bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concerted action of kinesins KIF5B and KIF13B promotes efficient secretory vesicle transport to microtubule plus ends
Authors: Serra-Marques Andrea , Martin Maud , Katrukha Eugene A. , Grigoriev Ilya , Peeters Cathelijn A.E. , Liu Qingyang , Hooikaas Peter Jan , Yao Yao , Solianova Veronika , Smal Ihor , Pedersen Lotte B. , Meijering Erik , Kapitein Lukas C. , Akhmanova Anna 
Published: April 2020

AbstractIntracellular transport relies on multiple kinesins, but it is poorly understood which kinesins are present on particular cargos, what their contributions are and whether they act simultaneously on the same cargo. Here, we show that Rab6-positive secretory vesicles are transported from the Golgi apparatus to the cell periphery by kinesin-1 KIF5B and kinesin-3 KIF13B, which determine the location of secretion events. KIF5B plays a dominant role, whereas KIF13B helps Rab6 vesicles to reach freshly polymerized microtubule ends, to which KIF5B binds poorly, likely because its cofactors, MAP7-family proteins, are slow in populating these ends. Sub-pixel localization demonstrated that during microtubule plus-end directed transport, both kinesins localize to the vesicle front and can be engaged on the same vesicle. When vesicles reverse direction, KIF13B relocates to the middle of the vesicle, while KIF5B shifts to the back, suggesting that KIF5B but not KIF13B undergoes a tug-of-war with a minus-end directed motor.
Single-cell RNA sequencing deconvolutes thein vivoheterogeneity of human bone marrow-derived mesenchymal stem cells
Authors: Wang Zun , Li Xiaohua , Yang Junxiao , Gong Yun , Zhang Huixi , Qiu Xiang , Liu Ying , Zhou Cui , Chen Yu , Greenbaum Jonathan , Cheng Liang , Hu Yihe , Xie Jie , Yang Xucheng , Li Yusheng , Schiller Martin R. , Tan Lijun , Tang Si-Yuan , Shen Hui , Xiao Hong-Mei , Deng Hong-Wen 
Published: April 2020

AbstractBone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stromal cells, which have a critical role in the maintenance of skeletal tissues such as bone, cartilage, and the fat found in bone marrow. In addition to providing microenvironmental support for hematopoietic processes, BM-MSCs can differentiate into various mesodermal lineages including osteoblast/osteocyte, chondrocyte, and adipocyte cells that are crucial for bone metabolism. While BM-MSCs have high cell-to-cell heterogeneity in gene expression, the cell subtypes that contribute to this heterogeneityin vivoin humans have not been characterized. To investigate the transcriptional diversity of BM-MSCs, we applied single-cell RNA sequencing (scRNA-seq) on freshly isolated CD271+BM-derived mononuclear cells (BM-MNCs) from two human subjects. We successfully identified LEPRhiCD45lowBM-MSCs within the CD271+BM-MNC population, and further codified the BM-MSCs into distinct subpopulations corresponding to the osteogenic, chondrogenic, and adipogenic differentiation trajectories, as well as terminal-stage quiescent cells. Biological functional annotations of transcriptomes suggest that osteoblast precursors may induce angiogenesis coupled with osteogenesis, and chondrocyte precursors may have the potential to differentiate into myocytes. We discovered transcripts for several cluster of differentiation (CD) markers that were highly expressed (e.g., CD167b, CD91, CD130 and CD118) or absent (e.g., CD74, CD217, CD148 and CD68) in BM-MSCs and could be novel markers for human BM-MSC purification. This study is the first systematicin vivodissection of human BM-MSCs cell subtypes at the single-cell resolution, revealing insight into the extent of their cellular heterogeneity and bone homeostasis.
Single-dimensional human brain signals for two-dimensional economic choice options
Authors: Seak Leo Chi U , Volkmann Konstantin , Pastor-Bernier Alexandre , Grabenhorst Fabian , Schultz Wolfram 
Published: April 2020

AbstractRewarding choice options typically contain multiple components, but neural signals in single brain voxels are scalar and primarily vary up or down. In a previous study, we had designed reward bundles that contained the same two milkshakes with independently set amounts; we had used psychophysics and rigorous economic concepts to estimate two-dimensional choice indifference curves (IC) that represented revealed stochastic preferences for these bundles in a systematic, integrated manner. All bundles on the same ICs were equally revealed preferred (and thus had same utility, as inferred from choice indifference); bundles on higher ICs (higher utility) were preferred to bundles on lower ICs (lower utility). In the current study, we used the established behavior for testing with functional magnetic resonance imaging (fMRI). We now demonstrate neural responses in reward-related brain structures of human female and male participants, including striatum, midbrain and medial orbitofrontal cortex that followed the characteristic pattern of ICs: similar responses along ICs (same utility despite different bundle composition), but monotonic change across ICs (different utility). Thus, these brain structures integrated multiple reward components into a scalar signal, well beyond the known subjective value coding of single-component rewards.Significance StatementRewards have several components, like the taste and size of an apple, but it is unclear how each component contributes to the overall value of the reward. While choice indifference curves of economic theory provide behavioural approaches to this question, it is unclear whether brain responses capture the preference and utility integrated from multiple components. We report activations in striatum, midbrain and orbitofrontal cortex that follow choice indifference curves representing behavioral preferences over and above variations of individual reward components. In addition, the concept-driven approach encourages future studies on natural, multi-component rewards that are prone to irrational choice of normal and brain-damaged individuals.
Machine Learning and Optimal Control of Enzyme Activities to Preserve Solvent Capacity in the Cell
Authors: Britton Samuel , Alber Mark , Cannon William R. 
Published: April 2020

ABSTRACTExperimental measurements or computational model predictions of the post-translational regulation of enzymes needed in a metabolic pathway is a difficult problem. Consequently, regulation is mostly known only for well-studied reactions of central metabolism in various model organisms. In this study, we utilize two approaches to predict enzyme regulation policies and investigate the hypothesis that regulation is driven by the need to maintain the solvent capacity in the cell. The first predictive method uses a statistical thermodynamics and metabolic control theory framework while the second method is performed using a hybrid optimization-reinforcement learning approach. Efficient regulation schemes were learned from experimental data that either agree with theoretical calculations or result in a higher cell fitness using maximum useful work as a metric. Model predictions provide the following novel general principles: (1) the regulation itself causes the reactions to be much further from equilibrium instead of the common assumption that highly non-equilibrium reactions are the targets for regulation; (2) regulation is used to maintain the concentrations of both immediate and downstream product concentrations rather than to maintain a specific energy charge; and (3) the minimal regulation needed to maintain metabolite levels at physiological concentrations also results in the maximal energy production rate that can be obtained at physiological conditions. The resulting energy production rate is an emergent property of regulation which may be represented by a high value of the adenylate energy charge. In addition, the predictions demonstrate that the amount of regulation needed can be minimized if it is applied at the beginning or branch point of a pathway, in agreement with common notions. The approach is demonstrated for three pathways in the central metabolism ofE. coli(gluconeogenesis, glycolysis-TCA and Pentose Phosphate-TCA) that each require different regulation schemes. It is shown quantitatively that hexokinase, glucose 6-phosphate dehydrogenase and glyceraldehyde phosphate dehydrogenase, all branch points of pathways, play the largest roles in regulating central metabolism.
Data-driven reduction of dendritic morphologies with preserved dendro-somatic responses
Authors: Wybo Willem A.M. , Jordan Jakob , Ellenberger Benjamin , Mengual Ulisses M. , Nevian Thomas , Senn Walter 
Published: April 2020

