bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-culture coevolution promotes rapid divergence of killer whale ecotypes
Authors: Foote Andrew D. , Vijay Nagarjun , Ávila-Arcos María C. , Baird Robin W. , Durban John W. , Fumagalli Matteo , Gibbs Richard A. , Hanson M. Bradley , Korneliussen Thorfinn S. , Martin Michael D. , Robertson Kelly M. , Sousa Vitor C. , Vieira Filipe G. , Vinař Tomáš , Wade Paul , Worley Kim C. , Excoffier Laurent , Morin Phillip A. , Gilbert M. Thomas P. , Wolf Jochen B.W.
Published: May 2016

Analysing population genomic data from killer whale ecotypes, which we estimate have globally radiated within less than 250,000 years, we show that genetic structuring including the segregation of potentially functional alleles is associated with socially inherited ecological niche. Reconstruction of ancestral demographic history revealed bottlenecks during founder events, likely promoting ecological divergence and genetic drift resulting in a wide range of genome-wide differentiation between pairs of allopatric and sympatric ecotypes. Functional enrichment analyses provided evidence for regional genomic divergence associated with habitat, dietary preferences and post-zygotic reproductive isolation. Our findings are consistent with expansion of small founder groups into novel niches by an initial plastic behavioural response, perpetuated by social learning imposing an altered natural selection regime. The study constitutes an important step towards an understanding of the complex interaction between demographic history, culture, ecological adaptation and evolution at the genomic level.
Correction: Corrigendum: Detection of DNA viruses in prostate cancer
Authors: Smelov Vitaly , Bzhalava Davit , Mühr Laila Sara Arroyo , Eklund Carina , Komyakov Boris , Gorelov Andrey , Dillner Joakim , Hultin Emilie
Published: May 2016

Scientific Reports 6: Article number: 25235; published online: 28 April 2016; updated: 31 May 2016 In the original version of this Article, Affiliations 1 and 2 were not listed in the correct order. The correct affiliations are listed below: Affiliation 1 Karolinska Institutet, Department of Laboratory Medicine, Stockholm, 141 86, Sweden.
Correction: Corrigendum: Spin-orbit coupling enhanced superconductivity in Bi-rich compounds ABi3 (A = Sr and Ba)
Authors: Shao D. F. , Luo X. , Lu W. J. , Hu L. , Zhu X. D. , Song W. H. , Zhu X. B. , Sun Y. P.
Published: May 2016

Scientific Reports 6: Article number: 21484; published online: 19 February 2016; updated: 31 May 2016 In this Article, some instances of ‘(A = Sr and Ba)’ are incorrectly written as ‘(A = Sr and Bi)’.
Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence
Authors: Flynn Padrig B. , Busetti Alessandro , Wielogorska Ewa , Chevallier Olivier P. , Elliott Christopher T. , Laverty Garry , Gorman Sean P. , Graham William G. , Gilmore Brendan F.
Published: May 2016

The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30–60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa.
Exogenous NAD+ decreases oxidative stress and protects H2O2-treated RPE cells against necrotic death through the up-regulation of autophagy
Authors: Zhu Ying , Zhao Ke-ke , Tong Yao , Zhou Ya-li , Wang Yi-xiao , Zhao Pei-quan , Wang Zhao-yang
Published: May 2016

Increased oxidative stress, which can lead to the retinal pigment epithelium (RPE) cell death by inducing ATP depletion and DNA repair, is believed to be a prominent pathology in age-related macular degeneration (AMD). In the present study, we showed that and 0.1 mM nicotinamide adenine dinucleotide (NAD+) administration significantly blocked RPE cell death induced by 300 μM H2O2. Further investigation showed that H2O2 resulted in increased intracellular ROS level, activation of PARP-1 and subsequently necrotic death of RPE cells. Exogenous NAD+ administration significantly decreased intracellular and intranuclear ROS levels in H2O2-treated RPE cells. In addition, NAD+ administration to H2O2-treated RPE cells inhibited the activation of PARP-1 and protected the RPE cells against necrotic death. Moreover, exogenous NAD+ administration up-regulated autophagy in the H2O2-treated RPE cells. Inhibition of autophagy by LY294002 blocked the decrease of intracellular and intranuclear ROS level. Besides, inhibition of autophagy by LY294002 abolished the protection of exogenous NAD+ against H2O2-induced cell necrotic death. Taken together, our findings indicate that that exogenous NAD+ administration suppresses H2O2-induced oxidative stress and protects RPE cells against PARP-1 mediated necrotic death through the up-regulation of autophagy. The results suggest that exogenous NAD+ administration might be potential value for the treatment of AMD.
Soil fungal community development in a high Arctic glacier foreland follows a directional replacement model, with a mid-successional diversity maximum
Authors: Dong Ke , Tripathi Binu , Moroenyane Itumeleng , Kim Woosung , Li Nan , Chu Haiyan , Adams Jonathan
Published: May 2016

Directional replacement and directional non-replacement models are two alternative paradigms for community development in primary successional environments. The first model emphasizes turnover in species between early and late successional niches. The second emphasizes accumulation of additional diversity over time. To test whether the development of soil fungal communities in the foreland of an Arctic glacier conforms to either of these models, we collected samples from the Midtre Lovénbreen Glacier, Svalbard, along a soil successional series spanning >80 years. Soil DNA was extracted, and fungal ITS1 region was amplified and sequenced on an Illumina Miseq. There was a progressive change in community composition in the soil fungal community, with greatest fungal OTU richness in the Mid Stage (50–80 years). A nestedness analysis showed that the Early Stage (20–50 years) and the Late Stage (>80 years) fungal communities were nested within the Mid Stage communities. These results imply that fungal community development in this glacier succession follows a directional replacement model. Soil development processes may initially be important in facilitating arrival of additional fungal species, to give a mid-successional diversity maximum that contains both early- and late-successional fungi. Competition may then decrease the overall diversity due to the loss of early successional species.
Correction: Corrigendum: Computational Approach Towards Exploring Potential Anti-Chikungunya Activity of Selected Flavonoids
Authors: Seyedi Seyedeh Somayeh , Shukri Munirah , Hassandarvish Pouya , Oo Adrian , Shankar Esaki Muthu , Abubakar Sazaly , Zandi Keivan
Published: May 2016

Scientific Reports 6: Article number: 24027; published online: 13 April 2016; updated: 31 May 2016 The original version of this Article contained an error in the spelling of the author Esaki Muthu Shankar, which was incorrectly given as Shankar Esaki Muthu. This has now been corrected in the PDF andHTML versions of the Article.
Metagenomic sequencing reveals the relationship between microbiota composition and quality of Chinese Rice Wine
Authors: Hong Xutao , Chen Jing , Liu Lin , Wu Huan , Tan Haiqin , Xie Guangfa , Xu Qian , Zou Huijun , Yu Wenjing , Wang Lan , Qin Nan
Published: May 2016

Chinese Rice Wine (CRW) is a common alcoholic beverage in China. To investigate the influence of microbial composition on the quality of CRW, high throughput sequencing was performed for 110 wine samples on bacterial 16S rRNA gene and fungal Internal Transcribed Spacer II (ITS2). Bioinformatic analyses demonstrated that the quality of yeast starter and final wine correlated with microbial taxonomic composition, which was exemplified by our finding that wine spoilage resulted from a high proportion of genusLactobacillus. Subsequently, based onLactobacillusabundance of an early stage, a model was constructed to predict final wine quality. In addition, three batches of 20 representative wine samples selected from a pool of 110 samples were further analyzed in metagenomics. The results revealed that wine spoilage was due to rapid growth ofLactobacillus brevisat the early stage of fermentation. Gene functional analysis indicated the importance of some pathways such as synthesis of biotin, malolactic fermentation and production of short-chain fatty acid. These results led to a conclusion that metabolisms of microbes influence the wine quality. Thus, nurturing of beneficial microbes and inhibition of undesired ones are both important for the mechanized brewery.
Bioengineered kidney tubules efficiently excrete uremic toxins
Authors: Jansen J. , Fedecostante M. , Wilmer M. J. , Peters J. G. , Kreuser U. M. , van den Broek P. H. , Mensink R. A. , Boltje T. J. , Stamatialis D. , Wetzels J. F. , van den Heuvel L. P. , Hoenderop J. G. , Masereeuw R.
Published: May 2016

The development of a biotechnological platform for the removal of waste products (e.g. uremic toxins), often bound to proteins in plasma, is a prerequisite to improve current treatment modalities for patients suffering from end stage renal disease (ESRD). Here, we present a newly designed bioengineered renal tubule capable of active uremic toxin secretion through the concerted action of essential renal transporters, viz. organic anion transporter-1 (OAT1), breast cancer resistance protein (BCRP) and multidrug resistance protein-4 (MRP4). Three-dimensional cell monolayer formation of human conditionally immortalized proximal tubule epithelial cells (ciPTEC) on biofunctionalized hollow fibers with maintained barrier function was demonstrated. Using a tailor made flow system, the secretory clearance of human serum albumin-bound uremic toxins, indoxyl sulfate and kynurenic acid, as well as albumin reabsorption across the renal tubule was confirmed. These functional bioengineered renal tubules are promising entities in renal replacement therapies and regenerative medicine, as well as in drug development programs.
Pcdh19 Loss-of-Function Increases Neuronal Migration In Vitro but is Dispensable for Brain Development in Mice
Authors: Pederick Daniel T. , Homan Claire C. , Jaehne Emily J. , Piltz Sandra G. , Haines Bryan P. , Baune Bernhard T. , Jolly Lachlan A. , Hughes James N. , Gecz Jozef , Thomas Paul Q.
Published: May 2016

Protocadherin 19 (Pcdh19) is an X-linked gene belonging to the protocadherin superfamily, whose members are predominantly expressed in the central nervous system and have been implicated in cell-cell adhesion, axon guidance and dendrite self-avoidance. Heterozygous loss-of-function mutations in humans result in the childhood epilepsy disorder PCDH19 Girls Clustering Epilepsy (PCDH19 GCE) indicating that PCDH19 is required for brain development. However, understanding PCDH19 function in vivo has proven challenging and has not been studied in mammalian models. Here, we validate a murine Pcdh19 null allele in which a β-Geo reporter cassette is expressed under the control of the endogenous promoter. Analysis of β-Geo reporter activity revealed widespread but restricted expression of PCDH19 in embryonic, postnatal and adult brains. No gross morphological defects were identified in Pcdh19+/β-Geo and Pcdh19Y/β-Geo brains and the location of Pcdh19 null cells was normal. However, in vitro migration assays revealed that the motility of Pcdh19 null neurons was significantly elevated, potentially contributing to pathogenesis in patients with PCDH19 mutations. Overall our initial characterization of Pcdh19+/β-Geo, Pcdh19β-Geo/β-Geo and Pcdh19Y/β-Geomice reveals that despite widespread expression of Pcdh19 in the CNS and its role in human epilepsy, its function in mice is not essential for brain development.
Analysis of the dynamic co-expression network of heart regeneration in the zebrafish
Authors: Rodius Sophie , Fournier Anna , Götz Lou , Liechti Robin , Crespo Isaac , Merz Susanne , Nazarov Petr V. , de Klein Niek , Jeanty Céline , González-Rosa Juan M. , Muller Arnaud , Bernardin Francois , Niclou Simone P. , Vallar Laurent , Mercader Nadia , Ibberson Mark , Xenarios Ioannis , Azuaje Francisco
Published: May 2016

The zebrafish has the capacity to regenerate its heart after severe injury. While the function of a few genes during this process has been studied, we are far from fully understanding how genes interact to coordinate heart regeneration. To enable systematic insights into this phenomenon, we generated and integrated a dynamic co-expression network of heart regeneration in the zebrafish and linked systems-level properties to the underlying molecular events. Across multiple post-injury time points, the network displays topological attributes of biological relevance. We show that regeneration steps are mediated by modules of transcriptionally coordinated genes, and by genes acting as network hubs. We also established direct associations between hubs and validated drivers of heart regeneration with murine and human orthologs. The resulting models and interactive analysis tools are available at http://infused.vital-it.ch. Using a worked example, we demonstrate the usefulness of this unique open resource for hypothesis generation and in silico screening for genes involved in heart regeneration.
Lanthanum induced B-to-Z transition in self-assembled Y-shaped branched DNA structure
Authors: Nayak Ashok K. , Mishra Aseem , Jena Bhabani S. , Mishra Barada K. , Subudhi Umakanta
Published: May 2016

Controlled conversion of right-handed B-DNA to left-handed Z-DNA is one of the greatest conformational transitions in biology. Recently, the B-Z transition has been explored from nanotechnological points of view and used as the driving machinery of many nanomechanical devices. Using a combination of CD spectroscopy, fluorescence spectroscopy and PAGE, we demonstrate that low concentration of lanthanum chloride can mediate B-to-Z transition in self-assembled Y-shaped branched DNA (bDNA) structure. The transition is sensitive to the sequence and structure of the bDNA. Thermal melting and competitive dye binding experiments suggest that La3+ ions are loaded to the major and minor grooves of DNA and stabilize the Z-conformation. Our studies also show that EDTA and EtBr play an active role in reversing the transition from Z-to-B DNA.
GC Preps: Fast and Easy Extraction of Stable Yeast Genomic DNA
Authors: Blount Benjamin A. , Driessen Maureen R. M. , Ellis Tom
Published: May 2016

Existing yeast genomic DNA extraction methods are not ideally suited to extensive screening of colonies by PCR, due to being too lengthy, too laborious or yielding poor quality DNA and inconsistent results. We developed the GC prep method as a solution to this problem. Yeast cells from colonies or liquid cultures are lysed by vortex mixing with glass beads and then boiled in the presence of a metal chelating resin. In around 12 minutes, multiple samples can be processed to extract high yields of genomic DNA. These preparations perform as effectively in PCR screening as DNA purified by organic solvent methods, are stable for up to 1 year at room temperature and can be used as the template for PCR amplification of fragments of at least 8 kb.
Spartina alterniflora invasion alters soil microbial community composition and microbial respiration following invasion chronosequence in a coastal wetland of China
Authors: Yang Wen , Jeelani Nasreen , Leng Xin , Cheng Xiaoli , An Shuqing
Published: May 2016

The role of exotic plants in regulating soil microbial community structure and activity following invasion chronosequence remains unclear. We investigated soil microbial community structure and microbial respiration following Spartina alterniflora invasion in a chronosequence of 6-, 10-, 17-, and 20-year-old by comparing with bare flat in a coastal wetland of China. S. alterniflora invasion significantly increased soil moisture and salinity, the concentrations of soil water-soluble organic carbon and microbial biomass carbon (MBC), the quantities of total and various types of phospholipid fatty acids (PLFAs), the fungal:bacterial PLFAs ratio and cumulative microbial respiration compared with bare flat. The highest MBC, gram-negative bacterial and saturated straight-chain PLFAs were found in 10-year-old S. alterniflora soil, while the greatest total PLFAs, bacterial and gram-positive bacterial PLFAs were found in 10- and 17-year-old S. alterniflora soils. The monounsaturated:branched PLFAs ratio declined, and cumulative microbial respiration on a per-unit-PLFAs increased following S. alterniflora invasion in the chronosequence. Our results suggest that S. alterniflora invasion significantly increased the biomass of soil various microbial groups and microbial respiration compared to bare flat soil by increasing soil available substrate, and modifying soil physiochemical properties. Soil microbial community reached the most enriched condition in the 10-year-old S. alterniflora community.
Assessment of polygenic effects links primary open-angle glaucoma and age-related macular degeneration
Authors: Cuellar-Partida Gabriel , Craig Jamie E. , Burdon Kathryn P. , Wang Jie Jin , Vote Brendan J. , Souzeau Emmanuelle , McAllister Ian L. , Isaacs Timothy , Lake Stewart , Mackey David A. , Constable Ian J. , Mitchell Paul , Hewitt Alex W. , MacGregor Stuart
Published: May 2016

Primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD) are leading causes of irreversible blindness. Several loci have been mapped using genome-wide association studies. Until very recently, there was no recognized overlap in the genetic contribution to AMD and POAG. At genome-wide significance level, only ABCA1 harbors associations to both diseases. Here, we investigated the genetic architecture of POAG and AMD using genome-wide array data. We estimated the heritability for POAG (h2g = 0.42 ± 0.09) and AMD (h2g = 0.71 ± 0.08). Removing known loci for POAG and AMD decreased the h2g estimates to 0.36 and 0.24, respectively. There was evidence for a positive genetic correlation between POAG and AMD (rg = 0.47 ± 0.25) which remained after removing known loci (rg = 0.64 ± 0.31). We also found that the genetic correlation between sexes for POAG was likely to be less than 1 (rg = 0.33 ± 0.24), suggesting that differences of prevalence among genders may be partly due to heritable factors.
Correction: Corrigendum: Integration of CdSe/CdSexTe1−x Type-II Heterojunction Nanorods into Hierarchically Porous TiO2 Electrode for Efficient Solar Energy Conversion
Authors: Lee Sangheon , Flanagan Joseph C. , Kang Joonhyeon , Kim Jinhyun , Shim Moonsub , Park Byungwoo
Published: May 2016

Scientific Reports 5: Article number: 17472; published online: 07 December 2015; updated: 31 May 2016 This Article contained errors. In the Abstract, “Additional ~32% enhancement in power conversion efficiency is achieved by introducing percolation channels of large pores in the mesoporous TiO2 electrode, which allow 1-D sensitizers to infiltrate the entire depth of electrode.
Fatty acid profile in the seeds and seed tissues of Paeonia L. species as new oil plant resources
Authors: Yu Shuiyan , Du Shaobo , Yuan Junhui , Hu Yonghong
Published: May 2016

Most common plant oils have little α-linolenic acid (C18:3Δ9,12,15, ALA) and an unhealthy ω6/ω3 ratio. Here, fatty acids (FAs) in the seeds of 11 species of Paeonia L., including 10 tree peony and one herbaceous species, were explored using gas chromatograph–mass spectrometer. Results indicated that all Paeonia had a ω6/ω3 ratio less than 1.0, and high amounts of ALA (26.7–50%), oleic acid (C18:1Δ9, OA) (20.8–46%) and linoleic acid (C18:2Δ9,12, LA) (10–38%). ALA was a dominant component in oils of seven subsection Vaginatae species, whereas OA was predominant in two subsection Delavayanae species. LA was a subdominant oil component in P. ostii and P. obovata. Moreover, the FA composition and distribution of embryo (22 FAs), endosperm (14 FAs) and seed coat (6 FAs) in P. ostii, P. rockii and P. ludlowii were first reported. Peony species, particularly P. decomposita and P. rockii, can be excellent plant resources for edible oil because they provide abundant ALA to balance the ω6/ω3 ratio. The differences in the ALA, LA and OA content proportion also make the peony species a good system for detailed investigation of FA biosynthesis pathway and ALA accumulation.
A Broadband THz-TDS System Based on DSTMS Emitter and LTG InGaAs/InAlAs Photoconductive Antenna Detector
Authors: Zhang Ying , Zhang Xiaoling , Li Shaoxian , Gu Jianqiang , Li Yanfeng , Tian Zhen , Ouyang Chunmei , He Mingxia , Han Jiaguang , Zhang Weili
Published: May 2016

We demonstrate a 4-f terahertz time-domain spectroscopy (THz-TDS) system using an organic crystal DSTMS as the THz emitter and a low temperature grown (LTG) InGaAs/InAlAs photoconductive antenna as the receiver. The system covers a frequency range from 0.2 up to 8 THz. The influences of the pump laser power, the probe laser power and the azimuthal angle of the DSTMS crystal on the time-domain THz amplitude are experimentally analyzed. The frequency accuracy of the system is verified by measuring two metamaterial samples and a lactose film in this THz-TDS system. The proposed combination of DSTMS emission and PC antenna detection realizes a compact and low-cost THz-TDS scheme with an ultra-broad bandwidth, which may promote the development and the applications of THz-TDS techniques.
A Phytophthora sojae effector PsCRN63 forms homo-/hetero-dimers to suppress plant immunity via an inverted association manner
Authors: Li Qi , Zhang Meixiang , Shen Danyu , Liu Tingli , Chen Yanyu , Zhou Jian-Min , Dou Daolong
Published: May 2016

Oomycete pathogens produce a large number of effectors to promote infection. Their mode of action are largely unknown. Here we show that a Phytophthora sojae effector, PsCRN63, suppresses flg22-induced expression of FRK1 gene, a molecular marker in pathogen-associated molecular patterns (PAMP)-triggered immunity (PTI). However, PsCRN63 does not suppress upstream signaling events including flg22-induced MAPK activation and BIK1 phosphorylation, indicating that it acts downstream of MAPK cascades. The PsCRN63-transgenic Arabidopsis plants showed increased susceptibility to bacterial pathogen Pseudomonas syringae pathovar tomato (Pst) DC3000 and oomycete pathogen Phytophthora capsici. The callose deposition were suppressed in PsCRN63-transgenic plants compared with the wild-type control plants. Genes involved in PTI were also down-regulated in PsCRN63-transgenic plants. Interestingly, we found that PsCRN63 forms an dimer that is mediated by inter-molecular interactions between N-terminal and C-terminal domains in an inverted association manner. Furthermore, the N-terminal and C-terminal domains required for the dimerization are widely conserved among CRN effectors, suggesting that homo-/hetero-dimerization of Phytophthora CRN effectors is required to exert biological functions. Indeed, the dimerization was required for PTI suppression and cell death-induction activities of PsCRN63.
Climatic change controls productivity variation in global grasslands
Authors: Gao Qingzhu , Zhu Wenquan , Schwartz Mark W. , Ganjurjav Hasbagan , Wan Yunfan , Qin Xiaobo , Ma Xin , Williamson Matthew A. , Li Yue
Published: May 2016

