bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of SMS/GPRS Printers in Reducing Time to Early Infant Diagnosis Compared With Routine Result Reporting: A Systematic Review and Meta-Analysis
Authors: Vojnov Lara , Markby Jessica , Boeke Caroline , Penazzato Martina , Urick Brittany , Ghadrshenas Anisa , Harris Lindsay , Ford Nathan , Peter Trevor
Published: August 2017

Background:

Despite significant gains made toward improving access, early infant diagnosis (EID) testing programs suffer from long test turnaround times that result in substantial loss to follow-up and mortality associated with delays in antiretroviral therapy initiation. These delays in treatment initiation are particularly impactful because of significant HIV-related infant mortality observed by 2–3 months of age. Short message service (SMS) and general packet radio service (GPRS) printers allow test results to be transmitted immediately to health care facilities on completion of testing in the laboratory.

Methods:

We conducted a systematic review and meta-analysis to assess the benefit of using SMS/GPRS printers to increase the efficiency of EID test result delivery compared with traditional courier paper–based results delivery methods.

Results:

We identified 11 studies contributing data for over 16,000 patients from East and Southern Africa. The test turnaround time from specimen collection to result received at the health care facility with courier paper–based methods was 68.0 days (n = 6835), whereas the test turnaround time with SMS/GPRS printers was 51.1 days (n = 6711), resulting in a 2.5-week (25%) reduction in the turnaround time.

Conclusions:

Courier paper–based EID test result delivery methods are estimated to add 2.5 weeks to EID test turnaround times in low resource settings and increase the risk that infants receive test results during or after the early peak of infant mortality. SMS/GPRS result delivery to health care facility printers significantly reduced test turnaround time and may reduce this risk. SMS/GPRS printers should be considered for expedited delivery of EID and other centralized laboratory test results.
Domestication as a model system for the extended evolutionary synthesis
Authors: Zeder Melinda A.
Published: August 2017

One of the challenges in evaluating arguments for extending the conceptual framework of evolutionary biology involves the identification of a tractable model system that allows for an assessment of the core assumptions of the extended evolutionary synthesis (EES). The domestication of plants and animals by humans provides one such case study opportunity. Here, I consider domestication as a model system for exploring major tenets of the EES. First I discuss the novel insights that niche construction theory (NCT, one of the pillars of the EES) provides into the domestication processes, particularly as they relate to five key areas: coevolution, evolvability, ecological inheritance, cooperation and the pace of evolutionary change. This discussion is next used to frame testable predictions about initial domestication of plants and animals that contrast with those grounded in standard evolutionary theory, demonstrating how these predictions might be tested in multiple regions where initial domestication took place. I then turn to a broader consideration of how domestication provides a model case study consideration of the different ways in which the core assumptions of the EES strengthen and expand our understanding of evolution, including reciprocal causation, developmental processes as drivers of evolutionary change, inclusive inheritance, and the tempo and rate of evolutionary change.
Human niche, human behaviour, human nature
Authors: Fuentes Agustin
Published: August 2017

The concept of a ‘human nature’ or ‘human natures’ retains a central role in theorizing about the human experience. InHomo sapiensit is clear that we have a suite of capacities generated via our evolutionary past, and present, and a flexible capacity to create and sustain particular kinds of cultures and to be shaped by them. Regardless of whether we label these capacities ‘human natures’ or not, humans occupy a distinctive niche and an evolutionary approach to examining it is critical. At present we are faced with a few different narratives as to exactly what such an evolutionary approach entails. There is a need for a robust and dynamic theoretical toolkit in order to develop a richer, and more nuanced, understanding of the cognitively sophisticated genusHomoand the diverse sorts of niches humans constructed and occupied across the Pleistocene, Holocene, and into the Anthropocene. Here I review current evolutionary approaches to ‘human nature’, arguing that we benefit from re-framing our investigations via the concept of the human niche and in the context of the extended evolutionary synthesis (EES). While not a replacement of standard evolutionary approaches, this is an expansion and enhancement of our toolkit. I offer brief examples from human evolution in support of these assertions.
Niche construction, sources of selection and trait coevolution
Authors: Laland Kevin , Odling-Smee John , Endler John
Published: August 2017

Organisms modify and choose components of their local environments. This ‘niche construction’ can alter ecological processes, modify natural selection and contribute to inheritance through ecological legacies. Here, we propose that niche construction initiates and modifies the selection directly affecting the constructor, and on other species, in an orderly, directed and sustained manner. By dependably generating specific environmental states, niche construction co-directs adaptive evolution by imposing a consistent statistical bias on selection. We illustrate how niche construction can generate this evolutionary bias by comparing it with artificial selection. We suggest that it occupies the middle ground between artificial and natural selection. We show how the perspective leads to testable predictions related to: (i) reduced variance in measures of responses to natural selection in the wild; (ii) multiple trait coevolution, including the evolution of sequences of traits and patterns of parallel evolution; and (iii) a positive association between niche construction and biodiversity. More generally, we submit that evolutionary biology would benefit from greater attention to the diverse properties of all sources of selection.
Developmental plasticity: re-conceiving the genotype
Authors: Sultan Sonia E.
Published: August 2017

In recent decades, the phenotype of an organism (i.e. its traits and behaviour) has been studied as the outcome of a developmental ‘programme’ coded in its genotype. This deterministic view is implicit in the Modern Synthesis approach to adaptive evolution as a sorting process among genetic variants. Studies of developmental pathways have revealed that genotypes are in fact differently expressed depending on environmental conditions. Accordingly, the genotype can be understood as a repertoire of potential developmental outcomes ornorm of reaction.Reconceiving the genotype as an environmental response repertoire rather than a fixed developmental programme leads to three critical evolutionary insights. First, plastic responses to specific conditions often comprise functionally appropriate trait adjustments, resulting in an individual-level, developmental mode of adaptive variation. Second, because genotypes are differently expressed depending on the environment, the genetic diversity available to natural selection is itself environmentally contingent. Finally, environmental influences on development can extend across multiple generations via cytoplasmic and epigenetic factors transmitted to progeny individuals, altering their responses to their own, immediate environmental conditions and, in some cases, leading to inherited but non-genetic adaptations. Together, these insights suggest a more nuanced understanding of the genotype and its evolutionary role, as well as a shift in research focus to investigating the complex developmental interactions among genotypes, environments and previous environments.
Human nature, human culture: the case of cultural evolution
Authors: Lewens Tim
Published: August 2017

In recent years, far from arguing that evolutionary approaches to our own species permit us to describe the fundamental character of human nature, a prominent group of cultural evolutionary theorists has instead argued that the very idea of ‘human nature’ is one we should reject. It makes no sense, they argue, to speak of human nature in opposition to human culture. The very same sceptical arguments have also led some thinkers—usually from social anthropology—to dismiss the intimately related idea that we can talk of human culture in opposition to human nature. How, then, are we supposed to understand the cultural evolutionary project itself, whose proponents seem to deny the distinction between human nature and human culture, while simultaneously relying on a closely allied distinction between ‘genetic’ (or sometimes ‘organic’) evolution and ‘cultural’ evolution? This paper defends the cultural evolutionary project against the charge that, in refusing to endorse the concept of human nature, it has inadvertently sabotaged itself.
The subject as cause and effect of evolution
Authors: Godfrey-Smith Peter
Published: August 2017

A family of arguments often presented in opposition to mainstream neo-Darwinian views of evolution assert an ‘active' role for organisms in determining the course of their evolution and other kinds of biological change. I assess several of these arguments, beginning with an early treatment by Lewontin and moving to more recent discussions. I then look at a subset of these phenomena, those in which organisms are efficacious in virtue of features and capacities related to
subjectivity
. In the history of the Earth from the Cambrian onwards, subjectivity has been an increasingly important causal factor.
Stenotrophomonas bentonitica sp. nov., isolated from bentonite formations
Authors: Sánchez-Castro Iván , Ruiz-Fresneda Miguel Angel , Bakkali Mohammed , Kämpfer Peter , Glaeser Stefanie P. , Busse Hans Jürgen , López-Fernández Margarita , Martínez-Rodríguez Pablo , Merroun Mohamed Larbi
Published: August 2017

A Gram-stain negative, rod-shaped, aerobic bacterial strain, BII-R7T, was isolated during a study targeting the culture-dependent microbial diversity occurring in bentonite formations from southern Spain. Comparative 16S rRNA gene sequence analysis showed that BII-R7T represented a member of the genus

Stenotrophomonas

(class

Gammaproteobacteria

), and was related most closely to

Stenotrophomonas rhizophila

e-p10T (99.2 % sequence similarity), followed by

Stenotrophomonas pavanii

ICB 89T (98.5 %),

Stenotrophomonas maltophilia

IAM 12423T,

Stenotrophomonas chelatiphaga

LPM-5T and

Stenotrophomonas tumulicola

T5916-2-1bT (all 98.3 %). Pairwise sequence similarities to all other type strains of species of the genus

Stenotrophomonas

were below 98 %. Genome-based calculations (orthologous average nucleotide identity, original average nucleotide identity, genome-to-genome distance and DNA G+C percentage) indicated clearly that the isolate represents a novel species within this genus. Different phenotypic analyses, such as the detection of a quinone system composed of the major compound ubiquinone Q-8 and a fatty acid profile with iso-C15 : 0 and anteiso-C15 : 0 as major components, supported this finding at the same time as contributing to a comprehensive characterization of BII-R7T. Based on this polyphasic approach comprising phenotypic and genotypic/molecular characterization, BII-R7T can be differentiated clearly from its phylogenetic neighbours, establishing a novel species for which the name Stenotrophomonas bentonitica sp. nov. is proposed with BII-R7T as the type strain (=LMG 29893T=CECT 9180T=DSM 103927T).
ICTV Virus Taxonomy Profile: Polyomaviridae
Authors: Moens Ugo , Calvignac-Spencer Sébastien , Lauber Chris , Ramqvist Torbjörn , Feltkamp Mariet C. W. , Daugherty Matthew D. , Verschoor Ernst J. , Ehlers Bernhard ,   ICTV Report Consortium
Published: August 2017

The Polyomaviridae is a family of small, non-enveloped viruses with circular dsDNA genomes of approximately 5 kbp. The family includes four genera whose members have restricted host range, infecting mammals and birds. Polyomavirus genomes have also been detected recently in fish. Merkel cell polyomavirus and raccoon polyomavirus are associated with cancer in their host; other members are human and veterinary pathogens. Clinical manifestations are obvious in immunocompromised patients but not in healthy individuals. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Polyomaviridae, which is available at www.ictv.global/report/polyomaviridae.
ICTV Virus Taxonomy Profile: Benyviridae
Authors: Gilmer David , Ratti Claudio ,   ICTV Report Consortium
Published: August 2017

