Remotely identifying potential vector habitat in areas of refugee and displaced person populations due to the Syrian civil war

Historically leishmaniasis is most prevalent in established urban centres but this research shows that refugees and, most significantly, internally displaced persons are now commonly in areas characterized by the presence of fly habitats potentially leading to higher prominence of Leishmania infection. Areas engulfed by the Syrian civil war has thus caused the dispersal of humans into previously unpopulated areas amid habitats of the sand fly Phlebotomus papatasi that hosts the parasite Leishmania. The addition of new places of exposure to this disease add to difficulties with respect to diagnosis as well as provision of care and treatment. We used geospatial methodology adapting it to remotely identifying and analyzing sand fly habitats with the aim of measuring how common it is. Our methodology helps avoid the issue of resolution in satellite imagery by measuring likelihood rather than strictly known locations. We followed up this information with spatial analysis identifying which civilian populations are most prone to sand fly exposure, and therefore leishmaniasis, due to their geographical situation. Our results suggest that those most likely to be exposed to Leishmania are internally displaced persons, those camps less likely to receive medical relief and typically having temporary residents migrating elsewhere

2008 NE 1020 Cold Hardy Wine Grape Cultivar Trial Performance in 2010

In conjunction with the Northeast Regional Research project NE 1020 “Multi-state Evaluation of Wine Grape Cultivars and Clones,” Iowa State University established a cold hardy wine grape cultivar trial in 2008 at the ISU Horticulture Research Station (HRS) and Tabor Home Vineyards and Winery (THV) near Baldwin, IA. The Iowa trial evaluates the performance of Corot noir, La Crescent, Marquette, Petit Amie, NY 95.0301- 01, MN-1189, MN-1200, MN-1220, MN- 1235, MN-1258, with Frontenac and St. Croix serving as controls. Similar plantings were established in SD, NE, and MO, as well as in CT, IN, KY, and MI. This report summarizes the results for the 2010 growing season

Real-time single-molecule observation of rolling-circle DNA replication

We present a simple technique for visualizing replication of individual DNA molecules in real time. By attaching a rolling-circle substrate to a TIRF microscope-mounted flow chamber, we are able to monitor the progression of single-DNA synthesis events and accurately measure rates and processivities of single T7 and Escherichia coli replisomes as they replicate DNA. This method allows for rapid and precise characterization of the kinetics of DNA synthesis and the effects of replication inhibitors

Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis

In all organisms, the protein machinery responsible for the replication of DNA, the replisome, is faced with a directionality problem. The antiparallel nature of duplex DNA permits the leading-strand polymerase to advance in a continuous fashion, but forces the lagging-strand polymerase to synthesize in the opposite direction. By extending RNA primers, the lagging-strand polymerase restarts at short intervals and produces Okazaki fragments. At least in prokaryotic systems, this directionality problem is solved by the formation of a loop in the lagging strand of the replication fork to reorient the lagging-strand DNA polymerase so that it advances in parallel with the leading-strand polymerase. The replication loop grows and shrinks during each cycle of Okazaki fragment synthesis. Here we use single-molecule techniques to visualize, in real time, the formation and release of replication loops by individual replisomes of bacteriophage T7 supporting coordinated DNA replication. Analysis of the distributions of loop sizes and lag times between loops reveals that initiation of primer synthesis and the completion of an Okazaki fragment each serve as a trigger for loop release. The presence of two triggers may represent a fail-safe mechanism ensuring the timely reset of the replisome after the synthesis of every Okazaki fragment.

