The triazatruxene derivative azatrux binds to the parallel form of the human telomeric G-quadruplex under molecular crowding conditions: Biophysical and molecular modeling studies

The present study has employed a combination of spectroscopic, calorimetric and computational methods to explore the binding of the three side-chained triazatruxene derivative, termed azatrux, to a human telomeric G-quadruplex sequence, under conditions of molecular crowding. The binding of azatrux to the tetramolecular parallel [d(TGGGGT)](4) quadruplex in the presence and absence of crowding conditions, was also characterized. The data indicate that azatrux binds in an end-stacking mode to the parallel G-quadruplex scaffold and highlights the key structural elements involved in the binding. The selectivity of azatrux for the human telomeric G-quadruplex relative to another biologically relevant G-quadruplex (c-Kit87up) and to duplex DNA was also investigated under molecular crowding conditions, showing that azatrux has good selectivity for the human telomeric G-quadruplex over the other investigated DNA structures. (C) 2011 Elsevier Masson SAS. All rights reserved.

Prokaryotes on the tentacles of deep-sea holothurians: A novel form of dietary supplementation

Bathyal and abyssal epibenthic holothurians have a layer of bacteria lying over the tentacular epidermis and below the cuticle. Thus the tentacles of deep-sea holothurians may provide ideal conditions for subcuticular bacteria. These bacteria appear to be regulated by phagocytosis, which, together with pinocytosis would facilitate transfer of bacterial metabolites to the holothurian. Their abundance suggests a previously unknown pathway for energy transformation and assimilation of particular significance in an environment where food is limiting.

Bioaccessibility of trace elements in soils in Northern Ireland

Assessment of elevated concentrations of potentially toxic elements (PTE) in soils and the association with specific soil parent material have been the focus of research for a number of years. Risk-based assessment of potential exposure scenarios to identified elevated PTE concentrations has led to the derivation of site- and contaminant-specific soil guideline values (SGVs), which represent generic assessment criteria (GACs) to identify exceeded levels that may reflect an unacceptable risk to human health. A better understanding of the ‘bioavailable’ or ‘bioaccessible’ contaminant concentrations offers an opportunity to better refine contaminant exposure assessments. Utilizing a comprehensive soil geochemical dataset for Northern Ireland provided by the Tellus Survey (GSNI) in conjunction with supplementary bioaccessibility testing of selected soil samples following the Unified BARGE Method, this paper uses exploratory data analysis and geostatistical analysis to investigate the spatial variability of pseudo-total and bioaccessible concentrations of As, Cd, Co, Cr. Cu, Ni, Pb, U, V and Zn. The paper investigates variations in individual element concentrations as well as cross-element correlations and observed lithological/pedological associations. The analysis of PTE concentrations highlighted exceeded levels of GAC values for V and Cr and exceeded SGV/GAC values for Cd, Cu, Ni, Pb, and Zn. UBM testing showed that for some soil parent materials associated with elevated PTE concentrations e.g. the Antrim Lava Group with high Ni concentrations, the measured oral bioaccessible fraction was relatively low. For other soil parent materials with relatively moderate PTE concentrations, measured oral bioaccessible fraction was relatively high (e.g. the Gala Sandstone Group of the Southern Uplands-Down Longford Terrain). These findings have implications for regional human health risk assessments for specific PTEs.

Maximising trace soil evidence: An improved recovery method developed during investigation of a $26 million bank robbery

Obtaining as much particulate material as possible from questioned items is desirable in forensic science as this allows a range of analyses to be undertaken and the retention of material for others to check. A method of maximising particulate recovery is described using a kidnap case, where minimal staining on clothing (socks) remained as possible indications of where the victim had been held captive. Police intelligence led to a hostage scene that was sampled. Brushing of the socks recovered about 50 sand grains with some silt: ultrasonic agitation and centrifuging recovered over 300 grains of sand, silt and clay. These were visually compared to scene and control samples, allowing exclusion of 52 samples and the retention of one comparison sample as well as other possibles, saving time and money, but maximising sample quantity and quality. © 2011 Elsevier Ireland Ltd.

Molecular investigations into vaginal immunization with HIV gp41 antigenic construct H4A in a quick release solid dosage form

A robust vaginal immune response is considered essential for an effective prophylactic vaccine that prevents transmission of HIV and other sexually acquired diseases. Considerable attention has recently focused on the potential of vaginally administered vaccines as a means to induce such local immunity. However, the potential for vaccination at this site remains in doubt as the vaginal mucosa is generally considered to have low immune inductive potential. In the current study, we explored for the first time the use of a quick release, freeze-dried, solid dosage system for practical vaginal administration of a protein antigen. These solid dosage forms overcome the common problem associated with leakage and poor retention of vaginally administered antigen solutions. Mice were immunized vaginally with H4A, an HIV gp41 envelope based recombinant protein, using quick release, freeze-dried solid rods, and the immune responses compared to a control group immunized via subcutaneous H4A injection. Vaginally immunized mice failed to elicit robust immune responses. Our detailed investigations, involving cytokine analysis, the stability of H4A in mouse cervicovaginal lavage, and elucidation of the state of H4A protein in the immediate-release dosage form, revealed that antigen instability in vaginal fluid, the state of the antigen in the dosage form, and the cytokine profile induced are all likely to have contributed to the observed lack of immunogenicity. These are important factors affecting vaginal immunization and provide a rational basis for explaining the typically poor and variable elicitation of immunity at this site, despite the presence of immune responsive cells within the vaginal mucosae. In future mucosal vaccine studies, a more explicit focus on antigen stability in the dosage form and the immune potential of available antigen-responsive cells is recommended. © 2012 Elsevier Ltd. All rights reserved.

Using smart people to form future mobile wireless networks

The concept of a body-to-body network, where smart communicating devices carried or worn by a person are used to form a wireless network with devices situated on other nearby persons. New innovations in this area will see the form factor of smart devices being modified, so that they may be worn on the human body or integrated into clothing, in the process creating a new generation of smart people. Applications of body-to-body networking will extend well beyond the support of cellular and Wi-Fi networks. They will also be used in short-range covert military applications, first responder applications, team sports and used to interconnect body area networks (BAN). Security will be a major issue as routing between multiple nodes will increase the risk of unauthorized access and compromise sensitive data. This will add complexity to the medium access layer (MAC) and network management. Antennas designed to operate in body centric communications systems may be broadly categorized as on- or off-body radiators, according to their radiation pattern characteristics when mounted on the human body.

Toenail trace element status and risk of Barrett's oesophagus and oesophageal adenocarcinoma. Results from the FINBAR study

Trace elements have been cited as both inhibitory and causative agents of cancer but importantly exposure to them is potentially modifiable. Our study aimed to examine toenail trace element status and risk of Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC). Toenail clippings from each hallux were obtained from 638 participants of the FINBAR (Factors Influencing the Barrett's Adenocarcinoma Relationship) study comprising 221 healthy controls, 98 reflux oesophagitis, 182 BO and 137 OAC cases. The concentrations of eight toenail trace elements were determined using instrumental neutron activation analysis. Using multivariable adjusted logistic regression analysis, odds ratios (OR) and 95% confidence intervals (CIs) were calculated within tertiles of trace element concentrations. A twofold increased risk of BO was observed, but not OAC, among individuals in the highest tertile of toenail zinc status OR 2.21 (95% CI, 1.11-4.40). A higher toenail selenium status was not associated with risk of OAC OR 0.94 (95% CI, 0.44-2.04) or BO OR 0.89 (95% CI, 0.37-2.12). A borderline significant increased risk of BO was detected with a higher toenail cobalt concentration, OR 1.97 (95% CI, 1.01-3.85). No association was found between toenail levels of chromium, cerium, mercury and OAC or BO risk. This is the first case-control study to investigate a variety of trace elements in relation to OAC and BO risk. Despite antioxidant and proapoptotic properties, no associations were found with selenium. Higher concentrations of toenail zinc and cobalt were associated with an increased BO risk, but not OAC. These findings need confirmation in prospective analysis.