The role of leptin in innate and adaptive immune responses

Leptin is produced primarily by adipocytes and functions in a feedback loop regulating body weight. Leptin deficiency results in severe obesity and a variety of endocrine abnormalities in animals and humans. Several studies indicated that leptin plays an important role in immune responses. It exerts protective anti-inflammatory effects in models of acute inflammation and during activation of innate immune responses. In contrast, leptin stimulates T lymphocyte responses, thus having rather a proinflammatory role in experimental models of autoimmune diseases. Clinical studies have so far yielded inconsistent results, suggesting a rather complex role for leptin in immune-mediated inflammatory conditions in humans.     

Cytological studies of triploids and their progeny from male-sterile (ms1) soybean

Summary Triploids (2n=3X=60) were obtained from genetic male-sterile (ms1 ms1) soybean [Glycine max (L.) Merr.] plants. Meiosis, pollen fertility, and chromosome number of their progeny were studied. Studies of meiosis in fertile and sterile triploids revealed no distinguishable differences in chromosome associations. Male-sterile plants formed coenocytic microspores characteristic of the ms1 mutant. Restitution of some dyad and tetrad nuclei were observed in male-sterile plants. Chromosomes of the triploids tended to occur in trivalents during diakinesis and metaphase I (MI), but multivalents, bivalents, and univalents also were observed. Average types and frequencies of chromosome associations per cell in diakinesis and MI from 542 pollen mother cells were 0.004 IX + 0.06 VI + 0.002 V + 0.005 IV + 16.99 III + 1.79 II + 5.03 I. Some secondary associations, nonhomologous pairing, and aberrant nucleolar distributions occasionally were observed. Such behavior support the hypothesis of duplicated genomes and the polyploid origin of soybean. Pollen fertility in male-fertile triploid plants (Ms1 ms1 ms1) varied from 57% to 82%, with an average of about 71%. Chromosome numbers of progenies obtained from these fertile triploids varied from 2n=40 to 2n=71, and exhibited a near-random distribution, with the majority (about 60%) being between 56 and 65. Progenies of the fertile triploids gave segregation ratios for the ms1 allele, which confirmed the Ms1 ms1 ms1 genotype.Joint contribution: Agricultural Research Service, U.S. Department of Agriculture, and Journal Paper No. J-11672 of the Iowa Agriculture and Home Economics Experiment Station, Ames, IA 50011, USA, Project 2471     

Isosteric ramatroban analogs: selective and potent CRTH-2 antagonists

The chemoattractant receptor-homologous molecule expressed on T(H)2 cells (CRTH-2), also found on eosinophils and basophils, is a prostaglandin D2 receptor involved in the recruitment of these cell types during an inflammatory response. In this report, we describe the synthesis and optimization of a ramatroban isostere that is a selective and potent antagonist of CRTH-2 which may be useful in the treatment of certain diseases.     

Biofilm ecology: On-line methods bring new insights into mic and microbial biofouling

Microbial biofilms were formed on coupons with defined coatings in once-through laminar flow fields of controlled bulk-phase composition and shear. Dilute media were utilized to select for biofilm growth. The formation, succession, and stability of the biofilms were monitored with non-destructive on-line methods (fluorescence, bioluminescence, attenuated total reflectance Fourier transform infrared spectrometry [ATR-FTIR] and electrochemical impedance spectroscopy) and by high resolution destructive analysts (viable and direct counts and phospholipid fatty acid signature methods) at the termination of the experiments. Biofilms of reproducible composition can be formed and the order of inoculation of multi-component biofilms affects their composition at harvest. The corrosion rates of mild steel depended on the biofilm composition but not the attached biomass. Examination of biofilms with the scanning vibrating electrode in a microscope field showed effects of heterogeneity in biofilm structure which promoted localized anodic activity. Pseudomonas stains were engineered to contain the lux gene cassette as a "reporter"; and the formation of the exopolymer alginate was shown not to promote attachment of the strain or secondary colonization by Vibrio. Examination of mutants forming different alginate structures showed differential attachment and biofilm structure. Studies of mutants of lipopolysaccharide structure showed differential attachment to substrata. Specific antifouling and fouling-release coatings showed a wide range of attachment and release properties as well as sublethal toxicity.     

SIMILARITY OF THE KINETICS OF INVERTASE ACTION IN VIVO AND IN VITRO

1. A method is given whereby the course of hydrolysis of sucrose by live yeast cells may be followed with precision equal to that found when invertase solutions prepared from autolyzed yeast are used to cause inversion. 2. The practical value of the equation of Nelson and Hitchcock as a means of following the course of enzymic hydrolysis of sucrose is hereby extended. 3. The inversion of sucrose by live yeast cells and by extracted invertase has been quantitatively compared. 4. The course of hydrolysis of sucrose by the invertase of Fleischmann''s yeast has been found to be identical in vivo and in vitro.     

The impact of a fox‐ and cat‐free safe haven on the bird fauna of remnant vegetation in southwestern Australia

Introduced predators are a serious threat to Australian vertebrates. However, the consequences of predation for an area's avifauna have rarely been quantified. We took advantage of the establishment of a 7,832 ha fox‐ and cat‐free safe haven at Mt Gibson, in Western Australia, to assess the consequences of excluding introduced mammal predators on the bird fauna. Bird surveys were conducted over 6 years, before and after the establishment of the introduced predator‐free safe haven. After 3 years, half the sites were enclosed by the fence that excluded introduced predators, while the remainder of sites remained outside the fence and were exposed to fox and cat activity. The sites were stratified by four major vegetation types. A total of 91 bird species were variously detectable with the survey approach, but were typically more detectable during morning surveys. Site occupancy varied considerably among species, but overall, occupancy by all species was most likely to be either not impacted or positively impacted by the safe haven. The most notable change was that avifaunal richness appeared to increase in woodland and shrubland habitats within, as compared to outside, the safe haven. We conclude that: (1) the safe haven had an overall positive impact on bird occupancy; and (2) there were no consistent trends with respect to the kinds of species whose occupancy was positively impacted, beyond them all being small‐ to medium‐sized birds and mostly insectivorous. However, these conclusions must be tempered by the poor detection probability of many species.     

