bluuebunny/crossref_metadata_2025_split huggingface dataset:
What matters to patients?: a timely question for Value Based Care
Authors: Hirpa Meron , Woreta Tinsay , Addis Hilena , Kebede Sosena 
Published: January 2020

AbstractBackgroundOur healthcare system is moving towards patient-centered and value-based care models that prioritize health outcomes that matter to patients. However, little is known about what aspects of care patients would prioritize when presented with choices of desirable attributes and whether these patient priorities differ based on certain demographics.ObjectiveTo assess patients’ priorities for a range of attributes in ambulatory care consultations across five key health service delivery domains and determine potential associations between patient priorities and certain demographic profiles.MethodsUsing aWhat Matters to Yousurvey patients ranked in order of importance various choices related to five health service domains (patient-physician relationship, personal responsibility, tests/procedures, medications and cost). Subjects were selected from two Johns Hopkins affiliated primary care clinics and a third gastroenterology subspecialty clinic over a period of 11 months. We calculated the percentage of respondents who selected each quality as their top 1-3 choice. Univariate and multivariate analyses determined demographic characteristics associated with patient priorities.ResultsHumanistic qualities of physicians, leading a healthy lifestyle, shared decision making (SDM) for medications and tests/procedures and knowledge about insurance coverage were the most frequently ranked choices. Privately insured and more educated patients were less likely to rank humanistic qualities highly. Those with younger age, higher educational attainment and private insurance had higher odds of ranking healthy lifestyle as a top choice. Those with more education had higher odds of ranking SDM as a top choice.ConclusionsIdentifying what matters most to patients is useful as we move towards patient-centered and value based care models. Our findings suggest that patients have priorities on qualities they value across key health service domains. Multiple factors including patient demographics can be predictors of these priorities. Elucidating these preferences is a challenging but a valuable step in the right direction.
Simultaneous Discovery of Positive and Negative Interactions Among Root Microbiome Bacteria Using Microwell Recovery Arrays
Authors: Barua Niloy , Herken Ashlee M. , Stern Kyle R. , Reese Sean , Powers Roger L. , Morrell-Falvey Jennifer L. , Platt Thomas G. , Hansen Ryan R. 
Published: January 2020

AbstractUnderstanding the consequences of microbe-microbe interactions is critical in efforts to predict the function of microbiomes and to manipulate or construct communities to achieve desired outcomes. The investigation of these interactions poses a significant challenge - in part due to the lack of suitable experimental tools. We present the Microwell Recovery Array, a high throughput approach designed to rapidly screen interactions across a microbiome and uncover higher-order combinations of strains that either inhibit or promote the function of a GFP-producing focal species. One experiment generates 104unique microbial communities that contain a focal species combined with a unique combination of previously uncharacterized cells from plant rhizosphere. Cells are then sequentially extracted from individual co-culture wells that display highest or lowest levels of focal species function using a novel high-resolution photopolymer extraction system. Microbes present are subsequently identified and the putative interactions are validated. Using this approach, we screen thePopulus trichocarparhizosphere for bacterial strains affecting the survival and growth ofPantoeasp. YR343, a plant growth promoting strain isolated from theP. trichocarparhizosphere. We were able to simultaneously isolate and validate multipleStenotrophomonasstrains that antagonize strain YR343 growth and a set ofEnterobacterstrains that promote strain YR343 growth. The latter demonstrates the unique ability of the platform to uncover multi-membered consortia that generate emergent phenotypes. This knowledge will inform the development of beneficial consortia that promote the production ofPopulusbiofuel feedstock, while the platform is adaptable to screening higher-order interactions in any microbiome of interest.Significance StatementAchieving a fundamental understanding of microbe-microbe interactions that occur within microbial communities is a grand challenge in microbiology due to the limited experimental tools available. In this report, we describe a new tool that enables one to screen microbial interactions across thousands of compositionally unique communities to discover collections of bacteria that antagonize or promote the survival and growth of bacteria with important functions. This approach has the unique ability to uncover higher-order combinations of bacteria that generate emergent phenotypes, information useful for development of biofertilizer, biocontrol, or probiotic consortia, as well as in the design of communities for biosynthetic compound production.
Engineering Cell-Permeable Proteins through Insertion of Cell-Penetrating Motifs into Surface Loops
Authors: Chen Kuangyu , Pei Dehua 
Published: January 2020

