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

Familial Mediterranean Fever is a disorder of unknown cause characterized by recurrent, self-limited paroxysms of serosal inflammation. Although the neutrophil is the predominant cell involved, no cellular abnormalities are known. Chemiluminescence was studied in neutrophils from 20 asymptomatic patients with this disease and 21 healthy controls to evaluate the oxidative response to formyl-methionyl-leucyl-phenylalanine (f-met-leu-phe). In a subset of patients with familial Mediterranean fever, neutrophils but not monocytes were shown to have significantly enhanced chemiluminescence compared to controls. The enhanced responsiveness of neutrophils to f-met-leu-phe in this disease was found to occur at a postreceptor level. Receptor binding assays demonstrated no differences in binding affinity and receptor number between patients and controls. In addition, a similar enhancement in chemiluminescence was observed with an alternative stimulus (zymosan). In contrast to chemiluminescence, chemotaxis induced by f-met-leu-phe was not enhanced in patients with familial Mediterranean fever. The enhanced neutrophil chemiluminescence may identify a subclinical inflammatory state in attack-free patients with familial Mediterranean fever, as enhanced chemiluminescence is also observed in chronic inflammatory diseases with active inflammation.

Enhanced neutrophil chemiluminescence in familial Mediterranean fever.

Purpose of reviewAlthough many studies of the microbiota have been specific to the colonic or faecal microbiota, several studies are relevant to or directly address the small bowel microbiota in health and disease. A selection of recent landmark findings is addressed here.Recent findingsThe complexi

The small bowel microbiota.

Objective: The aims of this study were to develop techniques for spatial microbial assessment in humans and to establish colonic luminal and mucosal spatial ecology, encompassing longitudinal and cross-sectional axes. Design: A microbiological protected specimen brush was used in conjunction with a biopsy forceps to sample the colon in nine healthy volunteers undergoing colonoscopy. Terminal Restriction Fragment Length Polymorphism analysis was used to determine the major variables in the spatial organization of the colonic microbiota. Results: Protected Specimen Brush sampling retrieved region-specific, uncontaminated samples that were enriched for bacterial DNA and depleted in human DNA when compared to biopsy samples. Terminal Restriction Fragment Length Polymorphism analysis revealed a segmentation of bacterial communities between the luminal brush and biopsy-associated ecological niches with little variability across the longitudinal axis of the colon and reduced diversity in brush samples. Conclusion: These results support the concept of a microbiota with little longitudinal variability but with some degree of segregation between luminal and mucosal communities.

/pdf/depth-dependent-differences-in-community-structure-of-the-5epcymwtvj.pdf

Depth-Dependent Differences in Community Structure of the Human Colonic Microbiota in Health

Acute adrenal crisis in patients with unrecognized chronic adrenocortical failure is difficult to diagnose and potentially fatal. We describe 2 patients with acute adrenal crisis whose diagnoses were hindered because of concomitant glucocorticoid treatment. Acute adrenal insufficiency is primarily a state of mineralocorticoid deficiency. Prednisolone and prednisone, the most frequently prescribed anti-inflammatory corticosteroid agents, have minimal mineralocorticoid activity. Several conditions that may be treated with pharmacological glucocorticoids are associated with an increased risk of Addison disease. An acute adrenal crisis, against which concurrent glucocorticoid therapy does not confer adequate protection, may develop in such patients.

Fergus Shanahan

Papers

Enhanced neutrophil chemiluminescence in familial Mediterranean fever.

The small bowel microbiota.

Depth-Dependent Differences in Community Structure of the Human Colonic Microbiota in Health

Addison disease in patients treated with glucocorticoid therapy.

Culture-independent analysis of the gut microbiota in colorectal cancer and polyposis. Corrects article in Vol 10 (3) pages 789-798