A sub-population of rat liver membrane-bound ribosomes that are detached in vitro by carcinogens and centrifugation.

The chemical-carcinogen-induced detachment of ribosomes from rat liver endoplasmic reticulum was studied in vitro. Incubation of postmitochondrial supernatant with 0.2 mM-diethylnitrosamine or N-2-acetylaminofluorene removed approx. 16% of membrane-bound ribosomes, measured as differences in RNA/protein values of membrane separated from unbound ribosomes by flotation. These ribosomes are also detached by exposure to high centrifugal forces (160000g) and are among those removed by NADPH-catalysed lipid peroxidation. Extensive lipid peroxidation prohibits any measurement. The ribosomes (polyribosomes) removed are not those detached from the membrane by exposure to high KC1 concentrations (loosely bound) or high KC1 concentrations in the presence of puromycin (tightly bound). It is concluded then that centrifugally labile and carcinogen-sensitive represent a previously unreported sub-population of membrane-bound ribosomes.     

Genome-wide linkage analysis of longitudinal phenotypes using σ<Superscript>2</Superscript><Subscript>A</Subscript> random effects (SSARs) fitted by Gibbs sampling

The study of change in intermediate phenotypes over time is important in genetics. In this paper we explore a new approach to phenotype definition in the genetic analysis of longitudinal phenotypes. We utilized data from the longitudinal Framingham Heart Study Family Cohort to investigate the familial aggregation and evidence for linkage to change in systolic blood pressure (SBP) over time. We used Gibbs sampling to derive sigma-squared-A-random-effects (SSARs) for the longitudinal phenotype, and then used these as a new phenotype in subsequent genome-wide linkage analyses. Additive genetic effects (sigma2A.time) were estimated to account for approximately 9.2% of the variance in the rate of change of SBP with age, while additive genetic effects (sigma2A) were estimated to account for approximately 43.9% of the variance in SBP at the mean age. The linkage results suggested that one or more major loci regulating change in SBP over time may localize to chromosomes 2, 3, 4, 6, 10, 11, 17, and 19. The results also suggested that one or more major loci regulating level of SBP may localize to chromosomes 3, 8, and 14. Our results support a genetic component to both SBP and change in SBP with age, and are consistent with a complex, multifactorial susceptibility to the development of hypertension. The use of SSARs derived from quantitative traits as input to a conventional linkage analysis appears to be valuable in the linkage analysis of genetically complex traits. We have now demonstrated in this paper the use of SSARs in the context of longitudinal family data.     

Genetic characterization of gram-positive homologs of the XerCD site-specific recombinases

Homologs of the XerCD enzymes, which in Escherichia coli have been shown to be responsible for resolving chromosomal multimers prior to chromosome segregation, were identified in the genomes of Staphylococcus aureus and Streptococcus pneumoniae. Phylogenetic and conservation pattern analysis suggests that the S. aureus gene products are orthologs of XerC and D. A S. aureus xerC null mutant displayed in vitro characteristics consistent with the segregation defect reported for E. coli xer mutants, and was found to be attenuated in a murine infection model. Strikingly, the S. aureus xerD gene appears to be absolutely required for viability, and may therefore be the first example of an essential gene of the lambda integrase family. In contrast, phylogenetic and conservation pattern analysis show that the S. pneumoniae gene products are more closely related to phage integrases than to XerCD. S. pneumoniae xer1, 2 and 3 null mutants were each found to be attenuated in a murine infection model, suggesting that they may control processes which affect virulence.     

A structured analysis of risk to important wildlife elements in three Australian Wildlife Conservancy sanctuaries

Where data and information are lacking, structured expert risk assessments can provide a powerful tool to progress natural resource planning. In many situations, practitioners make informal assessments of risk within small groups that typically constitute employees. In this study, we report on three small (in terms of experts) structured expert‐based risk assessment case studies conducted by expert employees of a not‐for‐profit organisation (Australian Wildlife Conservancy) to demonstrate the utility of the approach. The case studies were carried out for three wildlife sanctuaries managed by AWC: Faure Island, Karakamia and Paruna. The likelihood that a set of direct risk factors would cause management failure for sets of important wildlife elements in the three sanctuaries was elicited from the small group of ecological experts. The analysis was couched in terms of a management aim to not lose species from each wildlife element over the management period of 25 years with current management. The experts believed, in particular, that increasing temperature and decreasing water availability associated with climate change were likely to impact significantly upon the vegetation elements and water‐reliant fauna associated with the sanctuaries. Some vegetation elements were also thought likely to be at risk of over‐grazing, unsuitable fire regimes and, in some cases, disease. In addition to predation by exotic predators at one sanctuary, the experts identified additional direct risk factors for various fauna elements associated with expected changes to the vegetation elements, including reduction in food availability, nesting habitat, and generally important life media. From the risk analyses, a preliminary conceptual model was developed to underpin monitoring and to indicate areas for possible management intervention and research. The case studies demonstrate that even in a small workplace team, structured risk assessments can be efficiently accomplished and can provide expedient and transparent information that effectively captures and aggregates the views of the experts.