bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chitozyme: First Peroxidase-like Activity of Chitosan for Multiplexed Visual Detection of H2O2, Glucose and Lactate on Paper-based Device
Authors: Ahmed Syed Rahin , Weng Xuan , Neethirajan Suresh 
Published: July 2017

AbstractVisual read-out diagnostics tools are promising candidates for field applicable medical devices. Current colorimetric biosensors require introduction of natural enzymes or nanozymes, which has some serious drawbacks for practical applications. Chitosan, a natural polymer, provides safe and efficient compound in medical and pharmaceutical technology. Herein, we report on a simple, cost-efficient, field-portable, environmental friendly and ultra-sensitive multiplex detection platform based on peroxidase-like activity of chitosan in the presence of 3,3’,5,5’-Tetramethylbenzidine (TMBZ) and H2O2. This straight forward signal amplification strategy was successfully applied to detect H2O2, glucose and lactate with the limit of detection (LOD) of 2.64 pM, 0.104 μM and 2.8 nM respectively, represents the lowest LOD of H2O2, glucose and lactate with visual read-out. The chitosan-based assay performance was also retained in complex biological media for glucose and lactate detection. Furthermore, the proposed assay was successfully demonstrated as a paper-based colorimetric biosensor. Most importantly, the simplicity, biocompatibility and sensitivity of the proposed assay will open new doors for instrument free naked eye visual detection of H2O2, glucose and lactate detection.
Case-control analysis identifies shared properties of rare germline variation in cancer predisposing genes
Authors: Artomov Mykyta , Joseph Vijai , Tiao Grace , Thomas Tinu , Schrader Kasmintan , Klein Robert J. , Kiezun Adam , Gupta Namrata , Margolin Lauren , Stratigos Alexander J. , Kim Ivana , Shannon Kristen , Ellisen Leif W. , Haber Daniel , Getz Gad , Tsao Hensin , Lipkin Steven M. , Altshuler David , Offit Kenneth , Daly Mark J. 
Published: July 2017

ABSTRACTTraditionally, genetic studies in cancer are focused on somatic mutations found in tumors and absent from the normal tissue. Identification of shared attributes in germline variation could aid discrimination of high-risk from likely benign mutations and narrow the search space for new cancer predisposing genes. Extraordinary progress made in analysis of common variation with GWAS methodology does not provide sufficient resolution to understand rare variation. To fulfil missing classification for rare germline variation we assembled datasets of whole exome sequences from >2,000 patients with different types of cancers: breast cancer, colon cancer and cutaneous and ocular melanomas matched to more than 7,000 non-cancer controls and analyzed germline variation in known cancer predisposing genes to identify common properties of disease associated mutations and new candidate cancer susceptibility genes. Lists of all cancer predisposing genes were divided into subclasses according to the mode of inheritance of the related cancer syndrome or contribution to known major cancer pathways. Out of all subclasses only genes linked to dominant syndromes presented significant rare germline variants enrichment in cases. Separate analysis of protein-truncating and missense variation in this subclass of genes confirmed significant prevalence of protein-truncating variants in cases only in loss-of-function tolerant genes (pLI<0.1), while ultra-rare missense mutations were significantly overrepresented in cases only in constrained genes (pLI>0.9). Taken together, our findings provide insights into the distribution and types of mutations underlying inherited cancer predisposition.
Working memory implements distinct maintenance mechanisms depending on task goals
Authors: Fahrenfort Johannes J. , Van Leeuwen Jonathan , Foster Joshua J. , Awh Edward , Olivers Christian N.L. 
Published: July 2017

AbstractWorking memory is the function by which we temporarily maintain information to achieve current task goals. Models of working memory typically debate where this information is stored, rather than how it is stored. Here we ask instead what neural mechanisms are involved in storage, and how these mechanisms change as a function of task goals. Participants either had to reproduce the orientation of a memorized bar (continuous recall task), or identify the memorized bar in a search array (visual search task). The sensory input and retention interval were identical in both tasks. Next, we used decoding and forward modeling on multivariate electroencephalogram (EEG) and time-frequency decomposed EEG to investigate which neural signals carry more informational content during the retention interval. In the continuous recall task, working memory content was preferentially carried by induced oscillatory alpha-band power, while in the visual search task it was more strongly carried by the distribution of evoked (consistently elevated and non-oscillatory) EEG activity. To show the independence of these two signals, we were able to remove informational content from one signal without affecting informational content in the other. Finally, we show that the tuning characteristics of both signals change in opposite directions depending on the current task goal. We propose that these signals reflect oscillatory and elevated firing-rate mechanisms that respectively support location-based and object-based maintenance. Together, these data challenge current models of working memory that place storage in particular regions, but rather emphasize the importance of different distributed maintenance signals depending on task goals.Significance statement (120 words)Without realizing, we are constantly moving things in and out of our mind’s eye, an ability also referred to as ‘working memory’. Where did I put my screwdriver? Do we still have milk in the fridge? A central question in working memory research is how the brain maintains this information temporarily. Here we show that different neural mechanisms are involved in working memory depending on what the memory is used for. For example, remembering what a bottle of milk looks like invokes a different neural mechanism from remembering how much milk it contains: the first one primarily involved in being able to find the object, and the other one involving spatial position, such as the milk level in the bottle.
The beneficial effects of vaccination on the evolution of seasonal influenza
Authors: Wen Frank T. , Malani Anup , Cobey Sarah 
Published: July 2017

1AbstractAlthough vaccines against seasonal influenza are designed to protect against circulating strains, by affecting the emergence and transmission of antigenically divergent strains, they might also change the rate of antigenic evolution. Vaccination might slow antigenic evolution by increasing immunity, reducing the chance that even antigenically diverged strains can survive. Vaccination also reduces prevalence, decreasing the supply of potentially beneficial mutations and increasing the probability of stochastic extinction. But vaccination might accelerate antigenic evolution by increasing the transmission advantage of more antigenically diverged strains relative to less diverged strains (i.e., by positive selection). Such evolutionary effects could affect vaccination’s direct benefits to individuals and indirect benefits to the host population (i.e., the private and social benefits). To investigate these potential impacts, we simulated the dynamics of an influenza-like pathogen with seasonal vaccination. On average, more vaccination decreased the rate of viral antigenic evolution and the incidence of disease. Notably, this decrease was driven partly by a vaccine-induced decline in the rate of antigenic evolution. To understand how the evolutionary effects of vaccines might affect their social and private benefits, we fitted linear panel models to simulated data. By slowing evolution, vaccination increased the social benefit and decreased the private benefit. Thus, in the long term, vaccination’s potential social and private benefits may differ from current theory, which omits evolutionary effects. These results suggest that conventional seasonal vaccines against influenza, if protective against transmission and given to the appropriate populations, could further reduce disease burden by slowing antigenic evolution.
Assembly of hundreds of microbial genomes from the cow rumen reveals novel microbial species encoding enzymes with roles in carbohydrate metabolism
Authors: Stewart Robert , Auffret Marc D. , Warr Amanda , Snelling Tim , Dewhurst Richard , Walker Alan W. , Roehe Rainer , Watson Mick 
Published: July 2017

AbstractThe cow rumen is a specialised organ adapted for the efficient breakdown of plant material into energy and nutrients, and it is the rumen microbiome that encodes the enzymes responsible. Many of these enzymes are of huge industrial interest. Despite this, rumen microbes are under-represented in the public databases. Here we present 220 high quality bacterial and archaeal genomes assembled directly from 768 gigabases of rumen metagenomic sequence data. Comparative analysis with current publicly available genomes reveals that the majority of these represent previously unsequenced strains and species of bacteria and archaea. The genomes contain over 13,000 proteins predicted to be involved in carbohydrate metabolism, over 90% of which do not have a good match in the public databases. Inclusion of the 220 genomes presented here improves metagenomic read classification by 2-3-fold, both in our data and in other publicly available rumen datasets. This release improves the coverage of rumen microbes in the public databases, and represents a hugely valuable resource for biomass-degrading enzyme discovery and studies of the rumen microbiome
Consensus on Molecular Subtypes of Ovarian Cancer
Authors: Chen Gregory M , Kannan Lavanya , Geistlinger Ludwig , Kofia Victor , Safikhani Zhaleh , Gendoo Deena M A , Parmigiani Giovanni , Birrer Michael , Haibe-Kains Benjamin , Waldron Levi 
Published: July 2017

AbstractINTRODUCTIONVarious computational methods for gene expression-based subtyping of high-grade serous (HGS) ovarian cancer have been proposed. This resulted in the identification of molecular subtypes that are based on different datasets and were differentially validated, making it difficult to achieve consensus on which definitions to use in follow-up studies. We assess three major subtype classifiers for their robustness and association to outcome by a meta-analysis of publicly available expression data, and provide a classifier that represents their consensus.METHODSWe use a compendium of 15 microarray datasets consisting of 1,774 HGS ovarian tumors to assess 1) concordance between published subtyping algorithms, 2) robustness of those algorithms to re-clustering across datasets, and 3) association of subtypes with overall survival. A consensus classifier is trained on concordantly classified samples, and validated by leave-one-dataset-out validation.RESULTSEach subtyping classifier identified subsets significantly differing in overall survival, but were not robust to re-fitting in independent datasets and grouped only approximately one third of patients concordantly into four subtypes. We propose a consensus classifier to identify the minority of unambiguously classifiable tumors across multiple gene expression platforms, using a 100-gene signature. The resulting consensus subtypes correlate with patient age, survival, tumor purity, and lymphocyte infiltration.CONCLUSIONSOur analysis demonstrates that most HGS ovarian cancers are not able to be subtyped. A minority of tumors can be classified and our proposed consensus classifier consolidates and improves on the robustness of three previously proposed subtype classifiers. It provides reliable stratification of patients with HGS ovarian tumors of clearly defined subtype, and will assist in studying the role of polyclonality in the majority of tumors that are not robustly classifiable.
Sequanix: A Dynamic Graphical Interface for Snakemake Workflows
Authors: Desvillechabrol Dimitri , Legendre Rachel , Rioualen Claire , Bouchier Christiane , Helden Jacques van , Kennedy Sean , Cokelaer Thomas 
Published: July 2017

