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Biomedical subjects

Mark J Henderson

Publications and source records attributed to Mark J Henderson.

3 recordsLinked to original sources

Brown bullhead catfish melanoma represents a novel transmissible cancer.

Since 2012, brown bullhead catfish (Ameiurus nebulosus) in a lake that spans Vermont, USA, and Quebec, Canada, have shown a high rate of melanomas, suggesting a causal contaminant or contagion1. We tested the hypothesis that this affliction represents a clonally transmissible cancer, a rare phenomenon in which cancer cells themselves spread between individuals, behaving more like parasites than conventional tumours2. Whole-genome sequencing of tumour and matched non-tumour host tissues revealed that tumour mitochondrial and nuclear genomes are more closely related to each other than to their hosts or unaffected fish. Hundreds of thousands of genetic variants are shared among tumour samples but are absent from host fish, vastly exceeding levels seen in conventional cancers3. These findings indicate that melanoma in these brown bullheads represents the fourth documented type of naturally occurring transmissible cancer in animals, after dogs4, Tasmanian devils5 and several bivalve species6-13. This raises important questions about the cancer's origin, the mode of transmission and the long-term impact on fish populations.

Animals↗

Protein-poly(silicic) acid interactions at the air/solution interface.

The structure of the interface generated by a spread layer of beta-casein on an aqueous colloidal poly(silicic) acid subphase is described. The results are compared with data for the protein alone spread at the air/water interface and the silicate solution. Films develop at the air-solution interface and a strong pH dependence of the interaction causing this is demonstrated. Reflectometry with X-rays and neutrons was used to probe the interaction as a function of subphase pH and film compression. Film thickness, tau/A, scattering length density, rho/A(-2), water volume fraction, phi(w), and surface coverage, Gamma/mg m(-2), were used to quantify the interfacial structure. Where possible, the X-ray and neutron data sets were co-refined enabling phi(w) to be evaluated without assumption regarding the protein density. At pH 5-7, strong protein-silicate interaction occurred, the interface comprising three regions: a discrete protein upper layer on top of a 15 +/- 2 A layer of silicated material followed by a diffuse layer that extended into the subphase.

Air↗

GCF2/LRRFIP1 represses tumor necrosis factor alpha expression.

Tumor necrosis factor alpha (TNF-alpha) is an important mediator of inflammation, apoptosis, and the development of secondary lymphoid structures. Multiple polymorphic microsatellites have been identified in and around the gene, and there are also multiple single-base pair biallelic polymorphisms in the introns and promoter. The TNF-alpha -308 promoter polymorphism is a G-to-A transition which has been statistically associated with various autoimmune disorders. Some studies have found that it may directly mediate the increased transcription of TNF-alpha in some circumstances. This study characterizes proteins interacting at the polymorphic promoter site. Affinity purification of binding proteins and confirmatory chromatin immunoprecipitation assays were used to identify the proteins. Electrophoretic mobility shift analyses and surface plasmon resonance were used to define binding characteristics. Proteins interacting at this site include GCF2/LRRFIP1 and Ets-1. GCF2/LRRFIP1 appears to act as a repressor and occupies the -308 site in cells that do not make TNF-alpha. Cells competent to produce TNF-alpha have Ets-1 bound to the -308 promoter site. Active transcription is accompanied by NF-kappaB and c-Jun binding to the proximal promoter. Thus, dynamic changes on the TNF-alpha promoter, particularly at the -308 site, accompany the transition from repressed to active transcription. GCF2/LRRFIP1 is the first TNF-alpha repressor identified.

Base Sequence↗