ROCKing cytokine secretion balance in human T cells

Balanced regulation of cytokine secretion in T cells is critical for maintenance of immune homeostasis and prevention of autoimmunity. The Rho-associated kinase (ROCK) 2 signaling pathway was previously shown to be involved in controlling of cellular movement and shape. However, recent work from our group and others has demonstrated a new and important role of ROCK2 in regulating cytokine secretion in T cells. We found that ROCK2 promotes pro-inflammatory cytokines such as IL-17 and IL-21, whereas IL-2 and IL-10 secretion are negatively regulated by ROCK2 under Th17-skewing activation. Also, in disease, but not in steady state conditions, ROCK2 contributes to regulation of IFN-γ secretion in T cells from rheumatoid arthritis patients. Thus, ROCK2 signaling is a key pathway in modulation of T-cell mediated immune responses underscoring the therapeutic potential of targeted inhibition of ROCK2 in autoimmunity.     

The occurrence and frequency of 2n pollen in 2x, 4x,and 6x wild,tuber-bearing Solanum species from Mexico,and Central and South America

Summary The occurrence of 2n pollen-producing plants was investigated in 187 plant introductions (PIs) of 38 wild species of tuber-bearing Solanum. These 2x, 4x, and 6x species are from Mexico, and Central and South America. The determination of 2n pollen-producing plants was conducted using acetocarmine glycerol. Plants with more than 1% large-size pollen were regarded as 2n pollen-producing plants. 2n pollen-producing plants were identified in the following species: 10 out of 12 Mexican 2x species, seven of nine South American 2x species, seven of seven Mexican and Central American 4x species, five of five South American 4x species, and five of five Mexican 6x species. The frequency of 2n pollen-producing plants varied among species at the same ploidy level, but the range of frequency, generally between 2 and 10% among species, was similar over different ploidy levels. The general occurrence of 2n pollen in both 2x and polyploid species, which are evolutionarily related, is evidence that the mode of polyploidization in tuber-bearing Solanums is sexual polyploidization. Furthermore, the frequencies of 2n pollen-producing plants in autogamous disomic polyploid species were not markably different from those of their related diploid species. It is thought that the frequent occurrence of 2n gametes with autogamy tends to disturb the fertility and consequently reduce fitness of polyploids. Thus, we propose that the breeding behavior of polyploids and the occurrence of 2n gametes may be genetically balanced in order to conserve high fitness in polyploid species in tuberbearing Solanum.Paper No. 3114 from the Laboratory of Genetics. Research supported by the College of Agriculture and Life Sciences; International Potato Center; USDA, SEA, CGRO 84-CRCR-1-1389; and Frito Lay, Inc.     

Tuning cellular responses to BMP-2 with material surfaces

Bone morphogenetic protein 2 (BMP-2) has been known for decades as a strong osteoinductive factor and for clinical applications is combined solely with collagen as carrier material. The growing concerns regarding side effects and the importance of BMP-2 in several developmental and physiological processes have raised the need to improve the design of materials by controlling BMP-2 presentation. Inspired by the natural cell environment, new material surfaces have been engineered and tailored to provide both physical and chemical cues that regulate BMP-2 activity. Here we describe surfaces designed to present BMP-2 to cells in a spatially and temporally controlled manner. This is achieved by trapping BMP-2 using physicochemical interactions, either covalently grafted or combined with other extracellular matrix components. In the near future, we anticipate that material science and biology will integrate and further develop tools for in vitro studies and potentially bring some of them toward in vivo applications.     

Does re-creation of extensive pasture-forest mosaics provide an economically sustainable way of nature conservation in Sweden''s forest dominated regions?

There is a major risk that many of the remaining semi-natural pastures in Swedish forest dominated regions will lose their grazing in the near future with lost biodiversity as a result. The reason is the high costs of grazing small pastures with cattle from generally small herds. The approaching decoupling of the present EU income support per head of cattle will increase the risk. Calculations based on economies of scale in beef production and opportunity cost of forest and arable land suggest that re-creating extensive pasture-forest mosaics consisting of existing semi-natural pastures and adjacent arable fields and forests can secure economically sustainable grazing. The risk of local extinction of grassland species due to habitat isolation is also lower in large mosaics than in small, scattered pastures.     

Incidence,prevalence, mortality,disability-adjusted life years and risk factors of cancer in Australia and comparison with OECD countries, 1990–2015: findings from the Global Burden of Disease Study 2015

BackgroundComparative evidence on the burden, trend, and risk factors of cancer is limited. Using data from the Global Burden of Disease (GBD) study, we aimed to assess cancer burden – incidence, prevalence, mortality, disability-adjusted life years (DALYs) – and attributable risk factors for Australia between 1990 and 2015, and to compare them with those of 34 members of the Organisation for Economic Co-operation and Development (OECD).MethodsThe general GBD cancer estimation methods were used with data input from vital registration systems and cancer registries. A comparative risk assessment approach was used to estimate the population-attributable fractions due to risk factors.ResultsIn 2015 there were 198,880 (95% uncertainty interval [UI]: 183,908–217,365) estimated incident cancer cases and 47,562 (95% UI: 46,061–49,004) cancer deaths in Australia. Twenty-nine percent (95% UI: 28.2–29.8) of total deaths and 17.0% (95% UI: 15.0–19.1) of DALYs were caused by cancer in Australia in 2015. Cancers of the trachea, bronchus and lung, colon and rectum, and prostate were the most common causes of cancer deaths. Thirty-six percent (95% UI: 33.1–37.9) of all cancer deaths were attributable to behavioral risks. The age-standardized cancer incidence rate (ASIR) increased between 1990 and 2015, while the age-standardized cancer death rate (ASDR) decreased over the same period. In 2015, compared to 34 other OECD countries Australia ranked first (highest) and 24^th based on ASIR and ASDR, respectively.ConclusionThe incidence of cancer has increased over 25 years, and behavioral risks are responsible for a large proportion of cancer deaths. Scaling up of prevention (using strategies targeting cancer risk factors), early detection, and treatment of cancer is required to effectively address this growing health challenge.     

Oxygen: a master regulator of pancreatic development?

Beyond its role as an electron acceptor in aerobic respiration, oxygen is also a key effector of many developmental events. The oxygen‐sensing machinery and the very fabric of cell identity and function have been shown to be deeply intertwined. Here we take a first look at how oxygen might lie at the crossroads of at least two of the major molecular pathways that shape pancreatic development. Based on recent evidence and a thorough review of the literature, we present a theoretical model whereby evolving oxygen tensions might choreograph to a large extent the sequence of molecular events resulting in the development of the organ. In particular, we propose that lower oxygenation prior to the expansion of the vasculature may favour HIF (hypoxia inducible factor)‐mediated activation of Notch and repression of Wnt/β‐catenin signalling, limiting endocrine cell differentiation. With the development of vasculature and improved oxygen delivery to the developing organ, HIF‐mediated support for Notch signalling may decline while the β‐catenin‐directed Wnt signalling is favoured, which would support endocrine cell differentiation and perhaps exocrine cell proliferation/differentiation.     

Aging-related changes in the sensitivity of the system of respiratory control and the intensity of free-radical processes in humans

Results of a comparative study of the sensitivity of the system of respiratory control to increases in the CO₂ concentration and the intensity of free-radical processes in young and elderly subjects are described. It is shown that normal (natural) aging is accompanied by a decrease in the sensitivity of the respiratory system to hypercapnic stimulation and a parallel significant decrease in the activity of catalase in the blood of examined subjects. Mechanisms responsible for the modifications of the sensitivity of the system of respiratory control to hypercapnia are discussed; these shifts can be at least partly related to changes in the intensity of production of free radicals observed in elderly subjects. Neirofiziologiya/Neurophysiology, Vol. 40, No. 1, pp. 53–57, January–February, 2008.     

Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics.