bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Vc2 cyclic di-GMP dependent riboswitch ofVibrio choleraeregulates expression of an upstream small RNA by controlling RNA stability
Authors: Pursley Benjamin R. , Waters Christopher M. 
Published: April 2019

SUMMARYCyclic di-GMP (c-di-GMP) is a bacterial second messenger molecule that is important in the biology ofVibrio cholerae, but the molecular mechanisms by which this molecule regulates downstream phenotypes have not been fully characterized. We have previously shown that the Vc2 c-di-GMP-binding riboswitch, encoded upstream of the genetfoY, functions as an off-switch in response to c-di-GMP. However, the mechanism by which c-di-GMP controls expression oftfoYhas not been fully elucidated. During our studies of this mechanism, we determined that c-di-GMP binding to Vc2 also controls the abundance and stability of upstream non-coding small RNAs (sRNA) with 3’-ends located immediately downstream of the Vc2 riboswitch. Our results suggest these sRNAs are not generated by transcriptional termination but rather by preventing degradation of the upstream untranslated RNA when c-di-GMP is bound to Vc2.IMPORTANCERiboswitches are typically RNA elements located in the 5’ untranslated region of mRNAs. They are highly structured and specifically recognize and respond to a given chemical cue to alter transcription termination or the translation initiation. In this work, we report a novel mechanism of riboswitch mediated gene regulation inVibrio choleraewhereby a 3’ riboswitch, named Vc2, controls the stability of upstream untranslated RNA upon binding to its cognate ligand, the second messenger cyclic di-GMP, leading to the accumulation of previously undescribed sRNAs. We further demonstrate that binding of the ligand to the riboswitch prevents RNA degradation. As binding of riboswitches to their ligands often produces compactly structure RNA, we hypothesize this mechanism of gene regulation could be widespread.
LFMD: detecting low-frequency mutations in high-depth genome sequencing data without molecular tags
Authors: Ye Rui , Zhuang Xuehan , Ruan Jie , Qi Yanwei , An Yitai , Xu Jiaming , Mak Timothy , Liu Xiao , Zhang Xiuqing , Yang Huanming , Xu Xun , Baum Larry , Nie Chao , Sham Pak Chung 
Published: April 2019

AbstractAs next-generation sequencing (NGS) and liquid biopsy become more prevalent in research and in the clinic, there is an increasing need for better methods to reduce cost and improve sensitivity and specificity of low-frequency mutation detection (where the Alternative Allele Frequency, or AAF, is less than 1%). Here we propose a likelihood-based approach, called Low-Frequency Mutation Detector (LFMD), which combines the advantages of duplex sequencing (DS) and the bottleneck sequencing system (BotSeqS) to maximize the utilization of duplicate reads. Compared with the existing state-of-the-art methods, DS, Du Novo, UMI-tools, and Unified Consensus Maker, our method achieves higher sensitivity, higher specificity (< 4 × 10−10errors per base sequenced) and lower cost (reduced by ~70% at best) without involving additional experimental steps, customized adapters or molecular tags. LFMD is useful in areas where high precision is required, such as drug resistance prediction and cancer screening. As an example of LFMD’s applications, mitochondrial heterogeneity analysis of 28 human brain samples across different stages of Alzheimer’s Disease (AD) showed that the canonical oxidative damage related mutations, C:G>A:T, are significantly increased in the mid-stage group. This is consistent with the Mitochondrial Free Radical Theory of Aging, suggesting that AD may be linked to the aging of brain cells induced by oxidative damage.
TMC1 Confers a Leak Conductance to Modulate Excitability of Auditory Hair Cells in Mammals
Authors: Liu Shuang , Wang Shufeng , Zou Linzhi , Li Jie , Song Chenmeng , Chen Jiaofeng , Hu Qun , Liu Lian , Xiong Wei 
Published: April 2019

