bluuebunny/crossref_metadata_2025_split huggingface dataset:
Let-7miRNAs control auditory sensory progenitor behavior in the vertebrate inner ear
Authors: Evsen Lale , Zhang Shuran , Doetzlhofer Angelika 
Published: May 2019

ABSTRACTThe evolutionary conserved lethal-7 (let-7) family of microRNAs (miRNAs) is a well-known activator of terminal mitosis and differentiation. Surprisingly, we previously found that overexpression oflet-7miRNAs in the murine auditory organ accelerated the terminal mitosis of auditory sensory progenitors (pro-sensory cells) but failed to stimulate their differentiation into mechano-sensory hair cells (HCs). To further address the role oflet-7miRNAs in auditory sensory differentiation, we conducted gain and loss of function experiments in the developing chicken auditory organ, the basilar papilla (BP). Using a sponge approach, we show that the disruption oflet-7miRNA function in the developing BP delays pro-sensory cell exit and delays differentiation of auditory HCs, revealing that endogenouslet-7miRNAs limit pro-sensory cell self-renewal in the developing BP. However, consistent with the role oflet-7miRNAs in the murine auditory organ,let-7boverexpression in the developing BP delayed HC differentiation, suggesting that too low or too highlet-7miRNA levels disrupt HC differentiation. Furthermore, we provide evidence that the repressive role oflet-7miRNAs in HC differentiation may be due to its targeting of the chromatin remodeler CHD7. Mutation in the humanCHD7gene causes CHARGE syndrome, which amongst others is characterized by inner ear and hearing deficits. Using target prediction algorithms, we uncovered a highly predictive and evolutionary conservedlet-7binding site within theChd7transcript. Consistent with being a target oflet-7repression, we demonstrate thatlet-7boverexpression significantly reduced CHD7 protein expression in to the developing BP. Furthermore, utilizing an induciblelet-7gtransgenic mouse model, we show thatlet-7miRNAs negatively regulate CHD7 protein expression in developing murine cochlear, retinal and brain tissue. CHD7 is dosage dependent and the here described regulation bylet-7miRNAs may be critical to fine tune CHD7 protein levels during sensory and neuronal development.SIGNIFICANCEThe evolutionary highly conservedlet-7miRNAs are essential for proper timing of cell state transitions during embryogenesis. Even though abundantly expressed in the vertebrate auditory organ, surprisingly little is known about their function in auditory sensory differentiation. Here, we demonstrate that endogenouslet-7miRNAs are essential for limiting auditory sensory progenitor (pro-sensory) cell self-renewal. Furthermore, we find that precociouslet-7miRNAs expression interferes with auditory hair cell differentiation and identify chromatin remodeler CHD7 as a potential target gene oflet-7repressive function in HC differentiation.
Conservation and Divergence of Related Neuronal Lineages in theDrosophilaCentral Brain
Authors: Lee Ying-Jou , Yang Ching-Po , Huang Yu-Fen , He Yisheng , Ren Qingzhong , Chen Hui-Min , Miyares Rosa Linda , Otsuna Hideo , Aso Yoshi , Ito Kei , Lee Tzumin 
Published: May 2019

SummaryWiring a complex brain requires enormous cell specificity. This specificity is laid out via a developmental process where neural stem cells produce countless diverse neurons. To help elucidate this process and resolve the considerable dynamic specificity, we need to observe the development of multiple neuronal lineages.Drosophilacentral brain lineages are predetermined, comprised of a fixed set of neurons born in pairs in a specific order. To reveal specific roles of lineage identity, Notch-dependent sister fate specification, and temporal patterning in morphological diversification, we mapped approximately one quarter of theDrosophilacentral brain lineages. While we found large aggregate differences, we also discovered similar patterns of morphological specification and diversification. Lineage identity plus Notch state govern primary neuronal trajectories, whereas temporal fates diversify terminal elaborations in target-specific manners. In addition, we identified ‘related’ lineages of analogous neuron types produced in similar temporal patterns. Two stem cells even yield identical series of dopaminergic neuron types, but with completely disparate sister neurons. These phenomena suggest that large changes in morphological diversity can be the consequence of relatively small differences in lineage fating. Taken together, this large-scale lineage mapping study reveals that relatively simple rules drive incredible neuronal complexity.
Microbiome data enhances predictive models of lung function in people with cystic fibrosis
Authors: Zhao Conan Y. , Hao Yiqi , Wang Yifei , Varga John J. , Stecenko Arlene A. , Goldberg Joanna B. , Brown Sam P. 
Published: May 2019

AbstractBackgroundMicrobiome sequencing has brought increasing attention to the polymicrobial context of chronic infections. However, clinical microbiology continues to focus on canonical human pathogens, which may overlook informative, but non-pathogenic, biomarkers. We address this disconnect in lung infections in people with cystic fibrosis (CF).MethodsWe collected health information (lung function, age, BMI) and sputum samples from a cohort of 77 children and adults with CF. Samples were collected during a period of clinical stability and 16S rDNA sequenced for airway microbiome compositions. We use Elastic Net regularization to train linear models predicting lung function and extract the most informative features.ResultsModels trained on whole microbiome quantitation outperform models trained on pathogen quantitation alone, with or without the inclusion of patient metadata. Our most accurate models retain key pathogens as negative predictors (Pseudomonas, Achromobacter) along with established correlates of CF disease state (age, BMI, CF related diabetes). In addition, our models select non-pathogen taxa (Fusobacterium, Rothia) as positive predictors of lung health.ConclusionsThese results support a reconsideration of clinical microbiology pipelines to ensure the provision of informative data to guide clinical practice.
Reconstructing the blood metabolome and genotype using long-range chromatin interactions
Authors: Fadason Tayaza , Schierding William , Kolbenev Nikolai , Liu Jiamou , Ingram John , O’Sullivan Justin M. 
Published: May 2019

AbstractThe mechanisms of metabolism comprise a large number of biochemical pathways with a myriad of poorly characterised genetic influences. In this study, we perform a systematic integration of chromatin interaction (Hi-C), expression quantitative trait loci (eQTL), gene ontology, drug interaction, and literature-supported connections to deconvolute the genetic regulatory influences of 145 blood metabolite-associated single nucleotide polymorphisms (SNPs). We identify 577 genes that are regulated via chromatin looping to 130 distal and proximal SNPs across 48 different human tissues. The affected genes are enriched in categories that include metabolism, enzymes, plasma proteins, disease development, and potential drug targets. These novel SNP-gene-metabolite associations are a valuable resource for understanding the molecular mechanisms guiding pathologic metabolite levels in human tissues, and for further investigation into disease diagnosis and therapy.
Marine Cyanobacteria Tune Energy Transfer Efficiency in their Light-harvesting Antennae by Modifying Pigment Coupling
Authors: Kolodny Yuval , Zer Hagit , Propper Mor , Yochelis Shira , Paltiel Yossi , Keren Nir 
Published: May 2019

AbstractPhotosynthetic organisms regulate energy transfer to fit to changes in environmental conditions. The biophysical principles underlying the flexibility and efficiency of energy transfer in the light-harvesting process are still not fully understood. Here we examine how energy transfer is regulatedin-vivo. We compare different acclimation states of the photosynthetic apparatus in a marine cyanobacterial species that is well adapted to vertical mixing of the ocean water column and identify a novel acclimation strategy for photosynthetic life under low light intensities. Antennae rods extend, as expected, increasing light absorption. Surprisingly, in contrast to what was known for plants and predicted by classic calculations, these longer rods transfer energy fasteri.e.more efficiently. The fluorescence lifetime and emission spectra dependence on temperature, at the range of 4-300K, suggests that energy transfer efficiency is tuned by modifying the energetic coupling strength between antennae pigments.
White matter alterations in autism spectrum disorder and attention-deficit/hyperactivity disorder in relation to sensory profile
Authors: Ohta Haruhisa , Aoki Yuta , Itahashi Takashi , Kanai Chieko , Fujino Junya , Nakamura Motoaki , Kato Nobumasa , Hashimoto Ryu-ichiro 
Published: May 2019