Detection and identification of the impacts of climate change on ecosystems have been core issues in climate change research in recent years. In this study, we compared average annual values of the normalized difference vegetation index (NDVI) with theoretical net primary productivity (NPP) values based on temperature and precipitation to determine the effect of historic climate change on global grassland productivity from 1982 to 2011. Comparison of trends in actual productivity (NDVI) with climate-induced potential productivity showed that the trends in average productivity in nearly 40% of global grassland areas have been significantly affected by climate change. The contribution of climate change to variability in grassland productivity was 15.2–71.2% during 1982–2011. Climate change contributed significantly to long-term trends in grassland productivity mainly in North America, central Eurasia, central Africa, and Oceania; these regions will be more sensitive to future climate change impacts. The impacts of climate change on variability in grassland productivity were greater in the Western Hemisphere than the Eastern Hemisphere. Confirmation of the observed trends requires long-term controlled experiments and multi-model ensembles to reduce uncertainties and explain mechanisms.
Dietary, circulating beta-carotene and risk of all-cause mortality: a meta-analysis from prospective studies
Authors: Zhao Long-Gang , Zhang Qing-Li , Zheng Jia-Li , Li Hong-Lan , Zhang Wei , Tang Wei-Guo , Xiang Yong-Bing
Published: May 2016

Observational studies evaluating the relation between dietary or circulating level of beta-carotene and risk of total mortality yielded inconsistent results. We conducted a comprehensive search on publications of PubMed and EMBASE up to 31 March 2016. Random effect models were used to combine the results. Potential publication bias was assessed using Egger’s and Begg’s test. Seven studies that evaluated dietary beta-carotene intake in relation to overall mortality, indicated that a higher intake of beta-carotene was related to a significant lower risk of all-cause mortality (RR for highest vs. lowest group = 0.83, 95%CI: 0.78–0.88) with no evidence of heterogeneity between studies (I2 = 1.0%, P = 0.416). A random-effect analysis comprising seven studies showed high beta-carotene level in serum or plasma was associated with a significant lower risk of all-cause mortality (RR for highest vs. lowest group = 0.69, 95%CI: 0.59–0.80) with low heterogeneity (I2 = 37.1%, P = 0.145). No evidence of publication bias was detected by Begg’s and Egger’s regression tests. In conclusion, dietary or circulating beta-carotene was inversely associated with risk of all-cause mortality. More studies should be conducted to clarify the dose-response relationship between beta-carotene and all-cause mortality.
ALG-2 interacting protein-X (Alix) is essential for clathrin-independent endocytosis and signaling
Authors: Mercier Vincent , Laporte Marine H. , Destaing Olivier , Blot Béatrice , Blouin Cédric M. , Pernet-Gallay Karin , Chatellard Christine , Saoudi Yasmina , Albiges-Rizo Corinne , Lamaze Christophe , Fraboulet Sandrine , Petiot Anne , Sadoul Rémy
Published: May 2016

The molecular mechanisms and the biological functions of clathrin independent endocytosis (CIE) remain largely elusive. Alix (ALG-2 interacting protein X), has been assigned roles in membrane deformation and fission both in endosomes and at the plasma membrane. Using Alix ko cells, we show for the first time that Alix regulates fluid phase endocytosis and internalization of cargoes entering cells via CIE, but has no apparent effect on clathrin mediated endocytosis or downstream endosomal trafficking. We show that Alix acts with endophilin-A to promote CIE of cholera toxin and to regulate cell migration. We also found that Alix is required for fast endocytosis and downstream signaling of the interleukin-2 receptor giving a first indication that CIE is necessary for activation of at least some surface receptors. In addition to characterizing a new function for Alix, our results highlight Alix ko cells as a unique tool to unravel the biological consequences of CIE.
The molecular, temporal and region-specific requirements of the beta isoform of Calcium/Calmodulin-dependent protein kinase type 2 (CAMK2B) in mouse locomotion
Authors: Kool Martijn J. , van de Bree Jolet E. , Bodde Hanna E. , Elgersma Ype , van Woerden Geeske M.
Published: May 2016

Genetic approaches using temporal and brain region-specific restricted gene deletions have provided a wealth of insight in the brain regions and temporal aspects underlying spatial and associative learning. However, for locomotion such extensive studies are still scarce. Previous studies demonstrated that Camk2b–/– mice, which lack the β isoform of Calcium/Calmodulin-dependent protein kinase 2 (CAMK2B), show very severe locomotion deficits. However, where these locomotion deficits originate is unknown. Here we made use of novel Camk2b mutants (Camk2bf/f and Camk2bT287A), to explore the molecular, temporal and brain region-specific requirements of CAMK2B for locomotion. At the molecular level we found that normal locomotion requires Calcium/Calmodulin mediated activation of CAMK2B, but CAMK2B autonomous activity is largely dispensable. At a systems level, we found that global deletion of Camk2b in the adult mouse causes only mild locomotion deficits, suggesting that the severe locomotion deficits of Camk2b–/– mice are largely of developmental origin. However, early onset deletion of Camk2b in cerebellum, striatum or forebrain did not recapitulate the locomotion deficits, suggesting that these deficits cannot be attributed to a single brain area. Taken together, these results provide the first insights into the molecular, temporal and region-specific role of CAMK2B in locomotion.
Aerobic Exercise and Pharmacological Treatments Counteract Cachexia by Modulating Autophagy in Colon Cancer
Authors: Pigna Eva , Berardi Emanuele , Aulino Paola , Rizzuto Emanuele , Zampieri Sandra , Carraro Ugo , Kern Helmut , Merigliano Stefano , Gruppo Mario , Mericskay Mathias , Li Zhenlin , Rocchi Marco , Barone Rosario , Macaluso Filippo , Di Felice Valentina , Adamo Sergio , Coletti Dario , Moresi Viviana
Published: May 2016

