The Complete Genome Sequence of the Pathogenic Intestinal Spirochete Brachyspira pilosicoli and Comparison with Other Brachyspira Genomes

Background: The anaerobic spirochete Brachyspira pilosicoli colonizes the large intestine of various species of birds and mammals, including humans. It causes ''intestinal spirochetosis'', a condition characterized by mild colitis, diarrhea and reduced growth. This study aimed to sequence and analyse the bacterial genome to investigate the genetic basis of its specialized ecology and virulence. Methodology/Principal Findings: The genome of B. pilosicoli 95/1000 was sequenced, assembled and compared with that of the pathogenic Brachyspira hyodysenteriae and a near-complete sequence of Brachyspira murdochii. The B. pilosicoli genome was circular, composed of 2,586,443 bp with a 27.9 mol% G+C content, and encoded 2,338 genes. The three Brachyspira species shared 1,087 genes and showed evidence of extensive genome rearrangements. Despite minor differences in predicted protein functional groups, the species had many similar features including core metabolic pathways. Genes distinguishing B. pilosicoli from B. hyodysenteriae included those for a previously undescribed bacteriophage that may be useful for genetic manipulation, for a glycine reductase complex allowing use of glycine whilst protecting from oxidative stress, and for aconitase and related enzymes in the incomplete TCA cycle, allowing glutamate synthesis and function of the cycle during oxidative stress. B. pilosicoli had substantially fewer methyl-accepting chemotaxis genes than B. hyodysenteriae and hence these species are likely to have different chemotactic responses that may help to explain their different host range and colonization sites. B. pilosicoli lacked the gene for a new putative hemolysin identified in B. hyodysenteriae WA1. Both B. pilosicoli and B. murdochii lacked the rfbBADC gene cluster found on the B. hyodysenteriae plasmid, and hence were predicted to have different lipooligosaccharide structures. Overall, B. pilosicoli 95/1000 had a variety of genes potentially contributing to virulence. Conclusions/Significance: The availability of the complete genome sequence of B. pilosicoli 95/1000 will facilitate functional genomics studies aimed at elucidating host-pathogen interactions and virulence

Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148

Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele

Diffraction enhanced transparency in a hybrid gold-graphene THz metasurface

\u3cp\u3eDiffraction enhanced transparency (DET) is a phenomenon based on interference in periodic lattices of resonators, leading to sharp transmission peaks where the associated anomalous dispersion can be used to delay THz radiation traversing the lattice. In this contribution we use an atomically thin graphene layer to strongly suppress DET altering the THz propagation. The response of this system is investigated both in the far-and near-field, where the suppression of DET can be measured both in the spectral response of the sample and in the changing near-field distributions surrounding the resonators. Changing the properties of the graphene layer allows for control over the transparency window, which is relevant for active THz devices.\u3c/p\u3

Recyclable, strong thermosets and organogels via paraformaldehyde condensation with diamines

\u3cp\u3eNitrogen-based thermoset polymers have many industrial applications (for example, in composites), but are difficult to recycle or rework. We report a simple one-pot, low-temperature polycondensation between paraformaldehyde and 4,4′-oxydianiline (ODA) that forms hemiaminal dynamic covalent networks (HDCNs), which can further cyclize at high temperatures, producing poly(hexahydrotriazine)s (PHTs). Both materials are strong thermosetting polymers, and the PHTs exhibited very high Young's moduli (up to ∼14.0 gigapascals and up to 20 gigapascals when reinforced with surface-treated carbon nanotubes), excellent solvent resistance, and resistance to environmental stress cracking. However, both HDCNs and PHTs could be digested at low pH (<2) to recover the bisaniline monomers. By simply using different diamine monomers, the HDCN- and PHT-forming reactions afford extremely versatile materials platforms. For example, when poly(ethylene glycol) (PEG) diamine monomers were used to form HDCNs, elastic organogels formed that exhibited self-healing properties.\u3c/p\u3