ABSTRACTEffective delivery of proteins into the cytosol and nucleus of mammalian cells would open the door to a wide range of applications including treatment of many currently intractable diseases. However, despite great efforts from numerous investigators and the development of a variety of innovative methods, effective protein delivery in a clinical setting is yet to be accomplished. Herein we report a potentially general approach to engineering cell-permeable proteins by genetically grafting a short cell-penetrating peptide to an exposed loop region of a protein of interest. The grafted peptide is conformationally constrained by the protein structure, sharing the structural features of cyclic cell-penetrating peptides and exhibiting enhanced proteolytic stability and cellular entry efficiency. Insertion of an amphipathic motif, Arg-Arg-Arg-Arg-Trp-Trp-Trp, into the loop regions of enhanced green fluorescent protein (EGFP), protein-tyrosine phosphatase 1B (PTP1B), and purine nucleoside phosphorylase (PNP) rendered all three proteins cell-permeable and biologically active in cellular assays. When added into growth medium, the engineered PTP1B dose-dependently reduced the phosphotyrosine levels of intracellular proteins, while the modified PNP protected PNP-deficient mouse T lymphocytes (NSU-1) against toxic levels of deoxyguanosine, providing a potential enzyme replacement therapy for a rare genetic disease.
Bioethanol from Sago Waste Fermented by Baker’s and Tapai Yeast as a Renewable Energy Source
Authors: Rijal Muhammad 
Published: January 2020

AbstractRenewable energy is collected through sustainable natural processes. One of the examples of renewable energy is a biofuel. A biofuel is produced from organic materials, such as plants with high sugar content. Sago starch extracted from sago pith contains starch and fiber that can be converted into glucose by hydrolysis. Sago starch and fiber can be processed into bioethanol as the main ingredient of renewable energy source. In this study, bioethanol production from sago waste fermented by baker’s yeast and tapai underwent the following stages: delignification, hydrolysis, fermentation, and distillation. The highest bioethanol content was obtained from the BRT treatment where wet solid sago waste was fermented by baker’s yeast (45.7021%), while the lowest was found in the BTP treatment (0.9504%). Two or more than two peaks were shown by the ART, ATP, BTP, and KTP treatments, whereas only one peak was indicated by the BRT and KRT treatments suggesting that there was only one compound that can be identified as ethanol.
Capturing volumetric dynamics at high speed in the brain by confocal light field microscopy
Authors: Zhang Zhenkun , Bai Lu , Cong Lin , Yu Peng , Zhang Tianlei , Shi Wanzhuo , Li Funing , Du Jiulin , Wang Kai 
Published: January 2020

AbstractNeural network performs complex computations through coordinating collective neural dynamics that are fast and in three-dimensions. Meanwhile, its proper function relies on its 3D supporting environment, including the highly dynamic vascular system that drives energy and material flow. Better understanding of these processes requires methods to capture fast volumetric dynamics in thick tissue. This becomes challenging due to the trade-off between speed and optical sectioning capability in conventional imaging techniques. Here we present a new imaging method, confocal light field microscopy, to enable fast volumetric imaging deep into brain. We demonstrated the power of this method by recording whole brain calcium transients in freely swimming larval zebrafish and observed behaviorally correlated activities on single neurons during its prey capture. Furthermore, we captured neural activities and circulating blood cells over a volume ⌀ 800 μm × 150 μm at 70 Hz and up to 600 μm deep in the mice brain.
Cyano-assassins: Widespread cyanogenic production from cyanobacteria
Authors: Panou Manthos , Gkelis Spyros 
Published: January 2020

AbstractCyanobacteria have been linked with hydrogen cyanide, based on their ability to catabolize it by the nitrogenase enzyme, as a part of nitrogen fixation. Nitrogenase can also use hydrogen cyanide instead of its normal substrate, dinitrogen and convert it to methane and ammonia. In this study, we tested whether cyanobacteria are able, not only to reduce, but also to produce HCN. The production of HCN was examined in 78 cyanobacteria strains from all five principal sections of cyanobacteria, both non-heterocytous and heterocytous, representing a variety of lifestyles and habitats. Twenty-eight (28) strains were found positive for HCN production, with universal representation amongst 22 cyanobacterial planktic and epilithic genera inhabiting freshwater, brackish, marine (including sponges), and terrestrial (including anchialine) habitats. The HCN production could be linked with nitrogen fixation, as all of HCN producing strains are considered capable of fixing nitrogen. Epilithic lifestyle, where cyanobacteria are more vulnerable to a number of grazers and accumulate more glycine, had the largest percentage (75%) of HCN-producing cyanobacteria compared to strains from aquatic ecosystems. Further, we demonstrate the isolation and characterisation of taxa likeGeitleria calcareaandKovacikia muscicola, for which no strain existed andChlorogloeasp. TAU-MAC 0618 which is, to the best of our knowledge, the first bacterium isolate from anchialine ecosystems. Our results highlight the complexity of cyanobacteria secondary metabolism, as well as the diversity of cyanobacteria in underexplored habitats, providing a missing study material for this type of environments.
The G-protein coupled receptor SRX-97 is required for concentration dependent sensing of Benzaldehyde inCaenorhabditis elegans
Authors: Kadam Nagesh Y. , Behera Sukanta , Kumar Sandeep , Ghosh-Roy Anindya , Babu Kavita 
Published: January 2020

