There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

http://www.klinikaikozpont.u-szeged.hu/pedia/images/pdf/CME_TEL/Full-Text/25.pdf

The Hallmarks of Aging

This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.

/pdf/metagenomic-biomarker-discovery-and-explanation-x530ilzkca.pdf

Metagenomic biomarker discovery and explanation

We have catalogued the protein kinase complement of the human genome (the "kinome") using public and proprietary genomic, complementary DNA, and expressed sequence tag (EST) sequences. This provides a starting point for comprehensive analysis of protein phosphorylation in normal and disease states, as well as a detailed view of the current state of human genome analysis through a focus on one large gene family. We identify 518 putative protein kinase genes, of which 71 have not previously been reported or described as kinases, and we extend or correct the protein sequences of 56 more kinases. New genes include members of well-studied families as well as previously unidentified families, some of which are conserved in model organisms. Classification and comparison with model organism kinomes identified orthologous groups and highlighted expansions specific to human and other lineages. We also identified 106 protein kinase pseudogenes. Chromosomal mapping revealed several small clusters of kinase genes and revealed that 244 kinases map to disease loci or cancer amplicons.

http://science.sciencemag.org/content/sci/298/5600/1912.full.pdf

The Protein Kinase Complement of the Human Genome

An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.

/pdf/expert-consensus-document-the-international-scientific-1zd5d1fmxy.pdf

Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic

We have examined the biochemical and functional characteristics of mast cells grown in tissue culture from the mesenteric lymph node (MLN) of rats infected with the nematode Nippostrongylus brasiliensis and compared them with mast cells isolated from the small intestinal mucosa and peritoneal cavity of infected animals. Cultured mast cells (MC) and isolated intestinal mucosal mast cells (MMC) had a similar histamine content, and both contained type II protease (RMCP II) which was absent from peritoneal mast cells (PMC). PMC, MMC and cultured MC each responded to immunologically induced histamine secretion, but MMC and cultured MC were hyporesponsive to calcium ionophores and unresponsive to widely used PMC secretagogues including compound 48/80 and bee venom peptide 401. MMC and cultured MC also differed from PMC in their lack of responsiveness to the anti-allergic agent disodium cromoglycate. Thus, MC cultured from the MLN are distinct from PMC but have a biochemical and functional phenotype similar to that of intestinal MMC.

Functional characterization of mast cells generated in vitro from the mesenteric lymph node of rats infected with Nippostrongylus brasiliensis.

Crohn’s disease and ulcerative colitis are chronic inflammatory diseases of the intestine, the causes of which are not known. Although genetic factors, biochemical abnormalities, and infectious or other exogenous agents might contribute to the etiopathogenesis or trigger the onset of disease, the immune system probably mediates the tissue damage.1–3 The role of the immune system in the pathogenesis of inflammatory bowel disease was first suspected on clinical grounds. These included an association with other putative immunologically mediated disorders, a responsiveness to immunosuppressive agents and the failure to consistently detect an infectious culprit. Subsequent investigations revealed multiple and varied immunological alterations that have been difficult to interpret or to fit to a coherent concept of the pathogenetic sequence. A major problem has been the difficulty in distinguishing primary immunological abnormalities from those that are secondary to the disease process itself. In addition, research progress has been impeded by the absence of a suitable animal model of inflammatory bowel disease; most of the available models exhibit an acute mucosal inflammation and do not mimic the chronic relapsing condition in hu mans.4 However, several advances have been made, and the purpose of this chapter is to review current theories and experimental approaches to the im-munopathology of these disorders. Recent developments will be emphasized; other sources provide comprehensive accounts of earlier work.5–11

Immunology of Inflammatory Bowel Disease

Turning on T-cell death and turning off Crohn's disease.

C BERNSTEIN, F SHANAHAN. Immunosuppressive and immunomodulatory therapy for inflammatory bowel disease. Can J Gastroenterol 1993;(2):115, 120. Identification of the mechanisms and mediators involved in the patho­ genesis of inflammatory bowel disease (IBO) has provided a sound rationale for the therapeutic use of immunosuppressive agents and has led to novel therapeutic approaches. The efficacy of traditional immunosuppressives such as the purine analogues (azathioprine/6-mercaptopurine) in both Crohn's disease and ulcera­ tive colitis is now well established. However, the slow onset of clinical efficacy asrociated with purine analogues has prompted the investigation of other im­ munosuppressives such as cyclosporine and FK506 that have a more rapid onset of action. While early results appear promising, the exact role of these agents requires more investigation. Because of the potential for long term toxicity, many clinicians view the role of cyclosporine as an interim measure for acutely ill patients. More recent immunomodulatory approaches to IBO have been selected, not on the basis of empiric observation, but because of an improved under­ standing of the immunopathogenesis of these disorders. Novel approaches that are in an early phase of investigation include the modulation of cytokines and their receptors, inhibition of mucosa! antigen processing and presentation, and the use of monoclonal antibodies targeted to specific mucosa! effector lym­ phocytes.

/pdf/immunosuppressive-and-immunomodulatory-therapy-for-46zinj66cb.pdf

Fergus Shanahan

Papers

Functional characterization of mast cells generated in vitro from the mesenteric lymph node of rats infected with Nippostrongylus brasiliensis.

Immunology of Inflammatory Bowel Disease

Turning on T-cell death and turning off Crohn's disease.

Immunosuppressive and Immunomodulatory Therapy for Inflammatory Bowel Disease

attenuates Campylobacter jejuni virulence properties.