Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion <Emphasis Type="Italic">In Vitro</Emphasis>

Background  

MAdCAM-1 plays a central role in T-lymphocyte homing to the gut, but its role in chronic liver inflammation remains unknown. Therefore, this study measured MAdCAM-1 expression, regulation, and function in cultured murine hepatic endothelial cells.     

Induction of meningococcal group B polysaccharide-specific IgG antibodies in mice by using an N-propionylated B polysaccharide-tetanus toxoid conjugate vaccine

Conjugation of the group B meningococcal polysaccharide to tetanus toxoid failed to substantially enhance its immunogenicity in mice. Therefore, additional chemical manipulation of the basic structure of the group B meningococcal polysaccharide was attempted, on the premise that a synthetically derived artificial antigen might be capable of modulating the immune response in mice to produce elevated levels of cross-reactive group B meningococcal polysaccharide-specific antibodies. To achieve this, the antigenicity of the modified polysaccharide to group B meningococcal polysaccharide-specific antibodies had to be preserved, and this criterion could only be satisfied in modifications in which the carboxylate and N-carbonyl groups of the sialic acid residues of polysaccharide remained intact. Therefore, the most successful modifications were accomplished by N-deacetylation of the group B meningococcal polysaccharide with strong base to yield a precursor that could then be N-acetylated or N-arylated with different substituents. For example, the introduction of N-propionyl groups, followed by conjugation of the resultant N-propionylated group B meningococcal polysaccharide to tetanus toxoid, yielded an antigen that when injected in mice induced in them high levels of cross-reactive group B meningococcal polysaccharide-specific IgG antibodies. The T cell dependency of this antigen was established when it was demonstrated that the levels of these B polysaccharide-specific antibodies could be significantly boosted by using both the N-propionylated- and native N-acetylated-group B meningococcal polysaccharide-tetanus toxoid conjugates.     

Public Parks and Wellbeing in Urban Areas of the United States

Sustainable development efforts in urban areas often focus on understanding and managing factors that influence all aspects of health and wellbeing. Research has shown that public parks and green space provide a variety of physical, psychological, and social benefits to urban residents, but few studies have examined the influence of parks on comprehensive measures of subjective wellbeing at the city level. Using 2014 data from 44 U.S. cities, we evaluated the relationship between urban park quantity, quality, and accessibility and aggregate self-reported scores on the Gallup-Healthways Wellbeing Index (WBI), which considers five different domains of wellbeing (e.g., physical, community, social, financial, and purpose). In addition to park-related variables, our best-fitting OLS regression models selected using an information theory approach controlled for a variety of other typical geographic and socio-demographic correlates of wellbeing. Park quantity (measured as the percentage of city area covered by public parks) was among the strongest predictors of overall wellbeing, and the strength of this relationship appeared to be driven by parks’ contributions to physical and community wellbeing. Park quality (measured as per capita spending on parks) and accessibility (measured as the overall percentage of a city’s population within ½ mile of parks) were also positively associated with wellbeing, though these relationships were not significant. Results suggest that expansive park networks are linked to multiple aspects of health and wellbeing in cities and positively impact urban quality of life.     

Clonal growth of primary cultures of rabbit ear chondrocytes in a lipid-supplemented defined medium

Clonal growth of primary cultures of rabbit ear chondrocytes in a defined medium without serum or other undefined additives has been achieved. The clonal inoculum is a suspension of fully differentiated chondrocytes prepared by collagenase digestion of rabbit ear cartilage and used with no prior adaptation or selection in culture. When inoculated into medium MCDB 104 supplemented with 100 ng/ml fibroblast growth factor (FGF), 1 microgram/ml insulin, and 5 micrograms/ml of a lipid supplement previously developed for human fibroblasts, the isolated chondrocytes undergo clonal multiplication to form large colonies of epithelial-like cells. Colonies grown in the defined medium for 14 days accumulate at their centers refractile cartilage-like matrix that is stained by acidified Alcian green, although the amount is significantly less than with undefined additives. This system opens the way for detailed studies, in a defined background medium, of factors that regulate phenotypic expression of cartilage-like differentiated properties.     

Complex additivity of the effects of suppressor mutations in differing protein environments.

In the alpha-complementation of beta-galactosidase, a defective beta-galactosidase protein interacts with an autologous peptide fragment (alpha-peptide) to restore enzymatic activity. Within a specific site of a defective alpha-peptide we have previously isolated a large number of mutations, many of which suppress the functional defect. The alpha-peptide was originally defective due to both insertional and substitutional sequence alterations near its N-terminus, which provided an increase in the sensitivity of detection of (suppressor) secondary mutations which conferred improved function. We have now studied the effects of the suppressor mutations when the primary deleterious mutations are sequentially reversed. This was done in intact beta-galactosidase, as we have shown that mutations in the alpha-peptide have related functional effects in the whole protein. Evidence was obtained showing that the effects of at least some suppressor mutations were not simply additive when the mutations are placed into the original wild-type protein environment. One suppressor appeared to function less effectively in the normal environment, while another when tested in the same manner functioned at a relatively increased level. This failure to show simple additivity may be attributable to the physical proximity of the original defective mutations and the introduced suppressors. Nevertheless, even in such cases it may be feasible to use a defective protein as a sensitive starting point for the identification of mutations which improve the wild-type protein.     

The initial expression and patterned appearance of tenascin in scutate scales is absent from the dermis of the scaleless (sc/sc) chicken.

Morphogenesis of the anterior metatarsal skin (scutate scale region), from 9.5 to 12 days of development, results in the formation of orderly patterned scale ridges. It is after the initial formation of the Definitive Scale Ridge that the characteristic outer and inner epidermal surfaces differentiate. The hard, plate-like beta stratum, with its unique beta keratins, characterizes the epidermis of the outer surface, while the epidermis of the inner surface elaborates an alpha stratum. The anterior metatarsal region of the scaleless mutant does not undergo scale morphogenesis. Therefore, scale ridges do not form nor do the outer and inner epidermal surfaces with their characteristic beta and alpha strata. We have found that the extracellular matrix molecule, tenascin, first appears in the scutate scale dermis at 12 days of development when the scale ridge is established. Tenascin is found in the dermis only under the scale ridge and is not associated with the dermal-epidermal junction. Tenascin is not found in scaleless anterior metatarsal dermis at this time. As outgrowth of the Definitive Scale Ridge takes place, tenascin distribution correlates closely with the formation of the outer epidermal surface of each scale ridge. By 16 days of development tenascin is also found in close association with the dermal-epidermal junction. Tenascin does not appear in scaleless anterior metatarsal dermis until 16 days of development and then it is randomly and sparsely distributed at the dermal-epidermal junction. Tenascin's initial appearance and pattern of distribution in the scutate scale dermis and its abnormal expression in the scaleless dermis suggest that morphogenesis plays a significant role in regulation of its expression.