Inhibition of Aflatoxin Formation in Aspergillus Species by Peanut (Arachis hypogaea) Seed Stilbenoids in the Course of Peanut− Fungus Interaction

Common soil fungi, Aspergillus flavus and Aspergillus parasiticus, are opportunistic pathogens that invade preharvest peanut seeds. These fungi often produce carcinogenic aflatoxins that pose a threat to human and animal health through food chains and cause significant economic losses worldwide. Detection of aflatoxins and further processing of crops are mandated to ensure that contaminated agricultural products do not enter food channels. Under favorable conditions, the fungus-challenged peanut seeds produce phytoalexins, structurally related stilbenoids, capable of retarding fungal development. The purpose of the present study was to evaluate the potential influence of peanut phytoalexins on fungal development and aflatoxin formation in the course of peanut−fungus interaction. The present research revealed that during such interaction, aflatoxin formation was completely suppressed in A. flavus and A. parasiticus strains tested, when low concentrations of spores were introduced to wounded preincubated peanuts. In most of the experiments, when fungal spore concentrations were 2 orders of magnitude higher, the spores germinated and produced aflatoxins. Of all experimental seeds that showed fungal growth, 57.7% were aflatoxin-free after 72 h of incubation. The research provided new knowledge on the aflatoxin/phytoalexin formation in the course of peanut−fungus interaction

Transformation of Major Peanut (Arachis hypogaea) Stilbenoid Phytoalexins Caused by Selected Microorganisms

The peanut plant accumulates defensive stilbenoid phytoalexins in response to the presence of soil fungi, which in turn produce phytoalexin-detoxifying enzymes for successfully invading the plant host. Aspergillus spp. are opportunistic pathogens that invade peanut seeds; most common fungal species often produce highly carcinogenic aflatoxins. The purpose of the present research was to evaluate the in vitro dynamics of peanut phytoalexin transformation/detoxification by important fungal species. This work revealed that in feeding experiments, Aspergillus spp. from section Flavi were capable of degrading the major peanut phytoalexin, arachidin-3, into its hydroxylated homolog, arachidin-1, and a benzenoid, SB-1. However, Aspergillus niger from section Nigri as well as other fungal and bacterial species tested, which are not known to be involved in the infection of the peanut plant, were incapable of changing the structure of arachidin-3. The results of feeding experiments with arachidin-1 and resveratrol are also reported. The research provided new knowledge on the dynamics of peanut stilbenoid transformations by essential fungi. These findings may contribute to the elucidation of the phytoalexin detoxification mechanism involved in the infection of peanut by important toxigenic Aspergillus spp

Maxwellian gas undergoing a stationary Poiseuille flow in a pipe

The hierarchy of moment equations derived from the nonlinear Boltzmann equation is solved for a gas of Maxwell molecules undergoing a stationary Poiseuille flow induced by an external force in a pipe. The solution is obtained as a perturbation expansion in powers of the force (through third order). A critical comparison is done between the Navier-Stokes theory and the predictions obtained from the Boltzmann equation for the profiles of the hydrodynamic quantities and their fluxes. The Navier-Stokes description fails to first order and, especially, to second order in the force. Thus, the hydrostatic pressure is not uniform, the temperature profile exhibits a non-monotonic behavior, a longitudinal component of the flux exists in the absence of longitudinal thermal gradient, and normal stress differences are present. On the other hand, comparison with the Bhatnagar-Gross-Krook model kinetic equation shows that the latter is able to capture the correct functional dependence of the fields, although the numerical values of the coefficients are in general between 0.38 and 1.38 times the Boltzmann values. A short comparison with the results corresponding to the planar Poiseuille flow is also carried out.Comment: 31 pages, 6 figures; to be published in Physica

Images of photoreceptors in living primate eyes using adaptive optics two-photon ophthalmoscopy

In vivo two-photon imaging through the pupil of the primate eye has the potential to become a useful tool for functional imaging of the retina. Two-photon excited fluorescence images of the macaque cone mosaic were obtained using a fluorescence adaptive optics scanning laser ophthalmoscope, overcoming the challenges of a low numerical aperture, imperfect optics of the eye, high required light levels, and eye motion. Although the specific fluorophores are as yet unknown, strong in vivo intrinsic fluorescence allowed images of the cone mosaic. Imaging intact ex vivo retina revealed that the strongest two-photon excited fluorescence signal comes from the cone inner segments. The fluorescence response increased following light stimulation, which could provide a functional measure of the effects of light on photoreceptors

COMAP Early Science: II. Pathfinder Instrument

Line intensity mapping (LIM) is a new technique for tracing the global properties of galaxies over cosmic time. Detection of the very faint signals from redshifted carbon monoxide (CO), a tracer of star formation, pushes the limits of what is feasible with a total-power instrument. The CO Mapping Project (COMAP) Pathfinder is a first-generation instrument aiming to prove the concept and develop the technology for future experiments, as well as delivering early science products. With 19 receiver channels in a hexagonal focal plane arrangement on a 10.4 m antenna, and an instantaneous 26-34 GHz frequency range with 2 MHz resolution, it is ideally suited to measuring CO($J$=1-0) from $z\sim3$. In this paper we discuss strategies for designing and building the Pathfinder and the challenges that were encountered. The design of the instrument prioritized LIM requirements over those of ancillary science. After a couple of years of operation, the instrument is well understood, and the first year of data is already yielding useful science results. Experience with this Pathfinder will drive the design of the next generations of experiments.Comment: Paper 2 of 7 in series. 27 pages, 28 figures, submitted to Ap

Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease

Genetic association studies have identified 215 risk loci for inflammatory bowel disease, thereby uncovering fundamental aspects of its molecular biology. We performed a genome-wide association study of 25,305 individuals and conducted a meta-analysis with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new susceptibility loci, 3 of which contain integrin genes that encode proteins in pathways that have been identified as important therapeutic targets in inflammatory bowel disease. The associated variants are correlated with expression changes in response to immune stimulus at two of these genes ($\textit{ITGA4 }$ and $\textit{ITGB8}$) and at previously implicated loci ($\textit{ITGAL }$and $\textit{ICAM1}$). In all four cases, the expression-increasing allele also increases disease risk. We also identified likely causal missense variants in a gene implicated in primary immune deficiency, $\textit{PLCG2}$, and a negative regulator of inflammation, $\textit{SLAMF8}$. Our results demonstrate that new associations at common variants continue to identify genes relevant to therapeutic target identification and prioritization.This work was co-funded by the Wellcome Trust [098051] and the Medical Research Council, UK [MR/J00314X/1]. Case collections were supported by Crohn’s and Colitis UK. KMdL, LM, CAL, YL, DR, JG-A, NJP, CAA and JCB are supported by the Wellcome Trust [098051; 093885/Z/10/Z; 094491/Z/10/Z]. KMdL is supported by a Woolf Fisher Trust scholarship. CAL is a clinical lecturer funded by the NIHR. We thank Anna Stanton for co-ordinating the Guy’s and St Thomas’ patient recruitment. We acknowledge support from the Department of Health via the NIHR comprehensive Biomedical Research Centre awards to Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London and to Addenbrooke’s Hospital, Cambridge in partnership with the University of Cambridge. This research was also supported by the NIHR Newcastle Biomedical Research Centre. The UK Household Longitudinal Study is led by the Institute for Social and Economic Research at the University of Essex and funded by the Economic and Social Research Council

COMAP Early Science: I. Overview

The CO Mapping Array Project (COMAP) aims to use line intensity mapping of carbon monoxide (CO) to trace the distribution and global properties of galaxies over cosmic time, back to the Epoch of Reionization (EoR). To validate the technologies and techniques needed for this goal, a Pathfinder instrument has been constructed and fielded. Sensitive to CO(1-0) emission from $z=2.4$-$3.4$ and a fainter contribution from CO(2-1) at $z=6$-8, the Pathfinder is surveying $12$ deg$^2$ in a 5-year observing campaign to detect the CO signal from $z\sim3$. Using data from the first 13 months of observing, we estimate $P_\mathrm{CO}(k) = -2.7 \pm 1.7 \times 10^4\mu\mathrm{K}^2 \mathrm{Mpc}^3$ on scales $k=0.051-0.62 \mathrm{Mpc}^{-1}$ - the first direct 3D constraint on the clustering component of the CO(1-0) power spectrum. Based on these observations alone, we obtain a constraint on the amplitude of the clustering component (the squared mean CO line temperature-bias product) of $\langle Tb\rangle^2<49$ $\mu$K$^2$ - nearly an order-of-magnitude improvement on the previous best measurement. These constraints allow us to rule out two models from the literature. We forecast a detection of the power spectrum after 5 years with signal-to-noise ratio (S/N) 9-17. Cross-correlation with an overlapping galaxy survey will yield a detection of the CO-galaxy power spectrum with S/N of 19. We are also conducting a 30 GHz survey of the Galactic plane and present a preliminary map. Looking to the future of COMAP, we examine the prospects for future phases of the experiment to detect and characterize the CO signal from the EoR.Comment: Paper 1 of 7 in series. 18 pages, 16 figures, submitted to Ap

Divergent Genomic and Epigenomic Landscapes of Lung Cancer Subtypes Underscore the Selection of Different Oncogenic Pathways during Tumor Development

For therapeutic purposes, non-small cell lung cancer (NSCLC) has traditionally been regarded as a single disease. However, recent evidence suggest that the two major subtypes of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SqCC) respond differently to both molecular targeted and new generation chemotherapies. Therefore, identifying the molecular differences between these tumor types may impact novel treatment strategy. We performed the first large-scale analysis of 261 primary NSCLC tumors (169 AC and 92 SqCC), integrating genome-wide DNA copy number, methylation and gene expression profiles to identify subtype-specific molecular alterations relevant to new agent design and choice of therapy. Comparison of AC and SqCC genomic and epigenomic landscapes revealed 778 altered genes with corresponding expression changes that are selected during tumor development in a subtype-specific manner. Analysis of >200 additional NSCLCs confirmed that these genes are responsible for driving the differential development and resulting phenotypes of AC and SqCC. Importantly, we identified key oncogenic pathways disrupted in each subtype that likely serve as the basis for their differential tumor biology and clinical outcomes. Downregulation of HNF4α target genes was the most common pathway specific to AC, while SqCC demonstrated disruption of numerous histone modifying enzymes as well as the transcription factor E2F1. In silico screening of candidate therapeutic compounds using subtype-specific pathway components identified HDAC and PI3K inhibitors as potential treatments tailored to lung SqCC. Together, our findings suggest that AC and SqCC develop through distinct pathogenetic pathways that have significant implication in our approach to the clinical management of NSCLC

NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes

Bostonia: 1997-1998, no. 1-4

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs