Daily negative affect and smoking after a self-set quit attempt: The role of dyadic invisible social support in a daily diary study

Objectives Social support receipt from one's partner is assumed to be beneficial for successful smoking cessation. However, support receipt can have costs. Recent research suggests that the most effective support is unnoticed by the receiver (i.e., invisible). Therefore, this study examined the association between everyday levels of dyadic invisible emotional and instrumental support, daily negative affect, and daily smoking after a self-set quit attempt in smoker–non-smoker couples. Methods Overall, 100 smokers (72.0% men, mean age M = 40.48, SD = 9.82) and their non-smoking partners completed electronic diaries from a self-set quit date on for 22 consecutive days, reporting daily invisible emotional and instrumental social support, daily negative affect, and daily smoking. Results Same-day multilevel analyses showed that at the between-person level, higher individual mean levels of invisible emotional and instrumental support were associated with less daily negative affect. In contrast to our assumption, more receipt of invisible emotional and instrumental support was related to more daily cigarettes smoked. Conclusions The findings are in line with previous results, indicating invisible support to have beneficial relations with affect. However, results emphasize the need for further prospective daily diary approaches for understanding the dynamics of invisible support on smoking cessation.

New nucleoside analogues for the recognition of pyrimidine-purine inversion sites

A new nucleoside designed to enhance triplex stability has been synthesised in 15 steps starting from sugar 2. This pathway contains the sugar derivative 9 which is a useful intermediate for the introduction of other natural and unnatural bases into the 2'-aminoethoxy nucleoside containing scaffold

Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke

Each year about 650,000 Europeans die from stroke and a similar number lives with the sequelae of multiple sclerosis (MS). Stroke and MS differ in their etiology. Although cause and likewise clinical presentation set the two diseases apart, they share common downstream mechanisms that lead to damage and recovery. Demyelination and axonal injury are characteristics of MS but are also observed in stroke. Conversely, hallmarks of stroke, such as vascular impairment and neurodegeneration, are found in MS. However, the most conspicuous common feature is the marked neuroinflammatory response, marked by glia cell activation and immune cell influx. In MS and stroke the blood-brain barrier is disrupted allowing bone marrow-derived macrophages to invade the brain in support of the resident microglia. In addition, there is a massive invasion of auto-reactive T-cells into the brain of patients with MS. Though less pronounced a similar phenomenon is also found in ischemic lesions. Not surprisingly, the two diseases also resemble each other at the level of gene expression and the biosynthesis of other proinflammatory mediators. While MS has traditionally been considered to be an autoimmune neuroinflammatory disorder, the role of inflammation for cerebral ischemia has only been recognized later. In the case of MS the long track record as neuroinflammatory disease has paid off with respect to treatment options. There are now about a dozen of approved drugs for the treatment of MS that specifically target neuroinflammation by modulating the immune system. Interestingly, experimental work demonstrated that drugs that are in routine use to mitigate neuroinflammation in MS may also work in stroke models. Examples include Fingolimod, glatiramer acetate, and antibodies blocking the leukocyte integrin VLA-4. Moreover, therapeutic strategies that were discovered in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, turned out to be also effective in experimental stroke models. This suggests that previous achievements in MS research may be relevant for stroke. Interestingly, the converse is equally true. Concepts on the neurovascular unit that were developed in a stroke context turned out to be applicable to neuroinflammatory research in MS. Examples include work on the important role of the vascular basement membrane and the BBB for the invasion of immune cells into the brain. Furthermore, tissue plasminogen activator (tPA), the only established drug treatment in acute stroke, modulates the pathogenesis of MS. Endogenous tPA is released from endothelium and astroglia and acts on the BBB, microglia and other neuroinflammatory cells. Thus, the vascular perspective of stroke research provides important input into the mechanisms on how endothelial cells and the BBB regulate inflammation in MS, particularly the invasion of immune cells into the CNS. In the current review we will first discuss pathogenesis of both diseases and current treatment regimens and will provide a detailed overview on pathways of immune cell migration across the barriers of the CNS and the role of activated astrocytes in this process. This article is part of a Special Issue entitled: Neuro inflammation: A common denominator for stroke, multiple sclerosis and Alzheimer's disease, guest edited by Helga de Vries and Markus Swaninger.