AbstractThe G-protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors in the olfactory system function to sense the surroundings and respond to various odorants. The genes encoding for the olfactory receptors inC. elegansare larger in number in comparison to those in mammals, suggesting complexity in the receptor– odorant relationships. Recent studies have shown that the same odorant in different concentration could act on multiple receptors in different neurons to induce attractive or repulsive responses. The ASH neuron is known to be responsible for responding to high concentrations of volatile odorants. Here we characterize a new GPCR, SRX-97. We found that thesrx-97promoter shows expression specifically in the head ASH and tail PHB chemosensory neurons ofC. elegans. Further, the SRX-97 protein localizes to the ciliary ends of the ASH neurons. Analysis of CRISPR/based deletion mutants of thesrx-97gene suggest that this gene is involved in the recognition of high concentrations of benzaldehyde. This was further confirmed through rescue and neuronal ablation experiments. Our work gives insight into concentration dependent receptor function in the olfactory system and provides details of an additional molecule that could help the animal navigate its surroundings.
Derived ecological niches of indoor microbes are crucial for asthma symptoms in university dormitories
Authors: Fu Xi , Li Yanling , Meng Yi , Yuan Qianqian , Zhang Zefei , Norbäck Dan , Deng Yiqun , Zhang Xin , Sun Yu 
Published: January 2020

AbstractIncreasing evidences from home environment indicate that microbiome community is associated with asthma. However, indoor microbiome composition can be highly diverse and dynamic, and thus current studies fail to produce consistent association. Chinese university dormitories are special high-density dwellings with a standard built environment and personal characteristics for occupants, which can be used to disentangle the complex interactions between microbes, environmental characteristics and asthma.Settled air dust and floor dust was collected from 87 dormitory rooms in Shanxi University. Bacterial community was characterized by 16S rRNA amplicon sequencing. Students (n = 357) were surveyed for asthma symptoms.Asthma symptoms were not associated with the overall bacterial richness, but associated with different phylogenetic classes. Taxa richness and abundance in Clostridia and Bacteroidia were positively associated with asthma (p < 0.05), and these taxa were mainly derived from human gut. Taxa richness (p < 0.1) and abundance (p < 0.05) in Alphaproteobacteria and Actinobacteria were protectively associated with asthma, and these taxa were mainly derived from outdoor environment. Building age, floor and curtain cleaning frequency shaped the overall bacterial community of air dust (p < 0.05). Frequent curtain cleaning increased the relative abundance of 10 protective genera (p < 0.05), and old buildings had mix effects to protective genera (p < 0.05).Our data shows that taxa from different phylogenetic classes and ecological niches have different health effects, indicating the importance of incorporating evolutionary and ecological concepts in revealing general patterns in the microbiome asthma association analysis.
Variation in the expression of a transmembrane protein influences cell growth inArabidopsis thalianapetals by altering auxin availability
Authors: Miller Charlotte N. , Dumenil Jack , Smith Caroline , Lu Fu Hao , McKenzie Neil , Chapman Volodymyr , Ball Joshua , Box Mathew , Bevan Michael 
Published: January 2020

AbstractBackgroundThe same species of plant can exhibit highly diverse sizes and shapes of organs that are genetically determined. Defining genetic variation underlying this morphological diversity is an important objective in evolutionary studies and it also helps identify the functions of genes influencing plant growth and development. Extensive screens of mutagenised Arabidopsis populations have identified multiple genes and mechanisms affecting organ size and shape, but relatively few studies have exploited the rich diversity of natural populations to identify genes involved in growth control.ResultsWe screened a relatively well characterised collection ofArabidopsis thalianaecotypes for variation in petal size. Association analyses identified sequence and gene expression variation on chromosome 4 that made a substantial contribution to differences in petal area. Variation in expression of At4g16850 (named asKSK), encoding a hypothetical protein, had a substantial role on variation in organ size by influencing cell size. Over-expression ofKSKled to larger petals with larger cells and promoted the formation of stamenoid features. The expression of auxin-responsive genes known to limit cell growth was reduced in response toKSKover-expression. ANT expression was also reduced inKSKover-expression lines, consistent with altered floral identities. Auxin availability was reduced inKSKover-expressing cells, consistent with changes in auxin-responsive gene expression.KSKmay therefore influence auxin availability during petal development.ConclusionsUnderstanding how genetic variation influences plant growth is important for both evolutionary and mechanistic studies. We used natural populations ofArabidopsis thalianato identify sequence variation in a promoter region of Arabidopsis ecotypes that mediated differences in the expression of a previously uncharacterised membrane protein. This variation contributed to altered auxin availability and cell size during petal growth.
Different forms of variability could explain a difference between human and rat decision making
Authors: Nguyen Quynh Nhu , Reinagel Pamela 
Published: January 2020

