The Shapes of Dirichlet Defects

If the vacuum manifold of a field theory has the appropriate topological structure, the theory admits topological structures analogous to the D-branes of string theory, in which defects of one dimension terminate on other defects of higher dimension. The shapes of such defects are analyzed numerically, with special attention paid to the intersection regions. Walls (co-dimension 1 branes) terminating on other walls, global strings (co-dimension 2 branes) and local strings (including gauge fields) terminating on walls are all considered. Connections to supersymmetric field theories, string theory and condensed matter systems are pointed out.Comment: 24 pages, RevTeX, 21 eps figure

Very High-Risk ASCVD and Eligibility for Nonstatin Therapies Based on the 2018 AHA/ACC Cholesterol Guidelines

The 2018 American Heart Association/American College of Cardiology Multisociety Cholesterol Guidelines recommend risk stratification among patients with atherosclerotic cardiovascular disease (ASCVD) to identify “very high-risk ASCVD patients.” These patients have characteristics associated with a higher risk of recurrent ASCVD events; consequently, they derive a higher net absolute benefit from addition of ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) to statin therapy. From a clinical and payer’s perspective, we assessed the proportion of patients with ASCVD who will qualify as very high-risk based on the guideline criteria, their current lipid management, and how this will change with maximizing statin therapy and stepwise use of ezetimibe before consideration for a PCSK9i, as recommended by the 2018 cholesterol guideline

Zanos et al. reply

Clinical data have demonstrated rapid and sustained antidepressant effects of ketamine, a noncompetitive NMDAR (N-methyl-daspartate receptor) antagonist. Recently, Zanos et al.2 claimed that the ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) is essential for the antidepressant effects of ketamine in mice in an NMDAR-independent manner, although no alternative mechanism was proposed, beyond unspecific activation of AMPAR (α -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor). Here we report that (2R,6R)-HNK blocks synaptic NMDARs in a similar manner to its parent compound, and we show that the effects of (2R,6R)-HNK on intracellular signalling are coupled to NMDAR inhibition. These data demonstrate that (2R,6R)-HNK inhibits synaptic NMDARs and subsequently elicits the same signal transduction pathway previously associated with NMDAR inhibition by ketamine

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

Distribution of virulence markers in clinical and environmental Vibrio cholerae non-O1/non-O139 strains isolated in Brazil from 1991 to 2000 Distribuição dos marcadores de virulência em cepas clínicas e ambientais de Vibrio cholerae não O1/não O139, isoladas no Brasil no período de 1991 a 2000

One hundred seventy nine Vibrio cholerae non-O1/non-O139 strains from clinical and different environmental sources isolated in Brazil from 1991 to 2000 were serogrouped and screened for the presence of four different virulence factors. The Random Amplification of Polymorphic DNA (RAPD) technique was used to evaluate the genetic relatedness among strains. Fifty-four different serogroups were identified and V. cholerae O26 was the most common (7.8%). PCR analysis for three genes (ctxA, zot, ace) located of the CTX genetic element and one gene (tcpA) located on the VPI pathogenicity island showed that 27 strains harbored one or more of these genes. Eight (4.5%) strains possessed the complete set of CTX element genes and all but one of these belonged to the O26 serogroup suggesting that V. cholerae O26 has the potential to be an epidemic strain. The RAPD profiles revealed a wide variability among strains and no genetic correlation was observed.<br>Cento e setenta e nove amostras de V. cholerae não O1/não O139, isoladas de casos clínicos (139) e de meio ambiente (40), no período de 1991 a 2000 no Brasil, foram caracterizadas antigenicamente pelo National Institute of Health (Japão) e investigadas quanto ao seu potencial genético de virulência, representado pelos genes ctxA, zot, ace e tcpA. As análises fenotípicas revelaram extraordinária diversidade antigênica, com a ocorrência de 54 diferentes sorogrupos, com prevalência para O26 (7,8%). A técnica de PCR, empregada na detecção dos genes localizados no elemento genético CTX (ctxA, zot, ace) e na Ilha de Patogenicidade de Vibrio-VPI (tcpA), possibilitou a identificação de 27 cepas contendo qualquer um desses genes. O gene ctxA (codificador da sub-unidade A de CT), só foi evidenciado no sorogrupo O26, sendo também o único capaz de se apresentar com o cassete de virulência de forma intacta. Com base nos resultados obtidos deste estudo preliminar, admite-se a hipótese da potencialidade destas cepas, evoluir para raças epidêmicas