Instability of the Octarepeat Region of the Human Prion Protein Gene

Prion diseases are a family of unique fatal transmissible neurodegenerative diseases that affect humans and many animals. Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common prion disease in humans, accounting for 85–90% of all human prion cases, and exhibits a high degree of diversity in phenotypes. The etiology of sCJD remains to be elucidated. The human prion protein gene has an octapeptide repeat region (octarepeats) that normally contains 5 repeats of 24–27 bp (1 nonapeptide and 4 octapeptide coding sequences). An increase of the octarepeat numbers to six or more or a decrease of the octarepeat number to three is linked to genetic prion diseases with heterogeneous phenotypes in humans. Here we report that the human octarepeat region is prone to either contraction or expansion when subjected to PCR amplification in vitro using Taq or Pwo polymerase and when replicated in wild type E. coli cells. Octarepeat insertion mutants were even less stable, and the mutation rate for the wild type octarepeats was much higher when replicated in DNA mismatch repair-deficient E.coli cells. All observed octarepeat mutants resulting from DNA replication in E.coli were contained in head-to-head plasmid dimers and DNA mfold analysis (http://mfold.rna.albany.edu/?q=mfold/DNA-Folding-Form) indicates that both DNA strands of the octarepeat region would likely form multiple stable hairpin structures, suggesting that the octarepeat sequence may form stable hairpin structures during DNA replication or repair to cause octarepeat instability. These results provide the first evidence supporting a somatic octarepeat mutation-based model for human sCJD etiology: 1) the instability of the octarepeat region leads to accumulation of somatic octarepeat mutations in brain cells during development and aging, 2) this instability is augmented by compromised DNA mismatch repair in aged cells, and 3) eventually some of the octarepeat mutation-containing brain cells start spontaneous de novo prion formation and replication to initiate sCJD

A new hybrid Dawson-type molybdenum arsenate derivative: (H2bpy)3[As2Mo18O62] (bpy = 4,4′-bipyridine)

The title compound, tris­(4,4′-bipyridinium) diarsenoocta­deca­molybdate(VI), (C10H10N2)3[As2Mo18O62], featuring protonated bipyridine mol­ecules and a classical Dawson-type polyoxo-anion, has been synthesized under hydro­thermal conditions. The polyoxoanions are linked together via the bipyridyl cations, acting as hydrogen-bond donors, generating a two-dimensional supra­molecular network. The asymmetric unit contains 1.5 4,4′-bipyridinium (H2bpy) units, with an inversion centre in the central bond of the second H2bpy unit. The site symmetry of the anion is

Identification of Fur in Pasteurella multocida and the Potential of Its Mutant as an Attenuated Live Vaccine

Pasteurella multocida is a pathogenic microorganism that causes a variety of serious diseases in humans and animals worldwide. The global regulator gene, fur, plays an important role in pathogenesis and regulates the virulence of many bacteria. Here, we identified a fur gene in P. multocida by complementing a Salmonella Choleraesuis Δfur mutant, and characterized a fur mutant strain of P. multocida. The P. multocida Δfur mutant strain exhibited no significant differences in growth and outer membrane protein (OMP) profiles when the complemented strain was compared to the parent. Ducks were used as the model organism to determine the virulence and protection efficacy induced by Δfur mutant strain. Animal experiments showed that colonization by the mutant was decreased by oral infection of live Δfur mutant strain. The LD50 of the ducks infected with the Δfur mutant was 146-fold higher than that of the ducks infected with the wild-type strain when administered through the oral route. Evaluation of the immunogenicity and protective efficacy of the Δfur mutant of P. multocida revealed strong serum IgY and bile IgA immune responses following oral inoculation with the Δfur strain. Ducks that were orally inoculated with the Δfur mutant strain demonstrated 62% protection efficacy against severe lethal challenge with the wild-type P. multocida. This study provides new insights into P. multocida virulence and the potential use of an attenuated vaccine against P. multocida

DelicacyNet for nutritional evaluation of recipes

In this paper, we are interested in how computers can be used to better serve us humans, such as helping humans control their nutrient intake, with higher level shortcuts. Specifically, the neural network model was used to help humans identify and analyze the content and proportion of nutrients in daily food intake, so as to help humans autonomously choose and reasonably match diets. In this study, we formed the program we wanted to obtain by establishing four modules, in which the imagination module sampled the environment, then relied on the encoder to extract the implicit features of the image, and finally relied on the decoder to obtain the required feature vector from the implicit features, and converted it into the battalion formation table information through the semantic output module. Finally, the model achieved extremely high accuracy on recipe1M+ and food2K datasets

Cationic Porphyrins with Large Side Arm Substituents as Resonance Light Scattering Ratiometric Probes for Specific Recognition of Nucleic Acid G-quadruplexes

Specific G-quadruplex-probing is crucial for both biological sciences and biosensing applications. Most reported probes are focused on fluorescent or colorimetric recognition of G-quadruplexes. Herein, for the first time, we reported a new specific G-quadruplex-probing technique—resonance light scattering (RLS)-based ratiometric recognition. To achieve the RLS probing of G-quadruplexes in the important physiological pH range of 7.4-6.0, four water soluble cationic porphyrin derivatives, including an unreported octa-cationic porphyrin, with large side arm substituents were synthesized and developed as RLS probes. These RLS probes were demonstrated to work well for ratiometric recognition of G-quadruplexes with high specificity against single- and double-stranded DNAs, including long double-stranded ones. The working mechanism was speculated to be based on the RLS signal changes caused by porphyrin protonation that was promoted by the end-stacking of porphyrins on Gquadruplexes. This work adds an important member in G-quadruplex probe family, thus providing a useful tool for studies on G-quadruplex-related events concerning G-quadruplex formation, destruction and changes in size, shape and aggregation. As a proofof-concept example of applications, the RLS probes were demonstrated to work well for label-free and sequence-specific sensing of microRNA. This work also provides a simple and useful way for the preparation of cationic porphyrins with high charges

NATsDB: Natural Antisense Transcripts DataBase

Natural antisense transcripts (NATs) are reverse complementary at least in part to the sequences of other endogenous sense transcripts. Most NATs are transcribed from opposite strands of their sense partners. They regulate sense genes at multiple levels and are implicated in various diseases. Using an improved whole-genome computational pipeline, we identified abundant cis-encoded exon-overlapping sense–antisense (SA) gene pairs in human (7356), mouse (6806), fly (1554), and eight other eukaryotic species (total 6534). We developed NATsDB (Natural Antisense Transcripts DataBase, ) to enable efficient browsing, searching and downloading of this currently most comprehensive collection of SA genes, grouped into six classes based on their overlapping patterns. NATsDB also includes non-exon-overlapping bidirectional (NOB) genes and non-bidirectional (NBD) genes. To facilitate the study of functions, regulations and possible pathological implications, NATsDB includes extensive information about gene structures, poly(A) signals and tails, phastCons conservation, homologues in other species, repeat elements, expressed sequence tag (EST) expression profiles and OMIM disease association. NATsDB supports interactive graphical display of the alignment of all supporting EST and mRNA transcripts of the SA and NOB genes to the genomic loci. It supports advanced search by species, gene name, sequence accession number, chromosome location, coding potential, OMIM association and sequence similarity