Albumin Yanomama-2, a ‘private’ polymorphism of serum albumin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65429/1/j.1469-1809.1974.tb01949.x.pd

Bridging the gap between science and policy: the importance of mutual respect, trust and the role of mediators

Around the world there are widespread efforts to ensure that policy decisions are based upon a sound evidence base, and in particular to facilitate closer integration between the research and policy communities. This commentary provides an overview of the current situation in different parts of the world relating to the opportunities that exist for policy makers to assimilate scientific findings, as well as the existing barriers perceived by both the policy and research communities. Mutual trust and respect between the relevant parties emerge as crucial factors in successful collaboration. Skilled mediators are also considered essential to ensuring effective communication; this may be via third parties such as NGOs, or news services and online portals to convey, ‘translate’ and place in a policy context the scientific findings. Mechanisms for improving researchers’ communication skills as well as increasing their awareness of the need to communicate proactively with the policy community are also considered in order to inform future practice in this area

Particle-scale structure in frozen colloidal suspensions from small angle X-ray scattering

During directional solidification of the solvent in a colloidal suspension, the colloidal particles segregate from the growing solid, forming high-particle-density regions with structure on a hierarchy of length scales ranging from that of the particle-scale packing to the large-scale spacing between these regions. Previous work has mostly concentrated on the medium- to large-length scale structure, as it is the most accessible and thought to be more technologically relevant. However, the packing of the colloids at the particle-scale is an important component not only in theoretical descriptions of the segregation process, but also to the utility of freeze-cast materials for new applications. Here we present the results of experiments in which we investigated this structure across a wide range of length scales using a combination of small angle X-ray scattering and direct optical imaging. As expected, during freezing the particles were concentrated into regions between ice dendrites forming a microscopic pattern of high- and low-particle-density regions. X-ray scattering indicates that the particles in the high density regions were so closely packed as to be touching. However, the arrangement of the particles does not conform to that predicted by any standard inter-particle pair potentials, suggesting that the particle packing induced by freezing differs from that formed during equilibrium or steady-state densification processes

The molecular defect of albumin Tagliacozzo: 313 Lys → Asn

AbstractAlbumin Tagliacozzo is a fast-moving genetic variant of human serum albumin found in 19 unrelated families. The protein was isolated from the serum of a heterozygous healthy subject. Analysis of CNBr fragments by isoelectric focusing allowed us to localize the mutation to CNBr fragment IV (residues 299–329). This fragment was isolated on a preparative scale and subjected to tryptic digestion. Sequential analysis of the abnormal tryptic peptide, purified by RP-HPLC, revealed the variant was caused by 313 Lys → Asn substitution, probably due to a point mutation in the structural gene. The lack of a lysine residue accounts for the electrophoretic behavior of albumin Tagliacozzo

Distinct microenvironmental cues trigger divergent TLR4-mediated immune signalling in macrophages

Macrophages exhibit a phenotypic plasticity that enables them to orchestrate specific immune responses to distinct threats. However, the factors that control macrophage behaviour in a context dependent manner are not well understood. Lipopolysaccharide (LPS) and the extracellular matrix glycoprotein tenascin-C both activate toll-like receptor 4 (TLR4), and are released during bacterial infection and tissue injury, respectively. Here we report that these two TLR4 ligands induce distinct macrophage signalling pathways and phenotypes. Macrophages activated by LPS or tenascin-C display some common features, including NF-kB and MAP kinase signalling, and cytokine synthesis. However, different subsets of cytokines, and different phosphoproteomic signatures, are produced by each stimulus. Moreover, tenascin-C promotes macrophages more inclined to matrix synthesis and phosphorylation, whilst LPS-activated macrophages exhibit an elevated capacity to degrade matrix. These data reveal how activation of one pattern recognition receptor by different microenvironmental cues, signalling pathogen invasion or tissue damage, can create unique macrophage phenotypes

HLA AND CONGENITAL ADRENAL HYPERPLASIA LINKAGE CONFIRMED

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22612/1/0000162.pd

Transactivation of EGFR by LPS induces COX-2 expression in enterocytes

Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS) mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2), which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR) activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP) activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC