bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional analyses of a novel missense and other mutations of the vitamin D receptor in association with alopecia
Authors: Tamura Mayuko , Ishizawa Michiyasu , Isojima Tsuyoshi , Özen Samim , Oka Akira , Makishima Makoto , Kitanaka Sachiko 
Published: July 2017

AbstractHereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is a rare disorder, caused by bialellic mutations of the vitamin D receptor (VDR) gene, sometimes associated with alopecia. The aim of this study is to elucidate the mechanism of functional disruption of a novel mutation, detected in a patient with HVDRR, comparing to other mutations with or without alopecia. The patient was a 2-year-old girl with alopecia, who was clinically diagnosed as HVDRR. Genetic analysis revealed a novel homozygous mutation, S360P, located in ligand binding domain (LBD). The mutation was predicted as not disease causing by Polyphen2 and SIFT. But the transcriptional activity of S360P was disrupted as well as other reported mutations, Q152X (located in the hinge lesion), and R274L, H305Q (located in LBD). Following assays revealed no ligand binding affinity, no interaction with cofactors or RXR and no functioning of nuclear localization signals. Our results provide an additional evidence for the previous findings suggesting that DNA binding by the VDR/RXR heterodimer is essential for the function of the VDR in hair development. In conclusion, we identified a novel missense mutation of VDR causing HVDRR with alopecia. Functional analyses revealed that the single amino acid substitution could disrupt the function of the protein.
Metabolic reprogramming is associated with flavopiridol resistance in prostate cancer DU145 cells
Authors: Li Xiaoran , Lu Jie , Kan Quancheng , Li Xiaoli , Fan Qiong , Li Yaqing , Huang Ruixia , Slipicevic Ana , Dong Hiep Phuc , Eide Lars , Wang Junbai , Zhang Hongquan , Berge Viktor , Goscinski Mariusz Adam , Kvalheim Gunnar , Nesland Jahn M. , Suo Zhenhe 
Published: July 2017

AbstractFlavopiridol (FP) is a pan-cyclin dependent kinase inhibitor, which shows strong efficacy in inducing cancer cell apoptosis. Although FP is potent against most cancer cells in vitro, unfortunately it proved less efficacious in clinical trials in various aggressive cancers. To date, the molecular mechanisms of the FP resistance are mostly unknown. Here, we report that a small fraction human prostate cancer DU145 cells can survive long-term FP treatment and emerge as FP-resistant cells (DU145FP). These DU145FP cells show accumulated mitochondrial lesions with stronger glycolytic features, and they proliferate in slow-cycling and behave highly migratory with strong anti-apoptotic potential. In addition, the cells are less sensitive to cisplatin and docetaxel-induced apoptotic pressure, and over-express multiple stem cell associated biomarkers. Our studies collectively uncover for the first time that FP-resistant prostate cancer cells show metabolic remodeling, and the metabolic plasticity might be required for the FP resistance-associated cancer cell stemness up-regulation.
Dynamics and extreme plasticity of metallic microparticles in supersonic collisions
Authors: Xie Wanting , Alizadeh-Dehkharghani Arash , Chen Qiyong , Champagne Victor K. , Wang Xuemei , Nardi Aaron T. , Kooi Steven , Müftü Sinan , Lee Jae-Hwang 
Published: July 2017

AbstractMetallic microparticles can acquire remarkable nanoscale morphologies after experiencing high velocity collisions, but materials science regarding the extreme events has been limited due to a lack of controlled experiments. In this work, collision dynamics and nonlinear material characteristics of aluminum microparticles are investigated through precise single particle collisions with two distinctive substrates, sapphire and aluminum, across a broad range of collision velocities, from 50 to 1,100 m/s. An empirical constitutive model is calibrated based on the experimental results, and is used to investigate the mechanics of particle deformation history. Real-time and post-impact characterizations, as well as model based simulations, show that significant material flow occurs during the impact, especially with the sapphire substrate. A material instability stemming from plasticity-induced heating is identified. The presented methodology, based on the use of controlled single particle impact data and constitutive models, provides an innovative approach for the prediction of extreme material behavior.
An allelic variant of the PmrB sensor kinase responsible for colistin resistance in an Escherichia coli strain of clinical origin
Authors: Cannatelli Antonio , Giani Tommaso , Aiezza Noemi , Di Pilato Vincenzo , Principe Luigi , Luzzaro Francesco , Galeotti Cesira L. , Rossolini Gian Maria 
Published: July 2017

