bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of diffusionless and diffusional transformations usingin situcooling and heating techniques in a scanning electron microscope
Authors: Kumar Deepak , Sarkar Rajdeep , Singh Vajinder , Kumar Suraj , Mondal Chandan , Ghosal P. 
Published: October 2020

In situelectron microscopy can be an effective tool to investigate the underlying science of many transformation mechanisms in materials science. Useful utilization of these experimentations will provide greater insight into many of the existing theories, as microstructural changes can be visualized in real time under some applied constraints. In this study, we have investigated two basic phase transformation phenomena: diffusionless and diffusional mechanisms with the help ofin situcooling and heating techniques in scanning electron microscope (SEM).In situcooling experiments have been carried out on secondary hardening ultra-high-strength steels to understand the diffusionless transformation of austenite to martensite. Nucleation and growth of the martensites have been observed with cooling in different steps to −194°C. Details of the formation of different variants of martensites in steel were studied with the help of orientation imaging microscopy. Diffusional transformations were studied in terms of oxidation of pure copper in SEM usingin situheating technique. Different heating cycles were adopted for different samples byin situheating to a maximum temperature of 950°C for the oxidation study. Nucleation of copper oxides and subsequent growth of the copper oxides at different temperatures were studied systematically. Raman spectroscopy and orientation imaging were done to confirm the formation of oxides and their orientations. The thermal cycling phenomenon was replicated inside SEM with heating and cooling and it has been demonstrated how the nature of copper and its oxides changes with the thermal cycle.This article is part of a discussion meeting issue ‘Dynamicin situmicroscopy relating structure and function’.
Five Year Pediatric Use of a Digital Wearable Fitness Device: Lessons from a Pilot Case Study
Authors: Butte Kimayani D. , Bahmani Amir , Butte Atul J. , Li Xiao , Snyder Michael P. 
Published: October 2020

AbstractObjectivesWearable fitness devices are increasingly used by the general population, with new applications being proposed and designed for healthy adults as well as adults with chronic diseases. Fewer, if any, studies of these devices have been conducted in healthy adolescents and teenagers, especially over a long period of time. The goal of this work was to document the successes and challenges involved in 5 years of a wearable fitness device use in a pediatric case study.Materials and MethodsComparison of five years of step counts and minutes asleep from a teenaged girl and her father.ResultsAt 60 months, this may be the longest reported pediatric study involving a wearable fitness device, and the first simultaneously involving a parent and a child. We find step counts to be significantly higher for both the adult and teen on school/work days, along with less sleep. The teen walked significantly less towards the end of the 5 year study. Surprisingly, many of the adult’s and teen’s sleeping and step counts were correlated, possibly due to coordinated behaviors.DiscussionWe end with several recommendations for pediatricians and device manufacturers, including the need for constant adjustments of stride length and calorie counts as teens are growing.ConclusionWith periodic adjustments for growth, this pilot study shows these devices can be used for more accurate and consistent measurements in adolescents and teenagers over longer periods of time, to potentially promote healthy behaviors.
Microbiota compositions from infertile couples seeking in vitro fertilization (IVF), using 16S rRNA gene sequencing methods: any correlation to clinical outcomes?
Authors: Okwelogu Somadina I , Ikechebelu Joseph I , Agbakoba Nneka R , Anukam Kingsley C 
Published: October 2020