The Benyviridae is a family of multipartite plant viruses with rod-shaped virions. Genomes are segmented and comprised of single-stranded, positive-sense RNAs, each with a 5′ m7G cap. Unlike rod-shaped viruses classified in the Virgaviridae family, the genome segments have a 3′ polyA tract and there is post-translational cleavage of the viral replicase. The better-known members are transmitted by root-infecting vectors in the Plasmodiphorales family, once described as fungi but now classified as Cercozoa. The family has a single genus. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of Benyviridae, which is available at www.ictv.global/report/benyviridae.
ICTV Virus Taxonomy Profile: Circoviridae
Authors: Breitbart Mya , Delwart Eric , Rosario Karyna , Segalés Joaquim , Varsani Arvind ,   ICTV Report Consortium
Published: August 2017

The family Circoviridae comprises viruses with small, circular, single-stranded DNA (ssDNA) genomes, including the smallest known animal viruses. Members of this family are classified into two genera, Circovirus and Cyclovirus, which are distinguished by the position of the origin of replication relative to the coding regions and the length of the intergenic regions. Within each genus, the species demarcation threshold is 80 % genome-wide nucleotide sequence identity. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Circoviridae, which is available at www.ictv.global/report/circoviridae.
Assessing evidence for avian-to-human transmission of influenza A/H9N2 virus in rural farming communities in northern Vietnam
Authors: Hoa Le Nguyen Minh , Tuan Nguyen Anh , My Pham Ha , Huong Tran Thi Kieu , Chi Nguyen Thi Yen , Hau Thu Trang Thi , Carrique-Mas Juan , Duong Mai Thuy , Tho Nguyen Dang , Hoang Nguyen Dang , Thanh To Long , Diep Nguyen Thi , Duong Nguyen van , Toan Tran Khanh , Tung Trinh Son , Mai Le Quynh , Iqbal Munir , Wertheim Heiman , van Doorn H. Rogier , Bryant Juliet E. ,   the VIZIONS consortium
Published: August 2017

Rural farming communities in northern Vietnam do not routinely practice vaccination for influenza A viruses (IAV) for either humans or poultry, which enables us to study transmission intensity via seroepidemiology. Using samples from a longitudinal cohort of farming households, we determined the number of symptomatic and asymptomatic human infections for seasonal IAV and avian A/H9 over 2 years. As expected, we detected virologically confirmed acute cases of seasonal IAV in humans, as well as large numbers of subclinical seroconversions to A/H1pdm [55/265 (21 %)], A/H3 [95/265 (36 %)] and A/H9 [24/265 (9 %)]. Five of the A/H9 human seroconverters likely represented true infections rather than heterosubtypic immunity, because the individuals seroconverted solely to A/H9. Among co-located poultry, we found significantly higher seroprevalance for A/H5 compared to A/H9 in both chickens and ducks [for northern study sites overall, 337/1105 (30.5 %) seropositive for A/H5 and 123/1105 (11.1 %) seropositive for A/H9].
Missing Value Imputation Approach for Mass Spectrometry-based Metabolomics Data
Authors: Wei Runmin , Wang Jingye , Su Mingming , Jia Erik , Chen Tianlu , Ni Yan
Published: August 2017

Introduction

Missing values exist widely in mass-spectrometry (MS) based metabolomics data. Various methods have been applied for handling missing values, but the selection of methods can significantly affect following data analyses and interpretations. According to the definition, there are three types of missing values, missing completely at random (MCAR), missing at random (MAR), and missing not at random (MNAR).

Objectives

The aim of this study was to comprehensively compare common imputation methods for different types of missing values using two separate metabolomics data sets (977 and 198 serum samples respectively) to propose a strategy to deal with missing values in metabolomics studies.

Methods

Imputation methods included zero, half minimum (HM), mean, median, random forest (RF), singular value decomposition (SVD), k-nearest neighbors (kNN), and quantile regression imputation of left-censored data (QRILC). Normalized root mean squared error (NRMSE) and NRMSE-based sum of ranks (SOR) were applied to evaluate the imputation accuracy for MCAR/MAR and MNAR correspondingly. Principal component analysis (PCA)/partial least squares (PLS)-Procrustes sum of squared error were used to evaluate the overall sample distribution. Student’st-test followed by Pearson correlation analysis was conducted to evaluate the effect of imputation on univariate statistical analysis.

Results

Our findings demonstrated that RF imputation performed the best for MCAR/MAR and QRILC was the favored one for MNAR.