AbstractWe investigated the colistin resistance mechanism in an Escherichia coli strain (LC711/14) isolated in Italy in 2014, from an urinary tract infection, which was previously shown to express a colistin resistance mechanism different from mcr-1. LC711/14 was found to carry a novel mutation in the pmrB gene, resulting in a leucine to proline amino acid substitution at position 10 of the PmrB sensor kinase component of the PmrAB signal transduction system. The role of this substitution in colistin resistance was documented by expression of the wild-type and mutated alleles in a pmrB deletion derivative of the E. coli reference strain MG1655, in which expression of the mutated allele conferred colistin resistance and upregulation of the endogenous pmrHFIJKLM lipid A modification system. Complementation of LC711/14 with the wild-type pmrB allele restored colistin susceptibility and decreased expression of pmrHFIJKLM, confirming the role of this PmrB mutation. Substitution of leucine at position 10 of PmrB with other amino acids (glycine and glutamine) resulted in loss of function, underscoring a key role of this residue which is located in the cytoplasmic secretion domain of the protein. This work demonstrated that mutation in this domain of the PmrB sensor kinase can be responsible for acquired colistin resistance in E. coli strains of clinical origin.
Electrospray mode transition of microdroplets with semiconductor nanoparticle suspension
Authors: Castillo-Orozco Eduardo , Kar Aravinda , Kumar Ranganathan 
Published: July 2017

AbstractElectrosprays operate in several modes depending on the flow rate and electric potential. This allows the deposition of droplets containing nanoparticles into discrete nanodot arrays to fabricate various electronic devices. In this study, seven different suspensions with varying properties were investigated. In the dripping mode, the normalized dropsize decreases linearly with electric capillary number, Ca
e
, (ratio of electric to surface tension forces) up to Ca
e
≈ 1.0. The effect of viscous forces is found to be negligible in the dripping mode since the capillary number is small. For flow rates with low Reynolds number, the mode changes to microdripping mode, and then to a planar oscillating microdripping mode as Ca
e
increases. The normalized dropsize remains nearly constant at 0.07 for Ca
e
> 3.3. The microdripping mode which is important for depositing discrete array of nanodots is found to occur in the range, 2 ≤ Ca
e
≤ 2.5. The droplet frequency increases steadily from dripping to microdripping mode, but stays roughly constant in the oscillating microdripping mode. This work provides a physical basis by which the flow rate and the voltage can be chosen for any nanosuspension to precisely operate in the microdripping mode at a predetermined dropsize and droplet frequency.
Anaerobic oxidation of methane coupled with extracellular electron transfer to electrodes
Authors: Gao Yaohuan , Lee Jangho , Neufeld Josh D. , Park Joonhong , Rittmann Bruce E. , Lee Hyung-Sool 
Published: July 2017

AbstractAnaerobic oxidation of methane (AOM) is an important process for understanding the global flux of methane and its relation to the global carbon cycle. Although AOM is known to be coupled to reductions of sulfate, nitrite, and nitrate, evidence that AOM is coupled with extracellular electron transfer (EET) to conductive solids is relatively insufficient. Here, we demonstrate EET-dependent AOM in a biofilm anode dominated by Geobacter spp. and Methanobacterium spp. using carbon-fiber electrodes as the terminal electron sink. The steady-state current density was kept at 11.0 ± 1.3 mA/m2 in a microbial electrochemical cell, and isotopic experiments supported AOM-EET to the anode. Fluorescence in situ hybridization images and metagenome results suggest that Methanobacterium spp. may work synergistically with Geobacter spp. to allow AOM, likely by employing intermediate (formate or H2)-dependent inter-species electron transport. Since metal oxides are widely present in sedimentary and terrestrial environments, an AOM-EET niche would have implications for minimizing the net global emissions of methane.
Progressive Changes in CXCR4 Expression That Define Thymocyte Positive Selection Are Dispensable For Both Innate and Conventional αβT-cell Development
Authors: Lucas Beth , White Andrea J. , Parnell Sonia M. , Henley Peter M. , Jenkinson William E. , Anderson Graham 
Published: July 2017

