bluuebunny/crossref_metadata_2025 huggingface dataset:
-BOUNDS FOR PSEUDO-DIFFERENTIAL OPERATORS ON COMPACT LIE GROUPS
Authors: Delgado Julio , Ruzhansky Michael
Published: April 2017

Given a compact Lie group$G$, in this paper we establish$L^{p}$-bounds for pseudo-differential operators in$L^{p}(G)$. The criteria here are given in terms of the concept of matrix symbols defined on the noncommutative analogue of the phase space$G\times \widehat{G}$, where$\widehat{G}$is the unitary dual of$G$. We obtain two different types of$L^{p}$bounds: first for finite regularity symbols and second for smooth symbols. The conditions for smooth symbols are formulated using$\mathscr{S}_{\unicode[STIX]{x1D70C},\unicode[STIX]{x1D6FF}}^{m}(G)$classes which are a suitable extension of the well-known$(\unicode[STIX]{x1D70C},\unicode[STIX]{x1D6FF})$ones on the Euclidean space. The results herein extend classical$L^{p}$bounds established by C. Fefferman on$\mathbb{R}^{n}$. While Fefferman’s results have immediate consequences on general manifolds for$\unicode[STIX]{x1D70C}>\max \{\unicode[STIX]{x1D6FF},1-\unicode[STIX]{x1D6FF}\}$, our results do not require the condition$\unicode[STIX]{x1D70C}>1-\unicode[STIX]{x1D6FF}$. Moreover, one of our results also does not require$\unicode[STIX]{x1D70C}>\unicode[STIX]{x1D6FF}$. Examples are given for the case of$\text{SU}(2)\cong \mathbb{S}^{3}$and vector fields/sub-Laplacian operators when operators in the classes$\mathscr{S}_{0,0}^{m}$and$\mathscr{S}_{\frac{1}{2},0}^{m}$naturally appear, and where conditions$\unicode[STIX]{x1D70C}>\unicode[STIX]{x1D6FF}$and$\unicode[STIX]{x1D70C}>1-\unicode[STIX]{x1D6FF}$fail, respectively.
Intravital microscopy in historic and contemporary immunology
Authors: Secklehner Judith , Lo Celso Cristina , Carlin Leo M
Published: April 2017

In this review, we discuss intravital microscopy of immune cells, starting from its historic origins to current applications in diverse organs. It is clear from a quantitative review of the literature that intravital microscopy is a key tool in both historic and contemporary immunological research, providing unique advances in our understanding of immune responses. We have chosen to focus this review on how intravital microscopy methodologies are used to image specific organs or systems and we present recent descriptions of fundamental immunological processes that could not have been achieved by other methods. The following target organs/systems are discussed in more detail: cremaster muscle, skin (ear and dorsal skin fold chamber), lymph node, liver, lung, mesenteric vessels, carotid artery, bone marrow, brain, spleen, foetus and lastly vessels of the knee joint.
The conserved protein Seb1 drives transcription termination by binding RNA polymerase II and nascent RNA
Authors: Wittmann Sina , Renner Max , Watts Beth R. , Adams Oliver , Huseyin Miles , Baejen Carlo , El Omari Kamel , Kilchert Cornelia , Heo Dong-Hyuk , Kecman Tea , Cramer Patrick , Grimes Jonathan M. , Vasiljeva Lidia
Published: April 2017

Termination of RNA polymerase II (Pol II) transcription is an important step in the transcription cycle, which involves the dislodgement of polymerase from DNA, leading to release of a functional transcript. Recent studies have identified the key players required for this process and showed that a common feature of these proteins is a conserved domain that interacts with the phosphorylated C-terminus of Pol II (CTD-interacting domain, CID). However, the mechanism by which transcription termination is achieved is not understood. Using genome-wide methods, here we show that the fission yeast CID-protein Seb1 is essential for termination of protein-coding and non-coding genes through interaction with S2-phosphorylated Pol II and nascent RNA. Furthermore, we present the crystal structures of the Seb1 CTD- and RNA-binding modules. Unexpectedly, the latter reveals an intertwined two-domain arrangement of a canonical RRM and second domain. These results provide important insights into the mechanism underlying eukaryotic transcription termination.
Enabling valley selective exciton scattering in monolayer WSe2 through upconversion
Authors: Manca M. , Glazov M. M. , Robert C. , Cadiz F. , Taniguchi T. , Watanabe K. , Courtade E. , Amand T. , Renucci P. , Marie X. , Wang G. , Urbaszek B.
Published: April 2017

Excitons, Coulomb bound electron–hole pairs, are composite bosons and their interactions in traditional semiconductors lead to condensation and light amplification. The much stronger Coulomb interaction in transition metal dichalcogenides such as WSe2 monolayers combined with the presence of the valley degree of freedom is expected to provide new opportunities for controlling excitonic effects. But so far the bosonic character of exciton scattering processes remains largely unexplored in these two-dimensional materials. Here we show that scattering between B-excitons and A-excitons preferably happens within the same valley in momentum space. This leads to power dependent, negative polarization of the hot B-exciton emission. We use a selective upconversion technique for efficient generation of B-excitons in the presence of resonantly excited A-excitons at lower energy; we also observe the excited A-excitons state 2s. Detuning of the continuous wave, low-power laser excitation outside the A-exciton resonance (with a full width at half maximum of 4 meV) results in vanishing upconversion signal.
Wnt signaling in triple-negative breast cancer
Authors: Pohl SÖ-G , Brook N , Agostino M , Arfuso F , Kumar A P , Dharmarajan A
Published: April 2017

Wnt signaling regulates a variety of cellular processes, including cell fate, differentiation, proliferation and stem cell pluripotency. Aberrant Wnt signaling is a hallmark of many cancers. An aggressive subtype of breast cancer, known as triple-negative breast cancer (TNBC), demonstrates dysregulation in canonical and non-canonical Wnt signaling. In this review, we summarize regulators of canonical and non-canonical Wnt signaling, as well as Wnt signaling dysfunction that mediates the progression of TNBC. We review the complex molecular nature of TNBC and the emerging therapies that are currently under investigation for the treatment of this disease.
Young inversion with multiple linked QTLs under selection in a hybrid zone
Authors: Lee Cheng-Ruei , Wang Baosheng , Mojica Julius P. , Mandáková Terezie , Prasad Kasavajhala V. S. K. , Goicoechea Jose Luis , Perera Nadeesha , Hellsten Uffe , Hundley Hope N. , Johnson Jenifer , Grimwood Jane , Barry Kerrie , Fairclough Stephen , Jenkins Jerry W. , Yu Yeisoo , Kudrna Dave , Zhang Jianwei , Talag Jayson , Golser Wolfgang , Ghattas Kathryn , Schranz M. Eric , Wing Rod , Lysak Martin A. , Schmutz Jeremy , Rokhsar Daniel S. , Mitchell-Olds Thomas
Published: April 2017

Fixed chromosomal inversions can reduce gene flow and promote speciation in two ways: by suppressing recombination and by carrying locally favoured alleles at multiple loci. However, it is unknown whether favoured mutations slowly accumulate on older inversions or if young inversions spread because they capture pre-existing adaptive quantitative trait loci (QTLs). By genetic mapping, chromosome painting and genome sequencing, we have identified a major inversion controlling ecologically important traits inBoechera stricta. The inversion arose since the last glaciation and subsequently reached local high frequency in a hybrid speciation zone. Furthermore, the inversion shows signs of positive directional selection. To test whether the inversion could have captured existing, linked QTLs, we crossed standard, collinear haplotypes from the hybrid zone and found multiple linked phenology QTLs within the inversion region. These findings provide the first direct evidence that linked, locally adapted QTLs may be captured by young inversions during incipient speciation.
Adaptation to deep-sea chemosynthetic environments as revealed by mussel genomes
Authors: Sun Jin , Zhang Yu , Xu Ting , Zhang Yang , Mu Huawei , Zhang Yanjie , Lan Yi , Fields Christopher J. , Hui Jerome Ho Lam , Zhang Weipeng , Li Runsheng , Nong Wenyan , Cheung Fiona Ka Man , Qiu Jian-Wen , Qian Pei-Yuan
Published: April 2017

Hydrothermal vents and methane seeps are extreme deep-sea ecosystems that support dense populations of specialized macro­benthos such as mussels. But the lack of genome information hinders the understanding of the adaptation of these animals to such inhospitable environments. Here we report the genomes of a deep-sea vent/seep mussel (Bathymodiolus platifrons) and a shallow-water mussel (Modiolus philippinarum). Phylogenetic analysis shows that these mussel species diverged approximately 110.4 million years ago. Many gene families, especially those for stabilizing protein structures and removing toxic substances from cells, are highly expanded inB. platifrons,indicating adaptation to extreme environmental conditions. The innate immune system ofB. platifronsis considerably more complex than that of other lophotrochozoan species, includingM.philippinarum, with substantial expansion and high expression levels of gene families that are related to immune recognition, endocytosis and caspase-mediated apoptosis in the gill, revealing presumed genetic adaptation of the deep-sea mussel to the presence of its chemoautotrophic endosymbionts. A follow-up metaproteomic analysis of the gill ofB. platifronsshows methanotrophy, assimilatory sulfate reduction and ammonia metabolic pathways in the symbionts, providing energy and nutrients, which allow the host to thrive. Our study of the genomic composition allowing symbiosis in extremophile molluscs gives wider insights into the mechanisms of symbiosis in other organisms such as deep-sea tubeworms and giant clams.
The dual developmental origin of spinal cerebrospinal fluid-contacting neurons gives rise to distinct functional subtypes
Authors: Djenoune Lydia , Desban Laura , Gomez Johanna , Sternberg Jenna R. , Prendergast Andrew , Langui Dominique , Quan Feng B. , Marnas Hugo , Auer Thomas O. , Rio Jean-Paul , Del Bene Filippo , Bardet Pierre-Luc , Wyart Claire
Published: April 2017

Chemical and mechanical cues from the cerebrospinal fluid (CSF) can affect the development and function of the central nervous system (CNS). How such cues are detected and relayed to the CNS remains elusive. Cerebrospinal fluid-contacting neurons (CSF-cNs) situated at the interface between the CSF and the CNS are ideally located to convey such information to local networks. In the spinal cord, these GABAergic neurons expressing the PKD2L1 channel extend an apical extension into the CSF and an ascending axon in the spinal cord. In zebrafish and mouse spinal CSF-cNs originate from two distinct progenitor domains characterized by distinct cascades of transcription factors. Here we ask whether these neurons with different developmental origins differentiate into cells types with different functional properties. We show in zebrafish larva that the expression of specific markers, the morphology of the apical extension and axonal projections, as well as the neuronal targets contacted by CSF-cN axons, distinguish the two CSF-cN subtypes. Altogether our study demonstrates that the developmental origins of spinal CSF-cNs give rise to two distinct functional populations of sensory neurons. This work opens novel avenues to understand how these subtypes may carry distinct functions related to development of the spinal cord, locomotion and posture.
The TLR2 Binding Neisserial Porin PorB Enhances Antigen Presenting Cell Trafficking and Cross-presentation
Authors: Reiser Michael L. , Mosaheb Munir M. , Lisk Christina , Platt Andrew , Wetzler Lee M.
Published: April 2017

