Glutamate 301 of the mouse gonadotropin-releasing hormone receptor confers specificity for arginine 8 of mammalian gonadotropin-releasing hormone

The Arg residue at position 8 of mammalian GnRH is necessary for high affinity binding to mammalian GnRH receptors. This requirement has been postulated to derive from an electrostatic interaction of Arg8 with a negatively charged receptor residue. In order to identify such a residue, 8 conserved acidic residues of the mouse GnRH receptor were mutated to isosteric Asn or Gln. Mutant receptors were tested for decreased preference for Arg8-containing ligands by ligand binding and inositol phosphate production. One of the mutants, in which the Glu301 residue was mutated to Gln, exhibited a 56-fold decrease in apparent affinity for mammalian GnRH. The mutant receptor also exhibited decreased affinity for [Lys8]GnRH, but its affinity for [Gln8]GnRH was unchanged compared with the wild type receptor. The apparent affinity of the mutant receptor for the acidic analogue, [Glu8]GnRH, was increased more than 10-fold. The mutant receptor did not, therefore, distinguish mammalian GnRH from analogues with amino acid substitutions at position 8 as effectively as the wild type receptor. This loss of discrimination was specific for the residue at position 8, because the mutant receptor did distinguish mammalian GnRH from analogues with favorable substitutions at positions 5, 6, and 7. These findings show that Glu301 of the GnRH receptor plays a role in receptor recognition of Arg8 in the ligand and are consistent with an electrostatic interaction between these 2 residues

Fine structure in the gamma-ray sky

The EGRET results for gamma-ray intensities in and near the Galactic Plane have been analysed in some detail. Attention has been concentrated on energies above 1 GeV and the individual intensities in a $4^\circ$ longitude bin have been determined and compared with the large scale mean found from a nine-degree polynomial fit. Comparison has been made of the observed standard deviation for the ratio of these intensities with that expected from variants of our model. The basic model adopts cosmic ray origin from supernova remnants, the particles then diffusing through the Galaxy with our usual 'anomalous diffusion'. The variants involve the clustering of SN, a frequency distribution for supernova explosion energies, and 'normal', rather than 'anomalous' diffusion. It is found that for supernovae of unique energy, and our usual anomalous diffusion, clustering is necessary, particularly in the Inner Galaxy. An alternative, and preferred, situation is to adopt the model with a frequency distribution of supernova energies. The results for the Outer Galaxy are such that no clustering is required.Comment: 10 pages, 4 figures, 1 table, accepted for publication in J.Phys.G: Nucl.Part.Phy

Silver antimony Ohmic contacts to moderately doped n-type germanium

A self doping contact consisting of a silver/antimony alloy that produces an Ohmic contact to moderately doped n-type germanium (doped to a factor of four above the metal-insulator transition) has been investigated. An evaporation of a mixed alloy of Ag/Sb (99%/1%) onto n-Ge ( ND=1×1018 cm−3) annealed at 400 °C produces an Ohmic contact with a measured specific contact resistivity of (1.1±0.2)×10−5 Ω-cm2. It is proposed that the Ohmic behaviour arises from an increased doping concentration at the Ge surface due to the preferential evaporation of Sb confirmed by transmission electron microscope analysis. It is suggested that the doping concentration has increased to a level where field emission will be the dominate conduction mechanism. This was deduced from the low temperature electrical characterisation of the contact, which exhibits Ohmic behaviour down to a temperature of 6.5 K

Ambiguous figures and the content of experience

Representationalism is the position that the phenomenal character of an experience is either identical with, or supervenes on, the content of that experience. Many representationalists hold that the relevant content of experience is nonconceptual. I propose a counterexample to this form of representationalism that arises from the phenomenon of Gestalt switching, which occurs when viewing ambiguous figures. First, I argue that one does not need to appeal to the conceptual content of experience or to judgements to account for Gestalt switching. I then argue that experiences of certain ambiguous figures are problematic because they have different phenomenal characters but that no difference in the nonconceptual content of these experiences can be identified. I consider three solutions to this problem that have been proposed by both philosophers and psychologists and conclude that none can account for all the ambiguous figures that pose the problem. I conclude that the onus is on representationalists to specify the relevant difference in content or to abandon their position

Cataract, abnormal electroretinogram and visual evoked potentials in a child with SMA-LED2 - extending the phenotype.

This case report describes a girl who presented antenatal arthrogryposis and postnatal hypotonia, generalized and respiratory weakness, joint deformities particularly affecting the lower limbs and poor swallow. By 5 months, cataracts, abnormal electroretinograms, visual evoked potentials and global developmental impairments were recognized. No causative variants were identified on targeted gene panels. After her unexpected death at 11 months, gene-agnostic trio whole exome sequencing revealed a likely pathogenic de novo BICD2 missense variant, NM_001003800.1, c.593T>C, p.(Leu198Pro), confirming the diagnosis of spinal muscular atrophy lower extremity predominant type 2 (SMA-LED2). We propose that cataracts and abnormal electroretinograms are novel features of SMA-LED2

Behavioural responses to SARS-CoV-2 antibody testing in England: REACT-2 study

Background: This study assesses the behavioural responses to SARS-CoV-2 antibody test results as part of the REal-time Assessment of Community Transmission-2 (REACT-2) research programme, a large community-based surveillance study of antibody prevalence in England. Methods: A follow-up survey was conducted six weeks after the SARS-CoV-2 antibody test. The follow-up survey included 4500 people with a positive result and 4039 with a negative result. Reported changes in behaviour were assessed using difference-in-differences models. A nested interview study was conducted with 40 people to explore how they thought through their behavioural decisions. Results: While respondents reduced their protective behaviours over the six weeks, we did not find evidence that positive test results changed participant behaviour trajectories in relation to the number of contacts the respondents had, for leaving the house to go to work, or for leaving the house to socialise in a personal place. The qualitative findings supported these results. Most people did not think that they had changed their behaviours because of their test results, however they did allude to some changes in their attitudes and perceptions around risk, susceptibility, and potential severity of symptoms. Conclusions: We found limited evidence that knowing your antibody status leads to behaviour change in the context of a research study. While this finding should not be generalised to widespread self-testing in other contexts, it is reassuring given the importance of large prevalence studies, and the practicalities of doing these at scale using self-testing with lateral flow immunoassay (LFIA)