bluuebunny/crossref_metadata_2025 huggingface dataset:
Constellation: a tool for rapid, automated phenotype assignment of a highly polymorphic pharmacogene, CYP2D6, from whole-genome sequences
Authors: Twist Greyson P , Gaedigk Andrea , Miller Neil A , Farrow Emily G , Willig Laurel K , Dinwiddie Darrell L , Petrikin Josh E , Soden Sarah E , Herd Suzanne , Gibson Margaret , Cakici Julie A , Riffel Amanda K , Leeder J Steven , Dinakarpandian Deendayal , Kingsmore Stephen F
Published: January 2016

An important component of precision medicine—the use of whole-genome sequencing (WGS) to guide lifelong healthcare—is electronic decision support to inform drug choice and dosing. To achieve this, automated identification of genetic variation in genes involved in drug absorption, distribution, metabolism, excretion and response (ADMER) is required. CYP2D6 is a major enzyme for drug bioactivation and elimination. CYP2D6 activity is predominantly governed by genetic variation; however, it is technically arduous to haplotype. Not only is the nucleotide sequence of CYP2D6 highly polymorphic, but the locus also features diverse structural variations, including gene deletion, duplication, multiplication events and rearrangements with the nonfunctional, neighbouring CYP2D7 and CYP2D8 genes. We developed Constellation, a probabilistic scoring system, enabling automated ascertainment of CYP2D6 activity scores from 2×100 paired-end WGS. The consensus reference method included TaqMan genotyping assays, quantitative copy-number variation determination and Sanger sequencing. When compared with the consensus reference Constellation had an analytic sensitivity of 97% (59 of 61 diplotypes) and analytic specificity of 95% (116 of 122 haplotypes). All extreme phenotypes, i.e., poor and ultrarapid metabolisers were accurately identified by Constellation. Constellation is anticipated to be extensible to functional variation in all ADMER genes, and to be performed at marginal incremental financial and computational costs in the setting of diagnostic WGS.
Hippocampal subfield atrophy in relation to cerebrospinal fluid biomarkers and cognition in early Parkinson’s disease: a cross-sectional study
Authors: Stav Ane Løvli , Johansen Krisztina Kunszt , Auning Eirik , Kalheim Lisa Flem , Selnes Per , Bjørnerud Atle , Hessen Erik , Aarsland Dag , Fladby Tormod
Published: January 2016

Cognition is often affected early in Parkinson’s disease (PD). Lewy body and amyloid β (Aβ) pathology and cortical atrophy may be involved. The aim of this study was to examine whether medial temporal lobe structural changes may be linked to cerebrospinal fluid (CSF) biomarker levels and cognition in early PD. PD patients had smaller volumes of total hippocampus, presubiculum, subiculum, CA2–3, CA4-DG, and hippocampal tail compared with normal controls (NCs). In the PD group, lower CSF Aβ38 and 42 were significant predictors for thinner perirhinal cortex. Lower Aβ42 and smaller presubiculum and subiculum predicted poorer verbal learning and delayed verbal recall. Smaller total hippocampus, presubiculum and subiculum predicted poorer visuospatial copying. Lower Aβ38 and 40 and thinner perirhinal cortex predicted poorer delayed visual reproduction. In conclusion, smaller volumes of hippocampal subfields and subhippocampal cortex thickness linked to lower CSF Aβ levels may contribute to cognitive impairment in early PD. Thirty-three early PD patients (13 without, 5 with subjective, and 15 with mild cognitive impairment) and NC had 3 T magnetic resonance imaging (MRI) scans. The MRI scans were post processed for volumes of hippocampal subfields and entorhinal and perirhinal cortical thickness. Lumbar puncture for CSF biomarkers Aβ38, 40, 42, total tau, phosphorylated tau (Innogenetics), and total α-synuclein (Meso Scale Diagnostics) were performed. Multiple regression analyses were used for between-group comparisons of the MRI measurements in the NC and PD groups and for assessment of CSF biomarkers and neuropsychological tests in relation to morphometry in the PD group.
Surface passivation of semiconducting oxides by self-assembled nanoparticles
Authors: Park Dae-Sung , Wang Haiyuan , Vasheghani Farahani Sepehr K. , Walker Marc , Bhatnagar Akash , Seghier Djelloul , Choi Chel-Jong , Kang Jie-Hun , McConville Chris F.
Published: January 2016

Physiochemical interactions which occur at the surfaces of oxide materials can significantly impair their performance in many device applications. As a result, surface passivation of oxide materials has been attempted via several deposition methods and with a number of different inert materials. Here, we demonstrate a novel approach to passivate the surface of a versatile semiconducting oxide, zinc oxide (ZnO), evoking a self-assembly methodology. This is achieved via thermodynamic phase transformation, to passivate the surface of ZnO thin films with BeO nanoparticles. Our unique approach involves the use of BexZn1-xO (BZO) alloy as a starting material that ultimately yields the required coverage of secondary phase BeO nanoparticles and prevents thermally-induced lattice dissociation and defect-mediated chemisorption, which are undesirable features observed at the surface of undoped ZnO. This approach to surface passivation will allow the use of semiconducting oxides in a variety of different electronic applications, while maintaining the inherent properties of the materials.
Electrical current through individual pairs of phosphorus donor atoms and silicon dangling bonds
Authors: Ambal K. , Rahe P. , Payne A. , Slinkman J. , Williams C. C. , Boehme C.
Published: January 2016