Recent studies have correlated physical activity with a better prognosis in cachectic patients, although the underlying mechanisms are not yet understood. In order to identify the pathways involved in the physical activity-mediated rescue of skeletal muscle mass and function, we investigated the effects of voluntary exercise on cachexia in colon carcinoma (C26)-bearing mice. Voluntary exercise prevented loss of muscle mass and function, ultimately increasing survival of C26-bearing mice. We found that the autophagic flux is overloaded in skeletal muscle of both colon carcinoma murine models and patients, but not in running C26-bearing mice, thus suggesting that exercise may release the autophagic flux and ultimately rescue muscle homeostasis. Treatment of C26-bearing mice with either AICAR or rapamycin, two drugs that trigger the autophagic flux, also rescued muscle mass and prevented atrogene induction. Similar effects were reproduced on myotubesin vitro, which displayed atrophy following exposure to C26-conditioned medium, a phenomenon that was rescued by AICAR or rapamycin treatment and relies on autophagosome-lysosome fusion (inhibited by chloroquine). Since AICAR, rapamycin and exercise equally affect the autophagic system and counteract cachexia, we believe autophagy-triggering drugs may be exploited to treat cachexia in conditions in which exercise cannot be prescribed.
Changing ideas about others’ intentions: updating prior expectations tunes activity in the human motor system
Authors: Jacquet Pierre O. , Roy Alice C. , Chambon Valérian , Borghi Anna M. , Salemme Roméo , Farnè Alessandro , Reilly Karen T.
Published: May 2016

Predicting intentions from observing another agent’s behaviours is often thought to depend on motor resonance – i.e., the motor system’s response to a perceived movement by the activation of its stored motor counterpart, but observers might also rely on prior expectations, especially when actions take place in perceptually uncertain situations. Here we assessed motor resonance during an action prediction task using transcranial magnetic stimulation to probe corticospinal excitability (CSE) and report that experimentally-induced updates in observers’ prior expectations modulate CSE when predictions are made under situations of perceptual uncertainty. We show that prior expectations are updated on the basis of both biomechanical and probabilistic prior information and that the magnitude of the CSE modulation observed across participants is explained by the magnitude of change in their prior expectations. These findings provide the first evidence that when observers predict others’ intentions, motor resonance mechanisms adapt to changes in their prior expectations. We propose that this adaptive adjustment might reflect a regulatory control mechanism that shares some similarities with that observed during action selection. Such a mechanism could help arbitrate the competition between biomechanical and probabilistic prior information when appropriate for prediction.
Regulating the effects of GPR21, a novel target for type 2 diabetes
Authors: Leonard Siobhán , Kinsella Gemma K. , Benetti Elisa , Findlay John B. C.
Published: May 2016

Type 2 diabetes is a chronic metabolic disorder primarily caused by insulin resistance to which obesity is a major contributor. Expression levels of an orphan G protein-coupled receptor (GPCR), GPR21, demonstrated a trend towards a significant increase in the epididymal fat pads of wild type high fat high sugar (HFHS)-fed mice. To gain further insight into the potential role this novel target may play in the development of obesity-associated type 2 diabetes, the signalling capabilities of the receptor were investigated. Overexpression studies in HEK293T cells revealed GPR21 to be a constitutively active receptor, which couples to Gαq type G proteins leading to the activation of mitogen activated protein kinases (MAPKs). Overexpression of GPR21 in vitro also markedly attenuated insulin signalling. Interestingly, the effect of GPR21 on the MAPKs and insulin signalling was reduced in the presence of serum, inferring the possibility of a native inhibitory ligand. Homology modelling and ligand docking studies led to the identification of a novel compound that inhibited GPR21 activity. Its effects offer potential as an anti-diabetic pharmacological strategy as it was found to counteract the influence of GPR21 on the insulin signalling pathway.
Transcriptome Signatures Reveal Rapid Induction of Immune-Responsive Genes in Human Memory CD8+ T Cells
Authors: Yang Cheng , Khanniche Asma , DiSpirito Joanna R. , Ji Ping , Wang Shujun , Wang Ying , Shen Hao
Published: May 2016

Memory T cells (TM) play a prominent role in protection and auto-immunity due to their ability to mount a more effective response than naïve T cells (TN). However, the molecular mechanisms underlying enhanced functionality of TM are not well defined, particularly in human TM. We examined the global gene expression profiles of human CD8+ TN and TM before and after stimulation. There were 1,284, 1,373 and 1,629 differentially expressed genes between TN and TM at 0 hr, 4 hr and 24 hr after stimulation, respectively, with more genes expressed to higher levels in TM. Genes rapidly up-regulated in TN cells were largely involved in nitrogen, nucleoside and amino acid metabolisms. In contrast, those in CD8+ TM were significantly enriched for immune-response-associated processes, including cytokine production, lymphocyte activation and chemotaxis. Multiple cytokines were rapidly up-regulated in TM cells, including effector cytokines known to be produced by CD8+ T cells and important for their functions, as well as regulatory cytokines, both pro- and anti-inflammatory, that are not typically produced by CD8+ T cells. These results provide new insights into molecular mechanisms that contribute to the enhanced functionality of human CD8+ TM and their prominent role in protection and auto-immunity.
Insight into different environmental niches adaptation and allergenicity from the Cladosporium sphaerospermum genome, a common human allergy-eliciting Dothideomycetes
Authors: Yew Su Mei , Chan Chai Ling , Ngeow Yun Fong , Toh Yue Fen , Na Shiang Ling , Lee Kok Wei , Hoh Chee-Choong , Yee Wai-Yan , Ng Kee Peng , Kuan Chee Sian
Published: May 2016