AbstractThe ordered migration of immature thymocytes through thymic microenvironments generates both adaptive MHC restricted αβT-cells and innate CD1d-restricted iNKT-cells. While several chemokine receptors and ligands control multiple stages of this process, their involvement during early thymocyte development often precludes direct analysis of potential roles during later developmental stages. For example, because of early lethality of CXCR4−/−mice, and stage-specific requirements for CXCR4 in thymus colonisation and pre-TCR mediated selection, its role in thymic positive selection is unclear. Here we have examined CXCR4-CXCL12 interactions during the maturation of CD4+CD8+thymocytes, including downstream stages of iNKT and αβT-cell development. We show CXCL12 expression is a common feature of cortical thymic epithelial cells, indicating widespread availability throughout the cortex. Moreover, CXCR4 expression by CD4+CD8+pre-selection thymocytes is progressively downregulated following both MHC and CD1d-restricted thymic selection events. However, using CD4Cre-mediated deletion to bypass its involvement in CD4−CD8−thymocyte development, we show CXCR4 is dispensable for the maintenance and intrathymic positioning of CD4+CD8+thymocytes, and their ability to generate mature αβT-cells and CD1d-restricted iNKT-cells. Collectively, our data define dynamic changes in CXCR4 expression as a marker for intrathymic selection events, and show its role in T-cell development is restricted to pre-CD4+CD8+stages.
Tropic origins, a dispersal model for saprotrophic mushrooms in Agaricus section Minores with descriptions of sixteen new species
Authors: He Mao-Qiang , Chen Jie , Zhou Jun-Liang , Ratchadawan Cheewangkoon , Hyde Kevin D. , Zhao Rui-Lin 
Published: July 2017

AbstractAgaricus section Minores contains the richest species diversity within the genus. Its Phylogeny is firstly presented by a Maximum Likelihood tree generated through DNA sequences from four gene regions of 91 species. Furthermore, a molecular dating analysis is conducted used those sequences, and it provided the divergence times of the clades within section Minores. Study showed section Minores has a tropical origin. Four main dispersal routes are proposed: (1) species from South Asia migrated through the Tibetan Plateau and reached Europe ca. 9–13 Ma; (2) species from out of South Asia dispersed to Europe in the earlier time of ca. 22 Ma; (3) species from South Asia dispersed through North Asia to Alaska, and reached West America around ca. 9 Ma; and (4) species from South Asia dispersed south and reached Oceania by at least three invading events about ca. 9, 12 and 16–18 Ma respectively. Those routes excepting the second route coincide with those of ectomycorrhizal mushrooms. To know whether the second route existed in the saprotrophic mushrooms requires further studies, and the fourth route may explain why the secotioid species occurring in Australia are morphologically similar but cluster in different phylogenetic clades. This study also demonstrates a great biodiversity of A. section Minores in China. Sixteen new species and three new records are introduced from China with morphological descriptions, illustrations, color photographs and phylogenetic analyses.
Divergent evolution of Di-lysine ER retention vs. farnesylation motif-mediated anchoring of the AnkB virulence effector to the Legionella-containing vacuolar membrane
Authors: Perpich John D. , Kalia Awdhesh , Price Christopher T. D. , Jones Snake C. , Wong Kathy , Gehring Kalle , Kwaik Yousef Abu 
Published: July 2017

AbstractWithin macrophages and amoeba, the Legionella-containing vacuole (LCV) membrane is derived from the ER. The bona fide F-box AnkB effector protein of L. pneumophila strain AA100/130b is anchored to the cytosolic side of the LCV membrane through host-mediated farnesylation of its C-terminal eukaryotic “CaaX” motif. Here we show that the AnkB homologue of the Paris strain has a frame shift mutation that led to a loss of the CaaX motif and a concurrent generation of a unique C-terminal KNKYAP motif, which resembles the eukaryotic di-lysine ER-retention motif (KxKxx). Our phylogenetic analyses indicate that environmental isolates of L. pneumophila have a potential positive selection for the ER-retention KNKYAP motif. The AnkB-Paris effector is localized to the LCV membrane most likely through the ER-retention motif. Its ectopic expression in HEK293T cells localizes it to the perinuclear ER region and it trans-rescues the ankB mutant of strain AA100/130b in intra-vacuolar replication. The di-lysine ER retention motif of AnkB-Paris is indispensable for function; most likely as an ER retention motif that enables anchoring to the ER-derived LCV membrane. Our findings show divergent evolution of the ankB allele in exploiting either host farnesylation or the ER retention motif to be anchored into the LCV membrane.
The evolutionary advantage of heritable phenotypic heterogeneity
Authors: Carja Oana , Plotkin Joshua B. 
Published: July 2017