AbstractDendrites shape information flow in neurons. Yet, there is little consensus on the level of spatial complexity at which they operate. We present a flexible and fast method to obtain simplified neuron models at any level of complexity. Through carefully chosen parameter fits, solvable in the least squares sense, we obtain optimal reduced compartmental models. We show that (back-propagating) action potentials, calcium-spikes and NMDA-spikes can all be reproduced with few compartments. We also investigate whether afferent spatial connectivity motifs admit simplification by ablating targeted branches and grouping the affected synapses onto the next proximal dendrite. We find that voltage in the remaining branches is reproduced if temporal conductance fluctuations stay below a limit that depends on the average difference in input impedance between the ablated branches and the next proximal dendrite. Further, our methodology fits reduced models directly from experimental data, without requiring morphological reconstructions. We provide a software toolbox that automatizes the simplification, eliminating a common hurdle towards including dendritic computations in network models.
Small Molecule Channels Harness Membrane Potential to Concentrate Potassium in trk1Δtrk2Δ Yeast
Authors: Hou Jennifer , Daniels Page N. , Burke Martin D. 
Published: April 2020

ABSTRACTMany protein ion channels harness membrane potential to move ions in opposition to their chemical gradient. Deficiencies of such proteins cause several human diseases, including cystic fibrosis, Bartter Syndrome Type II, and proximal renal tubular acidosis. Using yeast as a readily manipulated eukaryotic model system, we asked whether, in the context of a deficiency of such protein ion channel functionin vivo, small molecule channels could similarly harness membrane potential to concentrate ions. In yeast, Trk potassium transporters use membrane potential to move potassium ions from a compartment of relatively low concentration outside cells (∼15mM) to one of >10 times higher concentration inside (150-500mM). trk1Δtrk2Δ yeast are missing these potassium transporters and thus cannot concentrate potassium or grow in standard media. Here we show that potassium permeable, but not potassium selective, small molecule ion channels formed by the natural product amphotericin B can harness membrane potential to concentrate potassium in trk1Δtrk2Δ cells and thereby restore growth. This finding expands the list of potential human channelopathies that might be addressed by a molecular prosthetics approach.
Autocrine insulin pathway signaling regulates actin dynamics in cell wound repair
Authors: Nakamura Mitsutoshi , Verboon Jeffrey M. , Allen Tessa E. , Abreu-Blanco Maria Teresa , Liu Raymond , Dominguez Andrew N.M. , Delrow Jeffrey J. , Parkhurst Susan M. 
Published: April 2020

AbstractCells are exposed to frequent mechanical and/or chemical stressors that can compromise the integrity of the plasma membrane and underlying cortical cytoskeleton. The molecular mechanisms driving the immediate repair response launched to restore the cell cortex and circumvent cell death are largely unknown. Using microarrays and drug-inhibition studies to assess gene expression, we find that initiation of cell wound repair in theDrosophilamodel is dependent on translation, whereas transcription is required for subsequent steps. We identified 253 genes whose expression is up-regulated (80) or down-regulated (173) in response to laser wounding. A subset of these genes were validated using RNAi knockdowns and exhibit aberrant actomyosin ring assembly and/or actin remodeling defects. Strikingly, we find that the canonical insulin signaling pathway controls actin dynamics through the actin regulators Girdin and Chickadee (profilin), and its disruption leads to abnormal wound repair. Our results provide new insight for understanding how cell wound repair proceeds in healthy individuals and those with diseases involving wound healing deficiencies.
Chromosome-scale assembly of the bread wheat genome,Triticum aestivum, reveals over 5700 new genes
Authors: Alonge Michael , Shumate Alaina , Puiu Daniela , Zimin Aleksey , Salzberg Steven L. 
Published: April 2020

ABSTRACTBread wheat (Triticum aestivum)is a major food crop and an important plant system for agricultural genetics research. However, due to the complexity and size of its allohexaploid genome, genomic resources are limited compared to other major crops. The IWGSC recently published a reference genome and associated annotation (IWGSC v1.0, Chinese Spring) that has been widely adopted and utilized by the wheat community. Although this reference assembly represents all 3 wheat subgenomes at chromosome scale, it was derived from short reads, and thus is missing a substantial portion of the expected 16 gigabases of genomic sequence. We earlier published an independent wheat assembly (Triticum 3.1, Chinese Spring) that came much closer in length to the expected genome size, although it was only a contig-level assembly lacking gene annotations. Here, we describe a reference-guided effort to scaffold those contigs into chromosome-length pseudomolecules, add in any missing sequence that was unique to the IWGSC 1.0 assembly, and annotate the resulting pseudomolecules with genes. Our updated assembly, Triticum 4.0, contains 15.07 gigabases of non-gap sequence anchored to chromosomes, which is 1.2 gigabases more than the previous reference assembly. It includes 108,639 genes unambiguously localized to chromosomes, including over 2000 genes that were previously unplaced. We also discovered more than 5700 new genes, all of them duplications in the Chinese Spring genome that are missing from the IWGSC assembly and annotation. The Triticum 4.0 assembly and annotations are freely available atwww.ncbi.nlm.nih.gov/bioproject/PRJNA392179.
Sudden hyposmia as a prevalent symptom of COVID-19 infection
Authors: Marchese-Ragona Rosario , Ottaviano Giancarlo , Piero Nicolai , Vianello Andrea , Miryam Carecchio 
Published: April 2020

ABSTRACTSevere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has recently caused a pandemic that has involved Italy as the second worldwide nation in terms of infected patients and deaths. The clinical manifestation of Covid-19 ranges from asymptomatic carrier status to severe pneumonia. Asymptomatic individuals in Covid-19 are those who are carriers of the virus but do not show clinical symptoms and are able to transmit the disease in the same degree as symptomatic carriers. In order to contain contagions is of supreme importance to identify asymptomatic patients because this subpopulation is one of the main factors contributing to the spread of this disease. We report on six Italian patients with COVID-19 who presented sudden hyposmia as the only or most prominent disease manifestation, without upper or lower respiratory tract involvement or other major features of the disease. A supra-threshold olfaction test confirmed the hyposmia in all patients. The onset of hyposmia during a Covid-19 outbreak should be considered as a warning sign of an infection that requires a diagnostic test for Covid-19
The effect of adding oat flour on the nutritional and sensory quality of wheat bread
Authors: Krochmal-Marczak Barbara , Tobiasz-Salach Renata , Kaszuba Joanna 
Published: April 2020

PurposeFlour from oat grain is characterised by a high content of protein andβ-glucans, with a favourable amino acid composition and a substantial content of fat, including unsaturated fatty acids. Additives to bread that enrich its nutritional value can worsen physical properties. It is important to know how to develop recipes for healthy bread based on wheat flour, with the appropriate addition of oat flour. The purpose of this study was to determine the influence on the physical properties of bread made of wheat flour, following the addition of oat flour. The purpose was also to find a recipe for a new product with higher nutritional value, which would then be acceptable for consumers.Design/methodology/approachIn addition to wheat flour, flour made of oat grains, obtained from the naked Nagus variety (hulless oat), was added. The flour was analysed for moisture, dry matter, proteins andβ-glucans, as well as total dietary fibre − soluble and insoluble. The dough was made with wheat flour according to a recipe, which included yeast, salt and water as well as extra oat flour in various proportions − 15, 25 and 30%, respectively. The bread was baked using a direct single-phase method developed by the Baking Institute in Berlin. Both the physicochemical and sensory evaluation were carried out on the bread.FindingsThe recipe for wheat bread that included 15% proportion of oat flour supplement was found to be the most acceptable in both the sensory (n = 30) and qualitative evaluation and would be suitable to produce nutritious bread. The use of 25% and 30% additions of oat flour resulted in a reduction in bread weight, volume and yield, which ultimately lead to an increase in overall baking losses.Originality/valueThis study proved that 15% oat flour could be used as an optimum addition for the production of wheat-oat bread. This bread may lead to a new assortment of bakery products with pro-health properties.
Exploring producers' motivations and challenges within a farmers' market
Authors: Michel-Villarreal Rosario , Vilalta-Perdomo Eliseo Luis , Hingley Martin 
Published: April 2020

