A nitrile-metabolising enzyme and a process for producing an acid using same

The present invention relates to an isolated nucleotide sequence and corresponding polypeptide derived from the nitrile-metabolising Pantoea strain deposited under NCIMB 41854. Said isolated polypeptide acts as a nitrilase and the invention extends to a process for producing a carboxylic acid using said isolated polypeptide to metabolise nitriles such as 3-hydroxyglutaronitrile, 3-hydroxybutyronitrile and 3- hydroxy-phenylpropionitrile to form corresponding carboxylic acids.

TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma

Increasing evidence suggests that asthma is a heterogeneous disorder regulated by distinct molecular mechanisms. In a cross-sectional study of asthmatics of varying severity (n = 51), endobronchial tissue gene expression analysis revealed three major patient clusters: TH2-high, TH17-high, and TH2/17-low. TH2-high and TH17-high patterns were mutually exclusive in individual patient samples, and their gene signatures were inversely correlated and differentially regulated by interleukin-13 (IL-13) and IL-17A. To understand this dichotomous pattern of T helper 2 (TH2) and TH17 signatures, we investigated the potential of type 2 cytokine suppression in promoting TH17 responses in a preclinical model of allergen-induced asthma. Neutralization of IL-4 and/or IL-13 resulted in increased TH17 cells and neutrophilic inflammation in the lung. However, neutralization of IL-13 and IL-17 protected mice from eosinophilia, mucus hyperplasia, and airway hyperreactivity and abolished the neutrophilic inflammation, suggesting that combination therapies targeting both pathways may maximize therapeutic efficacy across a patient population comprising both TH2 and TH17 endotypes.

Sound Art and Spatial Practices: Situating Sound Installation Art Since 1958

This dissertation examines the emergence and development of sound installation art, an under-recognized tradition that has developed between music, architecture, and media art practices since the late 1950s. Unlike many musical works, which are concerned with organizing sounds in time, sound installations organize sounds in space; they thus necessitate new theoretical and analytical models that take into consideration the spatial situated-ness of sound. Existing discourses on “spatial sound” privilege technical descriptions of sound localization. By contrast, this dissertation examines the ways in which concepts of space are socially, culturally, and politically construed, and how spatially-organized sound works reflect and resist these different constructions. Using an interdisciplinary methodology of critical spatial analysis and critical studies in music, this dissertation explores such topics as: conceptions of acoustic space in postwar Western art music, architecture, and media theory; the development of sound installation art in relation to philosophies of everyday life and social space; the historical links between musical performance, conceptual art, and sound sculpture; the body as a site for sound installations; and sonicspatial strategies that confront politics of race and gender. Through these different investigations, this dissertation proposes an “ontopological” model for considering sound: a critical model of analysis and reception that privileges an understanding of sound in relation to ontologies of space and place.

Classifying cerebral palsy: are we nearly there?

BACKGROUND: Cerebral palsy (CP) is the most common cause of physical disability in childhood in developed countries and encompasses a wide range of clinical phenotypes. Classification of CP according to movement disorder or topographical distribution is widely used. However, these classifications are not reliable nor do they accurately predict musculoskeletal pathology. More recently, the Gross Motor Function Classification System (GMFCS) has been introduced and its validity, reliability, and clinical utility have been confirmed. In 2005 it was suggested that children should be described and classified according to the GMFCS in all outcome studies involving children with CP, in the Journal of Pediatric Orthopaedics (JPO). This study aimed to describe utilization of the GMFCS in 3 journals: Journal of Bone and Joint Surgery (JBJS Am), JPO, and Developmental Medicine and Child Neurology (DMCN), over a 7-year period (2005 to 2011), and any relationship to the journal's impact factor. A secondary aim was to establish if differences in methodological quality existed between those studies utilizing GMFCS and those that did not.

METHODS: A targeted literature search of the 3 selected journals using the term "cerebral palsy" was conducted using the Medline database. Utilization of the GMFCS was assessed using report of these data in the methods or results section of the retrieved papers. The Methodological Index for Non-Randomized Studies (MINORS) was employed to evaluate the quality of papers published in JPO.

RESULTS: One hundred and fifty-four studies met the inclusion criteria and in 85 (68%) the GMFCS was used. Of these, 112 were published in JPO, of which 51 (46%) utilized the GMFCS, compared with 72% for JBJS Am, and 88% for DMCN. In the JPO, utilization of the GMFCS improved from 13% to 80%, over the 7-year study period.

CONCLUSIONS: Utilization of the GMFCS has increased rapidly over the past 7 years in the JPO but there is room for further improvement.

LEVEL OF EVIDENCE: Not applicable.