Do innate killing mechanisms activated by inflammasomes have a role in treating melanoma?

Melanoma, as for many other cancers, undergoes a selection process during progression that limits many innate and adaptive tumor control mechanisms. Immunotherapy with immune checkpoint blockade overcomes one of the escape mechanisms but if the tumor is not eliminated other escape mechanisms evolve that require new approaches for tumor control. Some of the innate mechanisms that have evolved against infections with microorganisms and viruses are proving to be active against cancer cells but require better understanding of how they are activated and what inhibitory mechanisms may need to be targeted. This is particularly so for inflammasomes which have evolved against many different organisms and which recruit a number of cytotoxic mechanisms that remain poorly understood. Equally important is understanding of where these mechanisms will fit into existing treatment strategies and whether existing strategies already involve the innate killing mechanisms.     

Invasive potential of golden and zebra mussels in present and future climatic scenarios in the new world

Hydrobiologia - Biological invasions and climate change are important drivers of biodiversity loss. In freshwater ecosystems, golden and zebra mussels are two highly aggressive invasive species...     

Early Life Stress and Physical and Psychosocial Functioning in Late Adulthood

Background

Severe stress experienced in early life may have long-term effects on adult physiological and psychological health and well-being. We studied physical and psychosocial functioning in late adulthood in subjects separated temporarily from their parents in childhood during World War II.

Methods

The 1803 participants belong to the Helsinki Birth Cohort Study, born 1934–44. Of them, 267 (14.8%) had been evacuated abroad in childhood during WWII and the remaining subjects served as controls. Physical and psychosocial functioning was assessed with the Short Form 36 scale (SF-36) between 2001 and 2004. A test for trends was based on linear regression. All analyses were adjusted for age at clinical examination, social class in childhood and adulthood, smoking, alcohol intake, physical activity, body mass index, cardiovascular disease and diabetes.

Results

Physical functioning in late adulthood was lower among the separated men compared to non-separated men (b = −0.40, 95% confidence interval [95% CI]: −0.71 to −0.08). Those men separated in school age (>7 years) and who were separated for a duration over 2 years had the highest risk for lower physical functioning (b = −0.89, 95% CI: −1.58 to −0.20) and (b = −0.65, 95% CI: −1.25 to −0.05), respectively). Men separated for a duration over 2 years also had lower psychosocial functioning (b = −0.70, 95% CI: −1.35 to −0.06). These differences in physical and psychosocial functioning were not observed among women.

Conclusion

Early life stress may increase the risk for impaired physical functioning in late adulthood among men. Timing and duration of the separation influenced the physical and psychosocial functioning in late adulthood.     

Climate change does not affect the seafood quality of a commonly targeted fish

Climate change can affect marine and estuarine fish via alterations to their distributions, abundances, sizes, physiology and ecological interactions, threatening the provision of ecosystem goods and services. While we have an emerging understanding of such ecological impacts to fish, we know little about the potential influence of climate change on the provision of nutritional seafood to sustain human populations. In particular, the quantity, quality and/or taste of seafood may be altered by future environmental changes with implications for the economic viability of fisheries. In an orthogonal mesocosm experiment, we tested the influence of near‐future ocean warming and acidification on the growth, health and seafood quality of a recreationally and commercially important fish, yellowfin bream (Acanthopagrus australis). The growth of yellowfin bream significantly increased under near‐future temperature conditions (but not acidification), with little change in health (blood glucose and haematocrit) or tissue biochemistry and nutritional properties (fatty acids, lipids, macro‐ and micronutrients, moisture, ash and total N). Yellowfin bream appear to be highly resilient to predicted near‐future ocean climate change, which might be facilitated by their wide spatio‐temporal distribution across habitats and broad diet. Moreover, an increase in growth, but little change in tissue quality, suggests that near‐future ocean conditions will benefit fisheries and fishers that target yellowfin bream. The data reiterate the inherent resilience of yellowfin bream as an evolutionary consequence of their euryhaline status in often environmentally challenging habitats and imply their sustainable and viable fisheries into the future. We contend that widely distributed species that span large geographic areas and habitats can be “climate winners” by being resilient to the negative direct impacts of near‐future oceanic and estuarine climate change.     

Lysozyme crystal growth, as observed by small angle X-ray scattering, proceeds without crystallization intermediates

A combination of small angle X-ray scattering and gel techniques was used to follow the kinetics of protein crystal growth as a function of time. Hen egg white lysozyme, at different protein concentrations, was used as a model system. A new sample holder was designed, in which supersaturation is induced in the presence of salt by decreasing the temperature. It had been shown previously that a decrease in temperature and/or an increase in crystallizing agent induces an increase in the attractive interactions present in the lysozyme solutions, the lysozyme remaining monomeric. In the present paper we show that similar behaviour is observed in NaCl when agarose gels are used. During crystal growth, special attention was paid to determine whether oligomers were formed as the protein in solution was incorporated in the newly formed crystals. From these first series of experiments, we did not find any indication of oligomer formation between monomer in solution and crystal. The results obtained are in agreement with the hypothesis that lysozyme crystals in NaCl grow by addition of monomeric particles. Received: 28 July 1997 / Revised version: 4 December 1997 / Accepted: 5 December 1997     

Nuclear membrane receptors for ET-1 in cardiovascular function

Plasma membrane endothelin type A (ET(A)) receptors are internalized and recycled to the plasma membrane, whereas endothelin type B (ET(B)) receptors undergo degradation and subsequent nuclear translocation. Recent studies show that G protein-coupled receptors (GPCRs) and ion transporters are also present and functional at the nuclear membranes of many cell types. Similarly to other GPCRs, ET(A) and ET(B) are present at both the plasma and nuclear membranes of several cardiovascular cell types, including human cardiac, vascular smooth muscle, endocardial endothelial, and vascular endothelial cells. The distribution and density of ET(A)Rs in the cytosol (including the cell membrane) and the nucleus (including the nuclear membranes) differ between these cell types. However, the localization and density of ET-1 and ET(B) receptors are similar in these cell types. The extracellular ET-1-induced increase in cytosolic ([Ca](c)) and nuclear ([Ca](n)) free Ca(2+) is associated with an increase of cytosolic and nuclear reactive oxygen species. The extracellular ET-1-induced increase of [Ca](c) and [Ca](n) as well as intracellular ET-1-induced increase of [Ca](n) are cell-type dependent. The type of ET-1 receptor mediating the extracellular ET-1-induced increase of [Ca](c) and [Ca](n) depends on the cell type. However, the cytosolic ET-1-induced increase of [Ca](n) does not depend on cell type. In conclusion, nuclear membranes' ET-1 receptors may play an important role in overall ET-1 action. These nuclear membrane ET-1 receptors could be targets for a new generation of antagonists.     

Successful infection of the common marmoset (Callithrix jacchus) with human varicella-zoster virus.

The common marmoset, Callithrix jacchus, can be infected with human varicella-zoster virus (VZV), both wild-type strain KMcC and attenuated vaccine strain Oka/Merck. Infection was accomplished with either whole-cell-associated or cell extract VZV by combined oral-nasal-conjunctival application and was characterized by substantial and persistent anti-VZV antibody responses. The infectivity of VZV for marmosets was destroyed by treatment of inocula with heat or UV light. Diluted inocula with as few as 40 PFU/ml were infectious for marmosets. The lungs were demonstrated to be a major site of viral replication; both the presence of viral antigens and signs of pneumonia were demonstrated in lung tissues. Four serial passages of VZV KMcC were carried out in C. jacchus by a process of in vitro isolation and culturing of VZV from infected lung tissue and reapplication of the cultured isolates to fresh animals. The isolated viruses were identified as VZV both serologically and by restriction endonuclease analyses. The C. jacchus infectivity model should prove useful for determining the efficacy of subunit and live recombinant VZV vaccines as well as for the study of zoster.