AbstractSummaryWe designed a PyQt graphical user interface – Sequanix – aiming at democratizing the use of Snakemake pipelines. Although the primary goal of Sequanix was to facilitate the execution of NGS Snakemake pipelines available in the Sequana project (http://sequana.readthedocs.io), it can also handle any Snakemake pipelines. Therefore, Sequanix should be useful to all Snakemake developers willing to expose their pipelines to a wider audience.AvailabilitySource code available onhttp://github.com/sequana/sequanaand standalone onhttp://bioconda.github.io(sequana package).
AMP-activated protein kinase protects against anoxia inDrosophila melanogaster
Authors: Evans Justin J. , Xiao Chengfeng , Robertson R. Meldrum 
Published: July 2017

AbstractDuring anoxia, proper energy maintenance is essential in order to maintain neural operation. Starvation activates AMP-activated protein kinase (AMPK), an evolutionarily conserved indicator of cellular energy status, in a cascade which modulates ATP production and consumption. We investigated the role of energetic status on anoxia tolerance inDrosophilaand discovered that starvation or AMPK activation increases the speed of locomotor recovery from an anoxic coma. Using temporal and spatial genetic targeting we found that AMPK in the fat body contributes to starvation-induced fast locomotor recovery, whereas, under fed conditions, disrupting AMPK in oenocytes prolongs recovery. By evaluating spreading depolarization in the fly brain during anoxia we show that AMPK activation reduces the severity of ionic disruption and prolongs recovery of electrical activity. Further genetic targeting indicates that glial, but not neuronal, AMPK affects locomotor recovery. Together, these findings support a model in which AMPK is neuroprotective inDrosophila.
cAMP Signaling Regulates DNA Demethylation by Augmenting the Intracellular Labile Ferrous Iron Pool
Authors: Camarena Vladimir , Sant David W. , Huff Tyler C. , Mustafi Sushmita , Muir Ryan K. , Renslo Adam R. , Monje Paula , Wang Gaofeng 
Published: July 2017

AbstractIt is widely accepted that cAMP regulates gene transcription principally by activating the protein kinase A (PKA)-targeted transcription factors. Here, we show that cAMP enhances the generation of 5-hydroxymethylcytosine (5hmC) in multiple cell types. 5hmC is converted from 5-methylcytosine (5mC) by Tet methylcytosine dioxygenases, for which Fe(II) is an essential cofactor. The promotion of 5hmC was mediated by a prompt increase of the intracellular labile Fe(II) pool (LIP). cAMP enhanced the acidification of endosomes for Fe(II) release to the LIP likely through RapGEF2. The effect of cAMP on Fe(II) and 5hmC was confirmed by adenylate cyclase activators, phosphodiesterase inhibitors, and most notably by stimulation of G protein-coupled receptors (GPCR). The transcriptomic changes caused by cAMP occurred in concert with 5hmC elevation in differentially transcribed genes. Collectively, these data show a previously unrecognized regulation of gene transcription by GPCR-cAMP signaling through augmentation of the intracellular labile Fe(II) pool and DNA demethylation.
Rapid and scalable preparation of bacterial lysates for cell-free gene expression
Authors: Didovyk Andriy , Tonooka Taishi , Tsimring Lev , Hasty Jeff 
Published: July 2017