AbstractWhen observers make rapid, difficult perceptual decisions, their response time is highly variable from trial to trial. In a visual motion discrimination task, it has been reported that human accuracy declines with increasing response time, whereas rat accuracy increases with response time. This is of interest because different mathematical theories of decision-making differ in their predictions regarding the correlation of accuracy with response time. On the premise that perceptual decision-making mechanisms are likely to be conserved among mammals, we seek to unify the rodent and primate results in a common theoretical framework. We show that a bounded drift diffusion model (DDM) can explain both effects with variable parameters: trial-to-trial variability in the starting point of the diffusion process produces the pattern typically observed in rats, whereas variability in the drift rate produces the pattern typically observed in humans. We further show that the same effects can be produced by deterministic biases, even in the absence of parameter stochasticity or parameter change within a trial.
Coupling of translation quality control and mRNA targeting to stress granules
Authors: Moon Stephanie L. , Morisaki Tatsuya , Stasevich Timothy J. , Parker Roy 
Published: January 2020

AbstractStress granules (SGs) are dynamic assemblies of non-translating RNAs and proteins that form with translation inhibition1. Stress granules are similar to neuronal and germ cell granules, play a role in survival during stress, and aberrant, cytotoxic SGs are implicated in neurodegeneration2–4. Perturbations in the ubiquitin-proteasome (UPS) system also cause neurodegeneration5–10, and alter the dynamicity and kinetics of SGs11–14. Using single mRNA imaging in live cells15, 16, we took an unbiased approach to determine if defects in the UPS perturb mRNA translation and partitioning into SGs during acute stress. We observe ribosomes stall on mRNAs during arsenite stress, and the release of transcripts from stalled ribosomes for their partitioning into SGs requires the activities of valosin-containing protein (VCP) and the proteasome, which is in contrast to previous work showing VCP primarily affected SG disassembly11, 13, 14, 17. Moreover, members of a specialized complex in the UPS that targets aberrant nascent proteins for decay upon ribosome stalling, referred to as ribosome-associated quality control complex (RQC)18, are also required for mRNA release from ribosomes and partitioning into SGs. VCP alleles that increase segregase activity and cause neurodegeneration and inclusion body myopathies5, 6, 19, 20increase mRNA recruitment to SGs, suggesting aberrant mRNA localization to SGs in disease contexts. This work identifies a new type of stress-activated RQC (saRQC) distinct from canonical RQC pathways in mRNA substrates, cellular context and mRNA fate.
Calpain-2 regulates hypoxia/HIF-induced amoeboid reprogramming and metastasis
Authors: te Boekhorst Veronika , Jiang Liying , Mählen Marius , Meerlo Maaike , Dunkel Gina , Durst Franziska C. , Yang Yanjun , Levine Herbert , Burgering Boudewijn M. T. , Friedl Peter 
Published: January 2020

SummaryHypoxia, through hypoxia inducible factor (HIF), drives cancer cell invasion and metastatic progression in various cancer types, leading to poor prognosis. In epithelial cancer, hypoxia further induces the transition to amoeboid cancer cell dissemination, yet the molecular mechanisms, relevance for metastasis, and effective interventions to combat hypoxia-induced amoeboid reprogramming remain unclear. Here, we identify calpain-2 as key regulator and anti-metastasis target of hypoxia-induced transition from collective to amoeboid dissemination of breast and head and neck (HN) carcinoma cells. Hypoxia-induced amoeboid dissemination occurred through low ECM-adhesive, bleb-based amoeboid movement, which effectively invaded into 3D collagen with low-oxidative and -glycolytic energy metabolism, revealing an microenvironmentally-induced, energy-conserving dissemination route in epithelial cancers. Hypoxia-induced calpain-2 mediated amoeboid conversion by de-activating beta1 integrins, through enzymatic cleavage of the focal adhesion adaptor protein talin-1. Consequently, targeted downregulation of calpain-2 or pharmacological intervention restored talin-1 integrity, beta1 integrin engagement and reverted blebbing-amoeboid to elongated phenotypes under hypoxia. Calpain-2 activity was required for hypoxia-induced blebbing-amoeboid conversion in the orthotopic mouse dermis, and upregulated in invasive HN tumor xenografts in vivo, and attenuation of calpain activity prevented hypoxia-induced metastasis to the lungs. This identifies the calpain-2/talin-1/beta1 integrin axis as mechanosignaling program and promising intervention target of plasticity of cancer cell invasion and metastasis formation in epithelial cancers under hypoxia.