AbstractBackgroundAutism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) have high rates of co-occurrence and share atypical behavioral characteristics, including sensory problems. The present diffusion tensor imaging (DTI) study was conducted to examine whether and how white matter abnormalities are observed in adult populations with developmental disabilities (DD) and to determine how brain-sensory relationships are either shared between or distinct to ASD and ADHD.MethodsWe collected DTI data from adult developmental disorder (DD) populations (a primary diagnosis of ASD: n=105, ADHD: n=55) as well as age and sex matched typically developed (TD) participants (n=58). Voxel-wise fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity (RD) were analyzed using tract-based spatial statistics. The severities of sensory problems were assessed using the Adolescent/Adult Sensory Profile (AASP).ResultsCategorical analyses identified voxel clusters showing significant effects of DD on FA and RD in the posterior portion of the corpus callosum and its extension in the right hemisphere. Furthermore, regression analyses using the AASP scores revealed that slopes in relationships of FA or RD with the degree of sensory problems were parallel between the two DDs in large parts of the affected corpus callosum regions, although a small but significant cluster did exist showing interaction between the diagnosis of DD and an AASP subscale score on RD.ConclusionsThese results indicate that white matter abnormalities and their relationships to sensory problems are largely shared between ASD and ADHD, with localized abnormalities showing significant between-diagnosis differences within DD. (247 words)
Effects of rocuronium, sugammadex and rocuronium-sugammadex complex on coagulation in rats
Authors: Cavalcanti Ismar L. , Schanaider Alberto , Barrucand Louis , Braga Estêvão L. C. , Verçosa Nubia , de Boer Hans D. , Vane Luiz A. 
Published: May 2019

AbstractBackgroundSugammadex is an alternative pharmacological drug that is capable of reversing neuromuscular blockades without the limitations that are presented by anticholinesterase drugs. Coagulation disorders that are related to treatment with sugammadex were reported. The exact mechanism of the effects on coagulation are not fully understood.ObjectiveTo evaluate the effects of rocuronium, sugammadex and the rocuronium-sugammadex complex on coagulation in an experimental model in rats.DesignAn experimental randomized animal study.SettingAn experimental unit at the State University of São Paulo (UNESP), Botucatu, SP, Brazil.InterventionsWistar rats were randomly assigned into the following groups: the Control group; the Ssal Group – 0.5 mL of intravenous saline; the Sugammadex group – intravenous sugammadex (100 mg/kg); and the Rocuronium-Sugammadex group – intravenous solution with rocuronium (3.75 mg/kg) and sugammadex (100 mg/kg). Anaesthesia was performed by using isoflurane with controlled ventilation.Main outcome measuresCoagulation factors were measured 10 minutes after the end of the preoperative preparation and 30 minutes after the administration of the drugs in accordance with the chosen groups.ResultsPlatelet counts, prothrombin times and activated partial thromboplastin times were similar between the groups and between the moments within each group. There were reductions in the plasma fibrinogen levels between sample times 1 and 2 in the Rocuronium-Sugammadex group (P = 0,035).ConclusionThe rocuronium-sugammadex complex promoted reductions in plasma fibrinogen counts, although the levels were still within normal limits.
Predictive factors for unfavourable treatment in MDR-TB and XDR-TB patients in Rio de Janeiro State, Brazil, 2000-2016
Authors: Bhering Marcela , Duarte Raquel , Kritski Afrânio 
Published: May 2019

AbstractSettingThe State of Rio de Janeiro stands out as having the second highest incidence and the highest mortality rate due to TB in Brazil. This study aims at identifying the factors associated with the unfavourable treatment of MDR/XDR-TB patients in that State.MethodData on 2269 MDR-TB cases reported in 2000-2016 in Rio de Janeiro State were collected from the Tuberculosis Surveillance System. Bivariate and multivariate logistic regressions were run to estimate the factors associated with unfavourable outcomes (failure, default, and death) and, specifically, default and death.ResultsThe proportion of unfavourable outcomes was 41.9% among MDR-TB and 81.5% among XDR-TB. Having less than 8 years of schooling, and being an Afro-Brazilian, under 40 years old and drug user were associated with unfavourable outcome and default. Bilateral disease, HIV positive, and comorbidities were associated with death. XDR-TB cases had a 4.7-fold higher odds of an unfavourable outcome, with 29.3% of such cases being in the first treatment for multidrug resistance.ConclusionAbout 30% of XDR-TB cases may have occurred by primary transmission. The high rates of failure and death in this category reflect the limitation of treatment options. This highlights the urgency to incorporate new drugs in the treatment.
A kinase-dependent checkpoint prevents escape of immature ribosomes into the translating pool
Authors: Parker Melissa D. , Collins Jason C. , Korona Boguslawa , Ghalei Homa , Karbstein Katrin 
Published: May 2019

AbstractPremature release of nascent ribosomes into the translating pool must be prevented, as these do not support viability and may be prone to mistakes. Here we show that the kinase Rio1, the nuclease Nob1, and its binding partner Pno1 cooperate to establish a checkpoint that prevents the escape of immature ribosomes into polysomes. Nob1 blocks mRNA recruitment, and rRNA cleavage is required for its dissociation from nascent 40S subunits, thereby setting up a checkpoint for maturation. Rio1 releases Nob1 and Pno1 from pre-40S ribosomes to discharge nascent 40S into the translating pool. Weakly binding Nob1 and Pno1 mutants can bypass the requirement for Rio1, and Pno1 mutants rescue cell viability. In these strains, immature ribosomes escape into the translating pool, where they cause fidelity defects and perturb protein homeostasis. Thus, the Rio1-Nob1-Pno1 network establishes a checkpoint that safeguards against the release of immature ribosomes into the translating pool.
Enabling management control systems, situated learning and intellectual capital development
Authors: Coyte Rodney 
Published: May 2019

PurposeThe purpose of this paper is to examine how an enabling management control system (MCS) affected intellectual capital (IC) development in an organisation. The study explores the effect of a change from a coercive to an enabling control system on situated learning and the development of IC.Design/methodology/approachA case study was conducted in a large manufacturing organisation to explore the effect of a redesigned MCS on IC development. Semi-structured interviews were used to elicit understanding of the effect of the new system on situated learning and valuable local knowledge and relationship development.FindingsThe enabling way in which the MCS was designed introduced empowerment and accountability for financial and operational performance at all levels of the organisational hierarchy, which stimulated situated learning in a way that developed the organisation’s IC.Originality/valueNew insight is provided into the way management accounting practice can deliver valuable outcomes to organisations. First, into how MCSs design can stimulate the development of valuable local knowledge and relationships as IC. Second, into how MCS design can affect non-management employees. While prior studies have focussed on managers, this research is novel in showing how enabling controls affect non-management employees.
Information encountering and sharing behaviour of research students in an online environment
Authors: Awan Waqar Ahmad , Ameen Kanwal , Soroya Saira Hanif 
Published: May 2019

PurposeInformation behaviour exists in two forms: first when information is sought with a clear purpose and second, when we encounter it accidentally or serendipitiously. The purpose of this paper is to estimate the information encountering (IE) and encountered information sharing (EIS) behaviour of research students in an online environment.Design/methodology/approachThe quantitative research approach was applied to carry out this research. The authors selected 120 MPhil and PhD research students (who research information as a part of their assignments) from six departments as sample for the study. Out of 120 research students, 93 returned the filled questionnaires. The collected data were analysed in SPSS version 22. First, descriptive statistics to estimate the IE and sharing behaviour; and later one-way ANOVA andpost hoccomparisons using the Tukey HSD tests were applied to investigate the EIS based on the frequency of internet usage.FindingsThe findings indicate that the mean scores of the responses remain between “sometimes” and “often”, in all the behavioural sub-constructs of the model of IE, i.e. noticing, stopping, examining, capturing, storing (keeping), sharing and returning. The extended model proved to be valid in an online environment in the context of Pakistani culture. While estimating EIS, the results indicated significantly higher sharing and large effect size among the research students who used the internet from 11 to 15 h a week than those who used it between 6 and 10 h.Practical implicationsKeeping in view the results the research students and parent organisations (universities) working for the improvement of research ranking and research students’ better performance, should know that research information is not only actively acquired but also huge amount of information is accidentally encountered and shared. Therefore, the universities should train their research students to enhance the information sharing of encountered information. That will promote the research culture and may enhance the speed of learning, research work and ultimately result in competitive advantage, without any extra effort.Originality/valueThis is the first study of its type in Pakistan to measure the IE behaviour of research students in an online environment. Moreover, it is the first study which investigates the extended model of IE using a quantitative approach in the Pakistani research environment, which originated in Japan via qualitative research approach.
Does consumer customization strategy always benefit the platform firm’s profit?
Authors: Wang Can-you , Li Cheng-long , Su Qin 
Published: May 2019

Purpose
The purpose of this paper is to study the price decisions and profits of two firms in a competitive market in which one platform firm considers whether to adopt a consumer customization strategy.

Design/methodology/approach
This study develops the consumer’s utility function, which captures consumers’ behavioural and emotional factors in the self-customizing process, and it adopts a game theory approach to analyze the equilibrium price and equilibrium profit for each firm.

Findings
The results show that increased sensitivity in consumer customization might not benefit the platform, especially when the size of the consumer group deriving positive additional utility from the self-customizing process is small. Interestingly, if the consumer customization sensitivity is high, increasing sensitivity can benefit both firms by relaxing competition between them, while it can hurt consumer surplus. The study also further identifies the conditions under which platforms can adopt a consumer customization strategy.

Research limitations/implications
Two major limitations of the study are that the model does not involve price discrimination or explore the value of adopting a consumer customization strategy in a vertically differentiated market.

Practical implications
This study offers managerial insights for the platforms that intend to invest in a consumer customization strategy, including providing a more simple, more efficient self-customizing process for consumers; empowering consumers to broadcast their creations to a large network by social media technologies; addressing how to determine what consumers really need and want; and so on.

Originality/value
Little research has been performed to analyze the impacts of adopting a consumer customization strategy on pricing decisions in a duopoly market by capturing consumers’ behavioural and emotional factors. While this study explores the above research issue, it also illustrates the effect of the adoption of a consumer customization strategy from a consumer surplus perspective.
The Baldrige Award’s falling fortunes
Authors: Cook David , Zhang Weiyong 
Published: May 2019

PurposeThe purpose of this paper is to explore two explanations for the Baldrige Award’s decline. The management fashion literature suggests that it is a waning management fad, and the marketing choice literature suggests the likely presence of an ISO 9000 substitution effect.Design/methodology/approachThis exploratory study utilizes data collected on Baldridge Award applications, publications, ISO 9000 certifications and economic indicators. These data are contrasted to explore patterns and trends, and correlation analyses conducted to reveal the plausibility of the fad and substitution effect explanations for the Baldrige Award’s decline.FindingsData analysis confirms the Baldrige Award’s prolonged decline and strongly suggests it is in the final stage of a management fashion life cycle with support provided for the presence of an ISO 9000 substitution effect.Research limitations/implicationsMany organizations have shifted their attention away from the Baldrige as a means to quality and performance excellence, and there is evidence that the ISO 9000 standards are a viable substitute.Practical implicationsThe Baldrige Program has served its purpose with the Baldrige Award being the pinnacle of recognition for performance excellence achievement. However, the Award is in decline and the Baldrige Program is on a path to financial exigency. The Baldrige must be reframed to recover its role as the preeminent approach to performance excellence.Originality/valueThe paper satisfies the need to examine potential causes for the diminishing role of the Baldrige Award and challenges both academicians and practitioners to reexamine the Baldrige Program.