Pathways linking socioeconomic position and diabetes: The role of psychosocial factors

Despite increasing interest in the relationship between socioeconomic position (SEP) and health, there remains little understanding of the mechanisms through which SEP is related to chronic disease. This dissertation utilized data from 2,592 U.S. households in the 1995 telephone survey of the Aging, Status, and the Sense of Control study to: (1) investigate potential mediating factors in the association between educational level and prevalence of diabetes and (2) to investigate the association between the three major measures of SEP—income, education, and occupation—and the prevalence of diabetes. Regression analyses were conducted to examine the degree to which sense of personal control and social support mediate the association between level of educational attainment and diabetes and to examine the contribution of each of the SEP measures to diabetes. After adjusting for age, obesity, sex, and race, respondents with less than a high school education had greater odds of having diabetes than those with a college degree or higher level of educational attainment, although the corresponding confidence interval contained the null value (OR = 1.2, 95% CI: 0.7, 2.0). Neither sense of control nor social support significantly mediated the association between education and diabetes. However, sense of control was associated with diabetes status (OR = 0.7, 95% CI: 0.5, 1.0). Compared with income and education, employment status was the most strongly associated measure of SEP with diabetes prevalence. After adjusting for age, obesity, sex, and race, respondents who were unable to work due to disability had fourfold greater odds of having diabetes than those who were employed full time (OR = 4.0; 95% CI: 1.9, 8.3). Adding income and/or education to the model did not improve the fit. Understanding the impact of socioeconomic factors on diabetes requires consideration of multiple measures of SEP as well as the psychosocial pathways through which SEP may influence diabetes. ^

The characterization of PKC-isozyme specific EGFR-dependent Erk1/2 activation in androgen-independent prostate cancer cell lines

One growth factor receptor commonly altered during prostate tumor progression is the epidermal growth factor receptor (EGFR). EGFR signaling regulates Erk1/2 phosphorylation through multiple mechanisms. We hypothesized that PKC isozymes play a role in EGFR-dependent signaling, and that through PKC isozyme selective inhibition, EGFR-dependent Erk1/2 activation can be attenuated in AICaP cells. ^ To test the hypothesis, PKC activation was induced by 12-O-tetradecanoyi-phorbol-13-acetate (TPA) in PC-3 cells. As a result, Erk1/2 was activated similarly to what was observed upon EGF stimulation. EGF-induced Erk1/2 activation in PC-3 cells was PKC-dependent, as demonstrated through use of a selective PKC inhibitor, GF109203X. This provides evidence for PKC regulatory control over Erk1/2 signaling downstream of EGFR. Next, we demonstrated that when PKC was inhibited by GF109203X, EGF-stimulated Erk1/2 activation was inhibited in PC-3, but not DU145 cells. TPA-stimulated Erk1/2 activation was EGFR-dependent in both DU145 and PC-3 cells, demonstrated through abrogation of Erk1/2 activation by a selective EGFR inhibitor AG1478. These data support PKC control at or upstream of EGFR in AICaP cells. We observed that interfering with ligand/EGFR binding abrogated Erk1/2 signaling in TPA-stimulated cells, revealing a role for PKC upstream of EGFR. ^ Next, we determined which PKC isozymes might be responsible for Erk1/2 regulation. We first determined that human AICaP cell lines express the same PKC isozymes as those observed in clinical prostate cancer specimens (α, ϵ, &zgr;, ι and PKD). Isozyme-selective methods were employed to characterize discrete PKC isozyme function in EGFR-dependent Erk1/2 activation. Pharmacologic inhibitors implicated PKCα in TPA-induced EGFR-dependent Erk1/2 activation in both PC-3 and DU145 cells. Further, the cPKC-specific inhibitor, Gö6976 decreased viablilty of DU145 cells, providing evidence that PKCα is necessary for growth and survival. Finally, resveratrol, a phytochemical with strong cancer therapeutic potential inhibited Erk1/2 activation, and this correlated with selective inhibition of PKCα. These results demonstrate that PKC regulates pathways critical to progression of CaP cells, including those mediated by EGFR. Thus, PKC isozyme-selective targeting is an attractive therapeutic strategy, and understanding the role of specific PKC isozymes in CaP cell growth and survival may aid in development of effective, non-toxic PKC-targeted therapies. ^

