MOLECULAR EVOLUTIONARY DIVERGENCE AMONG NORTH AMERICAN CAVE CRICKETS. I. ALLOZYME VARIATION

Forty-nine populations of nine species of North American cave crickets (genera Euhadenoecus and Hadenoecus) have been studied for genetic variation at 41 loci by electrophoresis. Wright's F_ST, Slatkin's Nm^* gene-flow estimator, and Nei's genetic distances (D) have been used to compare closely related species that have different ecological requirements (cave vs. forest species), distribution patterns, and/or different degrees of geographic isolation among populations. Cave and epigean (noncave) species differ greatly in their levels of genetic differentiation. Cave species have lower rates of gene exchange (low Nm, high D, and F_ST) than epigean species. Within cave species the degree of genetic differentiation among populations is correlated with the limestone structure of the area where the species occur. Species or groups of populations inhabiting areas where the limestone is continuous and highly fissured (e.g., H. subterraneus populations in the Mammoth Cave region) are genetically less differentiated than are populations occurring in regions where the limestone distribution is more fragmented, such as the Appalachian Ridge where E. fragilis occurs; this effect is more extreme in Central Tennessee where genetically differentiated E. insolitus populations occur only a few kilometers apart. This suggests that epigean dispersal through forest habitat in cave-dwelling species is negligable. For forest species, the data indicate relatively recent radiation with ongoing gene exchange among populations. For cave species, the distribution of protein polymorphisms is apparently more a function of historical patterns of gene exchange rather than current gene exchange. Phylogenetic relationships were studied using cluster analyses (UPGMA and Wagner algorithms) of Nei's and Edwards' genetic distances and multivariate analysis (correspondence analysis) of the raw allele frequencies. Different algorithms result in branching patterns that are similar but not entirely concordant with one another or with the phylogeny based on morphology.     

Transfer factor for the treatment of HBsAg-positive chronic active hepatitis

Transfer factor was obtained from four patients having recovered from acute type-B viral hepatitis. It was replicated in vitro using the LDV/7 lymphoblastoid cell line. This in vitro-produced transfer factor specific for hepatitis B (TFdL-H) was administered to 10 randomly selected patients with biochemically and histologically proven HBsAg-positive chronic active hepatitis (CAH) at 15-day intervals over a 6-month period. In three out of four initially HBeAg-positive patients, anti-HBe antibodies appeared when the HBeAg disappeared. In one of these patients and in two other HBsAg-positive patients, the appearance of anti-HBs antibodies was noted. The improvement in several biochemical parameters of the TFdL-H patients was statistically significant when compared with those of another group of 10 randomly selected untreated CAH patients. Liver biopsies in six out of eight treated patients showed a histological improvement at the end of the treatment. These results suggest that TFdL-H may be used with beneficial effect for the treatment of HBsAg-positive CAH.     

An increased burden of rare exonic variants in NRXN1 microdeletion carriers is likely to enhance the penetrance for autism spectrum disorder

Autism spectrum disorder (ASD) is characterized by a complex polygenic background, but with the unique feature of a subset of cases (~15%-30%) presenting a rare large-effect variant. However, clinical interpretation in these cases is often complicated by incomplete penetrance, variable expressivity and different neurodevelopmental trajectories. NRXN1 intragenic deletions represent the prototype of such ASD-associated susceptibility variants. From chromosomal microarrays analysis of 104 ASD individuals, we identified an inherited NRXN1 deletion in a trio family. We carried out whole-exome sequencing and deep sequencing of mitochondrial DNA (mtDNA) in this family, to evaluate the burden of rare variants which may contribute to the phenotypic outcome in NRXN1 deletion carriers. We identified an increased burden of exonic rare variants in the ASD child compared to the unaffected NRXN1 deletion-transmitting mother, which remains significant if we restrict the analysis to potentially deleterious rare variants only (P = 6.07 × 10⁻⁵). We also detected significant interaction enrichment among genes with damaging variants in the proband, suggesting that additional rare variants in interacting genes collectively contribute to cross the liability threshold for ASD. Finally, the proband's mtDNA presented five low-level heteroplasmic mtDNA variants that were absent in the mother, and two maternally inherited variants with increased heteroplasmic load. This study underlines the importance of a comprehensive assessment of the genomic background in carriers of large-effect variants, as penetrance modulation by additional interacting rare variants to might represent a widespread mechanism in neurodevelopmental disorders.     

Orally administered HSV-specific transfer factor (TF) prevents genital or labial herpes relapses

Forty-four patients suffering from genital (22) and labial (22) herpes were orally treated with HSV-1/2-specific transfer factor(TF). TF was obtained by in vitro replication of a HSV-1/2-specific bovine dialysable lymphocyte extract. Treatment was administered bi-weekly the first 2 weeks, and then weekly for 6 months, most patients received 2–3 courses. The total observation period for all patients before treatment was 26660 days, with 544 relapses, and a relapse index of 61.2, whereas the cumulative observation period during and after treatment was 16945 days, with a total of 121 relapsing episodes and a cumulative RI of 21.4 (P<0.0001). Results were equally significant when the 2 groups of patients (labial and genital) were considered separately. These observations confirm previous results obtained with bovine HSV-specific TF, and warrant further studies to establish HSV-specific TF as a choice of treatment for preventing herpes recurrences.     

Satellite cells in the tail muscles of the urodelan larvae during development

The incidence and ultrastructure of satellite cells in the tail muscles of urodelan larvae were examined during development during which the number of satellite cells is gradually reduced. They are found more frequently in red than in the white fibres in all four stages examined (stage 53, 64, 66+ and juvenile). As development proceeds, intercellular space between satellite cell and muscle fibre is in general gradually extended and is mostly filled with basal lamina. Small muscle cells, satellite fibres, which are situated under the basal lamina of the parent fibre, are morphologically similar to satellite cells but contain a small amount of myofibrils. Three types of satellite fibres are distinguishable on the basis of differences in K2-EDTA-treated ATPase activity, width of Z line, and parent fibre type. Neuromuscular junctions are visible in satellite fibres.     

Genetic regressive trajectories in colorectal cancer: A new hallmark of oligo-metastatic disease?

Colorectal cancer (CRC) originates as consequence of multiple genetic alterations. Some of the involved genes have been extensively studied (APC, TP53, KRAS, SMAD4, PIK3CA, MMR genes) in highly heterogeneous and poly-metastatic cohorts. However, about 10% of metastatic CRC patients presents with an indolent oligo-metastatic disease differently from other patients with poly-metastatic and aggressive clinical course. Which are the genetic dynamics underlying the differences between oligo- and poly-metastatic CRC? The understanding of the genetic trajectories (primary→metastatic) of CRC, in patients selected to represent homogenous clinical models, is crucial to make genotype/phenotype correlations and to identify the molecular events pushing the disease towards an increasing malignant phenotype. This information is crucial to plan innovative therapeutic strategies aimed to reverse or inhibit these phenomena. In the present study, we review the genetic evolution of CRC with the intent to give a developmental perspective on the border line between oligo- and poly-metastatic diseases.     

Anomalous Charge Transport: A New ��Time Domain�� Generalization of the Drude Model

We propose a new generalization of the Drude model for describing the conductors in nanostructured form. The new feature that appeared is the assumption of a collective mode at a finite frequency. This leads to the occurrence of anomalous charge transport. With appropriate scattering times it is possible to mimic the infrared properties of oxides and poor conductors in the form of nanoparticles and nanowires. The electron current in these cases reverses its direction before decaying to zero. Specific examples considered are ZnO, TiO₂, GaAs, Si, SWCN. The model also predicts that the current will have a damped oscillation in time, a possible new effect detectable with femtosecond time resolved techniques. Results are presented for the velocity correlation functions, the mean square deviation of position and the diffusion coefficient.