Nuclear spins of phosphorus [P] donor atoms in crystalline silicon are among the most coherent qubits found in nature. For their utilization in scalable quantum computers, distinct donor electron wavefunctions must be controlled and probed through electrical coupling by application of either highly localized electric fields or spin-selective currents. Due to the strong modulation of the P-donor wavefunction by the silicon lattice, such electrical coupling requires atomic spatial accuracy. Here, the spatially controlled application of electrical current through individual pairs of phosphorus donor electron states in crystalline silicon and silicon dangling bond states at the crystalline silicon (100) surface is demonstrated using a high‐resolution scanning probe microscope operated under ultra‐high vacuum and at a temperature of 4.3K. The observed pairs of electron states display qualitatively reproducible current-voltage characteristics with a monotonous increase and intermediate current plateaus.
Quantitative analysis of intrinsic and extrinsic factors in the aggregation mechanism of Alzheimer-associated Aβ-peptide
Authors: Meisl Georg , Yang Xiaoting , Frohm Birgitta , Knowles Tuomas P. J. , Linse Sara
Published: January 2016

Disease related mutations and environmental factors are key determinants of the aggregation mechanism of the amyloid-β peptide implicated in Alzheimer's disease. Here we present an approach to investigate these factors through acquisition of highly reproducible data and global kinetic analysis to determine the mechanistic influence of intrinsic and extrinsic factors on the Aβ aggregation network. This allows us to translate the shift in macroscopic aggregation behaviour into effects on the individual underlying microscopic steps. We apply this work-flow to the disease-associated Aβ42-A2V variant and to a variation in pH as examples of an intrinsic and an extrinsic perturbation. In both cases, our data reveal a shift towards a mechanism in which a larger fraction of the reactive flux goes via a pathway that generates potentially toxic oligomeric species in a fibril-catalyzed reaction. This is in agreement with the finding that Aβ42-A2V leads to early-onset Alzheimer’s disease and enhances neurotoxicity.
Microbial community profiling shows dysbiosis in the lesional skin of Vitiligo subjects
Authors: Ganju Parul , Nagpal Sunil , Mohammed MH , Nishal Kumar P , Pandey Rajesh , Natarajan Vivek T , Mande Sharmila S. , Gokhale Rajesh S.
Published: January 2016

Healthy human skin harbours a diverse array of microbes that comprise the skin microbiome. Commensal bacteria constitute an important component of resident microbiome and are intricately linked to skin health. Recent studies describe an association between altered skin microbial community and epidemiology of diseases, like psoriasis, atopic dermatitis etc. In this study, we compare the differences in bacterial community of lesional and non-lesional skin of vitiligo subjects. Our study reveals dysbiosis in the diversity of microbial community structure in lesional skin of vitiligo subjects. Although individual specific signature is dominant over the vitiligo-specific microbiota, a clear decrease in taxonomic richness and evenness can be noted in lesional patches. Investigation of community specific correlation networks reveals distinctive pattern of interactions between resident bacterial populations of the two sites (lesional and non-lesional). While Actinobacterial species constitute the central regulatory nodes (w.r.t. degree of interaction) in non-lesional skin, species belonging to Firmicutes dominate on lesional sites. We propose that the changes in taxonomic characteristics of vitiligo lesions, as revealed by our study, could play a crucial role in altering the maintenance and severity of disease. Future studies would elucidate mechanistic relevance of these microbial dynamics that can provide new avenues for therapeutic interventions.
PCNA appears in two populations of slow and fast diffusion with a constant ratio throughout S-phase in replicating mammalian cells
Authors: Zessin Patrick J. M. , Sporbert Anje , Heilemann Mike
Published: January 2016

DNA replication is a fundamental cellular process that precedes cell division. Proliferating cell nuclear antigen (PCNA) is a central scaffold protein that orchestrates DNA replication by recruiting many factors essential for the replication machinery. We studied the mobility of PCNA in live mammalian cells using single-particle tracking in combination with photoactivated-localization microscopy (sptPALM) and found two populations. The first population which is only present in cells with active DNA replication, showed slow diffusion and was found to be located in replication foci. The second population showed fast diffusion and represents the nucleoplasmic pool of unbound PCNA not involved in DNA replication. The ratio of these two populations remained constant throughout different stages of S-phase. A fraction of molecules in both populations showed spatially constrained mobility. We determined an exploration radius of ~100 nm for 13% of the slow-diffusing PCNA molecules and of ~600 nm for 46% of the fast-diffusing PCNA molecules.
Direct molecular mimicry enables off-target cardiovascular toxicity by an enhanced affinity TCR designed for cancer immunotherapy
Authors: Raman Marine C C , Rizkallah Pierre J , Simmons Ruth , Donnellan Zoe , Dukes Joseph , Bossi Giovanna , Le Provost Gabrielle S , Todorov Penio , Baston Emma , Hickman Emma , Mahon Tara , Hassan Namir , Vuidepot Annelise , Sami Malkit , Cole David K , Jakobsen Bent K.
Published: January 2016

Natural T-cell responses generally lack the potency to eradicate cancer. Enhanced affinity T-cell receptors (TCRs) provide an ideal approach to target cancer cells, with emerging clinical data showing significant promise. Nevertheless, the risk of off target reactivity remains a key concern, as exemplified in a recent clinical report describing fatal cardiac toxicity, following administration of MAGE-A3 specific TCR-engineered T-cells, mediated through cross-reactivity with an unrelated epitope from the Titin protein presented on cardiac tissue. Here, we investigated the structural mechanism enabling TCR cross-recognition of MAGE-A3 and Titin and applied the resulting data to rationally design mutants with improved antigen discrimination, providing a proof-of-concept strategy for altering the fine specificity of a TCR towards an intended target antigen. This study represents the first example of direct molecular mimicry leading to clinically relevant fatal toxicity, mediated by a modified enhanced affinity TCR designed for cancer immunotherapy. Furthermore, these data demonstrate that self-antigens that are expressed at high levels on healthy tissue should be treated with extreme caution when designing immuno-therapeutics.
Promotion of a cancer-like phenotype, through chronic exposure to inflammatory cytokines and hypoxia in a bronchial epithelial cell line model
Authors: Baird Anne-Marie , Gray Steven G. , Richard Derek J. , O’Byrne Kenneth J.
Published: January 2016

Globally, lung cancer accounts for approximately 20% of all cancer related deaths. Five-year survival is poor and rates have remained unchanged for the past four decades. There is an urgent need to identify markers of lung carcinogenesis and new targets for therapy. Given the recent successes of immune modulators in cancer therapy and the improved understanding of immune evasion by tumours, we sought to determine the carcinogenic impact of chronic TNF-α and IL-1β exposure in a normal bronchial epithelial cell line model. Following three months of culture in a chronic inflammatory environment under conditions of normoxia and hypoxia (0.5% oxygen), normal cells developed a number of key genotypic and phenotypic alterations. Important cellular features such as the proliferative, adhesive and invasive capacity of the normal cells were significantly amplified. In addition, gene expression profiles were altered in pathways associated with apoptosis, angiogenesis and invasion. The data generated in this study provides support that TNF-α, IL-1β and hypoxia promotes a neoplastic phenotype in normal bronchial epithelial cells. In turn these mediators may be of benefit for biomarker and/or immune-therapy target studies. This project provides an important inflammatoryin vitromodel for further immuno-oncology studies in the lung cancer setting.
Selective Audiovisual Semantic Integration Enabled by Feature-Selective Attention
Authors: Li Yuanqing , Long Jinyi , Huang Biao , Yu Tianyou , Wu Wei , Li Peijun , Fang Fang , Sun Pei
Published: January 2016

An audiovisual object may contain multiple semantic features, such as the gender and emotional features of the speaker. Feature-selective attention and audiovisual semantic integration are two brain functions involved in the recognition of audiovisual objects. Humans often selectively attend to one or several features while ignoring the other features of an audiovisual object. Meanwhile, the human brain integrates semantic information from the visual and auditory modalities. However, how these two brain functions correlate with each other remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study, we explored the neural mechanism by which feature-selective attention modulates audiovisual semantic integration. During the fMRI experiment, the subjects were presented with visual-only, auditory-only, or audiovisual dynamical facial stimuli and performed several feature-selective attention tasks. Our results revealed that a distribution of areas, including heteromodal areas and brain areas encoding attended features, may be involved in audiovisual semantic integration. Through feature-selective attention, the human brain may selectively integrate audiovisual semantic information from attended features by enhancing functional connectivity and thus regulating information flows from heteromodal areas to brain areas encoding the attended features.
A Fluctuating State in the Framework Compounds (Ba,Sr)Al2O4
Authors: Ishii Yui , Tsukasaki Hirofumi , Tanaka Eri , Mori Shigeo
Published: January 2016

The structural fluctuation in hexagonal Ba1−xSrxAl2O4 with a corner-sharing AlO4 tetrahedral network was characterized at various temperatures using transmission electron microscopy experiments. For x ≤ 0.05, soft modes of q ~ (1/2, 1/2, 0) and equivalent wave vectors condense at a transition temperature (TC) and form a superstructure with a cell volume of 2a × 2b × c. However, TC is largely suppressed by Sr-substitution and disappears for x ≥ 0.1. Furthermore, the q ~ (1/2, 1/2, 0) soft mode deviates from the commensurate value as temperature decreases and survives in nanoscaled regions below ~200 K. These results strongly suggest the presence of a new quantum criticality induced by the soft mode. Two distinct soft modes were observed as honeycomb-type diffuse scatterings in the high-temperature region up to 800 K. This intrinsic structural instability is a unique characteristic of the framework compound and is responsible for this unusually fluctuating state.
The trade-off between heat tolerance and metabolic cost drives the bimodal life strategy at the air-water interface
Authors: Fusi Marco , Cannicci Stefano , Daffonchio Daniele , Mostert Bruce , Pörtner Hans-Otto , Giomi Folco
Published: January 2016

The principle of oxygen and capacity limitation of thermal tolerance in ectotherms suggests that the long-term upper limits of an organism's thermal niche are equivalent to the upper limits of the organism's functional capacity for oxygen provision to tissues. Air-breathing ectotherms show wider thermal tolerances, since they can take advantage of the higher availability of oxygen in air than in water. Bimodal species move from aquatic to aerial media and switch between habitats in response to environmental variations such as cyclical or anomalous temperature fluctuations. Here we tested the prediction that bimodal species cope better with thermal stress than truly aquatic species using the crabPachygrapsus marmoratusas a model species. When in water, oxygen consumption rates ofP. marmoratusacutely rise during warming. Beyond a temperature threshold of 23 °C the crab's aerobic metabolism in air remains lower than in water. In parallel, the haemolymph oxygen partial pressure of submerged animals progressive decreases during warming, while it remains low but constant during emersion. Our results demonstrate the ability of a bimodal breathing ectotherm to extend its thermal tolerance during air-breathing, suggesting that there are temperature-related physiological benefits during the evolution of the bimodal life style.
Metabolic traits of an uncultured archaeal lineage -MSBL1- from brine pools of the Red Sea
Authors: Mwirichia Romano , Alam Intikhab , Rashid Mamoon , Vinu Manikandan , Ba-Alawi Wail , Anthony Kamau Allan , Kamanda Ngugi David , Göker Markus , Klenk Hans-Peter , Bajic Vladimir , Stingl Ulrich
Published: January 2016

The candidate Division MSBL1 (Mediterranean Sea Brine Lakes 1) comprises a monophyletic group of uncultured archaea found in different hypersaline environments. Previous studies propose methanogenesis as the main metabolism. Here, we describe a metabolic reconstruction of MSBL1 based on 32 single-cell amplified genomes from Brine Pools of the Red Sea (Atlantis II, Discovery, Nereus, Erba and Kebrit). Phylogeny based on rRNA genes as well as conserved single copy genes delineates the group as a putative novel lineage of archaea. Our analysis shows that MSBL1 may ferment glucose via the Embden–Meyerhof–Parnas pathway. However, in the absence of organic carbon, carbon dioxide may be fixed via the ribulose bisphosphate carboxylase, Wood-Ljungdahl pathway or reductive TCA cycle. Therefore, based on the occurrence of genes for glycolysis, absence of the core genes found in genomes of all sequenced methanogens and the phylogenetic position, we hypothesize that the MSBL1 are not methanogens, but probably sugar-fermenting organisms capable of autotrophic growth. Such a mixotrophic lifestyle would confer survival advantage (or possibly provide a unique narrow niche) when glucose and other fermentable sugars are not available.
Bispecific Antibody Affords Complete Post-Exposure Protection of Mice from Both Ebola (Zaire) and Sudan Viruses
Authors: Frei Julia C. , Nyakatura Elisabeth K. , Zak Samantha E. , Bakken Russell R. , Chandran Kartik , Dye John M. , Lai Jonathan R.
Published: January 2016

Filoviruses (Ebola and Marburg) cause severe hemorrhagic fever. There are five species of ebolavirus; among these, the Ebola (Zaire) and Sudan viruses (EBOV and SUDV, respectively) are highly pathogenic and have both caused recurring, large outbreaks. However, the EBOV and SUDV glycoprotein (GP) sequences are 45% divergent and thus antigenically distinct. Few antibodies with cross-neutralizing properties have been described to date. We used antibody engineering to develop novel bispecific antibodies (Bis-mAbs) that are cross-reactive toward base epitopes on GP from EBOV and SUDV. These Bis-mAbs exhibit potent neutralization against EBOV and SUDV GP pseudotyped viruses as well as authentic pathogens and confer a high degree (in one case 100%) post-exposure protection of mice from both viruses. Our studies show that a single agent that targets the GP base epitopes is sufficient for protection in mice; such agents could be included in panfilovirus therapeutic antibody cocktails.
Transcriptome analyses reveal genotype- and developmental stage-specific molecular responses to drought and salinity stresses in chickpea
Authors: Garg Rohini , Shankar Rama , Thakkar Bijal , Kudapa Himabindu , Krishnamurthy Lakshmanan , Mantri Nitin , Varshney Rajeev K. , Bhatia Sabhyata , Jain Mukesh
Published: January 2016

Drought and salinity are the major factors that limit chickpea production worldwide. We performed whole transcriptome analyses of chickpea genotypes to investigate the molecular basis of drought and salinity stress response/adaptation. Phenotypic analyses confirmed the contrasting responses of the chickpea genotypes to drought or salinity stress. RNA-seq of the roots of drought and salinity related genotypes was carried out under control and stress conditions at vegetative and/or reproductive stages. Comparative analysis of the transcriptomes revealed divergent gene expression in the chickpea genotypes at different developmental stages. We identified a total of 4954 and 5545 genes exclusively regulated in drought-tolerant and salinity-tolerant genotypes, respectively. A significant fraction (~47%) of the transcription factor encoding genes showed differential expression under stress. The key enzymes involved in metabolic pathways, such as carbohydrate metabolism, photosynthesis, lipid metabolism, generation of precursor metabolites/energy, protein modification, redox homeostasis and cell wall component biogenesis, were affected by drought and/or salinity stresses. Interestingly, transcript isoforms showed expression specificity across the chickpea genotypes and/or developmental stages as illustrated by the AP2-EREBP family members. Our findings provide insights into the transcriptome dynamics and components of regulatory network associated with drought and salinity stress responses in chickpea.
Levels of maternal care in dogs affect adult offspring temperament
Authors: Foyer Pernilla , Wilsson Erik , Jensen Per
Published: January 2016

Dog puppies are born in a state of large neural immaturity; therefore, the nervous system is sensitive to environmental influences early in life. In primates and rodents, early experiences, such as maternal care, have been shown to have profound and lasting effects on the later behaviour and physiology of offspring. We hypothesised that this would also be the case for dogs with important implications for the breeding of working dogs. In the present study, variation in the mother-offspring interactions of German Shepherd dogs within the Swedish breeding program for military working dogs was studied by video recording 22 mothers with their litters during the first three weeks postpartum. The aim was to classify mothers with respect to their level of maternal care and to investigate the effect of this care on pup behaviour in a standardised temperament test carried out at approximately 18 months of age. The results show that females differed consistently in their level of maternal care, which significantly affected the adult behaviour of the offspring, mainly with respect to behaviours classified as Physical and Social Engagement, as well as Aggression. Taking maternal quality into account in breeding programs may therefore improve the process of selecting working dogs.
Ectopic expression of R3 MYB transcription factor gene OsTCL1 in Arabidopsis, but not rice, affects trichome and root hair formation
Authors: Zheng Kaijie , Tian Hainan , Hu Qingnan , Guo Hongyan , Yang Li , Cai Ling , Wang Xutong , Liu Bao , Wang Shucai
Published: January 2016

In Arabidopsis, a MYB-bHLH-WD40 (MBW) transcriptional activator complex activates the homeodomain protein gene GLABRA2 (GL2), leading to the promotion of trichome formation and inhibition of root hair formation. The same MBW complex also activates single-repeat R3 MYB genes. R3 MYBs in turn, play a negative feedback role by competing with R2R3 MYB proteins for binding bHLH proteins, thus blocking the formation of the MBW complex. By BLASTing the rice (Oryza sativa) protein database using the entire amino acid sequence of Arabidopsis R3 MYB transcription factor TRICHOMELESS1 (TCL1), we found that there are two genes in rice genome encoding R3 MYB transcription factors, namely Oryza sativa TRICHOMELESS1 (OsTCL1) and OsTCL2. Expressing OsTCL1 in Arabidopsis inhibited trichome formation and promoted root hair formation and OsTCL1 interacted with GL3 when tested in Arabidopsis protoplasts. Consistent with these observations, expression levels of GL2, R2R3 MYB transcription factor gene GLABRA1 (GL1) and several R3 MYB genes were greatly reduced, indicating that OsTCL1 is functional R3 MYB. However, trichome and root hair formation in transgenic rice plants overexpressing OsTCL1 remained largely unchanged and elevated expression of OsGL2 was observed in the transgenic rice plants, indicating that rice may use different mechanisms to regulate trichome formation.
Genomic investigation reveals evolution and lifestyle adaptation of endophytic Staphylococcus epidermidis
Authors: Chaudhry Vasvi , Patil Prabhu B.
Published: January 2016

Staphylococcus epidermidis is a major human associated bacterium and also an emerging nosocomial pathogen. There are reports of its association to rodents, sheep and plants. However, comparative and evolutionary studies of ecologically diverse strains of S. epidermidis are lacking. Here, we report the whole genome sequences of four S. epidermidis strains isolated from surface sterilized rice seeds along with genome sequence of type strain. Phylogenomic analysis of rice endophytic S. epidermidis (RESE) with “type strain” unequivocally established their species identity. Whole genome based tree of 93 strains of S. epidermidis revealed RESE as distinct sub-lineage which is more related to rodent sub-lineage than to majority of human lineage strains. Furthermore, comparative genomics revealed 20% variable gene-pool in S. epidermidis, suggesting that genomes of ecologically diverse strains are under flux. Interestingly, we were also able to map several genomic regions that are under flux and gave rise to RESE strains. The largest of these genomic regions encodes a cluster of genes unique to RESE that are known to be required for survival and stress tolerance, apart from those required for adaptation to plant habitat. The genomes and genes of RESE represent distinct ecological resource/sequences and provided first evolutionary insights into adaptation of S. epidermidis to plants.
InGaN/Dilute-As GaNAs Interface Quantum Well for Red Emitters
Authors: Tan Chee-Keong , Borovac Damir , Sun Wei , Tansu Nelson
Published: January 2016

The design of InGaN/dilute-As GaNAs interface quantum well (QW) leads to significant redshift in the transition wavelength with improvement in electron-hole wave function overlap and spontaneous emission rate as compared to that of the conventional In0.2Ga0.8N QW. By using self-consistent six-band k·p band formalism, the nitride active region consisting of 30 Å In0.2Ga0.8N and 10 Å GaN0.95As0.05 interface QW leads to 623.52 nm emission wavelength in the red spectral regime. The utilization of 30 Å In0.2Ga0.8N/10 Å GaN0.95As0.05 interface QW also leads to 8.5 times enhancement of spontaneous emission rate attributed by the improvement in electron-hole wavefunction overlap, as compared to that of conventional 30 Å In0.35Ga0.65N QW for red spectral regime. In addition, the transition wavelength of the interface QW is relatively unaffected by the thickness of the dilute-As GaNAs interface layer (beyond 10 Å). The analysis indicates the potential of using interface QW concept in nitride-based light-emitting diodes for long wavelength emission.
Exposure to Polycyclic Aromatic Hydrocarbons, Plasma Cytokines and Heart Rate Variability
Authors: Yang Binyao , Deng Qifei , Zhang Wangzhen , Feng Yingying , Dai Xiayun , Feng Wei , He Xiaosheng , Huang Suli , Zhang Xiao , Li Xiaohai , Lin Dafeng , He Meian , Guo Huan , Sun Huizhen , Yuan Jing , Lu Jiachun , Hu Frank B. , Zhang Xiaomin , Wu Tangchun
Published: January 2016

Epidemiological studies have suggested associations between polycyclic aromatic hydrocarbons (PAHs) and heart rate variability (HRV). However, the roles of plasma cytokines in these associations are limited. In discovery stage of this study, we used Human Cytokine Antibody Arrays to examine differences in the concentrations of 280 plasma cytokines between 8 coke-oven workers and 16 community residents. We identified 19 cytokines with significant different expression (fold change ≥2 or ≤−2 and q-value <5%) between exposed workers and controls. 4 cytokines were selected to validate in 489 coke-oven workers by enzyme-linked immunosorbent assays in validation stage. We found OH-PAHs were inversely associated with brain-derived neurotrophic factor (BDNF) (p < 0.05) and interquartile range (IQR) increases in OH-PAHs were associated with >16% BDNF decreases. Additionally, OH-PAHs were positively associated with activated leukocyte cell adhesion molecule (ALCAM) and C-reactive protein (CRP) (p < 0.05) and IQR increases in OH-PAHs were associated with >20% increases in CRP. We also found significant associations between these cytokines and HRV (p < 0.05) and IQR increases in BDNF and CRP were associated with >8% decreases in HRV. Our results indicated PAH exposure was associated with plasma cytokines and higher cytokines were associated with decreased HRV, but additional human and potential mechanistic studies are needed.
An innovative platform for quick and flexible joining of assorted DNA fragments
Authors: De Paoli Henrique Cestari , Tuskan Gerald A. , Yang Xiaohan
Published: January 2016

