Simulation and study of the geometric parameters in the inguinal area and the genesis of inguinal hernias

We are interested in studying the genesis of a very common pathology: the human inguinal hernia. How the human inguinal hernia appears is not definitively clear, but it is accepted that it is caused by a combination of mechanical and biochemical alterations, and that muscular simulation plays an important role in this. This study proposes a model to explain how some physical parameters affect the ability to simulate the region dynamically and how these parameters are involved in generating inguinal hernias. We are particularly interested in understanding the mechanical alterations in the inguinal region because little is known about them or how they behave dynamically. Our model corroborates the most important theories regarding the generation of inguinal hernias and is an initial approach to numerically evaluating this affection.     

Synthesis of 1,5-Anhydrohexitol Nucleosides as Mimics of AZT,D4T and DDC

Abstract

1,5-Anhydrohexitol congeners of AZT, D4T and DDC were synthesized. These compounds did not show anti-HIV activity.

     

Potential effects of climate change on biological control systems: case studies from New Zealand

Biological control systems are integral to New Zealand’s success as a nation reliant on exporting quality agricultural, forestry and horticultural products. The likely impacts of climate change projections to 2090 on one weed and four invertebrate management systems in differing production sectors were investigated, and it was concluded that most natural enemies will track the changing distributions of their hosts. The key climate change challenges identified were: disparities in natural enemy capability to change distribution, lack of frosts leading to emergence of new pests and additional pest generations, non-target impacts from range and temperature changes, increased disruptions caused by extreme weather events, disruption of host-natural enemy synchrony, and insufficient genetic diversity to allow evolutionary adaptation. Five classical biological control systems based on the introduced species Longitarsus jacobaeae, Cotesia kazak, Aphelinus mali, Microctonus aethiopoides and Microctonus hyperodae are discussed in more detail.     

Wheat Zapper: a flexible online tool for colinearity studies in grass genomes

In the course of evolution, the genomes of grasses have maintained an observable degree of gene order conservation. The information available for already sequenced genomes can be used to predict the gene order of nonsequenced species by means of comparative colinearity studies. The “Wheat Zapper” application presented here performs on-demand colinearity analysis between wheat, rice, Sorghum, and Brachypodium in a simple, time efficient, and flexible manner. This application was specifically designed to provide plant scientists with a set of tools, comprising not only synteny inference, but also automated primer design, intron/exon boundaries prediction, visual representation using the graphic tool Circos 0.53, and the possibility of downloading FASTA sequences for downstream applications. Quality of the “Wheat Zapper” prediction was confirmed against the genome of maize, with good correlation (r?>?0.83) observed between the gene order predicted on the basis of synteny and their actual position on the genome. Further, the accuracy of “Wheat Zapper” was calculated at 0.65 considering the “Genome Zipper” application as the “gold” standard. The differences between these two tools are amply discussed, making the point that “Wheat Zapper” is an accurate and reliable on-demand tool that is sure to benefit the cereal scientific community. The Wheat Zapper is available at http://wge.ndsu.nodak.edu/wheatzapper/.     

Dectin-1 Is Essential for Reverse Transcytosis of Glycosylated SIgA-Antigen Complexes by Intestinal M Cells

Intestinal microfold (M) cells possess a high transcytosis capacity and are able to transport a broad range of materials including particulate antigens, soluble macromolecules, and pathogens from the intestinal lumen to inductive sites of the mucosal immune system. M cells are also the primary pathway for delivery of secretory IgA (SIgA) to the gut-associated lymphoid tissue. However, although the consequences of SIgA uptake by M cells are now well known and described, the mechanisms whereby SIgA is selectively bound and taken up remain poorly understood. Here we first demonstrate that both the Cα1 region and glycosylation, more particularly sialic acid residues, are involved in M cell–mediated reverse transcytosis. Second, we found that SIgA is taken up by M cells via the Dectin-1 receptor, with the possible involvement of Siglec-5 acting as a co-receptor. Third, we establish that transcytosed SIgA is taken up by mucosal CX3CR1⁺ dendritic cells (DCs) via the DC-SIGN receptor. Fourth, we show that mucosal and systemic antibody responses against the HIV p24-SIgA complexes administered orally is strictly dependent on the expression of Dectin-1. Having deciphered the mechanisms leading to specific targeting of SIgA-based Ag complexes paves the way to the use of such a vehicle for mucosal vaccination against various infectious diseases.     

Mechanistic Phenotypes: An Aggregative Phenotyping Strategy to Identify Disease Mechanisms Using GWAS Data

A single mutation can alter cellular and global homeostatic mechanisms and give rise to multiple clinical diseases. We hypothesized that these disease mechanisms could be identified using low minor allele frequency (MAF<0.1) non-synonymous SNPs (nsSNPs) associated with “mechanistic phenotypes”, comprised of collections of related diagnoses. We studied two mechanistic phenotypes: (1) thrombosis, evaluated in a population of 1,655 African Americans; and (2) four groupings of cancer diagnoses, evaluated in 3,009 white European Americans. We tested associations between nsSNPs represented on GWAS platforms and mechanistic phenotypes ascertained from electronic medical records (EMRs), and sought enrichment in functional ontologies across the top-ranked associations. We used a two-step analytic approach whereby nsSNPs were first sorted by the strength of their association with a phenotype. We tested associations using two reverse genetic models and standard additive and recessive models. In the second step, we employed a hypothesis-free ontological enrichment analysis using the sorted nsSNPs to identify functional mechanisms underlying the diagnoses comprising the mechanistic phenotypes. The thrombosis phenotype was solely associated with ontologies related to blood coagulation (Fisher''s p = 0.0001, FDR p = 0.03), driven by the F5, P2RY12 and F2RL2 genes. For the cancer phenotypes, the reverse genetics models were enriched in DNA repair functions (p = 2×10−5, FDR p = 0.03) (POLG/FANCI, SLX4/FANCP, XRCC1, BRCA1, FANCA, CHD1L) while the additive model showed enrichment related to chromatid segregation (p = 4×10−6, FDR p = 0.005) (KIF25, PINX1). We were able to replicate nsSNP associations for POLG/FANCI, BRCA1, FANCA and CHD1L in independent data sets. Mechanism-oriented phenotyping using collections of EMR-derived diagnoses can elucidate fundamental disease mechanisms.     