ABSTRACTHearing sensation relies on the mechano-electrical transducer (MET) channel of cochlear hair cells, in which Transmembrane channel-like 1 (TMC1) and TMC2 have been proposed to be the pore-forming subunits. Meanwhile it has been reported that TMCs regulate other biological processes in a variety of lower organisms ranging from sensations to motor functions. However, it is still an open question whether TMCs play roles other than their function in MET in mammals. In this study, we report that in mouse hair cells TMC1, but not TMC2, provides a background leak conductance, with properties distinct from those of the MET channels. By cysteine substitution, 4 amino acids of TMC1 are characterized critical for the leak conductance. The leak conductance is essential for action potential firing and tonotopic along the cochlear coil. Taken together, our results suggest that TMC1 confers a background leak conductance that modulates membrane excitability in cochlear hair cells.
Neo-sex chromosomes, genetic diversity and demographic history in the Critically Endangered Raso lark
Authors: Dierickx Elisa , Sin Simon , Veelen Pieter van , Brooke M. de L. , Liu Yang , Edwards Scott , Martin Simon 
Published: April 2019

ABSTRACTSmall effective population sizes could expose island species to inbreeding and loss of genetic variation. Here we investigate factors shaping genetic diversity in the Raso lark, which has been restricted to a single islet for ~500 years, with a population size of a few hundred. We assembled a reference genome for the related Eurasian skylark and then assessed diversity and demographic history using RAD-seq data (75 samples from Raso larks and two related mainland species). We first identify broad tracts of suppressed recombination in females, indicating enlarged neo-sex chromosomes. It is plausible that these regions might inadvertently and temporarily preserve pre-existing allelic variation in females that would otherwise be lost through genetic drift. We then show that genetic diversity across autosomes in the Raso lark is lower than in its mainland relatives, but inconsistent with long-term persistence at its current population size. Finally, we find that genetic signatures of the recent population contraction are overshadowed by an ancient expansion and persistence of a very large population until the human settlement of Cape Verde. Our findings show how genome-wide approaches to study endangered species can help avoid confounding effects of genome architecture on diversity estimates, and how present day diversity can be shaped by ancient demographic events.
The influence of canopy radiation parameter uncertainty on model projections of terrestrial carbon and energy cycling
Authors: Viskari T. , Shiklomanov A. , Dietze M.C. , Serbin S.P. 
Published: April 2019

AbstractReducing uncertainties in Earth System Model predictions requires carefully evaluating core model processes. Here we examined how canopy radiative transfer model (RTM) parameter uncertainties, in combination with canopy structure, affect terrestrial carbon and energy projections in a demographic land-surface model, the Ecosystem Demography model (ED2). Our analyses focused on temperate deciduous forests and tested canopies of varying structural complexity. The results showed a strong sensitivity of tree productivity, albedo, and energy balance projections to RTM parameters. Impacts of radiative parameter uncertainty on stand-level canopy net primary productivity ranged from ~2 to > 20% and was most sensitive to canopy clumping and leaf reflectance/transmittance in the visible spectrum (~400 – 750 nm). ED2 canopy albedo varied by ~1 to ~10% and was most sensitive to near-infrared reflectance (~800 – 1200 nm). Bowen ratio, in turn, was most sensitive to wood optical properties parameterization; this was much larger than expected based on literature, suggesting model instabilities. In vertically and spatially complex canopies the model response to RTM parameterization may show an apparent reduced sensitivity when compared to simpler canopies, masking much larger changes occurring within the canopy. Our findings highlight both the importance of constraining canopy RTM parameters in models and valuating how the canopy structure responds to those parameter values. Finally, we advocate for more model evaluation, similar to this study, to highlight possible issues with model behavior or process representations, particularly models with demographic representations, and identify potential ways to inform and constrain model predictions.Key pointsUncertainties in vegetation radiative parameter affect carbon, water and energy balances in ecosystem models.Radiative properties can lead to significant changes in demography and canopy structure even if aggregate model responses appear unchanged
Natural Amelioration of Mn-induced Chlorosis Facilitated by Mn Down-regulation, Ammonium and Rainwater in Sugarcane Seedlings
Authors: Ling Gui Zhi , Wang Xiao Xia , Yang Shu , Tang Xin Lian , Jia Shi Jin , Chang Min Min , Li Xiao Feng 
Published: April 2019

