in radial directions. The peptidoglycan on the inner surface of double-layered septa is organized into concentric rings, which are generated along with septum formation. Moreover, this study signifies the importance of new septum formation in initiating new cell cycles. This work unravels the structural basis underlying the “popping” mechanism that drivesStaphylococcuscell division and reveals a generic structure of the bacterial cell.IMPORTRANCEThis work shows that the septum ofStaphylococcus warneriis composed of two layers and the peptidoglycan on the inner surface of the double-layered septum is organized into concentric rings. Moreover, new cell cycles ofStaphylococcuscould be initiated before the previous cell cycle is complete. This work advances our knowledge about a basic structure of bacterial cell and provides the double layered structural information of septum for the bacterium that divide with the “popping” mechanism.
The common chromosomal periodicity of transcriptomes is correlated with the bacterial growth rate
Authors: Nagai Motoki , Kurokawa Masaomi , Ying Bei-Wen 
Published: May 2020

AbstractThe growth rate, representing the fitness of a bacterial population, is determined by the whole transcriptome. Chromosomal periodicity is a representative overall feature of the whole transcriptome; however, whether and how it is associated with the bacterial growth rate are unknown. To address these questions, we analyzed a total of 213 transcriptomes of genetically differentiatedEscherichia colistrains growing in an assortment of culture conditions varying in terms of temperature, nutrition level and osmotic pressure. Intriguingly, the Fourier transform identified a common chromosomal periodicity of transcriptomes, which was independent of the variation in genomes and environments. In addition, fitting of the theoretical model found that the amplitudes of the periodic transcriptomes were significantly correlated with the growth rates. This novel finding successfully identified a single parameter representing the global pattern of the whole transcriptome for the first time and indicated that bacterial growth was correlated with the magnitude of chromosomal differentiation in gene expression. These results provided an alternative global parameter for evaluating the adaptiveness of a growing bacterial population and provided a quantitative rule that makes it possible to predict the growth dynamics according to the gene expression pattern.
Functional near-infrared spectroscopy in conjunction with electroencephalography of cerebellar transcranial direct current stimulation responses in the latent neurovascular coupling space – a chronic stroke study
Authors: Rezaee Zeynab , Ranjan Shashi , Solanki Dhaval , Bhattacharya Mahasweta , Srivastava MV Padma , Lahiri Uttama , Dutta Anirban 
Published: May 2020

AbstractCerebellar transcranial direct current stimulation (ctDCS) can facilitate motor learning; however, ctDCS effects have not been investigated using portable neuroimaging vis-à-vis lobular electric field strength. This is important since the subject-specific residual architecture for cerebellar interconnections with the cerebral cortex, including the prefrontal cortex (PFC) and the sensorimotor cortex (SMC), can influence the ctDCS effects on the cerebral functional activation. In this study, we investigated functional near-infrared spectroscopy (fNIRS) in conjunction with electroencephalography (EEG) to measure the changes in the brain activation at the PFC and the SMC following virtual reality (VR)-based Balance Training (VBaT), before and after ctDCS treatment in 12 hemiparetic chronic stroke survivors. Furthermore, we performed general linear modeling (GLM) that can putatively associate the lobular electric field strength due to ctDCS priming with the changes in the fNIRS-EEG measures in the chronic stroke survivors. Here, fNIRS-EEG based measures were investigated in their latent space found using canonical correlation analysis (CCA) that is postulated to capture neurovascular coupling. We found that the ctDCS electrode montage, as well as the state (pre-intervention, during intervention, post-intervention), had a significant (p<0.05) effect on the changes in the canonical scores of oxy-hemoglobin (O2Hb) signal measured with fNIRS. Also, skill acquisition during first exposure to VBaT decreased the activation (canonical score of O2Hb) of PFC of the non-lesioned hemisphere in the novices at their first exposure before the ctDCS intervention. Moreover, ctDCS intervention targeting the leg representation in the cerebellum led to a decrease in the canonical scores of O2Hb at the lesioned SMC, which is postulated to be related to the cerebellar brain inhibition. Furthermore, ctDCS electrode montage, as well as the state, had a significant (p<0.05) interaction effect on the canonical scores of log10-transformed EEG bandpower. Our current study showed the feasibility of fNIRS-EEG imaging of the ctDCS responses in the latent neurovascular coupling space that can not only be used for monitoring the dynamical changes in the brain activation associated with ctDCS-facilitated VBaT, but may also be useful in subject-specific current steering for tDCS to target the cerebral fNIRS-EEG sources to reduce inter-individual variability.
Repurposing beta3-adrenergic receptor agonists for Alzheimer’s disease: Beneficial effects on recognition memory and amyloid pathology in a mouse model
Authors: Tournissac Marine , Vu Tra-My , Vrabic Nika , Hozer Clara , Tremblay Cyntia , Mélançon Koralie , Planel Emmanuel , Pifferi Fabien , Calon Frédéric 
Published: May 2020

ABSTRACTOld age, the most important risk factor for Alzheimer’s disease (AD), is associated with thermoregulatory deficits. Brown adipose tissue (BAT) is the main thermogenic driver in mammals and its stimulation, through β3-adrenergic receptor (β3AR) agonists or cold acclimation, counteracts metabolic deficits in rodents and humans. Studies in animal models show that AD neuropathology leads to thermoregulatory deficits and cold-induced tau hyperphosphorylation is prevented by BAT stimulation through cold acclimation. Since metabolic disorders and AD share strong pathogenic links, we hypothesized that BAT stimulation through a β3AR agonist could exert benefits in AD as well.Here, we show that β3AR agonist administration (CL-316,243, 1 mg/kg/day i.p., from 15 to 16 months of age) decreased body weight and improved peripheral glucose metabolism and BAT thermogenesis in both non-transgenic and 3xTg-AD mice. One-month treatment with a β3AR agonist increased recognition index by 19% in 16-month-old 3xTg-AD mice compared to pre-treatment (14-month-old). Locomotion, anxiety and tau pathology were not modified. Finally, insoluble Aβ42/Aβ40 ratio was decreased by 27% in the hippocampus of CL-316,243-injected 3xTg-AD mice.Overall, our results indicate that β3AR stimulation reverses memory deficits and shifts downward the insoluble Aβ42/Aβ40 ratio in 16-month-old 3xTg-AD mice. As β3AR agonists are being clinically developed for metabolic disorders, repurposing them in AD could be a valuable therapeutic strategy.
Why do academics become entrepreneurs? How do their motivations evolve? Results from an empirical study
Authors: Galati Francesco , Bigliardi Barbara , Passaro Renato , Quinto Ivana 
Published: May 2020

PurposeAccording to the paradigm of the Triple Helix, universities are moving from their traditional roles of research, teaching and knowledge dissemination to an entrepreneurial role. Specifically, they contribute to innovation and competitiveness by creating academic spin-offs (ASOs). In such a context, the diffusion of digital technologies is impacting both on the development of new forms of academic entrepreneurship and on the motivations of academics in launching ASOs. Grounded on a recent reconceptualization developed on identity theory, this study investigates the motivations that lead an academic to establish a spin-off and if, how and why these motivations vary over time.Design/methodology/approachAn extensive online survey was performed in order to obtain a final database of 151 Italian ASOs. Different statistical techniques were used, such as Cluster analysis and ANOVA, to identify different ASO profiles and to understand how and why these profiles change over time.FindingsThe results suggest that motivations change over time: while financial aspects become less important, academics give more importance to other issues. Time, experience and financial gain influence the evolution of academic entrepreneurs' motivations over time.Practical implicationsInsights derived from the study could help policy-makers and administrators in better understanding this phenomenon and the possible evolution of such academic motivations in the context of digitalization, and enable them to act accordingly to foster academic entrepreneurship.Originality/valueThe main contributions of the present study are the addition of empirical knowledge to the scant and anecdotal literature existing to date and the inclusion of cognitive and psychological theoretical perspectives in the academic entrepreneurship debate. Moreover, it is believed that no other study has investigated the above topics in the Italian context.
Developing students' mental health literacy through the power of sport
Authors: Glazzard Jonathan , Szreter Ben 
Published: May 2020

AbstractThis research is an evaluation of a six‐week mental health literacy programme, referred to as the Cambridge United Community Trust’s ‘Mind Your Head’ programme, which was delivered by sports professionals to secondary school students (11‐16) in Cambridge, England, during 2017–18. A Mental Health Literacy Scale was used to measure students’ knowledge of mental health issues pre‐ and post‐intervention. Statistical data from these surveys were analysed using an independent samples t‐test. Focus groups were held with students in each school, and individual semi‐structured interviews were conducted with one lead teacher in each school. The statistical data indicate that statistically significant improvements in mental health literacy were achieved, and this occurred across all genders and ethnicities. The qualitative data suggest that this programme resulted in positive attitudes towards mental health and improved knowledge of how to seek help. The data indicate that investment in similar programmes would be beneficial for schools in improving students’ knowledge of mental health and reducing stigma.
Optimization of ultrasonic‐assisted extraction conditions for bioactive components from coffee leaves using the Taguchi design and response surface methodology
Authors: Chen Xiumin , Ding Jian , Ji Dayi , He Suqun , Ma Haile 
Published: May 2020

AbstractCoffee leaves contain various bioactive compounds that are beneficial for human health. However, there are very limited researches related to the extraction of the bioactive phytochemicals from coffee leaves. In the present study, the extraction conditions for bioactive components from coffee leaves were optimized using Taguchi design and response surface methodology (RSM). Taguchi design was used to screen significant factors that affected the yield of phytochemicals including trigonelline, caffeine, chlorogenic acids, mangiferin, and rutin, total phenolic content (TPC) and antioxidant activity. Sequentially, a Box‐Behnken design (BBD) was used to optimize the extraction conditions. Three factors including Liquid‐to‐solid (L:S) ratio, ethanol concentration, and extraction temperature that significantly affected most of the phytochemical yields and antioxidant activity were selected from the six variables using Taguchi design. The optimal extraction conditions obtained from RSM were 30.3:1 L:S ratio, 54.5% ethanol, and 80 °C when simultaneously considered four responses, including TPC, the yields of mangiferin and 5‐CQA and DPPH scavenging capacity. Under the optimal conditions, the experimental results for the above four responses were 62.1 mg gallic acid/g, 4.1 mg/g, 11.4 mg/g, and 356.9 µmol Trolox/g, respectively, which were close to the predicted values. About 97% of phytochemicals can be extracted in the first two times of extraction. In conclusion, the combination of Taguchi design and response surface methodology can be successfully used to screen and optimize the significant factors that affected the bioactive components extracted from coffee leaves.Practical ApplicationCoffee leaves, the byproducts of coffee plants, are considered no‐ or low‐value although it has a long history for using them as tea‐like beverage and ethnomedicine by locals in the coffee plant growing countries. Bioactive components extracted from coffee leaves can be used as ingredients in functional beverages, functional food, and natural health products. These applications will add values to coffee leaves as well as increase the incomes of coffee farmers and workers.