AbstractPhenotypic plasticity is an evolutionary driving force in diverse biological processes, including the adaptive immune system, the development of neoplasms, and the persistence of pathogens despite drug pressure. It is essential, therefore, to understand the evolutionary advantage of an allele that confers on cells the ability to express a range of phenotypes. Here, we study the fate of a new mutation that allows the expression of multiple phenotypic states, introduced into a finite population of individuals that can express only a single phenotype. We show that the advantage of such a mutation depends on the degree of phenotypic heritability between generations, called phenotypic memory. We analyze the fixation probability of the phenotypically plastic allele as a function of phenotypic memory, the variance of expressible phenotypes, the rate of environmental changes, and the population size. We find that the fate of a phenotypically plastic allele depends fundamentally on the environmental regime. In constant environments, plastic alleles are advantageous and their fixation probability increases with the degree of phenotypic memory. In periodically fluctuating environments, by contrast, there is an optimum phenotypic memory that maximizes the probability of the plastic allele’s fixation. This same optimum memory also maximizes geometric mean fitness, in steady state. We interpret these results in the context of previous studies in an infinite-population framework. We also discuss the implications of our results for the design of therapies that can overcome persistence and, indirectly, drug resistance.
Controls on eDNA movement in streams: Transport, Retention, and Resuspension
Authors: Shogren Arial J. , Tank Jennifer L. , Andruszkiewicz Elizabeth , Olds Brett , Mahon Andrew R. , Jerde Christopher L. , Bolster Diogo 
Published: July 2017

AbstractAdvances in detection of genetic material from species in aquatic ecosystems, including environmental DNA (eDNA), have improved species monitoring and management. eDNA from target species can readily move in streams and rivers and the goal is to measure it, and with that infer where and how abundant species are, adding great value to delimiting species invasions, monitoring and protecting rare species, and estimating biodiversity. To date, we lack an integrated framework that identifies environmental factors that control eDNA movement in realistic, complex, and heterogeneous flowing waters. To this end, using an empirical approach and a simple conceptual model, we propose a framework of how eDNA is transported, retained, and resuspended in stream systems. Such an understanding of eDNA dispersal in streams will be essential for designing optimized sampling protocols and subsequently estimating biomass or organismal abundance. We also discuss guiding principles for more effective use of eDNA methods, highlighting the necessity of understanding these parameters for use in future predictive modeling of eDNA transport.
A combined case-control and molecular source attribution study of human Campylobacter infections in Germany, 2011–2014
Authors: Rosner Bettina M. , Schielke Anika , Didelot Xavier , Kops Friederike , Breidenbach Janina , Willrich Niklas , Gölz Greta , Alter Thomas , Stingl Kerstin , Josenhans Christine , Suerbaum Sebastian , Stark Klaus 
Published: July 2017

AbstractCampylobacter infection is the most commonly notified bacterial enteritis in Germany. We performed a large combined case-control and source attribution study (Nov 2011-Feb 2014) to identify risk factors for sporadic intestinal Campylobacter infections and to determine the relative importance of various animal sources for human infections in Germany. We conducted multivariable logistic regression analysis to identify risk factors. Source attribution analysis was performed using the asymmetric island model based on MLST data of human and animal/food isolates. As animal sources we considered chicken, pig, pet dog or cat, cattle, and poultry other than chicken. Consumption of chicken meat and eating out were the most important risk factors for Campylobacter infections. Additional risk factors were preparation of poultry meat in the household; preparation of uncooked food and raw meat at the same time; contact with poultry animals; and the use of gastric acid inhibitors. The mean probability of human C. jejuni isolates to originate from chickens was highest (74%), whereas pigs were a negligible source for C. jejuni infections. Human C. coli isolates were likely to originate from chickens (56%) or from pigs (32%). Efforts need to be intensified along the food chain to reduce Campylobacter load, especially on chicken meat.
Differential adiponectin signalling couples ER stress with lipid metabolism to modulate ageing in C. elegans
Authors: Kyriakakis Emmanouil , Charmpilas Nikolaos , Tavernarakis Nektarios 
Published: July 2017

AbstractThe metabolic and endocrine functions of adipose tissue and the ability of organisms to cope with cellular stress have a direct impact on physiological ageing and the aetiology of various diseases such as obesity-related pathologies and cancer. The endocrine effects of adipose tissue are mediated by secreted adipokines, which modulate metabolic processes and influence related maladies. Although a plethora of molecules and signaling pathways associate ageing with proteotoxic stress and cellular metabolism, our understanding of how these pathways interconnect to coordinate organismal physiology remains limited. We dissected the mechanisms linking adiponectin signalling pathways and endoplasmic reticulum (ER) proteotoxic stress responses that individually or synergistically affect longevity in C. elegans. Animals deficient for the adiponectin receptor PAQR-1 respond to ER stress, by rapidly activating the canonical ER unfolded protein response (UPRER) pathway, which is primed in these animals under physiological conditions by specific stress defence transcription factors. PAQR-1 loss enhances survival and promotes longevity under ER stress and reduced insulin/IGF-1 signalling. PAQR-1 engages UPRER, autophagy and lipase activity to modulate lipid metabolism during ageing. Our findings demonstrate that moderating adiponectin receptor -1 activity extends lifespan under stress, and directly implicate adiponectin signalling as a coupler between proteostasis and lipid metabolism during ageing.
Quality Measurement of Two-dimensional Shear Wave Speed Imaging for Breast Lesions: the Associated Factors and the Impact to Diagnostic Performance
Authors: Li Dan-Dan , Xu Hui-Xiong , Liu Bo-Ji , Bo Xiao-Wan , Li Xiao-Long , Wu Rong 
Published: July 2017

AbstractThis study aimed to identify the associated factors for quality measurement (QM) of shear wave speed (SWS) imaging and to validate the additional value of QM in the diagnosis of breast lesions. From September 2014 to February 2015, conventional ultrasound and SWS imaging were performed in 338 women with 361 breast lesions. Binary logistic regression was used to identify associated factors for QM. Sensitivity, specificity and the area under receiver operating characteristic (ROC) curve (AUC) among maximum SWS (SWS
max
), QM and SWS
max
plus QM (SWS
max
+QM) were compared to validate additional value of QM. Pathology confirmed 263 (72.9%) benign lesions and 98 (27.1%) malignancies. Maximum depth (Odds ratio [OR]: 1.398) and posterior features (OR: 1.206) were identified as independent associated factors for QM. Compared with SWS
max
and QM, the sensitivity of SWS
max
+QM increased from 67.3%, 64.3% to 83.7% whereas the specificity decreased from 90.5%, 72.6% to 65.4% (all P < 0.05). SWS
max
had the highest AUC in comparison with QM and SWS
max
+QM (0.849 vs. 0.685 vs. 0.745; P < 0.05). QM for breast lesions is associated with maximum depth and posterior features. Adding QM to SWS
max
is useful for breast cancer screening and SWS
max
alone is useful for breast cancer differentiation.
Transcriptome and metabolite analyses in Azadirachta indica: identification of genes involved in biosynthesis of bioactive triterpenoids
Authors: Bhambhani Sweta , Lakhwani Deepika , Gupta Parul , Pandey Ashutosh , Dhar Yogeshwar Vikram , Kumar Bag Sumit , Asif Mehar Hasan , Kumar Trivedi Prabodh 
Published: July 2017

AbstractAzadirachta indica A. Juss, commonly known as Neem, is the reservoir of triterpenoids of economic importance. Metabolite analysis of different developmental stages of leaf and fruit suggests tissue-specific accumulation of the major triterpenoids in this important tree. Though biosynthesis of these complex molecules requires substrate flux from the isoprenoid pathway, enzymes involved in late biosynthetic steps remain uncharacterized. We established and analyzed transcriptome datasets from leaf and fruit and identified members of gene families involved in intermediate steps of terpenoid backbone biosynthesis and those related to secondary transformation leading to the tissue-specific triterpenoid biosynthesis. Expression analysis suggests differential expression of number of genes between leaf and fruit and probable participation in the biosynthesis of fruit-specific triterpenoids. Genome-wide analysis also identified members of gene families putatively involved in secondary modifications in late biosynthetic steps leading to the synthesis of highly oxygenated triterpenoids. Expression and molecular docking analyses suggest involvement of specific members of CYP450 family in secondary modifications for the biosynthesis of bioactive triterpenoids. This study generated rich genomic resource and identified genes involved in biosynthesis of important molecules, which will aid in the advancement of tools for functional genomics and elucidation of the biosynthesis of triterpenoid from this important tree.