The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant peripheral neuropathy associated with a large DNA duplication on the short arm of human chromosome 17. The trembler (Tr) mouse serves as a model for CMT1A because of phenotypic similarities and because the Tr locus maps to mouse chromosome 11 in a region of conserved synteny with human chromosome 17. Recently, the peripheral myelin gene Pmp-22 was found to carry a point mutation in Tr mice. We have isolated cDNA and genomic clones for human PMP-22. The gene maps to human chromosome 17p11.2-17p12, is expressed at high levels in peripheral nervous tissue and is duplicated, but not disrupted, in CMT1A patients. Thus, we suggest that a gene dosage effect involving PMP-22 is at least partially responsible for the demyelinating neuropathy seen in CMT1A.     

The complete genome sequence of Francisella tularensis, the causative agent of tularemia

Francisella tularensis is one of the most infectious human pathogens known. In the past, both the former Soviet Union and the US had programs to develop weapons containing the bacterium. We report the complete genome sequence of a highly virulent isolate of F. tularensis (1,892,819 bp). The sequence uncovers previously uncharacterized genes encoding type IV pili, a surface polysaccharide and iron-acquisition systems. Several virulence-associated genes were located in a putative pathogenicity island, which was duplicated in the genome. More than 10% of the putative coding sequences contained insertion-deletion or substitution mutations and seemed to be deteriorating. The genome is rich in IS elements, including IS630 Tc-1 mariner family transposons, which are not expected in a prokaryote. We used a computational method for predicting metabolic pathways and found an unexpectedly high proportion of disrupted pathways, explaining the fastidious nutritional requirements of the bacterium. The loss of biosynthetic pathways indicates that F. tularensis is an obligate host-dependent bacterium in its natural life cycle. Our results have implications for our understanding of how highly virulent human pathogens evolve and will expedite strategies to combat them.     

Optical emission from a charge-tunable quantum ring

Quantum dots or rings are artificial nanometre-sized clusters that confine electrons in all three directions. They can be fabricated in a semiconductor system by embedding an island of low-bandgap material in a sea of material with a higher bandgap. Quantum dots are often referred to as artificial atoms because, when filled sequentially with electrons, the charging energies are pronounced for particular electron numbers; this is analogous to Hund's rules in atomic physics. But semiconductors also have a valence band with strong optical transitions to the conduction band. These transitions are the basis for the application of quantum dots as laser emitters, storage devices and fluorescence markers. Here we report how the optical emission (photoluminescence) of a single quantum ring changes as electrons are added one-by-one. We find that the emission energy changes abruptly whenever an electron is added to the artificial atom, and that the sizes of the jumps reveal a shell structure.     

Denitrifying bacteria of genus Alcaligenes isolated from soil]

The organism isolated is a small non-sporulating Gram-negative rod, motile by means of peritrichous flagellae. It is an oxidase-positive chemo-organotroph utilizing O2,NO-3,NO-2 and N2O as resiratory substrates. Primary alcohols as well as numerous organic and amino acids are utilized as carbon and energy sources. Carbohydrates are not assimilated. Poly-beta-hydroxybutyrate is accumulated intracellularly. The bacterium is assigned to the genus Alcaligenes and its phenotype characteristics are compared with those of A. faecalis.     

Effect of enkephalins in the presence of the antibiotic bacitracin in the longitudinal muscle strip preparation from guinea-pig ileum

Summary The antibiotic bacitracin (5×10^–5–4×10^–4 M) increases the inhibition of the contractile response caused by both enkephalin release and direct application of Met-enkephalin 5×10^–7 M in the longitudinal muscle strip preparation from guinea-pig ileum. This effect is attributed to an inhibition of enkephalin degrading peptidases by bacitracin.     

Two-step binding mechanism for T-cell receptor recognition of peptide MHC

T cells probe a diverse milieu of peptides presented by molecules of the major histocompatibility complex (MHC) by using the T-cell receptor (TCR) to scan these ligands with high sensitivity and specificity. Here we describe a physical basis for this scanning process by studying the residues involved in both the initial association and the stable binding of TCR to peptide-MHC, using the well-characterized TCR and peptide-MHC pair of 2B4 and MCC-IE(k) (moth cytochrome c, residues 88 103). We show that MHC contacts dictate the initial association, guiding TCR docking in a way that is mainly independent of the peptide. Subsequently, MCC-IE(k) peptide contacts dominate stabilization, imparting specificity and influencing T-cell activation by modulating the duration of binding. This functional subdivision of the peptide-MHC ligand suggests that a two-step process for TCR recognition facilitates the efficient scanning of diverse peptide-MHC complexes on the surface of cells and also makes TCRs inherently crossreactive towards different peptides bound by the same MHC.     

Validating Policy‐Induced Economic Change Using Sequential General Equilibrium SAMs

We present a novel sequential approach that explores the capacity of Computable general equilibrium (CGE) models to track down policy‐induced economic changes and their ability to generate contrastable data. We use an empirical Social accounting matrix (SAM) of the region of Andalusia, in the south of Spain, to construct an initial CGE model. This model is then perturbed with a set of policy shocks related to EU Structural Funds invested into Andalusia. These shocks are accompanied by some parameter adjustments that pick up the main external changes not explained by the model. We generate a sequence of model‐produced virtual SAMs. We then compare the last virtual SAM in the sequence with a new available empirical SAM. This allows us to check relatedness, for the same year, between the model produced and the empirical SAMs. The results show a good fit to the empirical data, providing further support to the CGE modelling tool. Copyright © 2016 John Wiley & Sons, Ltd.