Conclusion

Combining with “modified 80% rule”, we proposed a comprehensive strategy and developed a public-accessible web-tool for missing value imputation in metabolomics data.
Dynamic marine viral infections and major contribution to photosynthetic processes shown by regional and seasonal picoplankton metatranscriptomes
Authors: Sieradzki Ella T. , Cesar Ignacio-Espinoza J. , Needham David M. , Fichot Erin B. , Fuhrman Jed A.
Published: August 2017

Viruses are an important top-down control on microbial communities, yet their direct study in natural environments has been hindered by culture limitations1-3. The advance of sequencing and bioinformatics over the last decade enabled the cultivation independent study of viruses. Many studies focus on assembling new viral genomes4-6and studying viral diversity using marker genes amplified from free viruses7,8. We used cellular metatranscriptomics to study community-wide viral infections at three coastal California sites throughout a year. Generation of and recruitment to viral contigs (> 5kbp, N=66) allowed tracking of infection dynamics over time and space. Here we show that while these assemblies represent viral populations, they are likely biased towards clonal or low diversity assemblages. Furthermore, we demonstrate that published T4-like cyanophages (N=50) and pelagiphages (N=4), having genomic continuity between close relatives, are better tracked using marker genes. Additionally, we demonstrate determination of potential hosts by matching infection dynamics with microbial community composition. Finally, we quantify the relative contribution of various cyanobacteria and viruses to photosystem-IIpsbAexpression in our study sites. We show sometimes >50% of all cyanobacterial+viralpsbAexpression we observed is of viral origin, which highlights the proportion of infected cells and makes viruses a remarkable contributor to photosynthesis and oxygen production.
Feed-forward and Feedback Control in Astrocytes for Ca2+-based Molecular Communications Nanonetworks
Authors: Barros Michael Taynnan , Dey Subhrakanti
Published: August 2017

Synapses plasticity depends on the gliotransmitters’ concentration in the synaptic channel. And, an abnormal concentration of gliotransmitters is linked to neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Epilepsy. In this paper, a theoretical investigation of the cause of the abnormal concentration of gliotransmitters and how to achieve its control are presented through a Ca2+-signalling-based molecular communications framework. A feed-forward and feedback control technique is used to manipulate IP3 values to stabilise the concentration of Ca2+ inside the astrocytes. The theoretical analysis of the given model aims i) to stabilize the Ca2+ concentration around a particular desired level in order to prevent abnormal gliotransmitters’ concentration (extremely high or low concentration can result in neurodegeneration), ii) to improve the molecular communication performance that utilises Ca2+ signalling, and maintain gliotransmitters’ regulation remotely. It shows that the refractory periods from Ca2+ can be maintained to lower the noise propagation resulting in smaller time-slots for bit transmission, which can also improve the delay and gain performances. The proposed approach can potentially lead to novel nanomedicine solutions for the treatment of neurodegenerative diseases, where a combination of nanotechnology and gene therapy approaches can be used to elicit the regulated Ca2+ signalling in astrocytes, ultimately improving neuronal activity.
Genomics of Natural Populations: Evolutionary Forces that Establish and Maintain Gene Arrangements inDrosophila pseudoosbscura
Authors: Fuller Zachary L. , Haynes Gwilym D. , Richards Stephen , Schaeffer Stephen W.
Published: August 2017

The evolution of complex traits in heterogeneous environments may shape the order of genes within chromosomes.Drosophila pseudoobscurahas a rich gene arrangement polymorphism that allows one to test evolutionary genetic hypotheses about how chromosomal inversions are established in populations.D. pseudoobscurahas >30 gene arrangements on a single chromosome that were generated through a series of overlapping inversion mutations with > 10 inversions with appreciable frequencies and wide geographic distributions. This study analyzes the genomic sequences of 54 strains ofDrosophila pseudoobscurathat carry one of six different chromosomal arrangements to test whether (1) genetic drift, (2) hitchhiking with an adaptive allele, (3) direct effects of inversions to create gene disruptions caused by breakpoints, or (4) indirect effects of inversions in limiting the formation of recombinant gametes are responsible for the establishment of new gene arrangements. We found that the inversion events do not disrupt the structure of protein coding genes at the breakpoints. Population genetic analyses of 2,669 protein coding genes identified 277 outlier loci harboring elevated frequencies of arrangement-specific derived alleles. Significant linkage disequilibrium occurs among distant loci interspersed between regions with low levels of association indicating that distant allelic combinations are held together despite shared polymorphism among arrangements. Outlier genes showing evidence of genetic differentiation between arrangements are enriched for sensory perception and detoxification genes. The data presented here support the indirect effect of inversion hypothesis where chromosomal inversions are favored because they maintain linked associations among multi-locus allelic combinations among different arrangements.
Structural and functional MRI from a cross-sectional Southwest University Adult lifespan Dataset (SALD)
Authors: Wei Dongtao , Zhuang Kaixiang , Chen Qunlin , Yang Wenjing , Liu Wei , Wang Kangcheng , Sun Jiangzhou , Qiu Jiang
Published: August 2017

Recently, the field of developmental neuroscience has aimed to uncover the developmental trajectory of the human brain and understand the changes that occur as a function of aging. Here we present an adult lifespan dataset of functional magnetic resonance imaging (fMRI) data including structural MRI and resting-state functional MRI. 494 healthy adults (age range: 19-80 years; Males=187) were recruited and completed two multi-modal MRI scan sessions in the Brain Imaging Central of Southwest University, Chongqing, China. The goals of the dataset are to give researchers the opportunity to map the developmental trajectory of structural and functional changes of human brain and to replicate previous findings.
Whole-exome sequencing of plasma cell-free DNA portrays the somatic mutation landscape of refractory metastatic colorectal cancer and enables the discovery of mutatedKDR/VEGFR2 receptors as modulators of anti-angiogenic therapies
Authors: Toledo Rodrigo A. , Garralda Elena , Mitsi Maria , Pons Tirso , Monsech Jorge , Vega Estela , Otero Álvaro , Albarran Maria I. , Baños Natalia , Durán Yolanda , Bonilla Victoria , Sarno Francesca , Camacho-Artacho Marta , Sanchez-Perez Tania , Perea Sofia , Álvarez Rafael , De Martino Alba , Lietha Daniel , Blanco-Aparicio Carmen , Cubillo Antonio , Domínguez Orlando , Martínez-Torrecuadrada Jorge L. , Hidalgo Manuel
Published: August 2017

