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

Substance P (SP) is a proinflammatory neuropeptide that is secreted by sensory nerves and inflammatory cells Increased levels of SP are found in sarcoid bronchoalveolar lavage fluid SP acts by binding to the neurokinin-1 receptor and increases secretion of tumor necrosis factor-α in many cell types We sought to determine neurokinin-1 receptor expression in patients with sarcoidosis compared with normal controls Neurokinin-1 receptor messenger RNA and protein expression were below the limits of detection by reverse transcriptase-polymerase chain reaction and immunohistochemistry in peripheral blood mononuclear cells of healthy volunteers (n = 9) or patients with stage 1 or 2 pulmonary sarcoidosis (n = 10), but were detected in 1/9 bronchoalveolar lavage cells of controls compared with 8/10 patients with sarcoidosis (p = 0012) and 2/9 biopsies of controls compared with 9/10 patients with sarcoidosis (p = 0013) Immunohistochemistry localized upregulated neurokinin-1 receptor expression to bronchial and alveolar epithelial cells, macrophages, lymphocytes, and sarcoid granulomas The patient in whom neurokinin-1 receptor was not detected was taking corticosteroids Incubation of the type II alveolar and bronchial epithelial cell lines A549 and SK-LU 1 with dexamethasone downregulated neurokinin-1 receptor expression Upregulated neurokinin-1 receptor expression in patients with sarcoidosis may potentiate substance P-induced proinflammatory cytokine production in patients with sarcoidosis

Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis.

Infliximab Therapy for Complicated Sarcoidosis

A strategy for obtaining near full-length HCV cDNA clones (assemblicons) by assembly PCR

Background & aims: Impaired attention and response inhibition have been reported in patients with Crohn’s disease (CD) in clinical remission. Prospective studies are needed to determine whether this is a stable feature of CD and whether a similar impairment is evident in ulcerative colitis (UC). Thus, our aims were to examine whether patients with CD and UC exhibited a persistent impairment in attentional performance, and if this impairment was related to key biological indices of relevance to cognition.
 
Methods: A prospective observational study was conducted on fifteen patients with CD and 7 with UC in clinical remission recruited from a specialty clinic and 30 healthy matched control participants. A neuropsychological assessment was carried out at baseline (visit 1) and at a 6 month follow-up (visit 2). Plasma proinflammatory cytokines, the plasma kynurenine:tryptophan (Kyn:Trp) ratio and the salivary cortisol awakening response (CAR) were also determined at each visit. 
Results: Across visits, patients with CD exhibited impaired attentional performance (p ¼ 0.023). Plasma IL-6 (P ¼ 0.001) and the Kyn:Trp ratio (P ¼ 0.03) were consistently elevated and the CAR significantly blunted (P < 0.05) in patients with CD. No significant relationships were identified between any biochemical parameter and altered cognitive performance.
 
Conclusions: Impaired cognitive function is a stable feature of patients with CD. These data suggest that even where remission has been achieved, the functional impact of an organic gastrointestinal disorder on cognition is still evident. However, it is unclear at present if physiological changes due to disease activity play a role in cognitive impairment in CD.

Impaired cognitive function in Crohn's disease: Relationship to disease activity.

A strain of Bifidobacterium isolated from resected and washed human gastrointestinal tract is significantly immunomodulatory following oral consumption in humans. The strain is useful in the prophylaxis and/or treatment of undesirable inflammatroy activity, especially gastrointestinal inflammatory activity such as inflammatory bowel disease or irritable bowel syndrome. The inflammatory activity may also be due to cancer.

Fergus Shanahan

Papers

Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis.

Infliximab Therapy for Complicated Sarcoidosis

A strategy for obtaining near full-length HCV cDNA clones (assemblicons) by assembly PCR

Impaired cognitive function in Crohn's disease: Relationship to disease activity.

Bifidobacteriumin the treatment of inflammatory disease