Successful synthetic biology efforts rely on conceptual and experimental designs in combination with testing of multi-gene constructs. Despite recent progresses, several limitations still hinder the ability to flexibly assemble and collectively share different types of DNA segments. Here, we describe an advanced system for joining DNA fragments from a universal library that automatically maintains open reading frames (ORFs) and does not require linkers, adaptors, sequence homology, amplification or mutation (domestication) of fragments in order to work properly. This system, which is enhanced by a unique buffer formulation, provides unforeseen capabilities for testing and sharing, complex multi-gene circuitry assembled from different DNA fragments.
SALO, a novel classical pathway complement inhibitor from saliva of the sand fly Lutzomyia longipalpis
Authors: Ferreira Viviana P. , Fazito Vale Vladimir , Pangburn Michael K. , Abdeladhim Maha , Ferreira Mendes-Sousa Antonio , Coutinho-Abreu Iliano V. , Rasouli Manoochehr , Brandt Elizabeth A. , Meneses Claudio , Lima Kolyvan Ferreira , Nascimento Araújo Ricardo , Horácio Pereira Marcos , Kotsyfakis Michalis , Oliveira Fabiano , Kamhawi Shaden , Ribeiro Jose M. C. , Gontijo Nelder F. , Collin Nicolas , Valenzuela Jesus G.
Published: January 2016

Blood-feeding insects inject potent salivary components including complement inhibitors into their host’s skin to acquire a blood meal. Sand fly saliva was shown to inhibit the classical pathway of complement; however, the molecular identity of the inhibitor remains unknown. Here, we identified SALO as the classical pathway complement inhibitor. SALO, an 11 kDa protein, has no homology to proteins of any other organism apart from New World sand flies. rSALO anti-complement activity has the same chromatographic properties as the Lu. longipalpis salivary gland homogenate (SGH)counterparts and anti-rSALO antibodies blocked the classical pathway complement activity of rSALO and SGH. Both rSALO and SGH inhibited C4b deposition and cleavage of C4. rSALO, however, did not inhibit the protease activity of C1s nor the enzymatic activity of factor Xa, uPA, thrombin, kallikrein, trypsin and plasmin. Importantly, rSALO did not inhibit the alternative or the lectin pathway of complement. In conclusion our data shows that SALO is a specific classical pathway complement inhibitor present in the saliva of Lu. longipalpis. Importantly, due to its small size and specificity, SALO may offer a therapeutic alternative for complement classical pathway-mediated pathogenic effects in human diseases.
Liquid-induced colour change in a beetle: the concept of a photonic cell
Authors: Mouchet Sébastien R. , Van Hooijdonk Eloise , Welch Victoria L. , Louette Pierre , Colomer Jean-François , Su Bao-Lian , Deparis Olivier
Published: January 2016

The structural colour of male Hoplia coerulea beetles is notable for changing from blue to green upon contact with water. In fact, reversible changes in both colour and fluorescence are induced in this beetle by various liquids, although the mechanism has never been fully explained. Changes enacted by water are much faster than those by ethanol, in spite of ethanol’s more rapid spread across the elytral surface. Moreover, the beetle’s photonic structure is enclosed by a thin scale envelope preventing direct contact with the liquid. Here, we note the presence of sodium, potassium and calcium salts in the scale material that mediate the penetration of liquid through putative micropores. The result leads to the novel concept of a “photonic cell”: namely, a biocompatible photonic structure that is encased by a permeable envelope which mediates liquid-induced colour changes in that photonic structure. Engineered photonic cells dispersed in culture media could revolutionize the monitoring of cell-metabolism.
A Signaling Lipid Associated with Alzheimer’s Disease Promotes Mitochondrial Dysfunction
Authors: Kennedy Michael A. , Moffat Tia C. , Gable Kenneth , Ganesan Suriakarthiga , Niewola-Staszkowska Karolina , Johnston Anne , Nislow Corey , Giaever Guri , Harris Linda J. , Loewith Robbie , Zaremberg Vanina , Harper Mary-Ellen , Dunn Teresa , Bennett Steffany A. L. , Baetz Kristin
Published: January 2016

Fundamental changes in the composition and distribution of lipids within the brain are believed to contribute to the cognitive decline associated with Alzheimer’s disease (AD). The mechanisms by which these changes in lipid composition affect cellular function and ultimately cognition are not well understood. Although “candidate gene” approaches can provide insight into the effects of dysregulated lipid metabolism they require a preexisting understanding of the molecular targets of individual lipid species. In this report we combine unbiased gene expression profiling with a genome-wide chemogenomic screen to identify the mitochondria as an important downstream target of PC(O-16:0/2:0), a neurotoxic lipid species elevated in AD. Further examination revealed that PC(O-16:0/2:0) similarly promotes a global increase in ceramide accumulation in human neurons which was associated with mitochondrial-derived reactive oxygen species (ROS) and toxicity. These findings suggest that PC(O-16:0/2:0)-dependent mitochondrial dysfunction may be an underlying contributing factor to the ROS production associated with AD.
Parity and All-cause Mortality in Women and Men: A Dose-Response Meta-Analysis of Cohort Studies
Authors: Zeng Yun , Ni Ze-min , Liu Shu-yun , Gu Xue , Huang Qin , Liu Jun-an , Wang Qi
Published: January 2016