Investigating the Role of Small, Acid-Soluble Spore Proteins (SASPs) in the Resistance of Clostridium Perfringens Spores to Heat.

BACKGROUND: Clostridium perfringens type A food poisoning is caused by enterotoxigenic C. perfringens type A isolates that typically possess high spore heat-resistance. The molecular basis for C. perfringens spore heat-resistance remains unknown. In the current study, we investigated the role of small, acid-soluble spore proteins (SASPs) in heat-resistance of spores produced by C. perfringens food poisoning isolates. RESULTS: Our current study demonstrated the presence of all three SASP-encoding genes (ssp1, 2 and 3) in five surveyed C. perfringens clinical food poisoning isolates. beta-Glucuronidase assay showed that these ssp genes are expressed specifically during sporulation. Consistent with these expression results, our study also demonstrated the production of SASPs by C. perfringens food poisoning isolates. When the heat sensitivities of spores produced by a ssp3 knock-out mutant of a C. perfringens food poisoning isolate was compared with that of spores of the wild-type strain, spores of the ssp3 mutant were found to exhibit a lower decimal reduction value (D value) at 100 degrees C than exhibited by the spores of wild-type strain. This effect was restored by complementing the ssp3 mutant with a recombinant plasmid carrying wild-type ssp3, suggesting that the observed differences in D values between spores of wild-type versus ssp3 mutant was due to the specific inactivation of ssp3. Furthermore, our DNA protection assay demonstrated that C. perfringens SASPs can protect DNA from DNase I digestion. CONCLUSION: The results from our current study provide evidences that SASPs produced by C. perfringens food poisoning isolates play a role in protecting their spores from heat-damage, which is highly significant and relevant from a food safety perspective. Further detailed studies on mechanism of action of SASPs from C. perfringens should help in understanding the mechanism of protection of C. perfringens spores from heat-damage.

Identifying the roles of the Escherichia coli FtsZ-associated proteins by minimizing the requirements for division

Formation of the FtsZ ring (Z ring) in Escherichia coli is the first step in assembly of the divisome, a molecular machine composed of 14 known proteins which are all required for cell division. Although the biochemical functions of most divisome proteins are unknown, several of these have overlapping roles in ensuring that the Z ring assembles at the cytoplasmic membrane and is active. ^ We identified a single amino acid change in FtsA, R286W, renamed FtsA*, that completely bypasses the requirement for ZipA in cell division. This and other data suggest that FtsA* is a hyperactive form of FtsA that can replace the multiple functions normally assumed by ZipA, which include stabilization of Z rings, recruitment of downstream cell division proteins, and anchoring the Z ring to the membrane. This is the first example of complete functional replacement of an essential prokaryotic cell division protein by another. ^ Cells expressing ftsA* with a complete deletion of ftsK are viable and divide, although many of these ftsK null cells formed multiseptate chains, suggesting a role in cell separation for FtsK. In addition, strains expressing extra ftsAZ, ftsQ, ftsB, zipA or ftsN, were also able to survive and divide in the absence of ftsK. The cytoplasmic and transmembrane domains of FtsQ were sufficient to allow viability and septum formation to ftsK deleted strains. These findings suggest that FtsK is normally involved in stabilizing the divisome and shares functional overlap with other cell division proteins. ^ As well as permitting the removal of other divisome components, the presence of FtsA* in otherwise wild-type cells accelerated Z-ring assembly, which resulted in a significant decrease in the average length of cells. In support of its role in Z-ring stability, FtsA* suppressed the cell division inhibition caused by overexpressing FtsZ. FtsA* did not affect FtsZ turnover within the Z ring as measured by fluorescence recovery after photobleaching. Turnover of FtsA* in the ring was somewhat faster than wild-type FtsA. Yeast two-hybrid data suggest that FtsA* has an increased affinity for FtsZ relative to wild-type FtsA. These results indicate that FtsA* interacts with FtsZ more strongly, and its enhancement of Z ring assembly may explain why FtsA* can permit survival of cells lacking ZipA or FtsK.^

