Ovine fetal testis stage-specific sensitivity to environmental chemical mixtures.

Exposure of the fetal testis to numerous individual environmental chemicals (ECs) is frequently associated with dysregulated development, leading to impaired adult reproductive competence. However, 'real-life' exposure involves complex mixtures of ECs. Here we test the consequences, for the male fetus, of exposing pregnant ewes to EC mixtures derived from pastures treated with biosolids fertiliser (processed human sewage).

Polyvalent Diazonium Polymers Provide Efficient Protection of Oncolytic Adenovirus Enadenotucirev from Neutralizing Antibodies while Maintaining Biological Activity In Vitro and In Vivo.

Oncolytic viruses offer many advantages for cancer therapy when administered directly to confined solid tumors. However, the systemic delivery of these viruses is problematic because of the host immune response, undesired interactions with blood components, and inherent targeting to the liver. Efficacy of systemically administered viruses has been improved by masking viral surface proteins with polymeric materials resulting in modulation of viral pharmacokinetic profile and accumulation in tumors in vivo.

Alkyl-Modified Oligonucleotides as Intercalating Vehicles for Doxorubicin Uptake via Albumin Binding.

DNA-based drug delivery vehicles have displayed promise for the delivery of intercalating drugs. Here, we demonstrate that oligonucleotides modified with an alkyl chain can bind to human serum albumin, mimicking the natural binding of fatty acids. These alkyl-DNA-albumin complexes display excellent serum stability and are capable of strongly binding doxorubicin.

Influence of Polymer Size on Uptake and Cytotoxicity of Doxorubicin-Loaded DNA-PEG Conjugates.

Intercalation of drugs into assembled DNA systems offers versatile new mechanisms for controlled drug delivery. However, current systems are becoming increasingly complex, reducing the practicality of large scale production. Here, we demonstrate a more pragmatic approach where a short DNA sequence was modified with poly(ethylene glycol) (PEG) of various lengths at both 5'-termini to provide serum stability and compatibility.

The fetal ovary exhibits temporal sensitivity to a 'real-life' mixture of environmental chemicals.

The development of fetal ovarian follicles is a critical determinant of adult female reproductive competence. Prolonged exposure to environmental chemicals (ECs) can perturb this process with detrimental consequences for offspring. Here we report on the exposure of pregnant ewes to an environmental mixture of ECs derived from pastures fertilized with sewage sludge (biosolids): a common global agricultural practice.

Longitudinal study of Asian elephants, Elephas maximus, indicates intermittent shedding of elephant endotheliotropic herpesvirus 1 during pregnancy.

Introduction: EEHV-1 is a viral infection of elephants that has been associated with a fatal haemorrhagic syndrome in Asian elephants. Previous studies have suggested that pregnant animals may shed more virus than non-pregnant animals.

Methods: This study examined whether pregnancy affected the frequency or magnitude of shedding of elephant endotheliotropic herpesvirus 1 (EEHV1) using Taq man real-time PCR on trunk washes from four female elephants from a UK collection over three time periods between 2011 and 2014.

Sensitive detection of Xanthomonas oryzae Pathovars oryzae and oryzicola by loop-mediated isothermal amplification.

Molecular diagnostics for crop diseases can enhance food security by enabling the rapid identification of threatening pathogens and providing critical information for the deployment of disease management strategies. Loop-mediated isothermal amplification (LAMP) is a PCR-based tool that allows the rapid, highly specific amplification of target DNA sequences at a single temperature and is thus ideal for field-level diagnosis of plant diseases. We developed primers highly specific for two globally important rice pathogens, Xanthomonas oryzae pv.

Conducting HIV research in racial and ethnic minority communities: building a successful interdisciplinary research team.

HIV infection occurs in disproportionately high rates among racial and ethnic minorities in the United States, making it imperative that individuals from these groups be included in research studies. However, it is often difficult to recruit HIV-infected Hispanics and African Americans in clinical trials, but a skilled interdisciplinary team that includes researchers with racial and ethnic diversity can help. This article describes a successful approach for building an interdisciplinary team that values the participation of racial and ethnic minorities in clinical trials and has the skills to work with these groups.

Active adenoviral vascular penetration by targeted formation of heterocellular endothelial-epithelial syncytia.

The endothelium imposes a structural barrier to the extravasation of systemically delivered oncolytic adenovirus (Ad). Here, we introduced a transendothelial route of delivery in order to increase tumor accumulation of virus particles (vp) beyond that resulting from convection-dependent extravasation alone. This was achieved by engineering an Ad encoding a syncytium-forming protein, gibbon ape leukemia virus (GALV) fusogenic membrane glycoprotein (FMG).

Factors influencing retention of adenovirus within tumours following direct intratumoural injection.

Direct intratumoural (IT) administration of adenovirus is widely used, however little is known about the resulting distribution of virus particles. Here we have evaluated the influence of tumour size, volume of injectate and occlusion of injection sites (to prevent retrograde seepage) on particle biodistribution and transgene expression. In subcutaneous MDA-231 xenografts, IT injection of relatively large volumes (4 x 20% (vol/vol) injections) resulted in just 40% of the administered dose being retained in tumour tissue after 30 min, with 15% in the liver thought to reflect systemic 'overflow'.

A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly.

Unequivocal identification of the full composition of a gene is made difficult by the cryptic nature of regulatory elements. Regulatory elements are notoriously difficult to locate and may reside at considerable distances from the transcription units on which they operate and, moreover, may be incorporated into the structure of neighbouring genes. The importance of regulatory mutations as the basis of human abnormalities remains obscure.

The mouse bagpipe gene controls development of axial skeleton, skull, and spleen.

The mouse Bapx1 gene is homologous to the Drosophila homeobox containing bagpipe (bap) gene. A shared characteristic of the genes in these two organisms is expression in gut mesoderm. In Drosophila, bap functions to specify the formation of the musculature of the midgut.

Two enhancer domains control early aspects of the complex expression pattern of Msx1.

To understand how the complex embryonic expression pattern of the Msx1 gene is produced a transgenic analysis of 13 kb of DNA around the Msx1 locus was carried out. Most of the extensive expression pattern of the Msx1 gene was reproduced in transgenics using the LacZ gene fused to 5 kb of Msx1 5' flanking DNA. Two enhancer domains were identified which produced this pattern.