Find and fuse : Unsolved mysteries in sperm– egg recognition

Sexual reproduction is such a successful way of creating progeny with subtle genetic variations that the vast majority of eukaryotic species use it. In mammals, it involves the formation of highly specialised cells: the sperm in males and the egg in females, each carrying the genetic inheritance of an individual. The interaction of sperm and egg culminates with the fusion of their cell membranes, triggering the molecular events that result in the formation of a new genetically distinct organism. Although we have a good cellular description of fertilisation in mammals, many of the molecules involved remain unknown, and especially the identity and role of cell surface proteins that are responsible for sperm-egg recognition, binding, and fusion. Here, we will highlight and discuss these gaps in our knowledge and how the role of some recently discovered sperm cell surface and secreted proteins contribute to our understanding of this fundamental process

Establishment, optimisation and quantitation of a bioluminescent murine infection model of visceral leishmaniasis for systematic vaccine screening

Visceral leishmaniasis is an infectious parasitic disease caused by the protozoan parasites Leishmania donovani and Leishmania infantum. The drugs currently used to treat visceral leishmaniasis suffer from toxicity and the emergence of parasite resistance, and so a better solution would be the development of an effective subunit vaccine; however, no approved vaccine currently exists. The comparative testing of a large number of vaccine candidates requires a quantitative and reproducible experimental murine infection model, but the parameters that influence infection pathology have not been systematically determined. To address this, we have established an infection model using a transgenic luciferase-expressing L. donovani parasite and longitudinally quantified the infections using in vivo bioluminescent imaging within individual mice. We examined the effects of varying the infection route, the site of adjuvant formulation administration, and standardised the parasite preparation and dose. We observed that the increase in parasite load within the liver during the first few weeks of infection was directly proportional to the parasite number in the initial inoculum. Finally, we show that immunity can be induced in pre-exposed animals that have resolved an initial infection. This murine infection model provides a platform for systematic subunit vaccine testing against visceral leishmaniasis

Impact of an Adherence Program on the Health and Outlook of HIV-Infected Patients Failing Antiretroviral Therapy

Background: We prospectively studied the impact of an adherence counselor on the outcome of patients failing antiretroviral therapy because of nonadherence. Methods: Forty-six patients, identified as chronically nonadherent were enrolled. Individual attention was provided using the information, motivation and behavioral methodology. HIV RNA (viral load, in copies/mL), CD4 count (in cells/[mm.sup.3]), and body weight before and after the adherence counselor were measured. Qualitative outcome and patient satisfaction were assessed by deidentified third-party interviews. Results: Over half completed at least 1 year; only 8 patients were lost to follow-up. Mean CD4 counts increased significantly (P \u3c .05) for completers at 6 and 12 months. Viral loads decreased between baseline and 6 months. Most clients reported subjective benefit from working with the adherence counselor. Conclusion: Although few clients showed complete virologic suppression, the value of an adherence counselor was validated. Longer term adherence programs should be evaluated

Electric field and air ion exposures near high voltage overhead power lines and adult cancers: a case control study across England and Wales

Various mechanisms have been postulated to explain how electric fields emitted by high voltage overhead power lines, and the charged ions they produce, might be associated with possible adult cancer risk, but this has not previously been systematically explored in large scale epidemiological research.; We investigated risks of adult cancers in relation to modelled air ion density (per cm3) within 600 m (focusing analysis on mouth, lung, respiratory), and calculated electric field within 25 m (focusing analysis on non-melanoma skin), of high voltage overhead power lines in England and Wales, 1974-2008.; With adjustment for age, sex, deprivation and rurality, odds ratios (OR) in the highest fifth of net air ion density (0.504-1) compared with the lowest (0-0.1879) ranged from 0.94 [95% confidence interval (CI) 0.82-1.08] for mouth cancers to 1.03 (95% CI 0.97-1.09) for respiratory system cancers, with no trends in risk. The pattern of cancer risk was similar using corona ion estimates from an alternative model proposed by others. For keratinocyte carcinoma, adjusted OR in the highest (1.06-4.11 kV/m) compared with the lowest (<0.70 kV/m) thirds of electric field strength was 1.23 (95% CI 0.65-2.34), with no trend in risk.; Our results do not provide evidence to support hypotheses that air ion density or electric fields in the vicinity of power lines are associated with cancer risk in adults

The complex interplay between kidney injury and inflammation

Abstract Acute kidney injury (AKI) has gained significant attention following patient safety alerts about the increased risk of harm to patients, including increased mortality and hospitalization. Common causes of AKI include hypovolaemia, nephrotoxic medications, ischaemia and acute glomerulonephritis, although in reality it may be undetermined or multifactorial. A period of inflammation either as a contributor to the kidney injury or resulting from the injury is almost universally seen. This article was compiled following a workshop exploring the interplay between injury and inflammation. AKI is characterized by some degree of renal cell death through either apoptosis or necrosis, together with a strong inflammatory response. Studies interrogating the resolution of renal inflammation identify a whole range of molecules that are upregulated and confirm that the kidneys are able to intrinsically regenerate after an episode of AKI, provided the threshold of damage is not too high. Kidneys are unable to generate new nephrons, and dysfunctional or repeated episodes will lead to further nephron loss that is ultimately associated with the development of renal fibrosis and chronic kidney disease (CKD). The AKI to CKD transition is a complex process mainly facilitated by maladaptive repair mechanisms. Early biomarkers mapping out this process would allow a personalized approach to identifying patients with AKI who are at high risk of developing fibrosis and subsequent CKD. This review article highlights this process and explains how laboratory models of renal inflammation and injury assist with understanding the underlying disease process and allow interrogation of medications aimed at targeting the mechanistic interplay.</jats:p