Examination of the engraftment of exogenous mesenchymal stem cells in ovarian tumors and their potential use as delivery vehicles for therapeutic genes

Interactions between neoplastic cells and the host stroma play a role in both tumor cell migration and proliferation. Stromal cells provide structural support for malignant cells, modulate the tumor microenvironment, and influence phenotypic behavior as well as the aggressiveness of the malignancy. In response, the tumor provides growth factors, cytokines, and cellular signals that continually initiate new stromal reactions and recruit new cells into the microenvironment to further support tumor growth. Since growing tumors recruit local cells, as well as supplemental cells from the circulation, such as fibroblasts and endothelial precursors, the question arises if it would be possible to access circulating stromal cells to modify the tumor microenvironment for therapeutic benefits. One such cell type, mesenchymal stem cells (MSC), could theoretically be engrafted into stroma. MSC are pluripotent cells that have been shown to form stromal elements such as myofibroblasts, perivascular tissues and connective tissues. Several reports have demonstrated that MSC can incorporate into sites of wound healing and tissue repair, due to active tissue remodeling and local paracrine factors, and given the similarity between wound healing and the carcinoma induced stromal response one can hypothesize that MSC have the potential to be recruited to sites of tumor development. In addition, gene-modified MSC could be used as cellular vehicles to deliver gene products into tumors. My results indicate that MSC home to and participate in tumor stroma formation in ovarian tumor xenografts in mice. Additionally, once homed to tumor beds, MSC proliferate rapidly and integrate. My studies aim at understanding the fate of MSC in the tumor microenvironment, as well as utilizing them for cellular delivery of therapeutic genes into the stroma of ovarian carcinomas. ^

The role of plasmacytoid dendritic cells in the regulation of adaptive immunity

Plasmacytoid dendritic cells (pDCs) selectively express TLR7 which allows them to respond to RNA viruses and TLR9 which allows them to respond to DNA viruses and CpG oligonucleotides. Upon exposure to virus pDCs produce vast amounts of type I interferon (IFN) directly inhibiting viral replication and contributing to the activation of other immune cells. The ability of pDCs to promote B and T cell differentiation through type I IFN has been well documented although the role of additional factors including tumor necrosis factor (TNF) family members has not been thoroughly addressed. Here the expression of selected TNF family members in pDCs was examined and the role of TNF receptor-ligand interactions in the regulation of B and T lymphocyte growth and differentiation by pDCs was investigated. Upon stimulation with CpG-B, pDCs exhibit strong and stable expression of CD70, a TNF family ligand that binds to its receptor CD27 on memory B cells and promotes plasma cell differentiation and Ig secretion. Using an in vitro pDC/B cell co-culture system, it was determined that CpG-B-stimulated pDCs induce the proliferation of CD40L-activated human peripheral B cells and Ig secretion. This occurs independently of IFN and residual CpG, and requires physical contact between pDCs and B cells. CpG-stimulated pDCs induce the proliferation of both naive and memory B cells although Ig secretion is restricted to the memory subset. Blocking the interaction of CD70 with CD27 using an antagonist anti-CD70 antibody reduces the induction of B cell proliferation and IgG secretion by CpG-B-stimulated pDCs. Published studies have also indicated an important role for CD70 in promoting the expansion of CD4+ and CD8+ T cells and the development of effector function. CpG-B-stimulated pDCs induce naïve CD4+ T cell proliferation and production of multiple cytokines including IFN-γ, TNF-α, IL-10, IL-4, IL-5 and IL-13. Blocking the function of CD70 with an antagonist anti-CD70 antibody significantly reduced the induction of naïve CD4+ T cell proliferation by CpG-B-stimulated pDCs and the production of IL-4 and IL-13. Collectively these data indicate an important role for CD70 in the regulation of B and T lymphocyte growth and differentiation by pDCs. ^