Characterization of a New Chronic Lymphocytic Leukemia Cell Line for Mechanistic In Vitro and In Vivo Studies Relevant to Disease

Studies of chronic lymphocytic leukemia (CLL) have yielded substantial progress, however a lack of immortalized cell lines representative of the primary disease has hampered a full understanding of disease pathogenesis and development of new treatments. Here we describe a novel CLL cell line (OSU-CLL) generated by EBV transformation, which displays a similar cytogenetic and immunophenotype observed in the patient’s CLL (CD5 positive with trisomy 12 and 19). A companion cell line was also generated from the same patient (OSU-NB). This cell line lacked typical CLL characteristics, and is likely derived from the patient’s normal B cells. In vitro migration assays demonstrated that OSU-CLL exhibits migratory properties similar to primary CLL cells whereas OSU-NB has significantly reduced ability to migrate spontaneously or towards chemokine. Microarray analysis demonstrated distinct gene expression patterns in the two cell lines, including genes on chromosomes 12 and 19, which is consistent with the cytogenetic profile in this cell line. Finally, OSU-CLL was readily transplantable into NOG mice, producing uniform engraftment by three weeks with leukemic cells detectable in the peripheral blood spleen and bone marrow. These studies describe a new CLL cell line that extends currently available models to study gene function in this disease.     

High-Contrast Fluorescence Imaging in Fixed and Living Cells Using Optimized Optical Switches

We present the design, synthesis and characterization of new functionalized fluorescent optical switches for rapid, all-visible light-mediated manipulation of fluorescence signals from labelled structures within living cells, and as probes for high-contrast optical lock-in detection (OLID) imaging microscopy. A triazole-substituted BIPS (TzBIPS) is identified from a rational synthetic design strategy that undergoes robust, rapid and reversible, visible light-driven transitions between a colorless spiro- (SP) and a far-red absorbing merocyanine (MC) state within living cells. The excited MC-state of TzBIPS may also decay to the MC-ground state emitting near infra-red fluorescence, which is used as a sensitive and quantitative read-out of the state of the optical switch in living cells. The SP to MC transition for a membrane-targeted TzBIPS probe (C₁₂-TzBIPS) is triggered at 405 nm at an energy level compatible with studies in living cells, while the action spectrum of the reverse transition (MC to SP) has a maximum at 650 nm. The SP to MC transition is complete within the 790 ns pixel dwell time of the confocal microscope, while a single cycle of optical switching between the SP and MC states in a region of interest is complete within 8 ms (125 Hz) within living cells, the fastest rate attained for any optical switch probe in a biological sample. This property can be exploited for real-time correction of background signals in living cells. A reactive form of TzBIPS is linked to secondary antibodies and used, in conjunction with an enhanced scope-based analysis of the modulated MC-fluorescence in immuno-stained cells, for high-contrast immunofluorescence microscopic analysis of the actin cytoskeleton.     

Psychological and Social Factors Associated with Late Pregnancy Iron Deficiency Anaemia in Rural Viet Nam: A Population-Based Prospective Study

Objectives

The aim of this study was to examine the relationships between psychological and social factors and late pregnancy IDA among pregnant women in rural Viet Nam.

Methods

Pregnant women from 50 randomly-selected communes within Ha Nam province were recruited and assessed at 12 - 20 weeks gestation (Wave 1, W1). They were followed up in the last trimester (Wave 2, W2). IDA was defined as Haemoglobin < 11 g/dL and serum ferritin < 15 ng/mL. Symptoms of Common Mental Disorders (CMD) were assessed by the Edinburgh Postnatal Depression Scale-Vietnam (EPDS-V). Persistent antenatal CMD was defined as having an EPDS-V score ≥ 4 in both W1 and W2. Hypothesis models were tested by Structural Equation Modeling analyses.

Results

A total of 378 women provided complete data at both W1 and W2. The incidence risk of IDA in the third trimester was 13.2% (95% confidence interval (CI): 9.8-16.7). Persistent CMD was found in 16.9% (95% CI: 13.1-20.7) pregnant women and predicted by intimate partner violence, fear of other family members, experience of childhood abuse, coincidental life adversity, and having a preference for the sex of the baby. There was a significant pathway from persistent CMD to IDA in late pregnancy via the length of time that iron supplements had been taken. Receiving advice to take iron supplements and higher household wealth index were indirectly related to lower risk of late pregnancy IDA. Early pregnancy IDA and being multi-parous also contributed to late pregnancy IDA.

Conclusions

Antenatal IDA and CMD are prevalent public health problems among women in Viet Nam. The link between them suggests that while direct recommendations to use iron supplements are important, the social factors associated with common mental disorders should be addressed in antenatal care in order to improve the health of pregnant women and their infants.