Cladosporium sphaerospermum, a dematiaceous saprophytic fungus commonly found in diverse environments, has been reported to cause allergy and other occasional diseases in humans. However, its basic biology and genetic information are largely unexplored. A clinical isolate C. sphaerospermum genome, UM 843, was re-sequenced and combined with previously generated sequences to form a model 26.89 Mb genome containing 9,652 predicted genes. Functional annotation on predicted genes suggests the ability of this fungus to degrade carbohydrate and protein complexes. Several putative peptidases responsible for lung tissue hydrolysis were identified. These genes shared high similarity with the Aspergillus peptidases. The UM 843 genome encodes a wide array of proteins involved in the biosynthesis of melanin, siderophores, cladosins and survival in high salinity environment. In addition, a total of 28 genes were predicted to be associated with allergy. Orthologous gene analysis together with 22 other Dothideomycetes showed genes uniquely present in UM 843 that encode four class 1 hydrophobins which may be allergens specific to Cladosporium. The mRNA of these hydrophobins were detected by RT-PCR. The genomic analysis of UM 843 contributes to the understanding of the biology and allergenicity of this widely-prevalent species.
Understory herb layer exerts strong controls on soil microbial communities in subtropical plantations
Authors: Yin Kai , Zhang Lei , Chen Dima , Tian Yichen , Zhang Feifei , Wen Meiping , Yuan Chao
Published: May 2016

The patterns and drivers of soil microbial communities in forest plantations remain inadequate although they have been extensively studied in natural forest and grassland ecosystems. In this study, using data from 12 subtropical plantation sites, we found that the overstory tree biomass and tree cover increased with increasing plantation age. However, there was a decline in the aboveground biomass and species richness of the understory herbs as plantation age increased. Biomass of all microbial community groups (i.e. fungi, bacteria, arbuscular mycorrhizal fungi and actinomycete) decreased with increasing plantation age; however, the biomass ratio of fungi to bacteria did not change with increasing plantation age. Variation in most microbial community groups was mainly explained by the understory herb (i.e. herb biomass and herb species richness) and overstory trees (i.e. tree biomass and tree cover), while soils (i.e. soil moisture, soil organic carbon and soil pH) explained a relative low percentage of the variation. Our results demonstrate that the understory herb layer exerts strong controls on soil microbial community in subtropical plantations. These findings suggest that maintenance of plantation health may need to consider the management of understory herb in order to increase the potential of plantation ecosystems as fast-response carbon sinks.
miR-139-5p Inhibits the Epithelial-Mesenchymal Transition and Enhances the Chemotherapeutic Sensitivity of Colorectal Cancer Cells by Downregulating BCL2
Authors: Li Qingguo , Liang Xin , Wang Yuwei , Meng Xianke , Xu Ye , Cai Sanjun , Wang Zhimin , Liu Jianwen , Cai Guoxiang
Published: May 2016

MicroRNAs (miRNAs) are important regulators involved in various cancers, including colorectal cancer (CRC). The functions and mechanisms of the miRNAs involved in CRC progress and metastasis are largely unknown. In this study, miRNA microarray analysis was performed to screen crucial miRNAs involved in CRC progress and miR-139-5p was chosen for further study. The functional roles of miR-139-5p in colon cancer were demonstrated by CCK-8 proliferation assay, cell invasion and migration, cell apoptosis and in a KO mouse study. miR-139-5p expression was significantly decreased in cancer tissues compared to normal tissues. The miR-139-5p expression level was associated with tumour stage (P < 0.01). Function studies revealed that miR-139-5p was significantly correlated with the metastasis potential and drug resistance of colon cancer cells by affecting the epithelial-mesenchymal transition (EMT). Then, we identified BCL2 as a direct target of miR-139-5p cells in vitro. The patient samples and KO mice model showed that BCL2 expression was inversely correlated with the expression of miR-139-5p. In conclusion, we found that miR-139-5p targeted the BCL2 pathway to reduce tumour metastasis and drug sensitivity in CRC. This axis provided insight into the mechanism underlying miRNA regulation of CRC metastasis and a novel therapeutic target for CRC therapy.
Decreased sensitivity to paroxetine-induced inhibition of peripheral blood mononuclear cell growth in depressed and antidepressant treatment-resistant patients
Authors: Rzezniczek S , Obuchowicz M , Datka W , Siwek M , Dudek D , Kmiotek K , Oved K , Shomron N , Gurwitz D , Pilc A
Published: May 2016