The non-invasive detection of cancer mutations is a breakthrough in oncology. Here, we applied whole-exome sequencing of matched germline and basal plasma cell-free DNA samples (WES-cfDNA) on aRAS/BRAF/PIK3CAwild-type metastatic colorectal cancer patient with primary resistance to standard treatment regimens including VEGFR inhibitors. Using WES-cfDNA, we could detect 73% (54/74) of the somatic mutations uncovered by WES-tumor including a variety of mutation types: frameshift (indels), missense, noncoding (splicing), and nonsense mutations. Additionally, WES-cfDNA discovered 14 high-confidence somatic mutations not identified by WES-tumor. Importantly, in the absence of the tumor specimen, WES-cfDNA could identify 68 of the 88 (77.3%) total mutations that could be identified by both techniques. Of tumor biology relevance, we identified the novelKDR/VEGFR2 L840F somatic mutation, which we showed was a clonal mutation event in this tumor. Comprehensivein vitroandin vivofunctional assays confirmed that L840F causes strong resistance to anti-angiogenic drugs, whereas theKDR/VEGFR2 hot-spot mutant R1032Q confers sensitivity to cabozantinib. Moreover, we found a 1-3% of recurrentKDRsomatic mutations across large and non-overlapping cancer sequencing projects, and the majority of these mutations were located in protein residues frequently mutated in other cancer-relevant kinases, such as EGFR, ABL1, and ALK, suggesting a functional role.

In summary, the current study highlights the capability of exomic sequencing of cfDNA from plasma of cancer patients as a powerful platform for somatic landscape analysis and discovery of resistance-associated cancer mutations. Because of its advantage to generate results highly concordant to those of tumor sequencing without the hurdle of conventional tumor biopsies, we anticipate that WES-cfDNA will become frequently used in oncology. Moreover, our study identified for the first-timeKDR/VEGFR2 somatic mutations as potential genetic biomarkers of response to anti-angiogenic cancer therapies and will serve as reference for further studies on the topic.
The Epstein-Barr virus episome maneuvers between nuclear chromatin compartments during reactivation
Authors: Moquin Stephanie A. , Thomas Sean , Whalen Sean , Warburton Alix , Fernanadez Samantha G. , McBride Alison A. , Pollard Katherine S. , Miranda JJ L.
Published: August 2017

The human genome is structurally organized in three-dimensional space to facilitate functional partitioning of transcription. We learned that the latent episome of the human Epstein-Barr virus (EBV) preferentially associates with gene-poor chromosomes and avoids gene-rich chromosomes. Kaposi’s sarcoma-associated herpesvirus behaves similarly, but human papillomavirus does not. Contacts localize on the EBV side to OriP, the latent origin of replication. This genetic element, and the EBNA1 protein that binds there, are sufficient to reconstitute chromosome association preferences of the entire episome. Contacts localize on the human side to gene-poor regions of chromatin distant from transcription start sites. Upon reactivation from latency, however, the episome moves away from repressive heterochromatin and toward active euchromatin. Our work adds three-dimensional relocalization to the molecular events that occur during reactivation. Involvement of a myriad of interchromosomal associations also suggests a role for this type of long - range association in gene regulation.

IMPORTANCE

The human genome is structurally organized in three-dimensional space, and this structure functionally affects transcriptional activity. We set out to investigate whether a double stranded DNA virus, Epstein-Barr virus (EBV), uses similar mechanisms as the human genome to regulate transcription. We found that the EBV genome associates with repressive compartments of the nucleus during latency and active compartments during reactivation. This study is advances our knowledge of the EBV life cycle, adding three-dimensional re-localization as a novel component to the molecular events that occur during reactivation. Furthermore, the data adds to our understanding of nuclear compartments, showing that disperse interchromosomal interactions may be important for regulating transcription.
Investigating the existence of periodicity in activity of neural network by novel neural signal processing technique - quantifying induced learning in cell culture
Authors: Biswas Sayan
Published: August 2017

The network forming ability of neurons are huge for their sparking ability to form new connections and break existing ones. This sheer ability allows dynamic nature of the network for which this network are ever changing. The neurons being cells that are chemically and electrically excitable, electrical excitation of these cells cause variation of voltage in vicinity of the active neurons. These variation captured through electrical recording device records to activity points in the network. Cultured neuron cells on Multi electrode array dish is used to study disassociated cultures. A novel integrative model of neural signal processing termed as Activity Index is applied. AI variation is plotted graphically to show the evidence in periodicity of network analysis. The finding on periodicity are discussed along with how could it be used as a potential parameter to quantify learning ability of a cell culture.

Index Terms

neurons, dynamic, variation of voltage, Multi electrode array, Activity Index train, Periodicity, learning
Sequence-dependent nucleosome sliding in rotation-coupled and uncoupled modes revealed by molecular simulations
Authors: Niina Toru , Brandani Giovanni B. , Tan Cheng , Takada Shoji
Published: August 2017

While nucleosome positioning on eukaryotic genome play important roles for genetic regulation, molecular mechanisms of nucleosome positioning and sliding along DNA are not well understood. Here we investigated thermally-activated spontaneous nucleosome sliding mechanisms developing and applying a coarse-grained molecular simulation method that incorporates both long-range electrostatic and short-range hydrogen-bond interactions between histone octamer and DNA. The simulations revealed two distinct sliding modes depending on the nucleosomal DNA sequence. A uniform DNA sequence showed frequent sliding with one base pair step in a rotation-coupled manner, akin to screw-like motions. On the contrary, a strong positioning sequence, the so-called 601 sequence, exhibits rare, abrupt transitions of five and ten base pair steps without rotation. Moreover, we evaluated the importance of hydrogen bond interactions on the sliding mode, finding that strong and weak bonds favor respectively the rotation-coupled and -uncoupled sliding movements.

Author summary

Nucleosomes are fundamental units of chromatin folding consisting of double-stranded DNA wrapped ∼1.7 times around a histone octamer. By densely populating the eukaryotic genome, nucleosomes enable efficient genome compaction inside the cellular nucleus. However, the portion of DNA occupied by a nucleosome can hardly be accessed by other DNA-binding proteins, obstructing fundamental cellular processes such as DNA replication and transcription. DNA compaction and access by other proteins can simultaneously be achieved via the dynamical repositioning of nucleosomes, which can slide along the DNA sequence. In this study, we developed and used coarse-grained molecular dynamics simulations to reveal the molecular details of nucleosome sliding. We find that the sliding mode is highly dependent on the underlying DNA sequence. Specifically, a sequence with a strong nucleosome positioning signal slides via large jumps by five and ten base pairs, preserving the optimal DNA bending profile. On the other hand, uniform sequences without the positioning signal slide via a screw-like motion of DNA, one base pair at the time. These results show that sequence has a large effect not only on the formation of nucleosomes, but also on the kinetics of repositioning.
CTCF, WAPL and PDS5 proteins control the formation of TADs and loops by cohesin
Authors: Wutz Gordana , Várnai Csilla , Nagasaka Kota , Cisneros David A , Stocsits Roman , Tang Wen , Schoenfelder Stefan , Jessberger Gregor , Muhar Matthias , Hossain M Julius , Walther Nike , Koch Birgit , Kueblbeck Moritz , Ellenberg Jan , Zuber Johannes , Fraser Peter , Peters Jan-Michael
Published: August 2017

Mammalian genomes are organized into compartments, topologically-associating domains (TADs) and loops to facilitate gene regulation and other chromosomal functions. Compartments are formed by nucleosomal interactions, but how TADs and loops are generated is unknown. It has been proposed that cohesin forms these structures by extruding loops until it encounters CTCF, but direct evidence for this hypothesis is missing. Here we show that cohesin suppresses compartments but is essential for TADs and loops, that CTCF defines their boundaries, and that WAPL and its PDS5 binding partners control the length of chromatin loops. In the absence of WAPL and PDS5 proteins, cohesin passes CTCF sites with increased frequency, forms extended chromatin loops, accumulates in axial chromosomal positions (vermicelli) and condenses chromosomes to an extent normally only seen in mitosis. These results show that cohesin has an essential genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA by WAPL.
Delayed activation of the DNA replication licensing system in Lgr5(+) intestinal stem cells
Authors: Carroll T.D. , Newton I.P. , Chen Y. , Blow J.J. , Näthke I.
Published: August 2017

During late mitosis and early G1, replication origins are licensed for replication by binding to double hexamers of MCM2-7. Here, we investigate how licensing and proliferative commitment are coupled in the small-intestinal epithelium. We developed a method for identifying cells in intact tissue containing DNA-bound MCM2-7. Interphase cells above the transit-amplifying compartment had no DNA-bound MCM2-7, but still expressed MCM2-7 protein, suggesting that licensing is inhibited immediately upon differentiation. Strikingly, we found most proliferative Lgr5(+) stem cells are in an unlicensed state. This suggests that the elongated cell-cycle of intestinal stem-cells is caused by an increased G1length, characterised by dormant periods with unlicensed origins. Significantly, the unlicensed state is lost InApcmutant epithelium, which lacks a functional restriction point, causing licensing immediately upon G1entry. We propose that the unlicensed G1of intestinal stem cells creates a temporal window when proliferative fate decisions can be made.
BUSCO applications from quality assessments to gene prediction and phylogenomics
Authors: Waterhouse Robert M. , Seppey Mathieu , Simão Felipe A. , Manni Mosè , Ioannidis Panagiotis , Klioutchnikov Guennadi , Kriventseva Evgenia V. , Zdobnov Evgeny M.
Published: August 2017

