Genetic and clinical studies in 13 patients with the Wolf-Hirschhorn syndrome [del(4p)]

Summary Clinical and cytogenetic studies are reported on 13 patients with Wolf-Hirschhorn syndrome. The oldest of the living twelve probands is 24 years of age. Three of these patients has a translocation involving the short arm of chromosome 4, and in one of these the anomalous chromosome was inherited from the father. Another three patients were believed, on the basis of GTG-staining, to have a translocation although the origin of the translocated chromatin could not be identified. In the remaining seven patients the anomalous chromosome appeared to be a simple deletion, although in two cases a translocation could not be reled out. Cytogenetic studies in these patients suggest that the critical deletion involved in Wolf-Hirschhorn syndrome is within 4p 16.Supported in part by Grant No. 286 from the Maternal and Child Health Service, United States Public Health Service.     

A survey of chlortetracycline concentration in feed and its residue in chicken egg in commercial layer farms

The worldwide increase in the use of antibiotics as an integral part of poultry and livestock production industry has recently received increasing attention as a contributory factor in the international emergence of antibiotic-resistant bacteria in human beings. To gauge the presence of the aforementioned scenario in the Indian context, a preliminary survey was conducted to assess the use of chlortetracycline (CTC) in 12 commercial layer farms and to quantify and confirm its residue in the egg. Samples of feed and eggs were collected at day 0 (prior to CTC addition), 3rd, 5th and 7th day during treatment and on the 9th and 14th day (2nd and 7th day after withdrawal of CTC) from each of the 12 commercial poultry farms studied. Concentration of CTC in feed was significantly (P<0.01) high on the 3rd, 5th and 7th day. On the 9th day and 14th day CTC concentration in feed was significantly (P<0.01) lower compared to the earlier 3 days studied. A highly significant difference (P<0.01) of the antibiotic residue in egg was observed in all the 5 days with high residual levels of CTC in egg. CTC in feed and its residue in egg were detected even on the 9th and 14th day respectively.     

Loss of caveolin-1 impairs retinal function due to disturbance of subretinal microenvironment

Caveolin-1 (Cav-1), an integral component of caveolar membrane domains, is expressed in several retinal cell types, including photoreceptors, retinal vascular endothelial cells, Müller glia, and retinal pigment epithelium (RPE) cells. Recent evidence links Cav-1 to ocular diseases, including autoimmune uveitis, diabetic retinopathy, and primary open angle glaucoma, but its role in normal vision is largely undetermined. In this report, we show that ablation of Cav-1 results in reduced inner and outer retinal function as measured, in vivo, by electroretinography and manganese-enhanced MRI. Somewhat surprisingly, dark current and light sensitivity were normal in individual rods (recorded with suction electrode methods) from Cav-1 knock-out (KO) mice. Although photoreceptor function was largely normal, in vitro, the apparent K(+) affinity of the RPE-expressed α1-Na(+)/K(+)-ATPase was decreased in Cav-1 KO mice. Cav-1 KO retinas also displayed unusually tight adhesion with the RPE, which could be resolved by brief treatment with hyperosmotic medium, suggesting alterations in outer retinal fluid homeostasis. Collectively, these findings demonstrate that reduced retinal function resulting from Cav-1 ablation is not photoreceptor-intrinsic but rather involves impaired subretinal and/or RPE ion/fluid homeostasis.     

Optimized monoclonal antibody treatment against ELTD1 for GBM in a G55 xenograft mouse model

Glioblastoma is an aggressive brain tumour found in adults, and the therapeutic approaches available have not significantly increased patient survival. Recently, we discovered that ELTD1, an angiogenic biomarker, is highly expressed in human gliomas. Polyclonal anti‐ELTD1 treatments were effective in glioma pre‐clinical models, however, pAb binding is potentially promiscuous. Therefore, the aim of this study was to determine the effects of an optimized monoclonal anti‐ELTD1 treatment in G55 xenograft glioma models. MRI was used to assess the effects of the treatments on animal survival, tumour volumes, perfusion rates and binding specificity. Immunohistochemistry and histology were conducted to confirm and characterize microvessel density and Notch1 levels, and to locate the molecular probes. RNA‐sequencing was used to analyse the effects of the mAb treatment. Our monoclonal anti‐ELTD1 treatment significantly increased animal survival, reduced tumour volumes, normalized the vasculature and showed higher binding specificity within the tumour compared with both control‐ and polyclonal‐treated mice. Notch1 positivity staining and RNA‐seq results suggested that ELTD1 has the ability to interact with and interrupt Notch1 signalling. Although little is known about ELTD1, particularly about its ligand and pathways, our data suggest that our monoclonal anti‐ELTD1 antibody is a promising anti‐angiogenic therapeutic in glioblastomas.     

Gauging the Threat: The First Population Estimate for White Sharks in South Africa Using Photo Identification and Automated Software

South Africa is reputed to host the world’s largest remaining population of white sharks, yet no studies have accurately determined a population estimate based on mark-recapture of live individuals. We used dorsal fin photographs (fin IDs) to identify white sharks in Gansbaai, South Africa, from January 2007 – December 2011. We used the computer programme DARWIN to catalogue and match fin IDs of individuals; this is the first study to successfully use the software for white shark identification. The programme performed well despite a number of individual fins showing drastic changes in dorsal fin shape over time. Of 1682 fin IDs used, 532 unique individuals were identified. We estimated population size using the open-population POPAN parameterisation in Program MARK, which estimated the superpopulation size at 908 (95% confidence interval 808–1008). This estimated population size is considerably larger than those described at other aggregation areas of the species and is comparable to a previous South African population estimate conducted 16 years prior. Our assessment suggests the species has not made a marked recovery since being nationally protected in 1991. As such, additional international protection may prove vital for the long-term conservation of this threatened species.     

Translational research involving oxidative stress and diseases of aging

There is ample mounting evidence that reactive oxidant species are exacerbated in inflammatory processes, many pathological conditions, and underlying processes of chronic age-related diseases. Therefore there is increased expectation that therapeutics can be developed that act in some fashion to suppress reactive oxidant species and ameliorate the condition. This has turned out to be more difficult than at first expected. Developing therapeutics for indications in which reactive oxidant species are an important consideration presents some unique challenges. We discuss important questions including whether reactive oxidant species should be a therapeutic target, the need to recognize the fact that an antioxidant in a defined chemical system may be a poor antioxidant operationally in a biological system, and the importance of considering that reactive oxidant species may accompany the disease or pathological system rather than being a causative factor. We also discuss the value of having preclinical models to determine if the processes that are important in causing the disease under study are critically dependent on reactive oxidant species events and if the therapeutic under consideration quells these processes. In addition we discuss measures of success that must be met in commercial research and development and in preclinical and clinical trials and discuss as examples our translational research effort in developing nitrones for the treatment of acute ischemic stroke and as anti-cancer agents.