PurposeThe purpose of this study is to explore food producers' motivations and challenges whilst participating in short food supply chains (SFSCs). This paper compares findings with previous literature and investigates the topic in the context of producers' motivations.Design/methodology/approachThe paper includes a literature review concerning producers' motivations to engage in SFSCs. A case study was designed to investigate motivations underlying producers' engagement in SFSCs, as well as the challenges that they face. Semi-structured interviews were conducted in a farmers' market located in Mexico. Thematic analysis is used to identify the principal issues for producers'. Propositions based on findings are presented.FindingsFindings suggest that small, large, part-time and full-time producers are willing to engage with farmers' markets for diverse primary economic and non-economic motivations. Individual and collective challenges were also identified.Originality/valueThis research helps to explain producers' motivations and challenges within SFSCs in an under-researched context, namely a focus on producers' and in the Global South.
How do human resource management practices affect employee well-being? A mediated moderation model
Authors: Zhang Xinggui , Lin Zhibin , Liu Yizhu , Chen Xiao , Liu David Ming 
Published: April 2020

PurposeThe study examines how human resource management practices (HRMPs) – including ability practice, motivation practice and opportunity practice – affect employee well-being (EWB) – including life well-being, job well-being and psychological well-being – in the Chinese cultural context.Design/methodology/approachA sample of 529 employees from various industries in China participated in the survey for this study. Data were analyzed using structural equation modeling.FindingsThe findings indicate that HRMPs have a significant positive effect on EWB. Specifically, practices based on ability, motivation and opportunity have a significant positive effect on job well-being, life well-being and psychological well-being, respectively. Integrity leadership moderates the impact of HRMPs on EWB. Organizational justice has a partial mediating effect on the relationship between HRMPs and EWB. Integrity leadership moderates the mediation effect of organizational justice in the relationship between HRMPs and EWB.Practical implicationsHuman resource policies and practices need to create a fair organizational atmosphere, and managers implementing them must have integrity leadership. When selecting and promoting managers, organizations should pay attention to not only a candidate's ability but also his or her integrity.Originality/valueThis study uncovers how the important roles of organizational justice and integrity leadership act on the relationship between HRMPs and EWB, thus advancing our understanding of how HRMPs can effectively increase EWB.
Dialogic collaging to cultivate shame resilience in writing classrooms
Authors: Juzwik Mary , Antonucci Sal 
Published: April 2020

PurposeRecently, practitioner literature in English education has taken up the issue of writing-related shame in classrooms, calling for teachers to help students develop resilience. One possible approach for nurturing shame resilience around writing is dialogic collaging: students make and dialogically engage with collages and with colleagues to explore the self-as-writer and to connect with others around writing struggles and joys. The purpose of this paper is to share and critically reflect on this pedagogical approach.Design/methodology/approachTo share, interpret and consider the limitations and implications of the dialogic collaging pedagogy in service of writing-related shame resilience, the authors offer a multi-voiced narrative about one classroom instantiation of college, from the perspective of a university writing teacher and a student of writing.FindingsOn the interpretation, this story unfolds three central themes as follows: dialogic collaging can help students to develop a more realistic and situated sense of self-as-writer. That is, students can come to appreciate how “becoming a writer” is a process they – and others around them – are already in, rather than an unreachable achievement at which they will inevitably fail. The stance of playfulness nurtured through the dialogic collage process can provide a helpful distance between self and writing. These processes may – under certain conditions – support shame resilience.Research limitations/implicationsThe conclusion reflects on whether more explicit attention to shame could be fruitful and on the dynamics of teacher vulnerability in writing classrooms.Practical implicationsThe authors hope to inspire writing teachers – particularly in secondary, post-secondary and adult education – to engage with dialogic collaging as part of their pedagogical repertoires.Originality/valueDialogic collaging is a pedagogical approach not previously discussed in the literature on secondary and post-secondary writing instruction, offering one promising way to address writing-related shame. It can make visible and build solidarity around how others are also in the midst of a process of becoming – as writers and/or with writing. This appreciation can help nurture a more realistic, playful and shame-resilient stance toward self-as-writer.