The cost of publicly financed dental care in relation to community water fluoridation in Texas

Dental caries lead to children being less ready to learn and results in diminished productivity in the classroom. Tooth decay causes pain and infection, leading to impaired chewing, speech, and facial expression, in addition to a loss in self-esteem. There have been many studies supporting the safety and efficacy of community water fluoridation in reducing dental caries. Water fluoridation has been identified by the Centers for Disease Control and Prevention as one of 10 great public health achievements of the 20th century. The decline in the prevalence and severity of tooth decay in the United States during the past 60 years has been attributed largely to the increased use of fluoride; in particular, the widespread utilization of community water fluoridation. However, in the decades since fluoridation was first introduced, reductions in dental caries have declined, most likely due to the presence of other sources of fluoride. Questions have been raised regarding the need to continue to fluoridate community water supplies in the face of possible excessive exposure to fluoride. Nevertheless, dental caries continue to be a significant public health burden throughout the world, including the United States, especially among low-income and disadvantaged populations. Although many poor children receive their dental care through Medicaid, the percentage of Texas children with untreated dental caries continues to exceed the U.S. average and is well above Healthy People 2010 goals, even as state Medicaid expenditures continue to rise. The objective of this study is to determine the relationship between Medicaid dental expenditures and community water fluoridation levels in Texas counties. By examining this relationship, the cost-effectiveness of community water fluoridation in the Texas pediatric Medicaid beneficiary population, as measured by publicly financed dental care expenditures, may be ascertained.^

THE APPLICATION OF CIRRHOSIS MORTALITY AND SUICIDE MORTALITY AS INDICATORS FOR ALCOHOLISM PLANNING

This study provides a review of the current alcoholism planning process of the Houston-Galveston planning process of the Houston-Galveston Area Council, an agency carrying out planning for a thirteen county region in surrounding Houston, Texas. The four central groups involved in this planning are identified, and the role that each plays and how it effects the planning outcomes is discussed.^ The most substantive outcome of the Houston-Galveston Area Council's alcoholism planning, the Regional Alcoholism/Alcohol Abuse Plan is examined. Many of the shortcomings in the data provided, and the lack of other data necessary for planning are offered.^ A problem oriented planning model is presented as an alternative to the Houston-Galveston Area Council's current service oriented approach to alcoholism planning. Five primary phases of the model, identification of the problem, statement of objectives, selection of alternative programs, implementation, and evaluation, are presented, and an overview of the tasks involved in the application of this model to alcoholism planning is offered.^ A specific aspect of the model, the use of problem status indicators is explored using cirrhosis and suicide mortality data. A review of the literature suggests that based on five criteria, availability, subgroup identification, validity, reliability, and sensitivity, both suicide and cirrhosis are suitable as indicators of the alcohol problem when combined with other indicators.^ Cirrhosis and suicide mortality data are examined for the thirteen county Houston-Galveston Region for the years 1969 through 1976. Data limitations preclude definite conclusions concerning the alcohol problem in the region. Three hypotheses about the nature of the regional alcohol problem are presented. First, there appears to be no linear trend in the number of alcoholics that are at risk of suicide and cirrhosis mortality. Second, the number of alcoholics in the metropolitan areas seems to be greater than the number of rural areas. Third, the number of male alcoholics at risk of cirrhosis and suicide mortality is greater than the number of female alcoholics.^