Web-based treatment program using intensive therapeutic contact for patients with eating disorders: Before-after study

Contains fulltext : 116776.pdf (publisher's version ) (Open Access)Background: Although eating disorders are common in the Netherlands, only a few patients are treated by mental health care professionals. To reach and treat more patients with eating disorders, Tactus Addiction Treatment developed a web-based treatment program with asynchronous and intensive personalized communication between the patient and the therapist. Objective: This pilot study evaluated the web-based treatment program using intensive therapeutic contact in a population of 165 patients with an eating disorder. Methods: In a pre-post design with 6-week and 6-month follow-ups, eating disorder psychopathology, body dissatisfaction, Body Mass Index, physical and mental health, and quality of life were measured. The participant's satisfaction with the web-based treatment program was also studied. Attrition data were collected, and participants were classified as noncompleters if they did not complete all 10 assignments of the web-based treatment program. Differences in baseline characteristics between completers and noncompleters were studied, as well as reasons for noncompletion. Furthermore, differences in treatment effectiveness, treatment adherence, and baseline characteristics between participants of the three major eating disorder diagnostic groups EDNOS (n=115), BN purging (n=24), and BN nonpurging (n=24) were measured. Results: Of the 165 participants who started the web-based treatment program, 89 participants (54%) completed all of the program assignments (completers) and 76 participants (46%) ended the program prematurely (noncompleters). Severe body dissatisfaction and physical and mental health problems seemed to have a negative impact on the completion of the web-based treatment program. Among the participants who completed the treatment program, significant improvements were found in eating disorder psychopathology (F=54.6, df=68, P<.001, d=1.14). Body dissatisfaction, quality of life, and physical and mental health also significantly improved, and almost all of these positive effects were sustained up to 6 months after the participants had completed the web-based treatment program. Body Mass Index improved only within the group of participants suffering from obesity. The improvement in eating disorder psychopathology occurred in all three eating disorder diagnostic groups, and the percentage of completers did not differ significantly between these groups. Participants' satisfaction with the treatment program, as well as with their therapist, was high, and participants indicated that they would recommend the program to other patients with eating disorders. Conclusions: The results of this study suggest that the web-based treatment program has the potential to improve eating disorder psychopathology in patients with different types of eating disorders.15 p

CD4(+) T-cell responses and distribution at the colonic mucosa during Brachyspira hyodysenteriae-induced colitis in pigs

The spirochaete Brachyspira hyodysenteriae causes swine dysentery, a severe colitis characterized by mucosal enlargement as a result of crypt elongation and epithelial necrosis. Most efforts to understand the pathogenesis of this disease have focused on the aetiological agent and its virulence factors. However, the host immune response has been considered an important factor in disease development. Previous research has shown that B. hyodysenteriae induces systemic CD4(+) and γδ T-cell responses after intramuscular immunization. Here, we have evaluated changes in the CD4(+) and γδ T-cell composition and distribution the different compartments of the colonic mucosa of pigs challenged with B. hyodysenteriae. We report that, in infected pigs, γδ T cells were significantly depleted from the epithelial layer, although their numbers were maintained in the lamina propria. In addition, CD4(+) T cells aggregated in clusters located in the lamina propria and submucosa. Ex vivo analyses of CD4(+) T-cell responses to B. hyodysenteriae antigens correlated with the changes in the mucosal CD4(+) T-cell distribution observed in infected pigs; CD4(+) T cells recovered from peripheral blood and colonic lymph nodes of infected pigs proliferated to B. hyodysenteriae antigens, whereas no differences were found in the γδ T-cell responses between challenged and control groups. In addition, colonic lymph node CD4(+) T cells had a predominant memory/activated phenotype. These results indicate that infection with B. hyodysenteriae induces a mucosal CD4(+) T-cell response and points to CD4(+) T cells being important contributors to the immunopathogenesis of swine dysentery