AbstractWe had previously reported that manganese (Mn)-induced chlorosis is a serious problem in ratoon sugarcane seedlings grown in acidic soils. To further monitor the progression of chlorosis and elucidate the corresponding mechanism, both plant growth and nutrient status of sugarcane plants and soils were investigated in the growth seasons of ratoon cane seedlings in 2016 and 2018. The impacts of rainfall and ammonium on chlorosis were also investigated hydroponically. The results showed that the chlorotic seedlings could green in mid-summer; Mn content in the first expanded leaf decreased significantly, whereas iron (Fe) content increased significantly during the progression of greening. The leaf Mn content in the greened seedlings decreased by up to 78.1% when compared with that in the initial chlorotic seedlings. The seedlings also showed a significant increase in seedling height and weight of the expanded leaves, accompanied by a decrease in plant Mn content during the progression of greening. Moreover, young seedlings with less Mn content showed earlier greening than older seedlings with more Mn content. The exchangeable ammonium content in the soils increased significantly during the progression of greening, and the addition of 1 mM ammonium to the chlorotic seedlings resulted in a decrease in leaf Mn content by up to 80%. Furthermore, leaf SPAD value and Fe content increased by 2.0-fold and 1.4-fold, respectively, after rainwater was applied to the chlorotic seedling. These results indicate Mn-induced chlorotic seedlings can turn naturally green, and downregulation of plant Mn content, rainfall in summer, and soil ammonium contribute to the greening of chlorotic seedlings.
Optimization of spray drying conditions for the production of quality ber (Zizyphus mauritianaLamk.) fruit powder
Authors: Pandey Sonika , Poonia Amrita , Rai Suman 
Published: April 2019

PurposeTo overcome the need of seasonal fruit ber, consumers prefer to use fruits in such a form that can be prepared easily or consumed instantly. By transforming them into powders, they can be effortlessly attained as well as preserved, stored and processed.Design/methodology/approachTo optimize the spray drying conditions for development of ber fruit powder, response surface methodology was used. The experimental design consisted of 13 runs. The levels of independent variables, i.e. inlet air temperature, varied from 153.79ºC to 196.21ºC and maltodextrin concentration, from 4.17 to 9.83 per cent. The responses were moisture content, bulk density, solubility, vitamin C, ΔE and L value.FindingsThe second-order polynomial model fitted for moisture content, bulk density, solubility, vitamin C, ΔE and L value was highly significant (p< 0.001) for each response. The inlet air temperature showed maximum influence on moisture content, bulk density, solubility and vitamin C, whereas the maltodextrin concentration showed maximum influence on bulk density, solubility, ΔE and L value. The predicted values were attained as moisture 4.90 per cent, bulk density 0.35g/ml, solubility 89.11 per cent, vitamin C 91.06mg/100g, ΔE 31.03 and L 87.78. The recommended optimum spray drying conditions were inlet air temperature and maltodextrin concentration of 166.64°C and 9.26 per cent, respectively.Originality/valueSpray drying of the underused Indian fruit ber has enhanced its utility. Ber powder can further be used as an instant beverage, in sweets, as a flavoring agent and in soft drinks.
Ishikawa diagrams and Bayesian belief networks for continuous improvement applications
Authors: Rodgers Mark , Oppenheim Rosa 
Published: April 2019

PurposeIn continuous improvement (CI) projects, cause-and-effect diagrams are used to qualitatively express the relationship between a given problem and its root causes. However, when data collection activities are limited, and advanced statistical analyses are not possible, practitioners need to understand causal relationships. The paper aims to discuss these issues.Design/methodology/approachIn this research, the authors present a framework that combines cause-and-effect diagrams with Bayesian belief networks (BBNs) to estimate causal relationships in instances where formal data collection/analysis activities are too costly or impractical. Specifically, the authors use cause-and-effect diagrams to create causal networks, and leverage elicitation methods to estimate the likelihood of risk scenarios by means of computer-based simulation.FindingsThis framework enables CI practitioners to leverage qualitative data and expertise to conduct in-depth statistical analysis in the event that data collection activities cannot be fully executed. Furthermore, this allows CI practitioners to identify critical root causes of a given problem under investigation before generating solutions.Originality/valueThis is the first framework that translates qualitative insights from a cause-and-effect diagram into a closed-form relationship between inputs and outputs by means of BBN models, simulation and regression.
The case for psychology in human resource management research
Authors: Troth Ashlea C. , Guest David E. 
Published: April 2019