TOLL-like receptor (TLR) ligands activate both innate and adaptive immune cells, while modulating the cellular immune response. The outer membrane protein (OMP) fromNeisseria meninigitidis, PorB, is a naturally occurring TLR2 ligand and functions as an adjuvant. Here, we demonstrate that PorB increases the level of OVA in the endo-/lysosomal cellular compartment of BMDCs, increases antigen presenting cell (APC) trafficking to draining lymph nodes, and enhances antigen cross-presentation. PorB is capable of mounting an antigen specific T cell response by efficiently stimulating antigen cross-presentationin vivoandin vitroassessed by BMDC OT-I cocultivation assays. The enhanced antigen cross-presentation and the increased APC recruitment to secondary lymphoid tissues expand the scope of known adjuvant effects of PorB on the immune system. Our findings lead to a better understanding of how TLR-ligand based adjuvants can alter and modulate immune responses.
Contact Angle Measurement of Small Capillary Length Liquid in Super-repelled State
Authors: Liu Tingyi “Leo” , Kim Chang-Jin “CJ”
Published: April 2017

The difficulty of measuring very large contact angles (>150 degrees) has become more relevant with the increased popularity of super-repellent surfaces. Measurement is more difficult for dynamic contact angles, for which theoretical profiles do not fit well, and small capillary length liquids, whose sessile droplets sag by gravity. Here, we expand the issue to the limit by investigating dynamic contact angles of liquids with an extremely small capillary length (<1.0 mm), empowered by the superomniphobic surface that can super-repel even fluorinated solvents, which highly wet all materials. Numerically simulating and experimentally testing 13 different liquids on the superomniphobic surface, we discover their dynamic contact angles can be measured with a consistent accuracy despite their vastly different capillary lengths if one keeps the lens magnification inversely proportional to the capillary length. Verifying the droplet equator height is a key parameter, we propose a new Bond number defined by the equator height and optical resolution to represent the measurement accuracy of large contact angles. Despite negligible improvement for most liquids today, the proposed approach teaches how to measure very large contact angles with consistent accuracy when any of the liquids in consideration has a capillary length below 1.0 mm.
In vivo evidence of functional and anatomical stripe-based subdivisions in human V2 and V3
Authors: Dumoulin Serge O. , Harvey Ben M. , Fracasso Alessio , Zuiderbaan Wietske , Luijten Peter R. , Wandell Brian A. , Petridou Natalia
Published: April 2017

Visual cortex contains a hierarchy of visual areas. The earliest cortical area (V1) contains neurons responding to colour, form and motion. Later areas specialize on processing of specific features. The second visual area (V2) in non-human primates contains a stripe-based anatomical organization, initially defined using cytochrome-oxidase staining of post-mortem tissue. Neurons in these stripes have been proposed to serve distinct functional specializations, e.g. processing of color, form and motion. These stripes represent an intermediate stage in visual hierarchy and serve a key role in the increasing functional specialization of visual areas. Using sub-millimeter high-field functional and anatomical MRI (7T), we provide in vivo evidence for stripe-based subdivisions in humans. Using functional MRI, we contrasted responses elicited by stimuli alternating at slow and fast temporal frequencies. We revealed stripe-based subdivisions in V2 ending at the V1/V2 border. The human stripes reach into V3. Using anatomical MRI optimized for myelin contrast within gray matter, we also observe a stripe pattern. Stripe subdivisions preferentially responding to fast temporal frequencies are more myelinated. As such, functional and anatomical measures provide independent and converging evidence for functional organization into striped-based subdivisions in human V2 and V3.
DNA word analysis based on the distribution of the distances between symmetric words
Authors: Tavares Ana H. M. P. , Pinho Armando J. , Silva Raquel M. , Rodrigues João M. O. S. , Bastos Carlos A. C. , Ferreira Paulo J. S. G. , Afreixo Vera
Published: April 2017

We address the problem of discovering pairs of symmetric genomic words (i.e., words and the corresponding reversed complements) occurring at distances that are overrepresented. For this purpose, we developed new procedures to identify symmetric word pairs with uncommon empirical distance distribution and with clusters of overrepresented short distances. We speculate that patterns of overrepresentation of short distances between symmetric word pairs may allow the occurrence of non-standard DNA conformations, such as hairpin/cruciform structures. We focused on the human genome, and analysed both the complete genome as well as a version with known repetitive sequences masked out. We reported several well-defined features in the distributions of distances, which can be classified into three different profiles, showing enrichment in distinct distance ranges. We analysed in greater detail certain pairs of symmetric words of length seven, found by our procedure, characterised by the surprising fact that they occur at single distances more frequently than expected.
Associations of metabolic disorder factors with the risk of uncontrolled hypertension: a follow-up cohort in rural China
Authors: Xiao Jing , Hua Tianqi , Shen Huan , Zhang Min , Wang Xiao-Jian , Gao Yue-Xia , Lu Qinyun , Wu Chuanli
Published: April 2017

