A novel human glucocorticoid receptor SNP results in increased transactivation potential.

Glucocorticoids are one of the most widely used therapeutics in the treatment of a variety of inflammatory disorders. However, it is known that there are variable patient responses to glucocorticoid treatment; there are responders and non-responders, or those that need higher dosages. Polymorphisms in the glucocorticoid receptor (GR) have been implicated in this variability. In this study, ninety-seven volunteers were surveyed for polymorphisms in the human GR-alpha (hGRα), the accepted biologically active reference isoform. One isoform identified in our survey, named hGR DL-2, had four single nucleotide polymorphisms (SNPs), one synonymous and three non-synonymous, and a four base pair deletion resulting in a frame shift and early termination to produce a 743 amino acid putative protein. hGR DL-2 had a decrease in transactivation potential of more than 90%. Upon further analysis of the individual SNPs and deletion, one SNP, A829G, which results in a lysine to glutamic acid amino acid change at position 277, was found to increase the transactivation potential of hGR more than eight times the full-length reference. Furthermore, the hGRα-A829G isoform had a differential hyperactive response to various exogenous steroids. Increasing our knowledge as to how various SNPs affect hGR activity may help in understanding the unpredictable patient response to steroid treatment, and is a step towards personalizing patient care

Social and behavioural factors in Non-suspicious unexpected death in infancy; experience from metropolitan police project indigo investigation

BACKGROUND: Risk factors for Sudden Unexpected Death in Infancy (SUDI) are well described, and such cases are now investigated according to standard protocols. In London, Project Indigo of the Metropolitan Police provides a unique, detailed framework for such data collection. We investigate such data to provide a contemporary account of SUDI in a large city and further link data to publically available datasets to investigate interactions with social factors. METHODS: Retrospective analysis of data routinely collected by the Metropolitan Police Service in all cases of non-suspicious SUDI deaths in London during a six year period. RESULTS: SUDI deaths are associated with markers of social deprivation in London. A significant proportion of such deaths are associated with potentially modifiable risk factors such as cigarette smoking and co-sleeping, such behaviour also being associated with social factors, including accommodation issues. CONCLUSIONS: Routinely collected data provide valuable insight into patterns and associations of mortality, with SUDI remaining a significant issue in London. Risk factors include social disadvantage, which may manifest in part by affecting behavioural patterns such as co-sleeping and public health interventions to reduce rates require significant social modification

Differential Functions of mPer1, mPer2, and mPer3 in the SCN Circadian Clock

AbstractThe role of mPer1 and mPer2 in regulating circadian rhythms was assessed by disrupting these genes. Mice homozygous for the targeted allele of either mPer1 or mPer2 had severely disrupted locomotor activity rhythms during extended exposure to constant darkness. Clock gene RNA rhythms were blunted in the suprachiasmatic nucleus of mPer2 mutant mice, but not of mPER1-deficient mice. Peak mPER and mCRY1 protein levels were reduced in both lines. Behavioral rhythms of mPer1/mPer3 and mPer2/mPer3 double-mutant mice resembled rhythms of mice with disruption of mPer1 or mPer2 alone, respectively, confirming the placement of mPer3 outside the core circadian clockwork. In contrast, mPer1/mPer2 double-mutant mice were immediately arrhythmic. Thus, mPER1 influences rhythmicity primarily through interaction with other clock proteins, while mPER2 positively regulates rhythmic gene expression, and there is partial compensation between products of these two genes

Algorithmic decomposition for efficient multiple nuclear spin detection in diamond

Efficiently detecting and characterizing individual spins in solid-state hosts is an essential step to expand the fields of quantum sensing and quantum information processing. While selective detection and control of a few 13C nuclear spins in diamond have been demonstrated using the electron spin of nitrogen-vacancy (NV) centers, a reliable, efficient, and automatic characterization method is desired. Here, we develop an automated algorithmic method for decomposing spectral data to identify and characterize multiple nuclear spins in diamond. We demonstrate efficient nuclear spin identification and accurate reproduction of hyperfine interaction components for both virtual and experimental nuclear spectroscopy data. We conduct a systematic analysis of this methodology and discuss the range of hyperfine interaction components of each nuclear spin that the method can efficiently detect. The result demonstrates a systematic approach that automatically detects nuclear spins with the aid of computational methods, facilitating the future scalability of devices.Comment: 4 figures, 2 table

Αξιοβίωτη Ολοκληρωμένη Ανάπτυξη. Από την Θεωρία στην Πράξη: Η περίπτωση των αστέγων της Αθήνας

Εθνικό Μετσόβιο Πολυτεχνείο--Μεταπτυχιακή Εργασία. Διεπιστημονικό-Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών (Δ.Π.Μ.Σ.) “Περιβάλλον και Ανάπτυξη

Reference ranges for organ weights of infants at autopsy: results of >1,000 consecutive cases from a single centre.

Infancy is the most common period for childhood death, including both neonatal deaths from obstetric or medical complications and sudden unexpected infant deaths. The weighing of organs at autopsy is an established process and is recommended in current protocols. However, minimal contemporary data is available regarding reference ranges for organ weights of infants

Quantification of sulcal emergence timing and its variability in early fetal life: Hemispheric asymmetry and sex difference

Human fetal brains show regionally different temporal patterns of sulcal emergence following a regular timeline, which may be associated with spatiotemporal patterns of gene expression among cortical regions. This study aims to quantify the timing of sulcal emergence and its temporal variability across typically developing fetuses by fitting a logistic curve to presence or absence of sulcus. We found that the sulcal emergence started from the central to the temporo-parieto-occipital lobes and frontal lobe, and the temporal variability of emergence in most of the sulci was similar between 1 and 2 weeks. Small variability (\u3c 1 week) was found in the left central and postcentral sulci and larger variability (\u3e2 weeks) was shown in the bilateral occipitotemporal and left superior temporal sulci. The temporal variability showed a positive correlation with the emergence timing that may be associated with differential contributions between genetic and environmental factors. Our statistical analysis revealed that the right superior temporal sulcus emerged earlier than the left. Female fetuses showed a trend of earlier sulcal emergence in the right superior temporal sulcus, lower temporal variability in the right intraparietal sulcus, and higher variability in the right precentral sulcus compared to male fetuses. Our quantitative and statistical approach quantified the temporal patterns of sulcal emergence in detail that can be a reference for assessing the normality of developing fetal gyrification