AbstractA recent literature has developed criticising the growing influence of a psychological perspective within research on human resource management (HRM). This paper addresses and rebuts the various criticisms and outlines the positive contribution of work and organisational psychology to HRM research. In looking to the future and the continuing development of HRM research, we argue that there is a need to engage in research that is multidisciplinary, multilevel, multistakeholder, and multimethod. We propose a number of research topics that meet these criteria and to which work and organisational psychology can offer a distinctive contribution. We call for other disciplines to make a more positive contribution to ensure that HRM research continues to flourish.
Defoe's Tour and the Historiography of Early Modern Britain
Authors: Rogers Pat 
Published: April 2019

AbstractThe most heavily quarried contemporary source on Britain in the late seventeenth and early eighteenth centuries is Daniel Defoe's Tour (1724‐6). Its findings have been exploited in accounts of the politics, society, economy, architecture, literature and geography of the early modern nation. It has been used by historians of the family, women, religion, art, popular culture, shopping, weather, landscape, transport, leisure, travel and tourism, topography, antiquarianism, archaeology, gambling, the Navy, Civil War battlefields, dialect and industrial archaeology. This article charts the extent of Defoe's influence on our understanding of the age, analysing its value as a connected survey of Britain.
Lactate dehydrogenase and baseline markers associated with clinical outcomes of advanced esophageal squamous cell carcinoma patients treated with camrelizumab (SHR‐1210), a novel anti‐PD‐1 antibody
Authors: Wang Xi , Zhang Bo , Chen Xuelian , Mo Hongnan , Wu Dawei , Lan Bo , Li Qun , Xu Binghe , Huang Jing 
Published: April 2019

BackgroundA small proportion of patients with advanced esophageal squamous cell carcinoma (ESCC) could benefit from immune checkpoint inhibitors; however, reliable peripheral blood biomarkers for outcomes of anti‐PD‐1 immunotherapy in ESCC have not been identified.MethodsThe data of 43 patients in the ESCC cohort of a phase I trial at our center were retrospectively reviewed. All patients were administered intravenous camrelizumab (SHR‐1210), a novel anti‐PD‐1 antibody, at doses of 60 mg, 200 mg, or 400 mg (4‐week interval after first dose followed by a 2‐week schedule) until disease progression or intolerable toxicity. Associations between lactate dehydrogenase (LDH) and other peripheral blood biomarkers at baseline and the efficacy of camrelizumab were also investigated.ResultsAfter median follow‐up of 19.6 months, the overall response rate was 25.6% (11/43), including one complete response. Median progression‐free and overall survival rates were 2.0 and 8.0 months, respectively. Patients with an elevated baseline LDH had lower tumor response rates (P = 0.02) and shorter progression‐free (P = 0.002) and overall (P < 0.0001) survival than patients with normal LDH levels. An increase in LDH levels during treatment was significantly associated with disease progression. Multivariate Cox analysis identified LDH (hazard ratio [HR] 0.18), CRP (HR 0.27), the number of organs involved (HR 0.31), absolute monocyte count (HR 0.33), and Eastern Cooperative Oncology Group performance status (HR 0.36) as independent prognostic factors.ConclusionsSerum LDH, which is readily available in routine clinical practice, is a potential marker for response and a powerful independent factor for survival in advanced ESCC patients treated with anti‐PD‐1 therapy.
A new biomechanical glaucoma factor to discriminate normal eyes from normal pressure glaucoma eyes
Authors: Pillunat Karin R. , Herber Robert , Spoerl Eberhard , Erb Carl , Pillunat Lutz E. 
Published: April 2019

