Investigating DNA Radiation Damage Using X-Ray Absorption Spectroscopy

The biological influence of radiation on living matter has been studied for years; however, several questions about the detailed mechanism of radiation damage formation remain largely unanswered. Among all biomolecules exposed to radiation, DNA plays an important role because any damage to its molecular structure can affect the whole cell and may lead to chromosomal rearrangements resulting in genomic instability or cell death. To identify and characterize damage induced in the DNA sugar-phosphate backbone, in this work we performed x-ray absorption spectroscopy at the P K-edge on DNA irradiated with either UVA light or protons. By combining the experimental results with theoretical calculations, we were able to establish the types and relative ratio of lesions produced by both UVA and protons around the phosphorus atoms in DNA.     

Identification of a new simian immunodeficiency virus lineage with a vpu gene present among different cercopithecus monkeys (C. mona, C. cephus, and C. nictitans) from Cameroon

During a large serosurvey of wild-caught primates from Cameroon, we found 2 mona monkeys (Cercopithecus mona) out of 8 and 47 mustached monkeys (Cercopithecus cephus) out of 302 with human immunodeficiency virus (HIV)-simian immunodeficiency virus (SIV) cross-reactive antibodies. In this report, we describe the full-length genome sequences of two novel SIVs, designated SIVmon-99CMCML1 and SIVmus-01CM1085, isolated from one mona (CML1) and one mustached (1085) monkey, respectively. Interestingly, these viruses displayed the same genetic organization (i.e., presence of a vpu homologue) as members of the SIVcpz-HIV type 1 lineage and SIVgsn isolated from greater spot-nosed monkeys (Cercopithecus nictitans). Phylogenetic analyses of SIVmon and SIVmus revealed that these viruses were genetically distinct from other known primate lentiviruses but were more closely related to SIVgsn all across their genomes, thus forming a monophyletic lineage within the primate lentivirus family, which we designated the SIVgsn lineage. Interestingly, mona, mustached, and greater spot-nosed monkeys are phylogenetically related species belonging to three different groups of the genus Cercopithecus, the C. mona, C. cephus, and Cercopithecus mitis groups, respectively. The presence of new viruses closely related to SIVgsn in two other species reinforces the hypothesis that a recombination event between ancestral SIVs from the family Cercopithecinae is the origin of the present SIVcpz that is widespread among the chimpanzee population.     

Development of a fluorescence immunoassay for measurement of paclitaxel in human plasma

A new fluorescence immunoassay for the quantitative determination of paclitaxel (Pac) under equilibrium conditions was developed. Anti-Pac IgG2a antibody was immobilized through its Fc region to protein A covalently bound to the inside surface of a silanized glass capillary column and the antigen-binding sites of anti-Pac saturated with rhodamine-labeled Pac (Rh-Pac). Analyte Pac was circulated through the column in a closed loop and the steady-state fluorescence of the Rh-Pac displaced from the immobilized antibody was recorded after 6 min. The Rh-Pac fluorescence emission intensity was directly related to the concentration of the Pac analyte over a broad dynamic range of up to 400 ng/ml with a linear range up to 200 ng/ml and lower detection limit of 5.85 ng/ml. While there was no interference from the baccatin III and 10-deacetylbaccatin III, cephalomannine was found to interfere in Pac determination. When applied for measurement of Pac in human plasma, the concentration of Pac determined by the fluorescence assay was found to be in excellent agreement with the Pac added, confirming the potential of the fluorescence immunoassay for clinical application.     

Effects of inflammatory mediators on canine airway neuromuscular function.