AbstractBacterial infections are usually suspected in infertile couples seeking IVF with no clear understanding of the microbial compositions present in the seminal fluids and vaginal swabs of the patients. We used next-generation sequencing technology to correlate microbiota compositions with IVF clinical outcomes. Thirty-six couples were recruited to provide seminal fluids and vaginal swabs. Seminal fluid microbiota compositions had lower bacterial concentrations compared with the vagina, but species diversity was significantly higher in seminal fluid samples. Azoospermic subjects had more relative abundance of Mycoplasma and Ureaplasma. In Normospermic semen Lactobacillus (43.86%) was the most abundant, followed by Gardnerella (25.45%), while the corresponding vaginal samples, Lactobacillus (61.74%) was the most abundant, followed by Prevotella (6.07%), and Gardnerella (5.86%). Semen samples with positive IVF were significantly colonized by Lactobacillus jensenii (P=0.002), Faecalibacterium (P=0.042) and significantly less colonized by Proteobacteria, Prevotella, Bacteroides and lower Firmicutes/Bacteroidetes ratio compared with semen samples with negative IVF. Vaginal samples with positive IVF clinical outcome were significantly colonized by Lactobacillus gasseri, less colonized by Bacteroides, and Lactobacillus iners. This study has opened a window of possibility for Lactobacillus replenishments in men and women prior to IVF treatment.
Revisiting the UK Genetic Severity Score for NF2: a proposal for adding functional information
Authors: Catasús N. , García B. , Galvan I. , Plana A. , Negro A. , Rosas I. , Ros A. , Amilibia E. , Becerra JL. , Hostalot C. , Roca-Ribas F. , Bielsa I. , Lazaro C. , de Cid R. , Serra E. , Blanco I. , Castellanos E. 
Published: October 2020

AbstractBackgroundNeurofibromatosis Type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple schwannomas, particularly at vestibular nerves, and meningiomas. The UK NF2 Genetic Severity Score (GSS) helps predicting the disease course from germline NF2 pathogenic variants, optimizing the clinical follow-up and the genetic counselling offered to affected families.MethodsSpanish Reference Center patients were classified following the GSS and patients’ clinical severity was measured and compared between GSS groups. The GSS was reviewed considering phenotype quantification, genetic variant classification and functional assays of Merlin and its downstream pathways, studied by western blot in patient’s primary fibroblast. Principal component analysis and regression models were considered to evaluate the differences between severity and NF2 germline mutations.ResultsThe GSS was validated in the Spanish NF2 cohort. However, for some patients harboring mutations associated to mild and moderate phenotypes, GSS did not perform as well in predicting clinical outcomes as for pathogenic variants associated to severe phenotypes. We studied the possibility of modifying the mutation classification in GSS adding functional assays to evaluate the impact of pathogenic mutations on Merlin’s function. This revision help reducing variability within NF2 mutation classes and moderately enhances the correlation between patients’ phenotype and the different prognosis parameters analyzed.ConclusionsWe validated the UK NF2 GSS in a Spanish NF2 cohort although a significant phenotypic variability was identified. The revision of the GSS, named FGSS, could be an added value to the classification of mosaic patients and patients showing mild and moderate phenotypes.
Predictors of Anxiety in a Sample of Preschoolers with ASD
Authors: Behzadpoor Samaneh , Pouretemad Hamidreza , zardkhaneh Saeed Akbari 
Published: October 2020

AbstractObjectiveAnxiety is one of the most prevalent comorbid disorders in children with autism spectrum disorder (ASD). However, there is inconsistency in research investigating the predictors of anxiety in children with ASD. Also, most studies have focused on school-age children so research on anxiety in preschoolers with ASD has been somewhat neglected. Thus, the aim of this study was to investigate age, gender, ASD symptom severity, and functional language use as potential risk factors for developing anxiety in this sample.MethodIn total, 95 children with ASD and their caregivers participated in this study. The Gilliam Autism Rating Scale–Second Edition (GARS-2), and The Preschool Anxiety Scale (PAS) were used to gather data. Data were analyzed by Independent sample t-tests, MANOVA, Pearson’s r correlations, the point biserial correlation coefficient, and multiple regression analysis with the stepwise procedure.ResultsThe findings indicated that anxiety was positively correlated with age and functional language use and negatively with ASD symptom severity. There wasn’t a significant relationship between anxiety and gender.ConclusionThe findings suggest age and ASD symptom severity were significant predictors of anxiety in this sample. In other words, older children and cases with lower symptom severity are more likely to experience anxiety. It is also implied to examine the role of cognitive deficits in the development of anxiety in autism.
Lockdown related travel behavior undermines the containment of SARS-CoV-2
Authors: Kishore Nishant , Kahn Rebecca , Martinez Pamela P. , De Salazar Pablo M. , Mahmud Ayesha S. , Buckee Caroline O. 
Published: October 2020

ABSTRACTIn response to the SARS-CoV-2 pandemic, unprecedented policies of travel restrictions and stay-at-home orders were enacted around the world. Ultimately, the public’s response to announcements of lockdowns - defined here as restrictions on both local movement or long distance travel - will determine how effective these kinds of interventions are. Here, we measure the impact of the announcement and implementation of lockdowns on human mobility patterns by analyzing aggregated mobility data from mobile phones. We find that following the announcement of lockdowns, both local and long distance movement increased. To examine how these behavioral responses to lockdown policies may contribute to epidemic spread, we developed a simple agent-based spatial model. We find that travel surges following announcements of lockdowns can increase seeding of the epidemic in rural areas, undermining the goal of the lockdown of preventing disease spread. Appropriate messaging surrounding the announcement of lockdowns and measures to decrease unnecessary travel are important for preventing these unintended consequences of lockdowns.
RNF5 Regulation of RBBP4 Defines Acute Myeloid Leukemia Growth and Susceptibility to Histone Deacetylase Inhibitors
Authors: Khateb Ali , Deshpande Anagha , Feng Yongmei , Lee Joo Sang , Lazar Ikrame , Fabre Bertrand , Li Yan , Finlay Darren , Fujita Yu , Zhang Tongwu , Yin Jun , Pass Ian , Livneh Ido , Burian Carol , Mason James R. , Almog Ronit , Horesh Nurit , Ofran Yishai , Brown Kevin , Vuori Kristiina , Jackson Michael , Ruppin Eytan , Deshpande Aniruddha J. , Ronai Ze’ev A. 
Published: October 2020

ABSTRACTAcute myeloid leukemia (AML) remains incurable, largely due to its resistance to conventional treatments. Here, we found that increased expression and abundance of the ubiquitin ligase RNF5 contributes to AML development and survival. High RNF5 expression in AML patients correlated with poor prognosis. RNF5 inhibition decreased AML cell growth in culture andin vivo, and blocked development of MLL-AF9–driven leukemogenesis in mice, prolonging their survival. RNF5 inhibition led to transcriptional changes that overlapped with those seen upon HDAC1 inhibition. RNF5 induced the formation of K29 ubiquitin chains on the histone-binding protein RBBP4, promoting its recruitment and subsequent epigenetic regulation of genes involved in AML development and maintenance. Correspondingly, RNF5 or RBBP4 knockdown enhanced the sensitivity of AML cells to histone deacetylase (HDAC) inhibitors. Notably, low expression ofRNF5andHDACcoincided with a favorable prognosis. Our studies identified ERAD-independent role for RNF5, demonstrating that its control of RBBP4 constitutes an epigenetic pathway that drives AML while highlighting RNF5/RBBP4 as markers to stratify patients for treatment with HDAC inhibitors.
Label-free composition determination for biomolecular condensates with an arbitrarily large number of components
Authors: McCall Patrick M. , Kim Kyoohyun , Ruer-Gruß Martine , Peychl Jan , Guck Jochen , Hyman Anthony A. , Brugués Jan 
Published: October 2020

ABSTRACTBiomolecular condensates are membrane-less organelles made of multiple components, often including several distinct proteins and nucleic acids. However, current tools to measure condensate composition are limited and cannot capture this complexity quantitatively, as they either require fluorescent labels, which we show can perturb composition, or can distinguish only 1-2 components. Here, we describe a label-free method based on quantitative phase microscopy to measure the composition of condensates with an arbitrarily large number of components. We first validate the method empirically in binary mixtures, revealing sequence-encoded density variation and complex aging dynamics for condensates composed of full-length proteins. In simplified multi-component protein/RNA condensates, we uncover a regime of constant condensate density and a large range of protein:RNA stoichiometry when varying average composition. The unexpected decoupling of density and composition highlights the need to determine molecular stoichiometry in multi-component condensates. We foresee this approach enabling the study of compositional regulation of condensate properties and function.
Loss of KHSRP Increases Neuronal Growth and Synaptic Transmission and Alters Memory Consolidation Through RNA Stabilization
Authors: Olguin Sarah L. , Patel Priyanka , Dell’Orco Michela , Gardiner Amy S. , Cole Robert , Buchanan Courtney , Sundara Anitha , Mudge Joann , Allan Andrea M. , Ortinski Pavel , Brigman Jonathan L. , Twiss Jeffery L. , Perrone-Bizzozero Nora I. 
Published: October 2020

ABSTRACTThe KH-type splicing regulatory protein (KHSRP) is an RNA-binding protein linked to decay of AU-rich element containing mRNAs. We have previously shown that KHSRP destabilizes the mRNA encoding the growth-associated protein GAP-43 and decreases neurite growth in cultured embryonic neurons. In contrast, loss of KHSRP stabilizesGap43mRNA and increases neurite growth. Here, we have tested functions of neural KHSRPin vivo. We find upregulation of 1460 mRNAs in the neocortex of adultKhsrp−/−mice, of which 527 bind to KHSRP with high specificity. These KHSRP targets are involved in pathways for neuronal morphology, axon guidance, neurotransmission and long-term memory. Neocortical neurons show increased axon growth and dendritic spine density inKhsrp−/−mice. Analyses of neuronal cultures from embryonicKhsrp−/−mice point to a neuron-intrinsic alteration in axonal and dendritic growth and elevations in KHSRP-target mRNAs, including subcellularly localized mRNAs. Hippocampus and infralimbic cortex ofKhsrp−/−mice show presynaptic elevations in neurotransmission. TheKhsrp−/−mice have significant deficits in both trace conditioning and attention set-shifting tasks comparedKhsrp+/+mice, indicating impaired prefrontal- and hippocampal-dependent memory consolidation with loss of KHSRP. Overall, our results indicate that prenatal deletion of KHSRP impairs neuronal development resulting in alterations in neuronal morphology and function by changing post-transcriptional control of neuronal gene expression.
Trade-off between plasticity and velocity in mycelial growth
Authors: Fukuda Sayumi , Yamamoto Riho , Yanagisawa Naoki , Takaya Naoki , Sato Yoshikatsu , Riquelme Meritxell , Takeshita Norio 
Published: October 2020

AbstractTip-growing fungal cells maintain the cell polarity at the apical regions and elongate by de novo synthesis of cell wall. Cell polarity and growth rate affect the mycelial morphogenesis, however, it remains unclear how they act cooperatively to determine cell shape. Here we investigated their relationship by analyzing hyphal tip growth of filamentous fungi growing inside extremely narrow 1 μm-width channels of microfluidic devices. Since the channels are much narrower than the diameter of hyphae, the hyphae must change its morphology when they grow through the channels. Live imaging analysis revealed that hyphae of some species continued growing through the channels, whereas hyphae of other species often ceased growing when passing through the channels or lost the cell polarity after emerging from the channels. Fluorescence live imaging analysis of the Spitzenkörper, a collection of secretory vesicles and polarity-related proteins at hyphal tips, inNeurospora crassahyphae indicates that hyphal tip growth requires a very delicate balance of ordered exocytosis to maintain polarity in spatially confined environments. We analyzed the mycelial growth of seven fungal species from different lineages, which also include phytopathogenic fungi. This comparative cell biology showed that the growth defects in the channels were not correlated with their taxonomic classification nor with the width of hyphae, but, correlated with the hyphal elongation rate. This is the first report indicating a trade-off between plasticity and velocity in mycelial growth, and serves to understand fungal invasive growth into substrates or plant/animal cells, with direct impact on fungal biotechnology, ecology and pathogenicity.
Reversible coating of cells with synthetic polymers for mechanochemical regulation of cell adhesion
Authors: Kaizuka Yoshihisa , Machida Rika 
Published: October 2020

