Autism-associated SNPs in the clock genes _npas2_, _per1_ and the homeobox gene _en2_ alter DNA sequences that show characteristics of microRNA genes.

Intronic single nucleotide polymorphisms (SNPs) in the clock genes _npas2_ and _per1_ and the homeobox gene _en2_ are reported to be associated with autism. This bioinformatics analysis of the intronic regions which contain the autism-associated SNPs rs1861972 and rs1861973 in _en2_, rs1811399 in _npas2_, and rs885747 in _per1_, shows that these regions encode RNA transcripts with predicted structural characteristics of microRNAs. These microRNA-like structures are disrupted _in silico_ by the presence of the autism enriched alleles of rs1861972, rs1861973, rs1811399 and rs885747 specifically, as compared with the minor alleles of these SNPs. The predicted gene targets of these microRNA-like structures include genes reported to be implicated in autism (_gabrb3_, _shank3_) and genes causative of diseases co-morbid with autism (_mecp2_ and _rai1_). The inheritance of the AC haplotype of rs1861972 - rs1861973 in _en2_, the C allele of rs1811399 in _npas2_, and the C allele of rs1234747 in _per1_ may contribute to the causes of autism by affecting microRNA genes that are co-expressed along with the homeobox gene _en2_ and the circadian genes _npas2_ and _per1_

Time variability of Neptune's horizontal and vertical cloud structure revealed by VLT/SINFONI and Gemini/NIFS from 2009 to 2013

New observations of Neptune's clouds in the near infrared were acquired in October 2013 with SINFONI on ESO's Very Large Telescope (VLT) in Chile. SINFONI is an Integral Field Unit spectrometer returning a 64 × 64 pixel image with 2048 wavelengths. Image cubes in the J-band (1.09-1.41 μm) and H-band (1.43-1.87 μm) were obtained at spatial resolutions of 0.1″and 0.025″per pixel, while SINFONI's adaptive optics provided an effective resolution of approximately 0.1″. Image cubes were obtained at the start and end of three successive nights to monitor the temporal development of discrete clouds both at short timescales (i.e. during a single night) as well as over the longer period of the three-day observing run. These observations were compared with similar H-band observations obtained in September 2009 with the NIFS Integral Field Unit spectrometer on the Gemini-North telescope in Hawaii, previously reported by Irwin et al. (2011) [Icarus, 216, 141-158], and previously unreported Gemini/NIFS observations at lower spatial resolution made in 2011.We find both similarities and differences between these observations, spaced over four years. The same overall cloud structure is seen with high, bright clouds visible at mid-latitudes (30-40°N,S), with slightly lower clouds observed at lower latitudes, together with small discrete clouds seen circling the pole at a latitude of approximately 60°S. However, while discrete clouds were visible at this latitude at both the main cloud deck level (at 2-3 bar) and in the upper troposphere (100-500 mb) in 2009, no distinct deep (2-3 bar), discrete circumpolar clouds were visible in 2013, although some deep clouds were seen at the southern edge of the main cloud belt at 30-40°S, which have not been observed before. The nature of the deep sub-polar discrete clouds observed in 2009 is intriguing. While it is possible that in 2013 these deeper clouds were masked by faster moving, overlying features, we consider that it is unlikely that this should have happened in 2013, but not in 2009 when the upper-cloud activity was generally similar. Meanwhile, the deep clouds seen at the southern edge of the main cloud belt at 30-40°S in 2013, should also have been detectable in 2009, but were not seen. Hence, these observations may have detected a real temporal variation in the occurrence of Neptune's deep clouds, pointing to underlying variability in the convective activity at the pressure of the main cloud deck at 2-3 bar near Neptune's south pole and also in the main observable cloud belt at 30-40°S.</p

Naval History by Conspiracy Theory: The British Admiralty before the First World War and the Methodology of Revisionism

Revisionist interpretations of British naval policy in the Fisher era claim that an elaborate smoke screen was created to hide the Royal Navy’s real policies; while documents showing the true goals were systematically destroyed. By asserting this, revisionists are able to dismiss those parts of the documentary record that contradict their theories, while simultaneously excusing the lack of evidence for their theories by claiming it has been destroyed. This article shows that this methodology is misleading and untenable

Multiple effects of silymarin on the hepatitis C virus lifecycle

Silymarin, an extract from milk thistle (Silybum marianum), and its purified flavonolignans have been recently shown to inhibit hepatitis C virus (HCV) infection, both in vitro and in vivo. In the current study, we further characterized silymarin's antiviral actions. Silymarin had antiviral effects against hepatitis C virus cell culture (HCVcc) infection that included inhibition of virus entry, RNA and protein expression, and infectious virus production. Silymarin did not block HCVcc binding to cells but inhibited the entry of several viral pseudoparticles (pp), and fusion of HCVpp with liposomes. Silymarin but not silibinin inhibited genotype 2a NS5B RNA-dependent RNA polymerase (RdRp) activity at concentrations 5 to 10 times higher than required for anti-HCVcc effects. Furthermore, silymarin had inefficient activity on the genotype 1b BK and four 1b RDRPs derived from HCV-infected patients. Moreover, silymarin did not inhibit HCV replication in five independent genotype 1a, 1b, and 2a replicon cell lines that did not produce infectious virus. Silymarin inhibited microsomal triglyceride transfer protein activity, apolipoprotein B secretion, and infectious virion production into culture supernatants. Silymarin also blocked cell-to-cell spread of virus. CONCLUSION: Although inhibition of in vitro NS5B polymerase activity is demonstrable, the mechanisms of silymarin's antiviral action appear to include blocking of virus entry and transmission, possibly by targeting the host cell

Cis-effects on gene expression in the human prenatal brain associated with genetic risk for neuropsychiatric disorders

The majority of common risk alleles identified for neuropsychiatric disorders reside in non-coding regions of the genome and are therefore likely to impact gene regulation. However, the genes that are primarily affected and the nature and developmental timing of these effects remain unclear. Given the hypothesised role for early neurodevelopmental processes in these conditions, we here define genetic predictors of gene expression in the human fetal brain with which we perform transcriptome-wide association studies (TWASs) of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, bipolar disorder, major depressive disorder and schizophrenia. We identify prenatal cis-regulatory effects on 63 genes and 166 individual transcripts associated with genetic risk for these conditions. We observe pleiotropic effects of expression predictors for a number of genes and transcripts, including those of decreased DDHD2 expression in association with risk for schizophrenia and bipolar disorder, increased expression of a ST3GAL3 transcript with risk for schizophrenia and ADHD, and increased expression of an XPNPEP3 transcript with risk for schizophrenia, bipolar disorder and major depression. For the protocadherin alpha cluster genes PCDHA7 and PCDHA8, we find that predictors of low expression are associated with risk for major depressive disorder while those of higher expression are associated with risk for schizophrenia. Our findings support a role for altered gene regulation in the prenatal brain in susceptibility to various neuropsychiatric disorders and prioritize potential risk genes for further neurobiological investigation