Integrins in angiogenesis: multitalented molecules in a balancing act

Over the last 10–15 years the varied roles of cell adhesion molecules in the development of new blood vessels have received extensive attention. To date, more than 500 publications have been dedicated specifically to the role of a single family of adhesion molecules, namely integrins, in the process of angiogenesis. Although one can now appreciate the involvement of integrins in this process, and indeed antagonists of integrins are presently being tested as anti-angiogenic treatments, the precise regulation and exact action of integrins is still unclear. Here we will clarify the varied role of integrins and aim to elucidate and simplify the combined functions of these molecules in angiogenesis.     

Delay and probability discounting as related to different stages of adolescent smoking and non-smoking

This study examined relations between different patterns of adolescent cigarette smoking and discounting of monetary rewards due to delay (delay discounting) and probabilistic uncertainty (probability discounting). The study also examined the relation between smoking and the number of peer friends who smoke and level of parent education. Participants were 55 adolescents (28 females) between 14 and 16 years of age who were categorized according to the following patterns of smoking behavior: "never smokers" (n=19; 10 females) who had not tried even one cigarette; "triers" (n=17; 9 females) who had recently tried cigarettes for the first time; and "current smokers" (n=19; 9 females) who smoked a minimum of one cigarette every week for at least 6 months prior to data collection. It was hypothesized that current smokers would discount more than those who had never smoked. No specific hypotheses were made for participants only trying cigarettes. Unexpectedly, results indicated no differences in discounting between the current smokers and never smokers. However, the trier group discounted probabilistic rewards significantly more than the never- and current-smoker groups. Also, triers and current smokers both reported having more friends who smoked than never smokers, and fathers of never smokers had significantly more education than fathers of either triers or current smokers. These results suggest that impulsive discounting may be more related to adolescents trying cigarettes than to their becoming regular smokers, whereas number of peer friends who smoke and parent level of education seem to differentiate between those who have smoked to some extent (triers and current smokers) and those who have not even tried cigarettes (never smokers).     

The relationship between lifestyle regularity and subjective sleep quality

In previous work we have developed a diary instrument-the Social Rhythm Metric (SRM), which allows the assessment of lifestyle regularity-and a questionnaire instrument--the Pittsburgh Sleep Quality Index (PSQI), which allows the assessment of subjective sleep quality. The aim of the present study was to explore the relationship between lifestyle regularity and subjective sleep quality. Lifestyle regularity was assessed by both standard (SRM-17) and shortened (SRM-5) metrics; subjective sleep quality was assessed by the PSQI. We hypothesized that high lifestyle regularity would be conducive to better sleep. Both instruments were given to a sample of 100 healthy subjects who were studied as part of a variety of different experiments spanning a 9-yr time frame. Ages ranged from 19 to 49 yr (mean age: 31.2 yr, s.d.: 7.8 yr); there were 48 women and 52 men. SRM scores were derived from a two-week diary. The hypothesis was confirmed. There was a significant (rho = -0.4, p < 0.001) correlation between SRM (both metrics) and PSQI, indicating that subjects with higher levels of lifestyle regularity reported fewer sleep problems. This relationship was also supported by a categorical analysis, where the proportion of "poor sleepers" was doubled in the "irregular types" group as compared with the "non-irregular types" group. Thus, there appears to be an association between lifestyle regularity and good sleep, though the direction of causality remains to be tested.     

Synthesis of mannopyranose disaccharides as photoaffinity probes for mannosyltransferases in Mycobacterium tuberculosis

Mannosyltransferases play a crucial role in mycobacterial cell-wall biosynthesis and are potential new drug targets for the treatment of tuberculosis. Herein, we describe the synthesis of alpha-(1-->2)- and alpha-(1-->6)-linked mannopyranosyl disaccharides possessing a 5-azidonaphthlene-1-sulfonamidoethyl group as photoaffinity probes for active-site labeling studies of mannosyltransferases in Mycobacterium tuberculosis.     

DNA adduct analysis and histopathological biomarkers in European flounder (Platichthys flesus) sampled from UK estuaries

The presence of genotoxic and potentially carcinogenic chemical contaminants in the estuarine and coastal marine environment is well documented. In this study, European flounder (Platichthys flesus) sampled from eight UK estuaries were analysed for hepatic DNA adducts, using the 32P-postlabelling assay and liver histopathology as part of an on going survey to establish the health status of UK estuaries. Fish were collected from the estuaries Tyne, Mersey, Thames, Alde (reference site), Belfast, Forth, Clyde and Southampton. At the majority of contaminated sites (Southampton, Thames, Clyde, Tyne and Mersey) the predominant DNA adduct profile consisted of diagonal radioactive zones (DRZs). In contrast, flounder collected from the Forth, Alde and Belfast lacked DRZs with only background levels of DNA damage being observed. Statistically significant differences were observed between several of the sites sampled with the hepatic DNA adduct levels detected in flounder from Southampton, Thames and Clyde statistically elevated (P < 0.05) over those levels detected at the Tyne (Southampton and Thames only), Forth, Alde and Belfast. Histological analysis of these samples revealed a range of lesions including foci of cellular alteration, hepatocellular fibrillar inclusions, nuclear pleomorphisms along with non-toxicopathic changes/alterations, such as those associated with cell turnover (apoptosis, necrosis, regeneration) and immune-related functions (melanomacrophage aggregates, inflammation). Although it is difficult to associate higher prevalence of these lesion types with specific sites, generally, the lowest prevalence was seen in flounder captured from the Alde estuary, with higher prevalence (particularly of melanomacrophage aggregates, inflammation and necrotic foci) seen in fish from the contaminated sites.     

Plant responses to precipitation in desert ecosystems: integrating functional types,pulses, thresholds,and delays

The two-layer and pulse-reserve hypotheses were developed 30 years ago and continue to serve as the standard for many experiments and modeling studies that examine relationships between primary productivity and rainfall variability in aridlands. The two-layer hypothesis considers two important plant functional types (FTs) and predicts that woody and herbaceous plants are able to co-exist in savannas because they utilize water from different soil layers (or depths). The pulse-reserve model addresses the response of individual plants to precipitation and predicts that there are biologically important rain events that stimulate plant growth and reproduction. These pulses of precipitation may play a key role in long-term plant function and survival (as compared to seasonal or annual rainfall totals as per the two-layer model). In this paper, we re-evaluate these paradigms in terms of their generality, strengths, and limitations. We suggest that while seasonality and resource partitioning (key to the two-layer model) and biologically important precipitation events (key to the pulse-reserve model) are critical to understanding plant responses to precipitation in aridlands, both paradigms have significant limitations. Neither account for plasticity in rooting habits of woody plants, potential delayed responses of plants to rainfall, explicit precipitation thresholds, or vagaries in plant phenology. To address these limitations, we integrate the ideas of precipitation thresholds and plant delays, resource partitioning, and plant FT strategies into a simple threshold-delay model. The model contains six basic parameters that capture the nonlinear nature of plant responses to pulse precipitation. We review the literature within the context of our threshold-delay model to: (i) develop testable hypotheses about how different plant FTs respond to pulses; (ii) identify weaknesses in the current state-of-knowledge; and (iii) suggest future research directions that will provide insight into how the timing, frequency, and magnitude of rainfall in deserts affect plants, plant communities, and ecosystems.     

Root foraging for patchy resources in eight herbaceous plant species

The root foraging strategy of a plant species can be characterized by measuring foraging scale, precision, and rate. Trade-offs among these traits have been predicted to contribute to coexistence of competitors. We tested for trade-offs among root foraging scale (total root mass and length of structural roots), precision (ln-ratio of root lengths in resource-rich and resource-poor patches), and rate (days required for roots to reach a resource-rich patch, or growth rate of roots within a resource-rich patch) in eight co-occurring species. We found that root foraging scale and precision were positively correlated, as were foraging scale and the rate of reaching patches. High relative growth rate of a species did not contribute to greater scale, precision, or rate of root foraging. Introduced species had greater foraging scale, precision, and rate than native species. The positive correlations between foraging scale and foraging precision and rate may give larger species a disproportionate advantage in competition for patchy soil resources, leading to size asymmetric competition below ground.     

Investigation of the importance of the C-2 and C-13 oxygen functions in the transformation of stemodin analogues by Rhizopus oryzae ATCC 11145

Incubation of 2alpha,13(R)-dihydroxystemodane (3) with Rhizopus oryzae ATCC 11145 gave 2alpha,7beta,13(R)-trihydroxystemodane (11) while biotransformation of 13(R)-hydroxystemodan-2-one (5) yielded 6alpha,13(R)-dihydroxystemodan-2-one (12) and 7beta,13(R)-dihydroxystemodan-2-one (13). Bioconversion of 2beta,13(R)-dihydroxystemodane (7) with Rhizopus afforded 2beta,7,13(R)-trihydroxystemodane (14). The results complement data from our previous work and provide more information about the effect of functional groups of stemodane substrates on the site of hydroxylation.     

Identification of human and mouse CatSper3 and CatSper4 genes: Characterisation of a common interaction domain and evidence for expression in testis

Background  

CatSper1 and CatSper2 are two recently identified channel-like proteins, which show sperm specific expression patterns. Through targeted mutagenesis in the mouse, CatSper1 has been shown to be required for fertility, sperm motility and for cAMP induced Ca²⁺ current in sperm. Both channels resemble a single pore forming repeat from a four repeat voltage dependent Ca²⁺ /Na⁺ channel. However, neither CatSper1 or CatSper2 have been shown to function as cation channels when transfected into cells, singly or in conjunction. As the pore forming units of voltage gated cation channels form a tetramer it has been suggested that the known CatSper proteins require additional subunits and/or interaction partners to function.     

Epithelial carcinogenesis: dynamic interplay between neoplastic cells and their microenvironment

Matrix metalloproteinases (MMPs) have long been thought of as critical factors regulating matrix degradation associated with cell invasion into ectopic tissue compartments during primary tumor growth and metastasis. One member of the MMP family historically linked to these invasive processes is MMP-9/gelatinase B. By studying a transgenic mouse model of de novo epithelial carcinogenesis, new roles for MMP-9 have emerged that broaden the view of its functional contribution to malignant progression. The combined implication of these studies suggest that MMP-9 functionally contributes to cancer development; however, its major regulatory role may be in its ability to activate poorly diffusible and/or matrix-sequestered growth factors that regulate epithelial and/or endothelial cell growth as opposed to regulating cellular invasion across basement membranes.