Genomics promises comprehensive surveying of genomes and metagenomes, but rapidly changing technologies and expanding data volumes make evaluation of completeness a challenging task. Technical sequencing quality metrics can be complemented by quantifying completeness in terms of the expected gene content of Benchmarking Universal Single-Copy Orthologs (BUSCO,http://busco.ezlab.org). Now in its third release, BUSCO utilities extend beyond quality control to applications in comparative genomics, gene predictor training, metagenomics, and phylogenomics.
Single-cell RNA sequencing reveals cell-type specificcis-eQTLs in peripheral blood mononuclear cells
Authors: van der Wijst M.G.P. , Brugge H. , de Vries D.H. , Franke L.H.
Published: August 2017

Most disease-associated genetic risk factors are regulatory. Here, we generated single-cell RNA-seq data of ∼25,000 peripheral blood mononuclear cells from 45 donors to identify how genetic variants affect gene expression. We validated this approach by replicating previously published whole blood RNA-seqcis-expression quantitative trait loci effects (cis-eQTLs), but also identified new cell type-specificcis-eQTLs. These eQTLs give additional insight into the downstream consequences of genetic risk factors for immune-mediated diseases.
Measuring functional connectivity in stroke – approaches and considerations
Authors: Siegel Joshua S. , Shulman Gordon L. , Corbetta Maurizio
Published: August 2017

Recent research has demonstrated the importance of global changes to the functional organization of brain network following stroke. Resting functional MRI (R-fMRI) is a non-invasive tool that enables the measurement of functional connectivity (FC) across the entire brain while placing minimal demands on the subject. For these reasons, it is a uniquely appealing tool for studying the distant effects of stroke. However, R-fMRI studies rely on a number of premises that cannot be assumed without careful validation in the context of stroke. Here, we describe strategies to identify and mitigate confounds specific to R-fMRI research in cerebrovascular disease. Five main topics are discussed: 1) achieving adequate co-registration of lesioned brains, 2) identifying and removing hemodynamic lags in resting BOLD, 3) identifying other vascular disruptions that affect the resting BOLD signal, 4) selecting an appropriate control cohort, and 5) acquiring sufficient fMRI data to reliably identify FC changes. For each topic, we provide evidence-based guidelines for steps to improve the interpretability and reproducibility of FC-stroke research. We include a table of confounds and approaches to identify and mitigate each. Our recommendations extend to any research using R-fMRI to study diseases that might alter cerebrovascular flow and dynamics or brain anatomy.
A non-catalytic role of TET3 promotes open chromatin and enhances global transcription
Authors: Krueger Christel , Peat Julian R. , Eckersley-Maslin Melanie A. , Hore Timothy A. , Mohammed Hisham , Andrews Simon R. , Dean Wendy , Reik Wolf
Published: August 2017

The methylcytosine dioxygenase Tet3 is highly expressed as a specific isoform in oocytes and zygotes but essentially absent from later stages of mouse preimplantation development. Here, we show that Tet3 expression promotes transdifferentiation of embryonic stem cells to trophoblast-like stem cells. By genome-wide analyses we demonstrate that TET3 associates with and co-occupies chromatin with RNA Polymerase II. Tet3 expression induces a global increase of transcription and total RNA levels, and its presence further enhances chromatin accessibility in regions open for transcription. This novel function of TET3 is not specific to the oocyte isoform, independent of its catalytic activity, the CXXC domain, or its interaction with OGT, and is localised in its highly conserved exon 4. We propose a more general role for TET3 promoting open chromatin and enhancing global transcription during changes of cellular identity, separate from its catalytic function.
Dynamic, non-contact 3D sample rotation for microscopy
Authors: Berndt Frederic , Shah Gopi , Brugués Jan , Huisken Jan
Published: August 2017

In vivoimaging of growing and developing samples requires a dynamic adaptation of the sample orientation to continuously achieve optimal performance. Here, we present how, after the injection of magnetic beads, a sample can be freely positioned by applying a magnetic field. We demonstrate its performance for zebrafish on an epi-fluorescence microscope and on a light sheet system for superior multi-view acquisition.
Replication of early and recent Zika virus isolates throughout mouse brain development
Authors: Rosenfeld Amy B , Doobin David J , Warren Audrey L , Racaniello Vincent R , Vallee Richard B
Published: August 2017

Fetal infection with Zika virus (ZIKV) can lead to congenital Zika virus syndrome (cZVS), which includes cortical malformations and microcephaly. The aspects of cortical development that are affected during virus infection are unknown. Using organotypic brain slice cultures generated from embryonic mice of various ages, sites of ZIKV replication including the neocortical proliferative zone and radial columns, as well as the developing midbrain, were identified. The infected radial units are surrounded by uninfected cells undergoing apoptosis, suggesting that programmed cell death may limit viral dissemination in the brain and may constrain virus associated injury. Therefore, a critical aspect of ZIKV induced neuropathology may be defined by death of uninfected cells. All ZIKV isolates assayed replicated efficiently in early and mid-gestation cultures, and two isolates examined replicated in late-gestation tissue. Alteration of neocortical cytoarchitecture, such as disruption of the highly-elongated basal processes of the radial glial progenitor cells, and impairment of postmitotic neuronal migration were also observed. These data suggest that all lineages of ZIKV tested are neurotropic, and that ZIKV infection interferes with multiple aspects of neurodevelopment that contribute to the complexity of cZVS.

Significance

Zika virus infection has been associated with multiple pathologies of the central nervous system (CNS) including microcephaly, Guillain-Barré syndrome, lissencephaly, the loss of white and grey matter volume and acute myelitis. Using organotypic brain slice cultures, we determined that ZIKV replicates across different embryonic developmental stages, and viral infection can disrupt proper brain development leading to congenital CNS complications. These data illustrate that all lineages of ZIKV tested are neurotropic, and that infection may disrupt neuronal migration during brain development. The results expand our understanding of neuropathologies associated with congenital Zika virus syndrome.
Supramolecular architectures in the salt trimethoprimium ferrocene-1-carboxylate and the cocrystal 4-amino-5-chloro-2,6-dimethylpyrimidine–ferrocene-1-carboxylic acid (1/1)
Authors: Swinton Darious Robert , Thomas Muthiah Packianathan , Perdih Franc
Published: August 2017

In the salt trimethoprimium ferrocenecarboxylate [systematic name: 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidin-1-ium ferrocene-1-carboxylate], (C14H19N4O3)[Fe(C5H5)(C6H4O2)], (I), of the antibacterial compound trimethoprim, the carboxylate group interacts with the protonated aminopyrimidine group of trimethoprim via two N—H...O hydrogen bonds, generating a robust R
2
2(8) ring motif (heterosynthon). However, in the cocrystal 4-amino-5-chloro-2,6-dimethylpyrimidine–ferrocene-1-carboxylic acid (1/1), [Fe(C5H5)(C6H5O2)]·C6H8ClN3, (II), the carboxyl–aminopyrimidine interaction [R
2
2(8) motif] is absent. The carboxyl group interacts with the pyrimidine ring via a single O—H...N hydrogen bond. The pyrimidine rings, however, form base pairs via a pair of N—H...N hydrogen bonds, generating an R
2
2(8) supramolecular homosynthon. In salt (I), the unsubstituted cyclopentadienyl ring is disordered over two positions, with a refined site-occupation ratio of 0.573 (10):0.427 (10). In this study, the two five-membered cyclopentadienyl (Cp) rings of ferrocene are in a staggered conformation, as is evident from the C...Cg...Cg...C pseudo-torsion angles, which are in the range 36.13–37.53° for (I) and 22.58–23.46° for (II). Regarding the Cp ring of the minor component in salt (I), the geometry of the ferrocene ring is in an eclipsed conformation, as is evident from the C...Cg...Cg...C pseudo-torsion angles, which are in the range 79.26–80.94°. Both crystal structures are further stabilized by weak π–π interactions.
2017 publication guidelines for structural modelling of small-angle scattering data from biomolecules in solution: an update
Authors: Trewhella Jill , Duff Anthony P. , Durand Dominique , Gabel Frank , Guss J. Mitchell , Hendrickson Wayne A. , Hura Greg L. , Jacques David A. , Kirby Nigel M. , Kwan Ann H. , Pérez Javier , Pollack Lois , Ryan Timothy M. , Sali Andrej , Schneidman-Duhovny Dina , Schwede Torsten , Svergun Dmitri I. , Sugiyama Masaaki , Tainer John A. , Vachette Patrice , Westbrook John , Whitten Andrew E.
Published: August 2017

In 2012, preliminary guidelines were published addressing sample quality, data acquisition and reduction, presentation of scattering data and validation, and modelling for biomolecular small-angle scattering (SAS) experiments. Biomolecular SAS has since continued to grow and authors have increasingly adopted the preliminary guidelines. In parallel, integrative/hybrid determination of biomolecular structures is a rapidly growing field that is expanding the scope of structural biology. For SAS to contribute maximally to this field, it is essential to ensure open access to the information required for evaluation of the quality of SAS samples and data, as well as the validity of SAS-based structural models. To this end, the preliminary guidelines for data presentation in a publication are reviewed and updated, and the deposition of data and associated models in a public archive is recommended. These guidelines and recommendations have been prepared in consultation with the members of the International Union of Crystallography (IUCr) Small-Angle Scattering and Journals Commissions, the Worldwide Protein Data Bank (wwPDB) Small-Angle Scattering Validation Task Force and additional experts in the field.
Academic stratospheres-cum-underworlds: when highs and lows of publication cultures meet
Authors: Stöckelová Tereza , Vostal Filip
Published: August 2017

Purpose

The purpose of this paper is to link up and think through two bodies of literature, namely the critique of predatory publishing practices and the critique of political economy of established publishers, while introducing a reflection on the dynamic asymmetries of geopolitics and economics of globalizing knowledge production.

Design/methodology/approach

The authors deploy a conceptual approach developed with reference to a case study in order to explore the embedded logic of the current system of academic publishing.

Findings

The analysis shows that rather than examining two seemingly different issues (predatory publishing vs established publishers) as conflictual dualism, it is more productive to conceive them in associative and mutually constitutive fashion.

Research limitations/implications

A nuanced and multidimensional research approach is needed if we are to understand the dynamics of contemporary academic landscape.

Originality/value

The originality of the contribution lies in its problematizing of three established approaches that feature debates on the transformation of the academy. It moves beyond a micro-level explanation by (the lack of) individual morality as well as a structural explanatory framework preoccupied with publishing infrastructure and culturalist approach based on ready-made dichotomies of west/north vs south/east. Instead, the analysis provides an account that engages both with morality and geopolitics whilst tackling them as dynamic processes in making.