AbstractCell-free gene expression systems are emerging as an important platform for a diverse range of synthetic biology and biotechnology applications, including production of robust field-ready biosensors. Here, we combine programmed cellular autolysis with a freeze-thaw or freeze-dry cycle to create a practical, reproducible, and a labor- and cost-effective approach for rapid production of bacterial lysates for cell-free gene expression. Using this method, ro-bust and highly active bacterial cell lysates can be produced without specialized equipment at a wide range of scales, making cell-free gene expression easily and broadly accessible. More-over, live autolysis strain can be freeze-dried directly and subsequently lysed upon rehydration to produce active lysate. We demonstrate the utility of autolysates for synthetic biology by reg-ulating protein production and degradation, implementing quorum sensing, and showing quan-titative protection of linear DNA templates by GamS protein. To allow versatile and sensitive β-galactosidase (LacZ) based readout we produce autolysates with no detectable background LacZ activity and use them to produce sensitive mercury(II) biosensors with LacZ-mediated colorimetric and fluorescent outputs. The autolysis approach can facilitate wider adoption of cell-free technology for cell-free gene expression as well as other synthetic biology and biotechnology applications, such as metabolic engineering, natural product biosynthesis, or proteomics.
SQUID: Transcriptomic Structural Variation Detection from RNA-seq
Authors: Ma Cong , Shao Mingfu , Kingsford Carl 
Published: July 2017

AbstractTranscripts are frequently modified by structural variations, which leads to a fused transcript of either multiple genes (known as a fusion gene) or a gene and a previously non-transcribing sequence. Detecting these modifications (called transcriptomic structural variations, or TSVs), especially in cancer tumor sequencing, is an important and challenging computational problem. We introduce SQUID, a novel algorithm to accurately predict both fusion-gene and non-fusion-gene TSVs from RNA-seq alignments. SQUID unifies both concordant and discordant read alignments into one model, and doubles the accuracy on simulation data compared to other approaches. With SQUID, we identified novel non-fusion-gene TSVs on TCGA samples.
Long-term adaptive evolution of genomically recodedEscherichia coli
Authors: Wannier Timothy M. , Kunjapur Aditya M. , Rice Daniel P. , McDonald Michael J. , Desai Michael M. , Church George M. 
Published: July 2017

AbstractEfforts are underway to construct several recoded genomes anticipated to exhibit multi-virus resistance, enhanced non-standard amino acid (NSAA) incorporation, and capability for synthetic biocontainment. Though we succeeded in pioneering the first genomically recoded organism (Escherichia colistrain C321.ΔA), its fitness is far lower than that of its non-recoded ancestor, particularly in defined media. This fitness deficit severely limits its utility for NSAA-linked applications requiring defined media such as live cell imaging, metabolic engineering, and industrial-scale protein production. Here, we report adaptive evolution of C321.ΔA for more than 1,000 generations in independent replicate populations grown in glucose minimal media. Evolved recoded populations significantly exceed the growth rates of both the ancestral C321.ΔA and non-recoded strains, permitting use of the recoded chassis in several new contexts. We use next-generation sequencing to identify genes mutated in multiple independent populations, and we reconstruct individual alleles in ancestral strains via multiplex automatable genome engineering (MAGE) to quantify their effects on fitness. Several selective mutations occur only in recoded evolved populations, some of which are associated with altering the translation apparatus in response to recoding, whereas others are not apparently associated with recoding, but instead correct for off-target mutations that occurred during initial genome engineering. This report demonstrates that laboratory evolution can be applied after engineering of recoded genomes to streamline fitness recovery compared to application of additional targeted engineering strategies that may introduce further unintended mutations. In doing so, we provide the most comprehensive insight to date into the physiology of the commonly used C321.ΔA strain.Significance StatementAfter demonstrating construction of an organism with an altered genetic code, we sought to evolve this organism for many generations to improve its fitness and learn what unique changes natural selection would bestow upon it. Although this organism initially had impaired fitness, we observed that adaptive laboratory evolution resulted in several selective mutations that corrected for insufficient translation termination and for unintended mutations that occurred when originally altering the genetic code. This work further bolsters our understanding of the pliability of the genetic code, it will help guide ongoing and future efforts seeking to recode genomes, and it results in a useful strain for non-standard amino acid incorporation in numerous contexts relevant for research and industry.
Mobile shopping among young consumers: an empirical study in an emerging market
Authors: Mahapatra Sabita 
Published: July 2017

PurposeSuperior functionality of smartphones makes them a potential retailing channel, despite their slow adoption. The purpose of this paper is to identify convenience factors that influence consumption experience and intention to continue shopping on a mobile phone.Design/methodology/approachThis study was carried out on students using a survey method. This study was conducted in the National Capital Region of India due to its large and diverse population. A purposive sampling technique was used to contact 380 respondents.FindingsThe data were analysed using a structural equation model. The results indicate search and possession convenience to be positively related to consumption experience while search, evaluation and post-purchase convenience are positively related to continuance usage intention. The findings of this study provide evidence that mobile phone is an effective channel for shopping due to search, evaluation, possession and post-purchase convenience.Research limitations/implicationsThis study used student population between the age group of 20 and 30 years, thereby limiting the generality of the results.Practical implicationsThis study provides insights to retailers and brand managers for crafting their mobile marketing strategies.Originality/valueThis study explores and uncovers, for the first time, convenience dimensions of a mobile shopping channel across various stages of consumers’ purchase cycle.