We evaluated how metabolic disorders affected antihypertension therapy. 2,912 rural Chinese patients with hypertension who provided blood samples, demographic and clinical data at baseline and after 1 year of antihypertension therapy were evaluated. At baseline, 1,515 patients (52.0%) were already receiving drug therapy and 11.4% of them had controlled blood pressure (BP). After 1 year, all 2,912 patients were receiving antihypertension therapy that was administered by community physicians, and 59.42% of them had controlled BP. Central obesity and abnormal triglyceride, high-density lipoprotein cholesterol, and glucose were associated with 15–70% higher risks of uncontrolled hypertension. Metabolic syndrome using the JIS criteria was associated with poor BP control (odds ratio: 1.71 and 1.54 for the baseline and follow-up datasets, respectively). The risk of uncontrolled hypertension increased with the number of metabolic disorders (p for trend <0.01). The presence of ≥3 metabolic disorder factors was associated with higher risks of poor BP control. The associations of metabolic factors and uncontrolled hypertension were stronger for the standard and modified ATP III criteria, compared to the IDF and JIS criteria. Metabolic factors were associated with less effective antihypertension therapy, and all definitions of metabolic syndrome helped identify patients with elevated risks of uncontrolled hypertension.
RNA sequence analysis of rat acute experimental pancreatitis with and without fatty liver: a gene expression profiling comparative study
Authors: Wang Qian , Yan Hongkai , Wang Gang , Qiu Zhaoyan , Bai Bin , Wang Shiqi , Yu Pengfei , Feng Quanxin , Zhao Qingchuan , He Xianli , Liu Chaoxu
Published: April 2017

Fatty liver (FL) is one of the risk factors for acute pancreatitis and is also indicative of a worse prognosis as compared to acute pancreatitis without fatty liver (AP). The aim of the present study was to analyze, at the hepatic level, the differentially expressed genes (DEGs) between acute pancreatitis with fatty liver (APFL) rats and AP rats. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses of these DEGs indicated that PPARα signalling pathway and fatty acid degradation pathway may be involved in the pathological process of APFL, which indicated that fatty liver may aggravate pancreatitis through these pathways. Moreover, the excessive activation of JAK/STAT signaling pathway and toll-like receptor signaling pathway was also found in APFL group as shown in heat map. In conclusion, the inhibition of PPARα signaling pathway and the fatty acid degradation pathway may lead to the further disorder of lipid metabolism, which can aggravate pancreatitis.
Contrasting Granite Metallogeny through the Zircon Record: A Case Study from Myanmar
Authors: Gardiner Nicholas J. , Hawkesworth Chris J. , Robb Laurence J. , Whitehouse Martin J. , Roberts Nick M. W. , Kirkland Christopher L. , Evans Noreen J.
Published: April 2017

Granitoid-hosted mineral deposits are major global sources of a number of economically important metals. The fundamental controls on magma metal fertility are tectonic setting, the nature of source rocks, and magma differentiation. A clearer understanding of these petrogenetic processes has been forged through the accessory mineral zircon, which has considerable potential in metallogenic studies. We present an integrated zircon isotope (U-Pb, Lu-Hf, O) and trace element dataset from the paired Cu-Au (copper) and Sn-W (tin) magmatic belts in Myanmar. Copper arc zircons have juvenile εHf (+7.6 to +11.5) and mantle-like δ18O (5.2–5.5‰), whereas tin belt zircons have low εHf (−7 to −13) and heavier δ18O (6.2–7.7‰). Variations in zircon Hf and U/Yb reaffirm that tin belt magmas contain greater crustal contributions than copper arc rocks. Links between whole-rock Rb/Sr and zircon Eu/Eu* highlight that the latter can monitor magma fractionation in these systems. Zircon Ce/Ce* and Eu/Eu* are sensitive to redox and fractionation respectively, and here are used to evaluate zircon sensitivity to the metallogenic affinity of their host rock. Critical contents of Sn in granitic magmas, which may be required for the development of economic tin deposits, are marked by zircon Eu/Eu* values of ca. ≤0.08.
Improving Optical Temperature Sensing Performance of Er3+ Doped Y2O3 Microtubes via Co-doping and Controlling Excitation Power
Authors: Wang Xiangfu , Wang Ye , Marques-Hueso Jose , Yan Xiaohong
Published: April 2017

This work presents a new method to effectively improve the optical temperature behavior of Er3+ doped Y2O3 microtubes by co-doping of Tm3+ or Ho3+ ion and controlling excitation power. The influence of Tm3+ or Ho3+ ion on optical temperature behavior of Y2O3:Er3+ microtubes is investigated by analyzing the temperature and excitation power dependent emission spectra, thermal quenching ratios, fluorescence intensity ratios, and sensitivity. It is found that the thermal quenching of Y2O3:Er3+ microtubes is inhibited by co-doping with Tm3+ or Ho3+ ion, moreover the maximum sensitivity value based on the thermal coupled 4S3/2/2H11/2 levels is enhanced greatly and shifts to the high temperature range, while the maximum sensitivity based on 4F9/2(1)/4F9/2(2) levels shifts to the low temperature range and greatly increases. The sensitivity values are dependent on the excitation power, and reach two maximum values of 0.0529/K at 24 K and 0.0057/K at 457 K for the Y2O3:1%Er3+, 0.5%Ho3+ at 121 mW/mm2 excitation power, which makes optical temperature measurement in wide temperature range possible. The mechanism of changing the sensitivity upon different excitation densities is discussed.
Molecular classification of prostate adenocarcinoma by the integrated somatic mutation profiles and molecular network
Authors: Yang Lei , Wang Shiyuan , Zhou Meng , Chen Xiaowen , Jiang Wei , Zuo Yongchun , Lv Yingli
Published: April 2017

Prostate cancer is one of the most common cancers in men and a leading cause of cancer death worldwide, displaying a broad range of heterogeneity in terms of clinical and molecular behavior. Increasing evidence suggests that classifying prostate cancers into distinct molecular subtypes is critical to exploring the potential molecular variation underlying this heterogeneity and to better treat this cancer. In this study, the somatic mutation profiles of prostate cancer were downloaded from the TCGA database and used as the source nodes of the random walk with restart algorithm (RWRA) for generating smoothed mutation profiles in the STRING network. The smoothed mutation profiles were selected as the input matrix of the Graph-regularized Nonnegative Matrix Factorization (GNMF) for classifying patients into distinct molecular subtypes. The results were associated with most of the clinical and pathological outcomes. In addition, some bioinformatics analyses were performed for the robust subtyping, and good results were obtained. These results indicated that prostate cancers can be usefully classified according to their mutation profiles, and we hope that these subtypes will help improve the treatment stratification of this cancer in the future.
LF-MF inhibits iron metabolism and suppresses lung cancer through activation of P53-miR-34a-E2F1/E2F3 pathway
Authors: Ren Jing , Ding Liang , Xu Qianyun , Shi Guoping , Li Xiaojing , Li Xiujun , Ji Jianjian , Zhang Dongya , Wang Yaping , Wang Tingting , Hou Yayi
Published: April 2017

Our previous studies showed that low frequency magnetic fields (LF-MF) suppressed tumor growth and influenced the function of immune system. Nevertheless the mechanisms behind the effect of LF-MF still remain to be elucidated. In this study, Tumor- bearing mice subcutaneously inoculated with Lewis lung cancer cells were exposed to a LF-MF (0.4T, 7.5 Hz) for 35 days and Survival rate, tumor growth and the tumor markers were measured. Results showed that tumor growth was obviously inhibited with a prolonged survival of tumor- bearing mice by LF-MF exposure. In vitro experiments, LF-MF was found to induce cell growth arrest, cell senescence and inhibit iron metabolism of lung cancer cells. Moreover, LF-MF stabilized p53 protein via inhibiting cell iron metabolism and the stabilized p53 protein enhanced miR-34a transcription. Furthermore, increased expression of miR-34a induced cell proliferation inhibition, cell cycle arrest and cell senescence of lung cancer cells by targeting E2F1/E2F3. We also detected the relevant indicator in tumor tissue such as the iron content, the level of miR-34a and related protein, corresponding results were obtained. Taken together, these observations imply that LF-MF suppressed lung cancer via inhibiting cell iron metabolism, stabilizing p53 protein and activation P53- miR-34a-E2F1/E2F3 pathway.
Genetic and Proteomic characterization of Bile Salt Export Pump (BSEP) in Snake Liver
Authors: Tan Xinle , Gao Fei , Su Hexiu , Gong Yajun , Zhang Jie , Sullivan Mitchell A. , Chen Jiachun
Published: April 2017

Snake gallbladder, a traditional Chinese medicine, has been believed in various Asian countries to improve visual acuity and alleviate rheumatism. Bile acids, a major component of the gallbladder, are toxic to the liver and kidney in humans and animals due to its detergent effects, while also exhibiting therapeutic effects due to an increase in the gallbladder contractions of muscle strips in patients with cholesterol gallstones. Secretion of bile acids in human and mammals depends on the bile salt export pump (BSEP), a liver-specific adenosine triphosphate (ATP)-binding cassette transporter encoded by ABCB11. However, the presence of BSEP in snakes has not been thoroughly explored. Here we confirm the existence of BSEP and its coding DNA sequence in snakes on both the proteomic and genetic level. This work provides information on the snake ABCB11 sequence and helps further potential genetic manipulation to affect bile salt metabolism. Our study provides the foundation for research on bile acid production from snakes by using modern genetic and proteomic methodologies.
Actual measurement, hygrothermal response experiment and growth prediction analysis of microbial contamination of central air conditioning system in Dalian, China
Authors: Lv Yang , Hu Guangyao , Wang Chunyang , Yuan Wenjie , Wei Shanshan , Gao Jiaoqi , Wang Boyuan , Song Fangchao
Published: April 2017

The microbial contamination of central air conditioning system is one of the important factors that affect the indoor air quality. Actual measurement and analysis were carried out on microbial contamination in central air conditioning system at a venue in Dalian, China. Illumina miseq method was used and three fungal samples of two units were analysed by high throughput sequencing. Results showed that the predominant fungus in air conditioning unit A and B were Candida spp. and Cladosporium spp., and two fungus were further used in the hygrothermal response experiment. Based on the data of Cladosporium in hygrothermal response experiment, this paper used the logistic equation and the Gompertz equation to fit the growth predictive model of Cladosporium genera in different temperature and relative humidity conditions, and the square root model was fitted based on the two environmental factors. In addition, the models were carried on the analysis to verify the accuracy and feasibility of the established model equation.
Rapid, simple and direct detection of Meloidogyne hapla from infected root galls using loop-mediated isothermal amplification combined with FTA technology
Authors: Peng Huan , Long Haibo , Huang Wenkun , Liu Jing , Cui Jiangkuan , Kong Lingan , Hu Xianqi , Gu Jianfeng , Peng Deliang
Published: April 2017

The northern root-knot nematode (Meloidogyne hapla) is a damaging nematode that has caused serious economic losses worldwide. In the present study, a sensitive, simple and rapid method was developed for detection of M. hapla in infested plant roots by combining a Flinders Technology Associates (FTA) card with loop-mediated isothermal amplification (LAMP). The specific primers of LAMP were designed based on the distinction of internal transcribed spacer (ITS) sequences between M. hapla and other Meloidogyne spp. The LAMP assay can detect nematode genomic DNA at concentrations low to 1/200 000, which is 100 times more sensitive than conventional PCR. The LAMP was able to highly specifically distinguish M. hapla from other closely related nematode species. Furthermore, the advantages of the FTA-LAMP assay to detect M. hapla were demonstrated by assaying infected root galls that were artificially inoculated. In addition, M. hapla was successfully detected from six of forty-two field samples using FTA-LAMP technology. This study was the first to provide a simple diagnostic assay for M. hapla using the LAMP assay combined with FTA technology. In conclusion, the new FTA-LAMP assay has the potential for diagnosing infestation in the field and managing the pathogen M. hapla.
The human Cranio Facial Development Protein 1 (Cfdp1) gene encodes a protein required for the maintenance of higher-order chromatin organization
Authors: Messina Giovanni , Atterrato Maria Teresa , Prozzillo Yuri , Piacentini Lucia , Losada Ana , Dimitri Patrizio
Published: April 2017

