Biotransformations for Fine Chemical Production

Biotechnology has become an indispensable tool for the production of fine chemicals. The choice of route, chemical or biotechnological, for the manufacture of a given fine chemical is crucial. In general terms, biotechnology is the method of choice for large molecules with a high degree of functionalisation and multiple stereocentres. Most of LONZA's biotechnological bioprocesses for the production of fine chemicals are whole cell processes using microorganisms which form very specific enzymes. Process improvement at LONZA is discussed in this paper on three levels: upstream processing, biotransformation/biosynthesis, and downsteam processing

Interface strength and toughness measurements in multi-layered systems

Over the last years, miniaturization caused increasingly complex thin film combinations and geometries. Since macro scale tests are not suitable, small-scale experiments are suggested to study the materials response in current and future devices at small length scales. Here, focus is placed on the local determination of interface strength and toughness in layered thin films, also accounting for the presence of residual stresses. The investigated materials were sputter deposited Cu-W-Cu and W-Cu-W films with individual layer thicknesses of 500 nm on a Si(100) substrate [1]. Different geometries such as notched bending beams, double cantilever beams, and miniaturized shear specimens were fabricated via cross-section polishing and focused ion beam (FIB) milling to quantitatively test individual interfaces. A schematic representation of the involved test setups is shown in Figure 1. Subsequently, miniaturized fracture experiments parallel [2] and perpendicular [3] to the interfaces were performed in-situ in the SEM to obtain comprehensive knowledge of the fracture and interface toughness. Complementary, nanoindentation induced buckles were analyzed. Please click Additional Files below to see the full abstract

PU.1 controls fibroblast polarization and tissue fibrosis

Fibroblasts are polymorphic cells with pleiotropic roles in organ morphogenesis, tissue homeostasis and immune responses. In fibrotic diseases, fibroblasts synthesize abundant amounts of extracellular matrix, which induces scarring and organ failure. By contrast, a hallmark feature of fibroblasts in arthritis is degradation of the extracellular matrix because of the release of metalloproteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms that drive these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts remain unknown. Here we identify the transcription factor PU.1 as an essential regulator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms that normally control the expression of PU.1 expression is perturbed in various fibrotic diseases, resulting in the upregulation of PU.1, induction of fibrosis-associated gene sets and a phenotypic switch in extracellular matrix-producing pro-fibrotic fibroblasts. By contrast, pharmacological and genetic inactivation of PU.1 disrupts the fibrotic network and enables reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs

Cadherin-11 Provides Specific Cellular Adhesion between Fibroblast-like Synoviocytes

Cadherins are integral membrane proteins expressed in tissue-restricted patterns that mediate homophilic intercellular adhesion. During development, they orchestrate tissue morphogenesis and, in the adult, they determine tissue integrity and architecture. The synovial lining is a condensation of fibroblast-like synoviocytes (FLS) and macrophages one to three cells thick. These cells are embedded within the extracellular matrix, but the structure is neither an epithelium nor an endothelium. Previously, the basis for organization of the synovium into a tissue was unknown. Here, we cloned cadherin-11 from human rheumatoid arthritis (RA)-derived FLS. We developed L cell transfectants expressing cadherin-11, cadherin-11 fusion proteins, and anti–cadherin-11 mAb. Cadherin-11 was found to be expressed mainly in the synovial lining by immunohistologic staining of human synovium. FLS adhered to cadherin-11–Fc, and transfection of cadherin-11 conferred the formation of tissue-like sheets and lining-like structures upon fibroblasts in vitro. These findings support a key role for cadherin-11 in the specific adhesion of FLS and in synovial tissue organization and behavior in health and RA

A rare polymorphism in Toll Like Receptor 2 is associated with systemic sclerosis phenotype and increases production of inflammatory mediators

T.R. was sponsored by the Dutch association of Research (NWO). J.M. was sponsored by grants SAF2009-1110, cts-4977 T.R. and J.M. were sponsored by the Orphan Disease program grant from the European League Againts Rheumatism (EULAR)Peer Reviewe