Finishing a whole-genome shotgun: Release 3 of the Drosophila melanogaster euchromatic genome sequence

BACKGROUND: The Drosophila melanogaster genome was the first metazoan genome to have been sequenced by the whole-genome shotgun (WGS) method. Two issues relating to this achievement were widely debated in the genomics community: how correct is the sequence with respect to base-pair (bp) accuracy and frequency of assembly errors? And, how difficult is it to bring a WGS sequence to the accepted standard for finished sequence? We are now in a position to answer these questions. RESULTS: Our finishing process was designed to close gaps, improve sequence quality and validate the assembly. Sequence traces derived from the WGS and draft sequencing of individual bacterial artificial chromosomes (BACs) were assembled into BAC-sized segments. These segments were brought to high quality, and then joined to constitute the sequence of each chromosome arm. Overall assembly was verified by comparison to a physical map of fingerprinted BAC clones. In the current version of the 116.9 Mb euchromatic genome, called Release 3, the six euchromatic chromosome arms are represented by 13 scaffolds with a total of 37 sequence gaps. We compared Release 3 to Release 2; in autosomal regions of unique sequence, the error rate of Release 2 was one in 20,000 bp. CONCLUSIONS: The WGS strategy can efficiently produce a high-quality sequence of a metazoan genome while generating the reagents required for sequence finishing. However, the initial method of repeat assembly was flawed. The sequence we report here, Release 3, is a reliable resource for molecular genetic experimentation and computational analysis

Genetic modifiers in rare disorders: the case of fragile X syndrome.

Methods employed in genome-wide association studies are not feasible ways to explore genotype-phenotype associations in rare disorders due to limited statistical power. An alternative approach is to examine relationships among specific single nucleotide polymorphisms (SNPs), selected a priori, and behavioural characteristics. Here, we adopt this strategy to examine relationships between three SNPs (5-HTTLPR, MAOA, COMT) and specific clinically-relevant behaviours that are phenotypic of fragile X syndrome (FXS) but vary in severity and frequency across individuals. Sixty-four males with FXS participated in the current study. Data from standardised informant measures of challenging behaviour (defined as physical aggression, property destruction, stereotyped behaviour, and self-injury), autism symptomatology, attention-deficit-hyperactivity-disorder characteristics, repetitive behaviour and mood/interest and pleasure were compared between each SNP genotype. No association was observed between behavioural characteristics and either 5-HTTLPR (serotonin) or MAOA (monoamine oxidase) genotypes. However, compared to the COMT (dopamine) AG and GG genotypes, the AA genotype was associated with greater interest and pleasure in the environment, and with reduced risk for property destruction, stereotyped behaviour and compulsive behaviour. The results suggest that common genetic variation in the COMT genotype affecting dopamine levels in the brain may contribute to the variability of challenging and repetitive behaviours and interest and pleasure in this population. This study identifies a role for additional genetic risk in understanding the neural and genetic mechanisms contributing to phenotypic variability in neurodevelopmental disorders, and highlights the merit of investigating SNPs that are selected a priori on a theoretical basis in rare populations

Nearly Perfect Fluidity: From Cold Atomic Gases to Hot Quark Gluon Plasmas

Shear viscosity is a measure of the amount of dissipation in a simple fluid. In kinetic theory shear viscosity is related to the rate of momentum transport by quasi-particles, and the uncertainty relation suggests that the ratio of shear viscosity eta to entropy density s in units of hbar/k_B is bounded by a constant. Here, hbar is Planck's constant and k_B is Boltzmann's constant. A specific bound has been proposed on the basis of string theory where, for a large class of theories, one can show that eta/s is greater or equal to hbar/(4 pi k_B). We will refer to a fluid that saturates the string theory bound as a perfect fluid. In this review we summarize theoretical and experimental information on the properties of the three main classes of quantum fluids that are known to have values of eta/s that are smaller than hbar/k_B. These fluids are strongly coupled Bose fluids, in particular liquid helium, strongly correlated ultracold Fermi gases, and the quark gluon plasma. We discuss the main theoretical approaches to transport properties of these fluids: kinetic theory, numerical simulations based on linear response theory, and holographic dualities. We also summarize the experimental situation, in particular with regard to the observation of hydrodynamic behavior in ultracold Fermi gases and the quark gluon plasma.Comment: 76 pages, 11 figures, review article, extensive revision

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas