The Harderian gland of the Mexican volcano mouse Neotomodon alstoni alstoni (Merriam 1898): a morphological and biochemical approach

The Harderian glands of rodents are large intraorbital exocrine glands with histologic organization that varies among mammalian species. Here we describe some ultrastructural and biochemical features of the Harderian gland in the Mexican volcano mouse Neotomodon alstoni alstoni, a species of restricted habitat. The Harderian glands from male and female adult mice were dissected, processed and embedded in Epon 812 for light and electron microscopy studies. Porphyrin and total lipids were biochemically determined. The macroscopic appearance of the Harderian gland is similar in the male and female. The gland is a bilobulate structure, situated in the orbit towards the posterior side of the eyeball, of whitish color and is surrounded by a connective tissue capsule. The male gland is slightly heavier (127 mg) than that of the female (113 mg). The Harderian gland shows a tubulo-alveolar organization and is composed exclusively of one type of secretory cells. No branched duct system within the gland was found. Adrenergic nerves endings and mast cell were observed in the interstices of the alveoli. Male and female glands produce similar levels of porphyrins. Triglyceride levels were significantly higher (P < 0.05) in the female compared to the male. Abundance of lipids could induce corneal lubrication of the Harderian gland which may confer a protective and adaptative function to the volcano mouse in its natural habitat during the dry and cold seasons.     

D1S80 single-locus discrimination among African populations

The highly polymorphic D1S80 locus has no known genetic function. However, this variable number of tandem repeats (VNTR) locus has been highly valuable in forensic identification. In this study we report the allele and genotype frequencies of five African populations (Benin, Cameroon, Egypt, Kenya, and Rwanda), which can be used as databases to help characterize populations and identify individuals. The allele frequencies were used to infer genetic associations through phylogenetic, principal component, and G test statistical analyses. Compliance with Hardy-Weinberg equilibrium expectations was determined as were F(ST) estimates, theta p values, and power of discrimination assessment for each population. Our analyses of 28 additional populations demonstrate that the D1S80 locus alone can be used to discriminate geographic and ethnic groups. We have generated databases useful for human identification and phylogenetic studies.     

Selective impairment of TLR-mediated innate immunity in human newborns: neonatal blood plasma reduces monocyte TNF-alpha induction by bacterial lipopeptides, lipopolysaccharide, and imiquimod, but preserves the response to R-848

Newborns are at increased risk of overwhelming infection, yet the mechanisms underlying this susceptibility are incompletely defined. In this study we report a striking 1- to 3-log decrease in sensitivity of monocytes in human neonatal cord blood, compared with monocytes in adult peripheral blood, to the TNF-alpha-inducing effect of multiple TLR ligands, including bacterial lipopeptides (BLPs), LPS, and the imidazoquinoline compound, imiquimod. In marked contrast, TNF-alpha release in response to R-848, a TLR ligand that is a congener of imiquimod, was equivalent in newborn and adult blood. Differences in ligand-induced TNF-alpha release correlated with divergent ligand-induced changes in monocyte TNF-alpha mRNA levels. Newborn and adult monocytes did not differ in basal mRNA or protein expression of TLRs or mRNA expression of functionally related molecules. Newborn monocytes demonstrated diminished LPS-induced, but equivalent R-848-induced, phosphorylation of p38 mitogen-activated protein kinase and altered BLP- and LPS-induced acute modulation of cognate receptors, suggesting that the mechanism accounting for the observed differences may be localized proximal to ligand recognition by surface TLRs. Remarkably, newborn plasma conferred substantially reduced BLP-, LPS-, and imiquimod-induced TNF-alpha release on adult monocytes without any effect on R-848-induced TNF-alpha release, reflecting differences in a plasma factor(s) distinct from soluble CD14. Impaired response to multiple TLR ligands may significantly contribute to immature neonatal immunity. Conversely, relative preservation of responses to R-848 may present unique opportunities for augmenting innate and acquired immunity in the human newborn.     

Genetic heterogeneity in Italian families with IgA nephropathy: suggestive linkage for two novel IgA nephropathy loci

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, but its etiologic mechanisms are still poorly understood. Different prevalences among ethnic groups and familial aggregation, together with an increased familial risk, suggest important genetic influences on its pathogenesis. A locus for familial IgAN, called "IGAN1," on chromosome 6q22-23 has been described, without the identification of any responsible gene. The partners of the European IgAN Consortium organized a second genomewide scan in 22 new informative Italian multiplex families. A total of 186 subjects (59 affected and 127 unaffected) were genotyped and were included in a two-stage genomewide linkage analysis. The regions 4q26-31 and 17q12-22 exhibited the strongest evidence of linkage by nonparametric analysis (best P=.0025 and .0045, respectively). These localizations were also supported by multipoint parametric analysis, in which peak LOD scores of 1.83 ( alpha =0.50) and 2.56 ( alpha =0.65) were obtained using the affected-only dominant model, and by allowance for the presence of genetic heterogeneity. Our results provide further evidence for genetic heterogeneity among families with IgAN. Evidence of linkage to multiple chromosomal regions is consistent with both an oligo/polygenic and a multiple-susceptibility-gene model for familial IgAN, with small or moderate effects in determining the pathological phenotype. Although we identified new candidate regions, replication studies are required to confirm the genetic contribution to familial IgAN.     

Hypovirus papain-like protease p29 suppresses RNA silencing in the natural fungal host and in a heterologous plant system

Virulence-attenuating hypoviruses of the species Cryphonectria hypovirus 1 (CHV1) encode a papain-like protease, p29, that shares similarities with the potyvirus-encoded suppressor of RNA silencing HC-Pro. We now report that hypovirus CHV1-EP713-encoded p29 can suppress RNA silencing in the natural host, the chestnut blight fungus Cryphonectria parasitica. Hairpin RNA-triggered silencing was suppressed in C. parasitica strains expressing p29, and transformation of a transgenic green fluorescent protein (GFP)-silenced strain with p29 resulted in an increased number of transformants with elevated GFP expression levels. The CHV1-EP713 p29 protein was also shown to suppress both virus-induced and agroinfiltration-induced RNA silencing and systemic spread of silencing in GFP-expressing transgenic Nicotiana benthamiana line 16c plants. The demonstration that a mycovirus encodes a suppressor of RNA silencing provides circumstantial evidence that RNA silencing in fungi may serve as an antiviral defense mechanism. The observation that a phylogenetically conserved protein of related plant and fungal viruses functions as a suppressor of RNA silencing in both fungi and plants indicates a level of conservation of the mechanisms underlying RNA silencing in these two groups of organisms.     

Acetylcholinesterase inhibitors from the toadstool Cortinarius infractus

Inhibition of acetylcholinesterase (AChE) and therefore prevention of acetylcholine degradation is one of the most accepted therapy opportunities for Alzheimer´s disease (AD), today. Due to lack of selectivity of AChE inhibitor drugs on the market, AD-patients suffer from side effects like nausea or vomiting. In the present study the isolation of two alkaloids, infractopicrin (1) and 10-hydroxy-infractopicrin (2), from Cortinarius infractus Berk. (Cortinariaceae) is presented. Both compounds show AChE-inhibiting activity and possess a higher selectivity than galanthamine. Docking studies show that lacking π–π-interactions in butyrylcholinesterase (BChE) are responsible for selectivity. Studies on other AD pathology related targets show an inhibitory effect of both compounds on self-aggregation of Aβ-peptides but not on AChE induced Aβ-peptide aggregation. Low cytotoxicity as well as calculated pharmacokinetic data suggest that the natural products could be useful candidates for further drug development.     

Perspective on the host response to human metapneumovirus infection: what can we learn from respiratory syncytial virus infections?

Human metapneumovirus (HMPV) is a recently discovered pathogen first identified in respiratory specimens from young children suffering from clinical respiratory syndromes ranging from mild to severe lower respiratory tract illness. HMPV has worldwide prevalence, and is a leading cause of respiratory tract infection in the first years of life, with a spectrum of disease similar to respiratory syncytial virus (RSV). The disease burden associated with HMPV infection has not been fully elucidated; however, studies indicate that HMPV may cause upper or lower respiratory tract illness in patients between ages 2 months and 87 years, may co-circulate with RSV, and HMPV infection may be associated with asthma exacerbation. The mechanisms and effector pathways contributing to immunity or disease pathogenesis following infection are not fully understood; however, given the clinical significance of HMPV, there is a need for a fundamental understanding of the immune and pathophysiological processes that occur following infection to provide the foundation necessary for the development of effective vaccine or therapeutic intervention strategies. This review provides a current perspective on the processes associated with HMPV infection, immunity, and disease pathogenesis.     

Resistance and the jumping gene

Transposons are well-known architects of genetic change but their role in insecticide resistance has, until recently, only been speculated upon. Transposon insertion, or transposon-mediated transposition, could alter either metabolic enzymes capable of degrading pesticides or could change the functionality of insecticide targets. The recent work of Aminetzach and coworkers suggests an exciting alternative, that transposon insertion can cause resistance by altering gene product function. This hypothesis is discussed in the light of other examples in which transposons have been implicated in insecticide resistance.