The human Cranio Facial Development Protein 1 (Cfdp1) gene maps to chromosome 16q22.2-q22.3 and encodes the CFDP1 protein, which belongs to the evolutionarily conserved Bucentaur (BCNT) family. Craniofacial malformations are developmental disorders of particular biomedical and clinical interest, because they represent the main cause of infant mortality and disability in humans, thus it is important to understand the cellular functions and mechanism of action of the CFDP1 protein. We have carried out a multi-disciplinary study, combining cell biology, reverse genetics and biochemistry, to provide the first in vivo characterization of CFDP1 protein functions in human cells. We show that CFDP1 binds to chromatin and interacts with subunits of the SRCAP chromatin remodeling complex. An RNAi-mediated depletion of CFDP1 in HeLa cells affects chromosome organization, SMC2 condensin recruitment and cell cycle progression. Our findings provide new insight into the chromatin functions and mechanisms of the CFDP1 protein and contribute to our understanding of the link between epigenetic regulation and the onset of human complex developmental disorders.
Identification and expression of cuticular protein genes based on Locusta migratoria transcriptome
Authors: Zhao Xiaoming , Gou Xin , Qin Zhongyu , Li Daqi , Wang Yan , Ma Enbo , Li Sheng , Zhang Jianzhen
Published: April 2017

Many types of cuticular proteins are found in a single insect species, and their number and features are very diversified among insects. The cuticle matrix consists of many different proteins that confer the physical properties of the exoskeleton. However, the number and properties of cuticle proteins in Locusta migratoria remain unclear. In the present study, Illumina sequencing and de novo assembly were combined to characterize the transcriptome of L. migratoria. Eighty-one cuticular protein genes were identified and divided into five groups: the CPR family (51), Tweedle (2), CPF/CPFLs (9), CPAP family (9), and other genes (10). Based on the expression patterns in different tissues and stages, most of the genes as a test were distributed in the integument, pronotum and wings, and expressed in selected stages with different patterns. The results showed no obvious correlation between the expression patterns and the conservative motifs. Additionally, each cluster displayed a different expression pattern that may possess a different function in the cuticle. Furthermore, the complexity of the large variety of genes displayed differential expression during the molting cycle may be associated with cuticle formation and may provide insights into the gene networks related to cuticle formation.
Generation of Aptamers from A Primer-Free Randomized ssDNA Library Using Magnetic-Assisted Rapid Aptamer Selection
Authors: Tsao Shih-Ming , Lai Ji-Ching , Horng Horng-Er , Liu Tu-Chen , Hong Chin-Yih
Published: April 2017

Aptamers are oligonucleotides that can bind to specific target molecules. Most aptamers are generated using random libraries in the standard systematic evolution of ligands by exponential enrichment (SELEX). Each random library contains oligonucleotides with a randomized central region and two fixed primer regions at both ends. The fixed primer regions are necessary for amplifying target-bound sequences by PCR. However, these extra-sequences may cause non-specific bindings, which potentially interfere with good binding for random sequences. The Magnetic-Assisted Rapid Aptamer Selection (MARAS) is a newly developed protocol for generating single-strand DNA aptamers. No repeat selection cycle is required in the protocol. This study proposes and demonstrates a method to isolate aptamers for C-reactive proteins (CRP) from a randomized ssDNA library containing no fixed sequences at 5′ and 3′ termini using the MARAS platform. Furthermore, the isolated primer-free aptamer was sequenced and binding affinity for CRP was analyzed. The specificity of the obtained aptamer was validated using blind serum samples. The result was consistent with monoclonal antibody-based nephelometry analysis, which indicated that a primer-free aptamer has high specificity toward targets. MARAS is a feasible platform for efficiently generating primer-free aptamers for clinical diagnoses.
DOSCATs: Double standards for protein quantification
Authors: Bennett Richard J. , Simpson Deborah M. , Holman Stephen W. , Ryan Sheila , Brownridge Philip , Eyers Claire E. , Colyer John , Beynon Robert J.
Published: April 2017

The two most common techniques for absolute protein quantification are based on either mass spectrometry (MS) or on immunochemical techniques, such as western blotting (WB). Western blotting is most often used for protein identification or relative quantification, but can also be deployed for absolute quantification if appropriate calibration standards are used. MS based techniques offer superior data quality and reproducibility, but WB offers greater sensitivity and accessibility to most researchers. It would be advantageous to apply both techniques for orthogonal quantification, but workflows rarely overlap. We describe DOSCATs (DOuble Standard conCATamers), novel calibration standards based on QconCAT technology, to unite these platforms. DOSCATs combine a series of epitope sequences concatenated with tryptic peptides in a single artificial protein to create internal tryptic peptide standards for MS as well as an intact protein bearing multiple linear epitopes. A DOSCAT protein was designed and constructed to quantify five proteins of the NF-κB pathway. For three target proteins, protein fold change and absolute copy per cell values measured by MS and WB were in excellent agreement. This demonstrates that DOSCATs can be used as multiplexed, dual purpose standards, readily deployed in a single workflow, supporting seamless quantitative transition from MS to WB.
Extracellular Vesicle-functionalized Decalcified Bone Matrix Scaffolds with Enhanced Pro-angiogenic and Pro-bone Regeneration Activities
Authors: Xie Hui , Wang Zhenxing , Zhang Liming , Lei Qian , Zhao Aiqi , Wang Hongxiang , Li Qiubai , Cao Yilin , Jie Zhang Wen , Chen Zhichao
Published: April 2017

Vascularization is crucial for bone regeneration after the transplantation of tissue-engineered bone grafts in the clinical setting. Growing evidence suggests that mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are potently pro-angiogenic both in vitro and in vivo. In the current study, we fabricated a novel EV-functionalized scaffold with enhanced pro-angiogenic and pro-bone regeneration activities by coating decalcified bone matrix (DBM) with MSC-derived EVs. EVs were harvested from rat bone marrow-derived MSCs and the pro-angiogenic potential of EVs was investigated in vitro. DBM scaffolds were then coated with EVs, and the modification was verified by scanning electron microscopy and confocal microscopy. Next, the pro-angiogenic and pro-bone regeneration activities of EV-modified scaffolds were evaluated in a subcutaneous bone formation model in nude mice. Micro-computed tomography scanning analysis showed that EV-modified scaffolds with seeded cells enhanced bone formation. Enhanced bone formation was confirmed by histological analysis. Immunohistochemical staining for CD31 proved that EV-modified scaffolds promoted vascularization in the grafts, thereby enhancing bone regeneration. This novel scaffold modification method provides a promising way to promote vascularization, which is essential for bone tissue engineering.
Important roles of Vilse in dendritic architecture and synaptic plasticity
Authors: Lee Jin-Yu , Lee Li-Jen , Fan Chih-Chen , Chang Ho-Ching , Shih Hsin-An , Min Ming-Yuan , Chang Mau-Sun
Published: April 2017

Vilse/Arhgap39 is a Rho GTPase activating protein (RhoGAP) and utilizes its WW domain to regulate Rac/Cdc42-dependent morphogenesis in Drosophila and murine hippocampal neurons. However, the function of Vilse in mammalian dendrite architecture and synaptic plasticity remained unclear. In the present study, we aimed to explore the possible role of Vilse in dendritic structure and synaptic function in the brain. Homozygous knockout of Vilse resulted in premature embryonic lethality in mice. Changes in dendritic complexity and spine density were noticed in hippocampal neurons of Camk2a-Cre mediated forebrain-specific Vilse knockout (VilseΔ/Δ) mice. VilseΔ/Δ mice displayed impaired spatial memory in water maze and Y-maze tests. Electrical stimulation in hippocampal CA1 region revealed that the synaptic transmission and plasticity were defected in VilseΔ/Δ mice. Collectively, our results demonstrate that Vilse is essential for embryonic development and required for spatial memory.
A targeted illumination optical fiber probe for high resolution fluorescence imaging and optical switching
Authors: Shinde Anant , Perinchery Sandeep Menon , Murukeshan Vadakke Matham
Published: April 2017

An optical imaging probe with targeted multispectral and spatiotemporal illumination features has applications in many diagnostic biomedical studies. However, these systems are mostly adapted in conventional microscopes, limiting their use for in vitro applications. We present a variable resolution imaging probe using a digital micromirror device (DMD) with an achievable maximum lateral resolution of 2.7 μm and an axial resolution of 5.5 μm, along with precise shape selective targeted illumination ability. We have demonstrated switching of different wavelengths to image multiple regions in the field of view. Moreover, the targeted illumination feature allows enhanced image contrast by time averaged imaging of selected regions with different optical exposure. The region specific multidirectional scanning feature of this probe has facilitated high speed targeted confocal imaging.
Controlled droplet transport to target on a high adhesion surface with multi-gradients
Authors: Deng Siyan , Shang Weifeng , Feng Shile , Zhu Shiping , Xing Yan , Li Dan , Hou Yongping , Zheng Yongmei
Published: April 2017

We introduce multi-gradients including Laplace pressure gradient, wettable gradient and wettable different gradient on a high adhesion surface via special wedge-pattern and improved anodic oxidation method. As a result of the cooperative effect mentioned above, controlled directional motion of a droplet on a high adhesion surface is realized, even when the surface is turned upside down. The droplet motion can be predicted and the movement distances can be controlled by simply adjusting the wedge angle and droplet volume. More interestingly, when Laplace pressure gradient is introduced on a V-shaped wettable gradient surface, two droplets can move toward one another as designed.
Okanin, effective constituent of the flower tea Coreopsis tinctoria, attenuates LPS-induced microglial activation through inhibition of the TLR4/NF-κB signaling pathways
Authors: Hou Yue , Li Guoxun , Wang Jian , Pan Yingni , Jiao Kun , Du Juan , Chen Ru , Wang Bing , Li Ning
Published: April 2017