AbstractBackgroundTo test the ability of the newly calculated Dresden biomechanical glaucoma factor (DBGF) based on dynamic corneal response (DCR) deformation and corneal thickness parameters, to discriminate between healthy and normal pressure glaucoma (NPG) eyes.MethodsSeventy healthy and 70 NPG patients of Caucasian origin were recruited for this multicentre cross‐sectional pilot study, which included both eyes for analysis. Logistic regression analysis with generalized estimating equation (GEE) models to account for correlations between eyes and a threefold cross‐validation were performed to determine the optimal combination of Corvis ST parameters in order to separate normal from NPG eyes.ResultsThe DBGF was calculated using 5 Corvis ST parameters, which showed the best discrimination power: deformation amplitude ratio progression, highest concavity time, pachymetry slope, the biomechanically corrected intraocular pressure and pachymetry. In a threefold cross‐validation, the receiver operating characteristic (ROC) curve confirmed an area under the curve (AUC) of 0.814 with a sensitivity of 76% and a specificity of 77% using a logit cut‐off value of a DBGF = 0.5.ConclusionThe DBGF shows to be sensitive and specific to discriminate healthy from NPG eyes. Since diagnosis of NPG is often challenging, the DBGF may help with the differential diagnosis of NPG in daily clinical practice. Therefore, it might be considered as a new possible screening method for NPG.
Cytological diagnosis of Langerhans cell histiocytosis: A series of 47 cases
Authors: Phulware Ravi Hari , Guleria Prerna , Iyer Venkateswaran K , Bakhshi Sameer , Seth Rachna , Mridha Asit R , Jain Deepali , Mallick Saumyaranjan , Arava Sudheer Kumar , Agarwal Shipra , Kaushal Seema , Yadav Rajni , Mathur Sandeep R. 
Published: April 2019

AbstractObjectiveLangerhans cell histiocytosis (LCH) is a rare disease affecting predominantly children and young adults but can be found in any age group. Diagnosis of LCH is often difficult and can be delayed because of its rarity. The present study highlights the cytomorphological features in a large cohort of cases. An accurate cytological diagnosis may avoid unnecessary biopsy and guide appropriate management.MethodFourty seven (47) cases of LCH diagnosed on cytological material & fine‐needle aspiration (FNA) over a period of 14 years (2003‐2016) were retrieved from the archives. The cytological smears were evaluated and microscopic findings collected by semi‐quantitative assessment done by two different pathologistsResultThe age at the diagnosis of the patients ranged from 9 months to 28 years. The majority of cases were in the age group of 0‐5 years. The most common site was head and neck region, which included cervical lymphadenopathy and scalp swelling. Two cases were diagnosed each from inguinal lymph node and bronchio‐alveolar lavage (BAL). Cytological smears in the majority of the cases were moderate to highly cellular (58%) and showing abundant Langerhans cell in (72%) of cases. Areas of necrosis were seen in 38%, while 78% of cases showed giant cells. The majority of cases showed mild eosinophilia (61%), sparse lymphocytosis (83%) and mild neutrophilic infiltration (64%). There were 1‐2 mitoses per 10 high power field in 12 cases (25.5%). No abnormal mitoses were identified.ConclusionThe presence of cells with features of Langerhans cells associated with the expression of selected immunohistochemical markers allow the diagnosis of LCH on cytological samples, sparing more invasive procedure as a biopsy.
Thinking and Working Politically: Learning from practice. Overview to Special Issue
Authors: McCulloch Neil , Piron Laure‐Hélène 
Published: April 2019

AbstractOver the last 15 years, a set of ideas now referred to as “thinking and working politically” (TWP) has coalesced into a “second orthodoxy” about how to take context into account when implementing development interventions. This approach stresses the importance of obtaining a better understanding of the local context (“thinking politically”) in order to support local actors to bring about sustainable developmental change (“working politically”). However, the evidence base to justify this new approach remains thin, despite a growing number of programmes which purport to be implementing it. Officials in development agencies struggle with putting it into practice and it is unclear how TWP differs—or not—from similar approaches, such as Problem Driven Iterative Adaptation (PDIA) and Doing Development Differently (DDD). This Special Issue sheds light on what TWP means in practice by examining a set of initiatives undertaken by both development partners and government departments in Nigeria, the Occupied Palestinian Territories, China and India. This overview article outlines, in brief, each of the Special Issue's four papers and then draws out five lessons—for funders and for practitioners—from across all the papers. Our five lessons are: (1) the fundamental importance of undertaking political economy analysis (PEA) to adapt programmes to their contexts; (2) the importance of having a realistic level of ambition for interventions; (3) the need to support local ownership—not just “agreement ownership” (between a donor agency and government) or local “management ownership” of the programme, but critically “driver ownership” by generating trust with the key local actors driving change; (4) the need for a more effective set of tools for measuring results in complex programmes that attempt to achieve improvements in long‐run governance; and, (5) that although the political economy of donors is often seen as a barrier to applying TWP, the articles show how much can be done with a TWP approach if the analysis takes into account the political economy of donors as well as that of the local context. We conclude with a set of operational recommendations for donors and implementors, as well as suggestions of avenues for further research.