Distribution models for mountain plant species: The value of elevation

The climatic conditions of mountain habitats are greatly influenced by topography. Large differences in microclimate occur with small changes in elevation, and this complex interaction is an important determinant of mountain plant distributions. In spite of this, elevation is not often considered as a relevant predictor in species distribution models (SDMs) for mountain plants. Here, we evaluated the importance of including elevation as a predictor in SDMs for mountain plant species. We generated two sets of SDMs for each of 73 plant species that occur in the Pacific Northwest of North America; one set of models included elevation as a predictor variable and the other set did not. AUC scores indicated that omitting elevation as a predictor resulted in a negligible reduction of model performance. However, further analysis revealed that the omission of elevation resulted in large over-predictions of species' niche breadths-this effect was most pronounced for species that occupy the highest elevations. In addition, the inclusion of elevation as a predictor constrained the effects of other predictors that superficially affected the outcome of the models generated without elevation. Our results demonstrate that the inclusion of elevation as a predictor variable improves the quality of SDMs for high-elevation plant species. Because of the negligible AUC score penalty for over-predicting niche breadth, our results support the notion that AUC scores alone should not be used as a measure of model quality. More generally, our results illustrate the importance of selecting biologically relevant predictor variables when constructing SDMs.

Multibeam and seismic survey, physical oceanography, and sea-bottom videos from the Bay of Biscay

We report the northernmost and deepest known occurrence of deep-water pycnodontine oysters, based on two surveys along the French Atlantic continental margin to the La Chapelle continental slope (2006) and the Guilvinec Canyon (2008). The combined use of multibeam bathymetry, seismic profiling, CTD casts and a remotely operated vehicle (ROV) made it possible to describe the physical habitat and to assess the oceanographic control for the recently described species Neopycnodonte zibrowii. These oysters have been observed in vivo in depths from 540 to 846 m, colonizing overhanging banks or escarpments protruding from steep canyon flanks. Especially in the Bay of Biscay, such physical habitats may only be observed within canyons, where they are created by both long-term turbiditic and contouritic processes. Frequent observations of sand ripples on the seabed indicate the presence of a steady, but enhanced bottom current of about 40 cm/s. The occurrence of oysters also coincides with the interface between the Eastern North Atlantic Water and the Mediterranean Outflow Water. A combination of this water mass mixing, internal tide generation and a strong primary surface productivity may generate an enhanced nutrient flux, which is funnelled through the canyon. When the ideal environmental conditions are met, up to 100 individuals per m² may be observed. These deep-water oysters require a vertical habitat, which is often incompatible with the requirements of other sessile organisms, and are only sparsely distributed along the continental margins. The discovery of these giant oyster banks illustrates the rich biodiversity of deep-sea canyons and their underestimation as true ecosystem hotspots.

Evaluating the Effectiveness of GMS Economic Corridors: Why is There More Focus on the Bangkok-Hanoi Road than the East-West Corridor?

Since the inauguration of the Greater Mekong Sub-region (GMS) Economic Cooperation Program in 1992, road infrastructure projects have played a very important role. Their economic significance, especially, has become a focal point after the introduction of the concept of the three economic corridors in 1998: the East-West Economic Corridor; the North-South Economic Corridor; and the Southern Economic Corridor (Figure 1). The completion of the Second International Mekong Bridge between Mukdahan, Thailand and Savannakhet, Laos was an epoch-making event in the development of the East-West Economic Corridor. The business community, however, has paid more attention to the Bangkok-Hanoi Road than the East-West Economic Corridor. This study examines the reasons why the former has received more focus than the latter, by using criteria such as population density and the economic scale at a provincial or state level. Thereafter, the effectiveness of other economic corridors is examined, by applying the same criteria.

The British Influence in the Birth of Spanish Sport

Sports started to gain relevance in Spain around the end of the nineteenth century and the beginning of the twentieth century as a leisure and health option of the upper classes imported from Britain. Its early development was intertwined with the spread of other kinds of physical activities with much more tradition on the continent: gymnastics and physical education. First played by the ruling classes – aristocracy and high bourgeoisie – sports permeated towards petty bourgeoisie and middle classes in urban areas such as Madrid, Barcelona, San Sebastián and Santander. This pattern meant that the expansion of sports was unavoidably tied to the degree of industrialisation and cultural modernisation of the country. Since 1910, and mainly during the 1920s, sport grew in popularity as a spectacle and, toa much lesser degree, as a practice among the Spanish population.