Dietary fat accumulates in lipid droplets or endolysosomal compartments that undergo selective expansion under normal or pathophysiological conditions. We find that genetic defects in a peroxisomal β-oxidation pathway cause size expansion in lipid droplets that are distinct from the lysosome-related organelles in Caenorhabditis elegans. Expansion of lipid droplets is accompanied by an increase in triglycerides (TAG) that are resistant to fasting-or TAG lipase-triggered lipolysis. Nevertheless, in mutant animals, a diet poor in vaccenic acid reduced the TAG level and lipid droplet size. Our results implicate peroxisomal dysfunction in pathologic lipid droplet expansion in animals and illustrate how dietary factors modulate the phenotype of such genetic defects.peroxisome | β-oxidation | daf-22 | dhs-28 | maoc-1

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Plants have evolved complex nanofibril-based cell walls to meet diverse biological and physical constraints. How strength and extensibility emerge from the nanoscale-to-mesoscale organization of growing cell walls has long been unresolved. We sought to clarify the mechanical roles of cellulose and matrix polysaccharides by developing a coarse-grained model based on polymer physics that recapitulates aspects of assembly and tensile mechanics of epidermal cell walls. Simple noncovalent binding interactions in the model generate bundled cellulose networks resembling that of primary cell walls and possessing stress-dependent elasticity, stiffening, and plasticity beyond a yield threshold. Plasticity originates from fibril-fibril sliding in aligned cellulose networks. This physical model provides quantitative insight into fundamental questions of plant mechanobiology and reveals design principles of biomaterials that combine stiffness with yielding and extensibility.

Abstract. Variations in fecal Schistosoma japonicum egg counts were studied in ZhuXi administrative village, JiangXi Province, China. Population stool examinations were collected with duplicate, standard, 41.5-mg Kato-Katz thick smears on seven consecutive days for 570 individuals from two natural (individual) villages: village I with high endemicity and village II with low endemicity. The proportion of individuals with at least one positive count increased from 42.4% after a single measurement to 68.3% after seven measurements in village I (n ϭ 356), and from 17.0% to 36.0% in village II (n ϭ 214), respectively. This demonstrates a very high variation in repeated S. japonicum egg counts and a considerable lack of sensitivity of the Kato-Katz technique; light and moderate infections are especially missed with a single or a few measurements. The observed day-to-day variation in individual egg counts is highly aggregated (variance higher than the mean) and suggestive of a negative binomial distribution. For five individuals on three days, repeated sampling from different locations of a stool specimen shows a clear trend with egg counts decreasing from the beginning of the stool to the end and from the outside layer to the center. Ten multiple samples from a particular subsection (10-30 g) of a stool specimen for 44 positive individuals still showed aggregation in egg counts, particularly for high intensities of infection. This means that the aggregation in repeated daily S. japonicum egg counts cannot be explained alone by a specific day-to-day component and variation in the concentration of eggs at different locations in the stool. There also exists clustering of eggs within parts of the stool.Most control programs and epidemiologic studies on Schistosoma japonicum and S. mansoni infection are based on the detection of parasite eggs using the modified KatoKatz method. 1-4 Generally, levels of egg excretion are used as an index of the intensity of infection. Individual diagnosis of infection is commonly based on one stool examination. However, for S. mansoni it has been shown that a single stool examination considerably underestimates the prevalence; many light infections are especially missed. 5 Fecal egg counts as a quantitative measure of infection on S. mansoni in epidemiologic studies are the result of inter-and intraindividual variations: the former reflecting egg counts varying from individual to individual caused by differences in worm loads, and the latter reflecting egg count fluctuation for an individual with a given worm load from time to time and/or within a fecal specimen. [5][6][7][8][9] Based on a stochastic model that takes into account this inter-and intra-individual variation in egg counts, projections can be made of how many individuals are truly infected with S. mansoni in a population. 10 We expect similar mechanisms to exist for S. japonicum infection, but thus far detailed studies have not been undertaken. 11 Imperfect diagnosis of S. japonicum by routine stool examination has however been ...

Taken together, these findings demonstrate that simple topological changes in cardiac fibroblast organization are sufficient to induce chromatin remodeling and global changes in gene expression with potential functional consequences for the healing heart.

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BackgroundCryptococcal meningitis is the most common fungal infection of the central nervous system (CNS) in HIV/AIDS. HIV-1 virotoxins (e.g., gp41) are able to induce disorders of the blood-brain barrier (BBB), which mainly consists of BMEC. Our recent study suggests that α7 nAChR is an essential regulator of inflammation, which contributes to regulation of NF-κB signaling, neuroinflammation and BBB disorders caused by microbial (e.g., HIV-1 gp120) and non-microbial [e.g., methamphetamine (METH)] factors. However, the underlying mechanisms for multiple comorbidities are unclear.MethodsIn this report, an aggravating role of α7 nAChR in host defense against CNS disorders caused by these comorbidities was demonstrated by chemical [inhibitor: methyllycaconitine (MLA)] and genetic (α7−/− mice) blockages of α7 nAChR.ResultsAs shown in our in vivo studies, BBB injury was significantly reduced in α7−/− mice infected with C. neoformans. Stimulation by the gp41 ectodomain peptide (gp41-I90) and METH was abolished in the α7−/− animals. C. neoformans and gp41-I90 could activate NF-κB. Gp41-I90- and METH-induced monocyte transmigration and senescence were significantly inhibited by MLA and CAPE (caffeic acid phenethyl ester, an NF-κB inhibitor).ConclusionsCollectively, our data suggest that α7 nAChR plays a detrimental role in the host defense against C. neoformans- and HIV-1 associated comorbidity factors-induced BBB injury and CNS disorders.

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