Contraction of isolated airway smooth muscle by synthetic leukotrienes C4 and D4

The pharmacology of leukotrienes (LT) C4 and D4 in isolated airway smooth muscle was investigated. In rat trachea, neither LTC4 or D4 elicited a response. In contrast, LTC4 was a potent contractile agonist in guinea-pig trachea, bronchus and parenchymal lung strip. Similar effects were obtained with LTD4 in trachea and parenchyma. In trachea and bronchus, the concentration-response curve to LTC4 was biphasic: indomethacin converted the biphasic response curve to a simple sigmoidal shape and enhanced the maximum contractile response. The SRS-A antagonist FPL 55712 antagonized the effect of LTD4 in both trachea and parenchyma. As regards LTC4-induced contraction of trachea and bronchus, FPL 55712, depending on concentration, either antagonized, or antagonized and enhanced the maximum contractile response. The enhancement of the maximum contractile response by FPL 55712 was not apparent when indomethacin was present. FPL 55712 failed to antagonize the effect of LTC4 in parenchyma.     

c-FLIP(L) is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis

Activation of the caspase cascade is a pivotal step in apoptosis and can occur via death adaptor-mediated homo-oligomerization of initiator procaspases. Here we show that c-FLIP(L), a protease-deficient caspase homolog widely regarded as an apoptosis inhibitor, is enriched in the CD95 death-inducing signaling complex (DISC) and potently promotes procaspase-8 activation through hetero-dimerization. c-FLIP(L) exerts its effect through its protease-like domain, which associates efficiently with the procaspase-8 protease domain and induces the enzymatic activity of the zymogen. Ectopic expression of c-FLIP(L) at physiologically relevant levels enhances procaspase-8 processing in the CD95 DISC and promotes apoptosis, while a decrease of c-FLIP(L) expression results in inhibition of apoptosis. c-FLIP(L) acts as an apoptosis inhibitor only at high ectopic expression levels. Thus, c-FLIP(L) defines a novel type of caspase regulator, distinct from the death adaptors, that can either promote or inhibit apoptosis.     

Potent and specific inhibition of human immunodeficiency virus type 1 replication by RNA interference

Synthetic small interfering RNAs (siRNAs) have been shown to induce the degradation of specific mRNA targets in human cells by inducing RNA interference (RNAi). Here, we demonstrate that siRNA duplexes targeted against the essential Tat and Rev regulatory proteins encoded by human immunodeficiency virus type 1 (HIV-1) can specifically block Tat and Rev expression and function. More importantly, we show that these same siRNAs can effectively inhibit HIV-1 gene expression and replication in cell cultures, including those of human T-cell lines and primary lymphocytes. These observations demonstrate that RNAi can effectively block virus replication in human cells and raise the possibility that RNAi could provide an important innate protective response, particularly against viruses that express double-stranded RNAs as part of their replication cycle.     

Siscowet lake charr (Salvelinus namaycush siscowet) visual foraging habitat in relation to daily and seasonal light cycles

Hydrobiologia - Using siscowet lake charr (Salvelinus namaycush siscowet) as an example organism, we modeled visual foraging habitat in relation to: (i) daily solar and lunar intensity, (ii)...     

A conserved inhibitory and differential stimulatory action of nucleotides on K(IR)6.0/SUR complexes is essential for excitation-metabolism coupling by K(ATP) channels.

The mechanism by which ubiquitous adenine nucleotide-gated K(IR)6.0(4)/SUR(4) channels link membrane excitability with cellular metabolism is controversial. Is a decreased sensitivity to inhibitory ATP required, or is the Mg-ADP/ATP-dependent stimulatory action of the ATPase, sulfonylurea receptor (SUR), on K(IR) sufficient to elicit a physiologically significant open channel probability? To evaluate the roles of nucleotide inhibition versus stimulation, we compared K(IR)6.1-based K(NDP) channels with K(IR)6.2-based K(ATP) channels and all possible K(IR)6.1/6.2 hybrids. Although K(NDP) channels are thought to be poorly sensitive to inhibitory ATP and to require Mg-nucleotide diphosphates for activity, we demonstrate that, like K(ATP), and hybrid channels, they are inhibited with an IC(50(ATP)) 100-fold lower than [ATP](i). K(IR)6.1 is, however, more efficiently stimulated by SUR than K(IR)6.2, thus providing a mechanism for differential nucleotide regulation, in addition to the known differential interactions of Mg-nucleotides with SUR isoforms. The on-cell and spontaneous activities of K(NDP), K(ATP), and hybrid channels identified in native cells, are different; thus, their similar IC(50(ATP)) values argue the regulatory "beta" SUR subunits play a preeminent role in coupling excitation to metabolism and pose questions about the physiologic significance of models, which assume the ATP insensitivity of open K(IR)s.     

Human ecology, crime, and crime control: linking individual behavior and aggregate crime

The paper extends previous research published by Cohen, Machalek, Vila, and others on the evolutionary-ecological paradigm for understanding criminal behavior. After reviewing literature related to human ecology and crime, the paper focuses on elements relevant to human ecology-biology, development, and ecological factors--and their role in criminal behavior. Major emphasis is placed on the linkages between individual factors and macro-level crime using chronic offending as a case in point. The principles of evolutionary ecology then are used to discuss counterstrategies to crime, and the prospects for protection/avoidance, deterrent, and nurturant strategies in light of evidence on chronic offending.     

HAPPY mapping in a plant genome: reconstruction and analysis of a high-resolution physical map of a 1.9 Mbp region of Arabidopsis thaliana chromosome 4

HAPPY mapping is an in vitro approach for defining the order and spacing of DNA markers directly on native genomic DNA. This cloning-free technique is based on analysing the segregation of markers amplified from high molecular weight genomic DNA which has been broken randomly and 'segregated' by limiting dilution into subhaploid samples. It is a uniquely versatile tool, allowing for the construction of genome maps with flexible ranges and resolutions. Moreover, it is applicable to plant genomes, for which many of the techniques pioneered in animal genomes are inapplicable or inappropriate. We report here its demonstration in a plant genome by reconstructing the physical map of a 1.9 Mbp region around the FCA locus of Arabidopsis thaliana. The resulting map, spanning around 10% of chromosome 4, is in excellent agreement with the DNA sequence and has a mean marker spacing of 16 kbp. We argue that HAPPY maps of any required resolution can be made immediately and with relatively little effort for most plant species and, furthermore, that such maps can greatly aid the construction of regional or genome-wide physical maps.     

Obesity and impairment in psychosocial functioning in women: the mediating role of eating disorder features

Objective: The objective was to test the hypothesis that, in women, the association between obesity and impairment in psychosocial functioning is mediated by levels of weight and shape concerns and/or binge‐eating frequency. Research Methods and Procedures: Self‐report measures of eating disorder psychopathology, mental health functioning, subjective quality of life in the psychological and social domains, and days “out‐of‐role” associated with any (physical or mental) health problem, were completed by a community sample of women classified as obese (BMI ≥30 kg/m², n = 639) or non‐obese (BMI <30 kg/m², n = 4253). For each of the dependent measures, regression models were used to test the hypothesis of mediation by comparing the strength of the relationship between independent and dependent variables with and without inclusion of the putative mediator in the regression model. Results: On each measure, the conditions for perfect mediation were satisfied when weight or shape concerns acted as the putative mediator, indicating that there was no association between obesity and functional impairment after controlling for weight or shape concerns. In contrast, associations between obesity and impairment in psychosocial functioning remained highly significant when binge‐eating frequency was the putative mediator. Discussion: The findings suggest that in women, weight and shape concerns are an important mediator of the relationship between obesity and impairment in psychosocial functioning, whereas binge eating may not be of primary importance. A greater focus on body acceptance in obesity treatment may be indicated.     

Rain Forest Structure at Forest-Pasture Edges in Northeastern Costa Rica

Land-use change in the Sarapiquí region of Costa Rica has resulted in a fragmented forest landscape with abrupt edges between forest and pasture. Forest responses to edge effects vary widely and can significantly affect ecosystem integrity. Our objective was to examine forest structure at 20+ yr old forest-pasture edges in Sarapiquí. Three transects with 0.095-ha plots at seven distances from forest edges were established in each of six forest patches. Stem density, basal area, and aboveground biomass in trees and palms ≥ 10-cm diameter at breast height were measured in all plots. In addition, hemispherical photographs were taken to determine leaf area index, understory light availability, and percent canopy openness. Linear mixed-effects models showed significantly higher tree stem density at forest edges, relative to interiors, a pattern reflected by increased stem density, basal area, and aboveground biomass in small diameter trees (≤ 20 cm) growing near edges. No differences in total tree basal area, aboveground biomass, or hemispherical photograph-derived parameters were detected across the forest edge to interior gradient. The recruitment of small diameter trees following edge creation has contributed to the development of dense vegetation at the forest edge and has aided in the maintenance of similar tree basal area and aboveground biomass between edge and interior environments. These data reflect on the robustness of forest edges in Sarapiquí, a characteristic that will likely minimize future detrimental edge effects and promote a number of high-value environmental services in these forests.