The EtOAc extract ofCoreopsis tinctoriaNutt. significantly inhibited LPS-induced nitric oxide (NO) production, as judged by the Griess reaction, and attenuated the LPS-induced elevation in iNOS, COX-2, IL-1β, IL-6 and TNF-α mRNA levels, as determined by quantitative real-time PCR, when incubated with BV-2 microglial cells. Immunohistochemical results showed that the EtOAc extract significantly decreased the number of Iba-1-positive cells in the hippocampal region of LPS-treated mouse brains. The major effective constituent of the EtOAc extract, okanin, was further investigated. Okanin significantly suppressed LPS-induced iNOS expression and also inhibited IL-6 and TNF-α production and mRNA expression in LPS-stimulated BV-2 cells. Western blot analysis indicated that okanin suppressed LPS-induced activation of the NF-κB signaling pathway by inhibiting the phosphorylation of IκBα and decreasing the level of nuclear NF-κB p65 after LPS treatment. Immunofluorescence staining results showed that okanin inhibited the translocation of the NF-κB p65 subunit from the cytosol to the nucleus. Moreover, okanin significantly inhibited LPS-induced TLR4 expression in BV-2 cells. In summary, okanin attenuates LPS-induced activation of microglia. This effect may be associated with its capacity to inhibit the TLR4/NF-κB signaling pathways. These results suggest that okanin may have potential as a nutritional preventive strategy for neurodegenerative disorders.
Network-based characterization and prediction of human DNA repair genes and pathways
Authors: Li Yan-Hui , Zhang Gai-Gai
Published: April 2017

Network biology is a useful strategy to understand cell’s functional organization. In this study, for the first time, we successfully introduced network approaches to study properties of human DNA repair genes. Compared with non-DNA repair genes, we found distinguishing features for DNA repair genes: (i) they tend to have higher degrees; (ii) they tend to be located at global network center; (iii) they tend to interact directly with each other. Based on these features, we developed the first algorithm to predict new DNA repair genes. We tested several machine-learning models and found that support vector machine with kernel function of radial basis function (RBF) achieve the best performance, with precision = 0.74 and area under curve (AUC) = 0.96. In the end, we applied the algorithm to predict new DNA repair genes and got 32 new candidates. Literature supporting four of the predictions was found. We believe the network approaches introduced here might open a new avenue to understand DNA repair genes and pathways. The suggested algorithm and the predicted genes might be helpful for scientists in the field.
Cholinesterase-like organocatalysis by imidazole and imidazole-bearing molecules
Authors: Nieri Paola , Carpi Sara , Fogli Stefano , Polini Beatrice , Breschi Maria Cristina , Podestà Adriano
Published: April 2017

Organocatalysis, which is mostly explored for its new potential industrial applications, also represents a chemical event involved in endogenous processes. In the present study, we provide the first evidence that imidazole and imidazole derivatives have cholinesterase-like properties since they can accelerate the hydrolysis of acetylthiocholine and propionylthiocholine in a concentration-dependent manner. The natural imidazole-containing molecules as L-histidine and histamine show a catalytic activity, comparable to that of imidazole itself, whereas synthetic molecules, as cimetidine and clonidine, were less active. In the experimental conditions used, the reaction progress curves were sigmoidal and the rational of such unexpected behavior as well as the mechanism of catalysis is discussed. Although indirectly, findings of the present study suggests that imidazolic compounds may interfere with the homeostasis of the cholinergic system in vivo.
Structural heterogeneity of the μ-opioid receptor’s conformational ensemble in the apo state
Authors: Sena Diniz M. , Cong Xiaojing , Giorgetti Alejandro , Kless Achim , Carloni Paolo
Published: April 2017

G-protein coupled receptors (GPCRs) are the largest and most pharmaceutically relevant family of membrane proteins. Here, fully unbiased, enhanced sampling simulations of a constitutively active mutant (CAM) of a class A GPCR, the μ-opioid receptor (μOR), demonstrates repeated transitions between the inactive (IS) and active-like (AS-L) states. The interconversion features typical activation/inactivation patterns involving established conformational rearrangements of conserved residues. By contrast, wild-type μOR remains in IS during the same course of simulation, consistent with the low basal activity of the protein. The simulations point to an important role of residue W2936.48 at the “toggle switch” in the mutation-induced constitutive activation. Such role has been already observed for other CAMs of class A GPCRs. We also find a significantly populated intermediate state, rather similar to IS. Based on the remarkable accord between simulations and experiments, we suggest here that this state, which has escaped so far experimental characterization, might constitute an early step in the activation process of the apo μOR CAM.
Accelerometer assessed moderate-to-vigorous physical activity and successful ageing: results from the Whitehall II study
Authors: Menai Mehdi , van Hees Vincent T. , Elbaz Alexis , Kivimaki Mika , Singh-Manoux Archana , Sabia Séverine
Published: April 2017

Physical activity is key for successful ageing, but questions remain regarding the optimal physical activity pattern. We examined the cross-sectional association between physical activity and successful ageing using data on 3,749 participants (age range = 60–83years) of the Whitehall II study. The participants underwent a clinical assessment, completed a 20-item physical activity questionnaire, and wore a wrist-mounted accelerometer for 9 days. Successful ageing was defined as good cognitive, motor, and respiratory functioning, along with absence of disability, mental health problems, and major chronic diseases. Time spent in moderate-to-vigorous physical activity (MVPA) episodes assessed by accelerometer was classified as “short” (1–9.59 minutes) and “long” (≥10 minutes) bouts. Linear multivariate regression showed that successful agers (N = 789) reported 3.79 (95% confidence interval (CI): 1.39–6.19) minutes more daily MVPA than other participants. Accelerometer data showed this difference to be 3.40 (95% CI:2.44–4.35) minutes for MVPA undertaken in short bouts, 4.16 (95% CI:3.11–5.20) minutes for long bouts, and 7.55 (95% CI:5.86–9.24) minutes for all MVPA bouts lasting 1 minute or more. Multivariate logistic regressions showed that participants undertaking ≥150 minutes of MVPA per week were more likely to be successful agers with both self-reported (Odd Ratio (OR) = 1.29,95% (CI):1.09–1.53) and accelerometer data (length bout ≥1 minute:OR = 1.92, 95%CI:1.60–2.30). Successful agers practice more MVPA, having both more short and long bouts, than non-successful agers.