AbstractThe chemical control of cell–cell interactions using synthetic materials is useful for a wide range of biomedical applications. Herein, we report a method to regulate cell adhesion and dispersion by introducing repulsive forces to live cell membranes. To induce repulsion, we tethered amphiphilic polymers, such as cholesterol-modified polyethylene glycol (PEG-CLS) to cell membranes. These amphiphilic polymers both bind to and dissociate rapidly from membranes and thus, enable the reversible coating of cells by mixing and washout without requiring genetic manipulation or chemical synthesis in the cells. We found that the repulsive forces introduced by these tethered polymers can induce cell detachment from a substrate and allow cell dispersion in a suspension, modulate the speed of cell migration, and improve the separation of cells from tissues. Our analyses showed that coating the cells with tethered polymers most likely generated two distinct repulsive forces, lateral tension and steric repulsion, on the surface, which can be tuned by altering the polymer size and density. We also modeled how these two forces can be generated in kinetically distinctive manners to explain the various responses of cells to the coating. Collectively, our observations and analyses show how we can mechanochemically regulate cell adhesion and dispersion and may contribute to the optimization of chemical coating strategies for regulating various types of cell–cell interacting systems.
The Arabidopsis E3 ubiquitin ligase PUB4 regulates BIK1 homeostasis and is targeted by a bacterial type-III effector
Authors: Derkacheva Maria , Yu Gang , Rufian Jose S. , Jiang Shushu , Derbyshire Paul , Morcillo Rafael J. L. , Stransfeld Lena , Wei Yali , Menke Frank L.H. , Zipfel Cyril , Macho Alberto P. 
Published: October 2020

SummaryPlant immunity is tightly controlled by a complex and dynamic regulatory network, which ensures optimal activation upon detection of potential pathogens. Accordingly, each component of this network is a potential target for manipulation by pathogens. Here, we report that RipAC, a type III-secreted effector from the bacterial pathogenRalstonia solanacearum, targets the plant E3 ubiquitin ligase PUB4 to inhibit pattern-triggered immunity (PTI). PUB4 plays a positive role in PTI by regulating the homeostasis of the central immune kinase BIK1. Before PAMP perception, PUB4 promotes the degradation of non-activated BIK1, while, after PAMP perception, PUB4 contributes to the accumulation of activated BIK1. RipAC leads to BIK1 degradation, which correlates with its PTI-inhibitory activity. RipAC causes a reduction in pathogen-associated molecular pattern (PAMP)-induced PUB4 accumulation and phosphorylation. Our results shed light on the role played by PUB4 in immune regulation, and illustrate an indirect targeting of the immune signalling hub BIK1 by a bacterial effector.
Disruption of a GATA2, TAL1, ERG regulatory circuit promotes erythroid transition in healthy and leukemic stem cells
Authors: Thoms Julie A. I , Knezevic Kathy , Harvey Gregory , Huang Yizhou , Seneviratne Janith A. , Carter Daniel R. , Subramanian Shruthi , Skhinas Joanna , Chacon Diego , Shah Anushi , de Jong Ineke , Beck Dominik , Göttgens Berthold , Larsson Jonas , Wong Jason W. H. , Zanini Fabio , Pimanda John E. 
Published: October 2020

ABSTRACTChanges in gene regulation and expression govern orderly transitions from hematopoietic stem cells to terminally differentiated blood cell types. These transitions are disrupted during leukemic transformation but knowledge of the gene regulatory changes underpinning this process is elusive. We hypothesised that identifying core gene regulatory networks in healthy hematopoietic and leukemic cells could provide insights into network alterations that perturb cell state transitions. A heptad of transcription factors (LYL1, TAL1, LMO2, FLI1, ERG, GATA2, RUNX1) bind key hematopoietic genes in human CD34+ haematopoietic stem and progenitor cells (HSPCs) and have prognostic significance in acute myeloid leukemia (AML). These factors also form a densely interconnected circuit by binding combinatorially at their own, and each other’s, regulatory elements. However, their mutual regulation during normal haematopoiesis and in AML cells, and how perturbation of their expression levels influences cell fate decisions remains unclear. Here, we integrated bulk and single cell data and found that the fully connected heptad circuit identified in healthy HSPCs persists with only minor alterations in AML, and that chromatin accessibility at key heptad regulatory elements was predictive of cell identity in both healthy progenitors and in leukemic cells. The heptad factors GATA2, TAL1 and ERG formed an integrated sub-circuit that regulates stem cell to erythroid transition in both healthy and leukemic cells. Components of this triad could be manipulated to facilitate erythroid transition providing a proof of concept that such regulatory circuits could be harnessed to promote specific cell type transitions and overcome dysregulated haematopoiesis.