The Wolbachia Genome of Brugia malayi: Endosymbiont Evolution within a Human Pathogenic Nematode

Complete genome DNA sequence and analysis is presented for Wolbachia, the obligate alpha-proteobacterial endosymbiont required for fertility and survival of the human filarial parasitic nematode Brugia malayi. Although, quantitatively, the genome is even more degraded than those of closely related Rickettsia species, Wolbachia has retained more intact metabolic pathways. The ability to provide riboflavin, flavin adenine dinucleotide, heme, and nucleotides is likely to be Wolbachia's principal contribution to the mutualistic relationship, whereas the host nematode likely supplies amino acids required for Wolbachia growth. Genome comparison of the Wolbachia endosymbiont of B. malayi (wBm) with the Wolbachia endosymbiont of Drosophila melanogaster (wMel) shows that they share similar metabolic trends, although their genomes show a high degree of genome shuffling. In contrast to wMel, wBm contains no prophage and has a reduced level of repeated DNA. Both Wolbachia have lost a considerable number of membrane biogenesis genes that apparently make them unable to synthesize lipid A, the usual component of proteobacterial membranes. However, differences in their peptidoglycan structures may reflect the mutualistic lifestyle of wBm in contrast to the parasitic lifestyle of wMel. The smaller genome size of wBm, relative to wMel, may reflect the loss of genes required for infecting host cells and avoiding host defense systems. Analysis of this first sequenced endosymbiont genome from a filarial nematode provides insight into endosymbiont evolution and additionally provides new potential targets for elimination of cutaneous and lymphatic human filarial disease

Untranslated parts of genes interpreted: making heads or tails of high-throughput transcriptomic data via computational methods

The fate of eukaryotic transcripts is closely linked to their untranslated regions, which are determined by where transcription starts and ends on a genomic locus. The extent of alternative transcription start and alternative poly-adenylation has been revealed by sequencing methods focused on the ends of transcripts, but the application of these methods is not yet widely adopted by the community. In this review we highlight the importance of defining the untranslated parts of transcripts and suggest that computational methods applied to standard high-throughput technologies are a useful alternative to the expertise-demanding 5’ and 3’ sequencing. We present a number of computational approaches for the discovery and quantification of alternative transcription start and poly-adenylation events, focusing on technical challenges and arguing for the need to include better normalization of the data and more appropriate statistical models of the expected variation in the signal

Shared metabolic pathways in a coevolved insect-bacterial symbiosis

The symbiotic bacterium Buchnera aphidicola lacks key genes in the biosynthesis of five essential amino acids (EAAs), and yet its animal hosts (aphids) depend on the symbiosis for the synthesis of these EAAs (isoleucine, leucine, methionine, phenylalanine, and valine). We tested the hypothesis, derived from genome annotation, that the missing Buchnera reactions are mediated by host enzymes, with the exchange of metabolic intermediates between the partners. The specialized host cells bearing Buchnera were separated into a Buchnera fraction and a Buchnera-free host cell fraction (HF). Addition of HF to isolated Buchnera preparations significantly increased the production of leucine and phenylalanine, and recombinant enzymes mediating the final reactions in branched-chain amino acid and phenylalanine synthesis rescued the production of these EAAs by Buchnera preparations without HF. The likely precursors for the missing proximal reactions in isoleucine and methionine synthesis were identified, and they differed from predictions based on genome annotations: synthesis of 2-oxobutanoate, the aphid-derived precursor of isoleucine synthesis, was stimulated by homoserine and not threonine via threonine dehydratase, and production of the homocysteine precursor of methionine was driven by cystathionine, not cysteine, via reversal of the transsulfuration pathway. The evolution of shared metabolic pathways in this symbiosis can be attributed to host compensation for genomic deterioration in the symbiont, involving changes in host gene expression networks to recruit specific enzymes to the host cell

Histological Correlates of Penile Sexual Sensation: Does Circumcision Make a Difference?

Introduction: The question of whether removal of sensory receptors in the prepuce by circumcision affects sensitivity and/or sexual pleasure is often debated. Aims: To examine histological correlates relevant to penile sensitivity and sexual pleasure. Methods: Systematic review of the scientific literature on penile structures that might affect sensitivity and sexual sensation. Articles were included if they contained original data on human male penile histology or anatomy. Individual articles, including reference lists, were evaluated. They were then considered in relation to physiological data from articles retrieved by a previous systematic review. Results: We retrieved 41 publications on penile structure. Considered in the light of 12 reporting physiological measurements, our evaluation finds that sexual response is unlikely to involve Meissner's corpuscles, whose density in the prepuce diminishes at the time of life when male sexual activity is increasing. Free nerve endings also show no correlation with sexual response. Because tactile sensitivity of the glans decreases with sexual arousal, it is unrelated to sexual sensation. Thermal sensitivity seems part of the reward mechanism of intercourse. Vibrational sensitivity is not related to circumcision status. Observations that penile sexual sensation is higher post circumcision are consistent with greater access of genital corpuscles to sexual stimuli after removal of the prepuce. This is based on the distribution of these corpuscles (which are located in the glans) and, in uncircumcised men, the position of the retracted prepuce during intercourse, rather than any change in the number of genital corpuscles. The scientific literature suggests that any sexual effect of circumcised men may depend solely on exposure of the glans and not on the absence of the prepuce. Conclusion: Based on histological findings and correlates of sexual function, loss of the prepuce by circumcision would appear to have no adverse effect on sexual pleasure. Our evaluation supports overall findings from physiological measurements and survey data. Cox G, Krieger JN, and Morris BJ. Histological correlates of penile sexual sensation: Does circumcision make a difference? Sex Med 2015;3:76–85

Bevacizumab plus irinotecan in recurrent or progressive malign glioma: a multicenter study of the Anatolian Society of Medical Oncology (ASMO)

The overall prognosis for recurrent malignant glioma (MG) is extremely poor, and treatment options are limited. We evaluated our multicenter retrospective experience for patients with recurrent MG administering bevacizumab and irinotecan in combination therapy