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Gephyrin is an ubiquitously expressed protein that, in the central nervous system, generates a protein scaffold to anchor inhibitory neurotransmitter receptors in the postsynaptic membrane. It was first identified as a protein component of the glycine receptor complex. Recent studies have demonstrated that gephyrin is colocalized with several subtypes of GABAA receptors and is part of postsynaptic GABAA receptor clusters. Here, we describe a study of the regional and cellular distribution of gephyrin in the human brain, determined by immunohistochemical localisation at the light and confocal laser scanning microscopic levels. At the regional level, gephyrin immunoreactivity was observed in most of the major brain regions examined. The most intense staining was in the cerebral cortex, hippocampus and caudate-putamen, in various brainstem nuclei with more moderate levels in the thalamus and cerebellum. At the cellular level gephyrin immunoreactivity was present on the plasma membranes of the soma and dendrites of pyramidal neurons throughout the various cortical regions examined. In the hippocampus, intense staining was observed on the granule cells of the dentate gyrus, and neurons of the CA1 and CA3 regions showed intense punctate gephyrin staining on their apical dendrites and cell bodies. Gephyrin immunoreactivity was also observed on neurons in the thalamus, globus pallidus and substantia nigra. In the putamen intense labelling of the striosomes was observed; most of the medium-sized neurons in the caudate-putamen were weakly labelled and many large neurons of the striatum were conspicuously stained. Many of the brainstem nuclei, notably the dorsal motor nucleus of the vagus, hypoglossal nucleus, trigeminal nucleus and inferior olive were all labelled with gephyrin. The spinal cord also showed high levels of gephyrin immunoreactivity. Our results demonstrate that the anchoring protein gephyrin is ubiquitously present in the human brain. We therefore suggest that gephyrin may have a central organizer role in assembling and stabilizing inhibitory postsynaptic membranes in human brain and is similar in function to those observed in the rodent brain. These findings contribute towards elucidating the role of gephyrin in the human brain. [Copyright &y& Elsevier]

The objective of this study was to estimate genetic correlations among milk fatty acid (FA) concentrations in New Zealand dairy cattle. Concentrations of each of the most common FA, expressed as a percentage of the total FA, were determined by gas chromatography on a specific cohort of animals. Using this data set, prediction equations were derived using mid-infrared (MIR) spectroscopy data collected from the same samples. These prediction equations were applied to a large data set of MIR measurements in 34,141 milk samples from 3,445 Holstein-Friesian, 2,935 Jersey, and 3,609 crossbred Holstein-Friesian × Jersey cows, sampled an average of 3.42 times during the 2007–2008 season. Data were analyzed using univariate and bivariate repeatability animal models. Heritability of predicted FA concentration in milk fat ranged from 0.21 to 0.42, indicating that genetic selection could be used to change the FA composition of milk. The de novo synthesized FA (C6:0, C8:0, C10:0, C12:0, and C14:0) showed strong positive genetic correlations with each other, ranging from 0.24 to 0.99. Saturated FA were negatively correlated with unsaturated (−0.93) and polyunsaturated (−0.84) FA. The saturated FA were positively correlated with milk fat yield and fat percentage, whereas the unsaturated FA were negatively associated with fat yield and fat percentage. Our results indicate that bovine milk FA composition can be changed through genetic selection using MIR as a phenotypic proxy. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDDs) are incapacitating disorders that result in progressive motor and cognitive impairment. These diseases include Alzheimer’s disease, the most common cause of dementia, frontotemporal dementia, amyotrophic lateral sclerosis, dementia with Lewy bodies, Parkinson’s, Huntington’s, Friedreich’s ataxia, and prion disease. Dementia causing NDDs impose a high social and economic burden on communities around the world. Rapid growth in knowledge regarding the pathogenic mechanisms and disease-associated biomarkers of these diseases in the past few decades have accelerated the development of new diagnostic methods and therapeutic opportunities. Continuous effort is being applied to the development of more advanced, easy-to-apply and reliable methods of diagnosis, that are able to identify disease manifestation at its earliest stages and before clinical symptoms become apparent. Development of these diagnostic tools are essential in aiding effective disease management through accurate monitoring of disease progression, timely application of therapeutics and evaluation of treatment efficacy. Recently, several studies have identified novel biomarkers based on compounds in exhaled breath associated with specific NDDs. The use of breath testing, as a means of monitoring neurodegenerative disease onset and progression, has the potential to have a significant impact on augmenting the diagnosis of NDDs as the approach is non-invasive, relatively cost effective and straight forward to implement. This review highlights key features of current diagnostic methods utilised to identify NDDs, and describes the potential application and limitations associated with the use of breath analysis for disease diagnosis and progression monitoring. [ABSTRACT FROM AUTHOR]

Abstract: TATA binding protein (TBP) is a general transcription factor that plays an important role in initiation of transcription. In recent years evidence has emerged implicating TPB in the molecular mechanism of a number of neurodegenerative diseases. Wild type TBP in humans contains a long polyglutamine stretch ranging in size from 29 to 42. It has been found associated with aggregated proteins in several of the polyglutamine disorders. Expansion in the CAA/CAG composite repeat beyond 42 has been shown to cause a cerebellar ataxia, SCA17. The involvement of such an important housekeeping protein in the disease mechanism suggests a major impact on the functioning of cells. The question remains, does TBP contribute to these diseases through a loss of normal function, likely to be catastrophic to a cell, or the gain of an aberrant function? This review deals with the function of TBP in transcription and cell function. The distribution of the polyglutamine coding allele lengths in TBP of the normal population and in SCA17 is reviewed and an outline is given on the reported cases of SCA17. The role of TBP in other polyglutamine disorders will be addressed as well as its possible role in other neurodegenerative diseases. [Copyright &y& Elsevier]