Inflammatory mediators can both enhance or inhibit canine airway reactivity. PGE2 and PGI2 in general are inhibitory, interfering with release of acetylcholine and with responses to bronchoconstrictors. These prostaglandins may be more effective against agonists that open voltage-dependent Ca2+ channels to induce Ca2+ influx and contraction compared with those agonists that release internal Ca2+. Other mediators are excitatory: histamine, PGD2, thromboxane A2 (TxA2), and leukotrienes (LT) C4, D4, and E4. In canine airway only histamine and TxA2 have effects in the absence of indomethacin, i.e., in the presence of the large amounts of PGE2 and PGI2 produced in vitro LTs are ineffective. Effects of TxA2 and histamine may be potentiated if the synthesis of these inhibitory PGs is inhibited. Whether histamine or TxA2 normally promote synthesis and release of PGE2 and PGI2 in a kind of homeostasis remains to be explored. It is also unclear whether pre- as well as post-junctional TxA2 receptors exist and have different pharmacological sensitivities to antagonists. LTC4 and LTD4 also constrict canine bronchi but only when PGE2 and PGI2 synthesis is blocked and, again, whether this is a result of LT-induced release of inhibitory mediators is unknown. The concept that airway responsiveness can be caused by turning off PGE2 and PGI2 production and turning on TxA2 or LT production (or unmasking their actions) needs further exploration. Our recent data suggest that such a mechanism may explain ozone-induced responsiveness in dogs.     

Female-Driven Multiple Concurrent Sexual Partnership Systems in a Rural Part of a Southern Tanzanian Province

Background

Multiple concurrent sexual relationships are one of the major challenges to HIV prevention in Tanzania. This study aims to explore sexual behaviour patterns including the practice of multiple concurrent sexual partnerships in a rural Tanzanian setting.

Methods

This qualitative study used focus group discussions and in-depth interviews with men and women from the community as well as ethnographic participant observations. The data was collected during 16 months of fieldwork in 2007, 2008, and 2009. The focus group discussions and in-depth interviews were transcribed verbatim and translated into English. The data was analysed through the process of latent content analysis. An open coding coding process was applied to create categories and assign themes.

Findings

Mafiga matatu was an expression used in this society to describe women’s multiple concurrent sexual partners, usually three partners, which was described as a way to ensure social and financial security for their families as well as to achieve sexual pleasure. Adolescent initiation ceremonies initiated and conducted by grand mothers taught young women why and how to engage successfully in multiple concurrent sexual relationships. Some men expressed support for their female partners to behave according to mafiga matatu, while other men were hesitant around this behaviour. Our findings indicate that having multiple concurrent sexual partners is common and a normative behaviour in this setting. Economical factors and sexual pleasure were identified as drivers and viewed as legitimate reason for women to have multiple concurrent sexual partnerships.

Conclusions

Structural changes improving women’s financial opportunities and increasing gender equality will be important to enable women to not depend on multiple concurrent sexual partnerships for financial security. Future research should explore how normative sexual behaviour changes as these structural changes take place.     

Resected Brain Tissue,Seizure Onset Zone and Quantitative EEG Measures: Towards Prediction of Post-Surgical Seizure Control

BackgroundEpilepsy surgery is a potentially curative treatment option for pharmacoresistent patients. If non-invasive methods alone do not allow to delineate the epileptogenic brain areas the surgical candidates undergo long-term monitoring with intracranial EEG. Visual EEG analysis is then used to identify the seizure onset zone for targeted resection as a standard procedure.MethodsDespite of its great potential to assess the epileptogenicty of brain tissue, quantitative EEG analysis has not yet found its way into routine clinical practice. To demonstrate that quantitative EEG may yield clinically highly relevant information we retrospectively investigated how post-operative seizure control is associated with four selected EEG measures evaluated in the resected brain tissue and the seizure onset zone. Importantly, the exact spatial location of the intracranial electrodes was determined by coregistration of pre-operative MRI and post-implantation CT and coregistration with post-resection MRI was used to delineate the extent of tissue resection. Using data-driven thresholding, quantitative EEG results were separated into normally contributing and salient channels.ResultsIn patients with favorable post-surgical seizure control a significantly larger fraction of salient channels in three of the four quantitative EEG measures was resected than in patients with unfavorable outcome in terms of seizure control (median over the whole peri-ictal recordings). The same statistics revealed no association with post-operative seizure control when EEG channels contributing to the seizure onset zone were studied.ConclusionsWe conclude that quantitative EEG measures provide clinically relevant and objective markers of target tissue, which may be used to optimize epilepsy surgery. The finding that differentiation between favorable and unfavorable outcome was better for the fraction of salient values in the resected brain tissue than in the seizure onset zone is consistent with growing evidence that spatially extended networks might be more relevant for seizure generation, evolution and termination than a single highly localized brain region (i.e. a “focus”) where seizures start.