To quantitatively assess the association between parity and all-cause mortality, we conducted a meta-analysis of cohort studies. Relevant reports were identified from PubMed and Embase databases. Cohort studies with relative risks (RRs) and 95% confidence intervals (CIs) of all-cause mortality in three or more categories of parity were eligible. Eighteen articles with 2,813,418 participants were included. Results showed that participants with no live birth had higher risk of all-cause mortality (RR= 1.19, 95% CI = 1.03–1.38; I2 = 96.7%, P < 0.001) compared with participants with one or more live births. Nonlinear dose-response association was found between parity and all-cause mortality (P for non-linearity < 0.0001). Our findings suggest that moderate-level parity is inversely associated with all-cause mortality.
High Efficiency Dye-sensitized Solar Cells Constructed with Composites of TiO2 and the Hot-bubbling Synthesized Ultra-Small SnO2 Nanocrystals
Authors: Mao Xiaoli , Zhou Ru , Zhang Shouwei , Ding Liping , Wan Lei , Qin Shengxian , Chen Zhesheng , Xu Jinzhang , Miao Shiding
Published: January 2016

An efficient photo-anode for the dye-sensitized solar cells (DSSCs) should have features of high loading of dye molecules, favorable band alignments and good efficiency in electron transport. Herein, the 3.4 nm-sized SnO2 nanocrystals (NCs) of high crystallinity, synthesized via the hot-bubbling method, were incorporated with the commercial TiO2 (P25) particles to fabricate the photo-anodes. The optimal percentage of the doped SnO2 NCs was found at ~7.5% (SnO2/TiO2, w/w) and the fabricated DSSC delivers a power conversion efficiency up to 6.7%, which is 1.52 times of the P25 based DSSCs. The ultra-small SnO2 NCs offer three benefits, (1) the incorporation of SnO2 NCs enlarges surface areas of the photo-anode films and higher dye-loading amounts were achieved; (2) the high charge mobility provided by SnO2 was confirmed to accelerate the electron transport and the photo-electron recombination was suppressed by the highly-crystallized NCs; (3) the conduction band minimum (CBM) of the SnO2 NCs was uplifted due to the quantum size effects and this was found to alleviate the decrement in the open-circuit voltage. This work highlights great contributions of the SnO2 NCs to the improvement of the photovoltaic performances in the DSSCs.
Bacterial flagellar motility on hydrated rough surfaces controlled by aqueous film thickness and connectedness
Authors: Tecon Robin , Or Dani
Published: January 2016

Recent studies have shown that rates of bacterial dispersion in soils are controlled by hydration conditions that define size and connectivity of the retained aqueous phase. Despite the ecological implications of such constraints, microscale observations of this phenomenon remain scarce. Here, we quantified aqueous film characteristics and bacterial flagellated motility in response to systematic variations in microhydrological conditions on porous ceramic surfaces that mimic unsaturated soils. We directly measured aqueous film thickness and documented its microscale heterogeneity. Flagellar motility was controlled by surface hydration conditions, as cell velocity decreased and dispersion practically ceased at water potentials exceeding –2 kPa (resulting in thinner and disconnected liquid films). The fragmentation of aquatic habitats was delineated indirectly through bacterial dispersal distances within connected aqueous clusters. We documented bacterial dispersal radii ranging from 100 to 10 μm as the water potential varied from 0 to –7 kPa, respectively. The observed decrease of flagellated velocity and dispersal ranges at lower matric potentials were in good agreement with mechanistic model predictions. Hydration-restricted habitats thus play significant role in bacterial motility and dispersal, which has potentially important impact on soil microbial ecology and diversity.
Two-Photon Excitation STED Microscopy with Time-Gated Detection
Authors: Coto Hernández Iván , Castello Marco , Lanzanò Luca , d’Amora Marta , Bianchini Paolo , Diaspro Alberto , Vicidomini Giuseppe
Published: January 2016

We report on a novel two-photon excitation stimulated emission depletion (2PE-STED) microscope based on time-gated detection. The time-gated detection allows for the effective silencing of the fluorophores using moderate stimulated emission beam intensity. This opens the possibility of implementing an efficient 2PE-STED microscope with a stimulated emission beam running in a continuous-wave. The continuous-wave stimulated emission beam tempers the laser architecture’s complexity and cost, but the time-gated detection degrades the signal-to-noise ratio (SNR) and signal-to-background ratio (SBR) of the image. We recover the SNR and the SBR through a multi-image deconvolution algorithm. Indeed, the algorithm simultaneously reassigns early-photons (normally discarded by the time-gated detection) to their original positions and removes the background induced by the stimulated emission beam. We exemplify the benefits of this implementation by imaging sub-cellular structures. Finally, we discuss of the extension of this algorithm to future all-pulsed 2PE-STED implementationd based on time-gated detection and a nanosecond laser source.
An efficient full-length cDNA amplification strategy based on bioinformatics technology and multiplexed PCR methods
Authors: Chen Nan , Wang Wei-Min , Wang Huan-Ling
Published: January 2016

A novel strategy for amplification full-length cDNA and promoter sequences has been developed using bioinformatics technology and multiplexed PCR methods in this study. The amplification of 3′ ends of cDNA is performed according to the modified classic 3′ RACE techniques, therein the more efficient and effective oligo(dT)-anchor primer with hairpin structure is specially designed. For the amplification of 5′ ends of cDNA, two or three-round TAIL-PCR or touch-down PCR using arbitrary degenerate (AD) and sequence-specific reverse (SPR) primers is performed until the 5′ sequence of multi-assembled fragment reaches the exon1 region identified by aligning this fragment to reference genome database. Then another TAIL-PCR or touch-down PCR using genomic DNA as template is conducted to obtain the remaining 5′ and promoter sequences. The 5′ end sites of cDNA are predicted by aligning finally assembled fragment to homologous reference genes of other species and screening the relative locations of common characteristic cis-elements in silico on promoter. The putative 5′ ends are further validated by primers corresponding to these predicted sites in cDNAs. This method is suitable for researchers to isolate limited full-length cDNA sequences due to its operability, inexpensiveness, efficiency and speediness.
Venturing in coral larval chimerism: a compact functional domain with fostered genotypic diversity
Authors: Rinkevich Baruch , Shaish Lee , Douek Jacob , Ben-Shlomo Rachel
Published: January 2016

The globally distributed coral speciesPocillopora damicornisis known to release either sexual or asexual derived planula-larvae in various reef locations. Using microsatellite loci as markers, we documented the release of asexually derived chimeric larvae (CL), originating from mosaicked maternal colonies that were also chimeras, at Thai and Philippines reefs. The CL, each presenting different combinations of maternal genotypic constituents, create genetically-complex sets of asexual propagules. This novel mode of inheritance in corals challenges classical postulations of sexual/asexual reproduction traits, as asexual derived CL represent an alliance between genotypes that significantly sways the recruits’ absolute fitness. This type of inherited chimerism, while enhancing intra-entity genetic heterogeneity, is an evolutionary tactic used to increase genetic-heterogeneity, primarily in new areas colonized by a limited number of larvae. Chimerism may also facilitate combat global change impacts by exhibiting adjustable genomic combinations of within-chimera traits that could withstand alterable environmental pressures, helpingPocilloporabecome a successful cosmopolitan species.
Stochastic expression of a multiple antibiotic resistance activator confers transient resistance in single cells
Authors: El Meouche Imane , Siu Yik , Dunlop Mary J.
Published: January 2016

Transient resistance can allow microorganisms to temporarily survive lethal concentrations of antibiotics. This can be accomplished through stochastic mechanisms, where individual cells within a population display diverse phenotypes to hedge against the appearance of an antibiotic. To date, research on transient stochastic resistance has focused primarily on mechanisms where a subpopulation of cells enters a dormant, drug-tolerant state. However, a fundamental question is whether stochastic gene expression can also generate variable resistance levels among growing cells in a population. We hypothesized that stochastic expression of antibiotic-inducible resistance mechanisms might play such a role. To investigate this, we focused on a prototypical example of such a system: the multiple antibiotic resistance activator MarA. Previous studies have shown that induction of MarA can lead to a multidrug resistant phenotype at the population level. We asked whether MarA expression also has a stochastic component, even when uninduced. Time lapse microscopy showed that isogenic cells express heterogeneous, dynamic levels of MarA, which were correlated with transient antibiotic survival. This finding has important clinical implications, as stochastic expression of resistance genes may be widespread, allowing populations to hedge against the sudden appearance of an antibiotic.
A versatile proximity-dependent probe based on light-up DNA-scaffolded silver nanoclusters
Authors: Ma Jin-Liang , Yin Bin-Cheng , Ye Bang-Ce
Published: January 2016

It is well-known that proximity-dependent probes containing an analyte recognization site and a signal formation domain could be assembled specifically into a sandwich-like structure (probe–analyte–probe) via introducing an analyte.
Determination of volatile compounds in rose-water and fruit juices using indirectly suspended droplet microextraction of water-miscible organic solvents by the salting-out effect
Authors: Babaee Shirin , Daneshfar Ali
Published: January 2016

In this work, extraction of volatile compounds (α-pinene, limonene, linalool, borneol, 2-phenylethanol, thymol and decanoic acid) in rose-water and fruit juices was followed using indirectly suspended droplet microextraction (ISDME).
Simultaneous temperature-assisted dispersive liquid–liquid microextraction of cobalt, copper, nickel and zinc ions from high-volume water samples and determination by graphite furnace atomic absorption spectrometry
Authors: Sorouraddin Saeed Mohammad , Nouri Saeed
Published: January 2016

A rapid, efficient, and reliable sample preparation method based on temperature-assisted dispersive liquid–liquid microextraction was developed for simultaneous extraction of cobalt, copper, nickel, and zinc ions at a low level from high volume water samples.
Covalent triazine framework-supported palladium as a ligand-free catalyst for the selective double carbonylation of aryl iodides under ambient pressure of CO
Authors: Wang Zhifang , Liu Cuibo , Huang Yi , Hu Yuchen , Zhang Bin
Published: January 2016

Carbonylation of aryl iodides with amines under atmospheric pressure of CO, catalyzed by Pd/CTFs (covalent triazine frameworks) without any specific additives, leads to the highly selective synthesis of α-ketoamides.
Effect of band structure on the hot-electron transfer over Au photosensitized brookite TiO2
Authors: Zhao Ming , Xu Hua , Ouyang Shuxin , Li Dewang , Meng Xianguang , Ye Jinhua
Published: January 2016

Taking brookite TiO2 with controlled band structure as example, it reveals that the accumulation of electrons will negatively shift the EF of Au caused by the intense light excitation, thus the effect of Schottky barrier will weaken and TiO2 with more negative reduction potential will exhibit higher activity.