Major depression disorder (MDD) is the most widespread mental disorder. Selective serotonin reuptake inhibitors (SSRIs) are used as first-line MDD treatment but are effective in <70% of patients. Thus, biomarkers for the early identification of treatment-resistant (TR) MDD patients are needed for prioritizing them for alternative therapeutics. SSRI-induced inhibition of the growth of peripheral blood mononuclear cells (PBMCs) is mediated via their target, the serotonin transporter (SERT). Here, we examined whether antidepressant drug-induced inhibition of the growth of PBMCs differed between MDD patients and healthy controls. PBMCs from well-characterized 33 treatment-sensitive (TS) and 33 TR MDD patients, and 24 healthy volunteers were studied. Dose-dependent inhibition of PBMCs growth was observed for both the non-SSRI antidepressant mirtazapine and the SSRI antidepressant paroxetine. Significantly lower sensitivities to 20 μmparoxetine were observed in MDD compared with control PBMCs prior to treatment onset (13% and 46%, respectively;P<0.05). Following antidepressant drug treatment for 4 or 7 weeks, theex vivoparoxetine sensitivity increased to control levels in PBMCs from TS but not from TR MDD patients. This suggests that the lowex vivoparoxetine sensitivity phenotype reflects a state marker of depression. A significantly lower expression ofintegrin beta-3(ITGB3), a co-factor of the SERT, was observed in the PBMCs of MDD patients prior to treatment onset compared with healthy controls, and may explain their lower paroxetine sensitivity. Further studies with larger cohorts are required for clarifying the potential of reduced PBMCs paroxetine sensitivity and lowerITGB3expression as MDD biomarkers.
Prenatal immune programming of the sex-dependent risk for major depression
Authors: Gilman S E , Cherkerzian S , Buka S L , Hahn J , Hornig M , Goldstein J M
Published: May 2016

Maternal immune functioning during pregnancy contributes to sex-dependent deficits in neurodevelopment and to behaviors associated with affective traits in preclinical studies, and has been indirectly associated with offspring depression in epidemiologic studies. We therefore investigated the association between immune activity during pregnancy and the risk of depression among male and female offspring. We conducted a case–control study of depression (n=484 cases and n=774 controls) using data from the New England Family Study, a pregnancy cohort enrolled between 1959 and 1966 that assessed psychiatric outcomes in adult offspring (mean age=39.7 years). We assayed concentrations of three pro-inflammatory cytokines, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and the anti-inflammatory cytokine, IL-10, in maternal serum collected at the end of the second and beginning of the third trimesters. High maternal TNF-α was associated with reduced odds of depression among both male and female offspring (odds ratio (OR)=0.68; confidence interval (CI)=0.48, 0.98). However, when considering the TNF-α to IL-10 ratio, a measure of the ratio of pro- to anti-inflammatory loading, maternal immune effects on offspring depression differed significantly by sex (χ2=13.9, degrees of freedom=4, P=0.008). Among females, higher maternal TNF-α:IL-10 was associated with reduced odds of depression (OR=0.51; CI=0.32, 0.81), whereas, among males, high maternal TNF-α:IL-10 was associated with elevated odds of depression (OR=1.86; CI=1.02, 3.39). Thus, the balance between TNF-α and IL-10 in maternal prenatal serum was associated with depression in a sex-dependent manner. These findings are consistent with the role of TNF-α in the maturation of the sexually dimorphic fetal brain circuitry that regulates stress and affective responses, and support a prenatal stress-immune model of depression pathogenesis.
The effects of a probiotic formulation (Lactobacillus rhamnosus and L. helveticus) on developmental trajectories of emotional learning in stressed infant rats
Authors: Cowan C S M , Callaghan B L , Richardson R
Published: May 2016

Recently, scientific interest in the brain–gut axis has grown dramatically, particularly with respect to the link between gastrointestinal and psychiatric dysfunction. However, the role of gut function in early emotional dysregulation is yet to be examined, despite the prevalence and treatment resistance of early-onset psychiatric disorders. The present studies utilized a developmental rodent model of early-life stress (ELS) to explore this gap. Rats were exposed to maternal separation (MS) on postnatal days 2–14. Throughout MS, dams received either vehicle or a probiotic formulation (previously shown to reduce gastrointestinal dysfunction) in their drinking water. Replicating past research, untreated MS infants exhibited an adult-like profile of long-lasting fear memories and fear relapse following extinction. In contrast, probiotic-exposed MS infants exhibited age-appropriate infantile amnesia and resistance to relapse. These effects were not mediated by changes in pups’ or dams’ anxiety at the time of training, nor by maternal responsiveness. Overall, probiotics acted as an effective and non-invasive treatment to restore normal developmental trajectories of emotion-related behaviors in infant rats exposed to ELS. These results provide promising initial evidence for this novel approach to reduce the risk of mental health problems in vulnerable individuals. Future studies are needed to test this treatment in humans exposed to ELS and to elucidate mechanisms for the observed behavioral changes.
Combining density functional theory (DFT) and collision cross-section (CCS) calculations to analyze the gas-phase behaviour of small molecules and their protonation site isomers
Authors: Boschmans Jasper , Jacobs Sam , Williams Jonathan P. , Palmer Martin , Richardson Keith , Giles Kevin , Lapthorn Cris , Herrebout Wouter A. , Lemière Filip , Sobott Frank
Published: May 2016

Computational methods are employed to study the protomers in ESI-IM-MS.
Active chemisorption sites in functionalized ionic liquids for carbon capture
Authors: Cui Guokai , Wang Jianji , Zhang Suojiang
Published: May 2016

Carbon capture with site-containing ionic liquids is reviewed with particular attention on the activation and design of the interaction sites.
A novel microscale preparative gel electrophoresis system
Authors: Hao Feiran , Li Jiabin , Zhai Rui , Jiao Fenglong , Zhang Yangjun , Qian Xiaohong
Published: May 2016

A novel microscale preparative gel electrophoresis system is designed and manufactured for protein separation and preparation.