Crossing paths: interactions between the cell death machinery and growth factor survival signals

Cytokines and growth factors play a crucial role in the maintenance of haematopoietic homeostasis. They transduce signals that regulate the competing commitments of haematopoietic stem cells, quiescence or proliferation, retention of stem cell pluripotency or differentiation, and survival or demise. When the balance between these commitments and the requirements of the organisms is disturbed, particularly when it favours survival and proliferation, cancer may result. Cell death provoked by loss of growth factor signalling is regulated by the Bcl-2 family of apoptosis regulators, and thus survival messages transduced by growth factors must regulate the activity of these proteins. Many aspects of direct interactions between cytokine signalling and regulation of apoptosis remain elusive. In this review, we explore the mechanisms by which cytokines, in particular Interleukin-3 and granulocyte–macrophage colony-stimulating factor, promote cell survival and suppress apoptosis as models of how cytokine signalling and apoptotic pathways intersect.     

Near-isothermal conditions in the middle and lower crust induced by melt migration

The thermal structure of the crust strongly influences deformation, metamorphism and plutonism. Models for the geothermal gradient in stable crust predict a steady increase of temperature with depth. This thermal structure, however, is incompatible with observations from high-temperature metamorphic terranes exhumed in orogens. Global compilations of peak conditions in high-temperature metamorphic terranes define relatively narrow ranges of peak temperatures over a wide range in pressure, for both isothermal decompression and isobaric cooling paths. Here we develop simple one-dimensional thermal models that include the effects of melt migration. These models show that long-lived plutonism results in a quasi-steady-state geotherm with a rapid temperature increase in the upper crust and nearly isothermal conditions in the middle and lower crust. The models also predict that the upward advection of heat by melt generates granulite facies metamorphism, and widespread andalusite-sillimanite metamorphism in the upper crust. Once the quasi-steady-state thermal profile is reached, the middle and lower crust are greatly weakened due to high temperatures and anatectic conditions, thus setting the stage for gravitational collapse, exhumation and isothermal decompression after the onset of plutonism. Near-isothermal conditions in the middle and lower crust result from the thermal buffering effect of dehydration melting reactions that, in part, control the shape of the geotherm.     

The Nonprofit Response to the Migration Crisis: Systems-Theoretic Reflections on the Austrian and Slovak Experiences

The present paper discusses the response of the Austrian and Slovak nonprofits to the recent migration crisis. In both countries, nonprofits delivered crucial problem-solving contributions but faced serious challenges related to scaling up, capacity building, and improving coordination. Drawing on the Luhmannian systems-theoretic approach, the paper argues that these challenges gave a boost to the systemic identity of nonprofits. Triggered by the substantial inflows of public money, the systemic identity explains why nonprofits can successfully operate in the polarized societal environment and develop unique expertise which is valuable to the public sector. At the same time, the systemic identity lowers the responsiveness of nonprofits to the societal environment. The major policy implication is that this responsiveness has to be continually improved through rational discourses and stakeholder dialogues.     

Dynamics of ostracod populations from shallow lakes of Patagonia: life history insights

Wetlands are one of the most valuable natural resources, providing a number of ecosystem services and socio-economic values. Small ponds sustain a rich aquatic biodiversity and because of their short hydrological regimen and small size are excellent environments for population studies of microcrustaceans such as ostracods. This study describes the population dynamics of the Ostracoda fauna in three temporary shallow lakes during one hydroperiod in Argentine Patagonia. Three cosmopolitan species were determined: Cypris pubera, Tonnacypris lutaria and Eucypris virens. Among them, T. lutaria is here reported for the first time from the Neotropical region. Multivariate ordination techniques were used to examine the relationships among environmental variables and ostracod density on each sampling site. High values of conductivity, absorption at 320 nm (as a measure of dissolved organic matter), dissolved oxygen concentration, temperature and chlorophyll a concentration correlated positively with ostracod density. All the populations studied reproduced parthenogenetically, and the life cycles of E.virens and C. pubera were followed in detail by weekly sampling of their populations. The former displayed continuous reproduction, whereas the latter showed a multivoltine strategy. The life history of C. pubera was affected by the seasonality of the habitat. The development rate correlated positively with water temperature; conductivity and temperature had a positive effect on adult size in C. pubera, while conductivity had a negative effect on adult size in E. virens. In this study, we present the first data set on the development and life history of ostracods in Patagonian freshwater environments. However, several questions remain and encourage us to further investigate the relative importance of ostracods in food webs, as well as the importance of inter-specific interactions between ostracods and other taxa.     

Tubulin pools in human erythrocytes: altered distribution in hypertensive patients affects Na<Superscript>+</Superscript>, K<Superscript>+</Superscript>-ATPase activity

The presence of tubulin in human erythrocytes was demonstrated using five different antibodies. Tubulin was distributed among three operationally distinguishable pools: membrane, sedimentable structure and soluble fraction. It is known that in erythrocytes from hypertensive subjects (HS), the Na⁺, K⁺-ATPase (NKA) activity is partially inhibited as compared with erythrocytes from normal subjects (NS). In erythrocytes from HS the membrane tubulin pool is increased by ~150%. NKA was found to be forming a complex with acetylated tubulin that results in inhibition of enzymes. This complex was also increased in erythrocytes from HS. Treatment of erythrocytes from HS with nocodazol caused a decrease of acetylated tubulin in the membrane and stimulation of NKA activity, whereas taxol treatment on erythrocytes from NS had the opposite effect. These results suggest that, in erythrocytes from HS, tubulin was translocated to the membrane, where it associated with NKA with the consequent enzyme inhibition.     

Changes in plant community composition lag behind climate warming in lowland forests

Climate change is driving latitudinal and altitudinal shifts in species distribution worldwide, leading to novel species assemblages. Lags between these biotic responses and contemporary climate changes have been reported for plants and animals. Theoretically, the magnitude of these lags should be greatest in lowland areas, where the velocity of climate change is expected to be much greater than that in highland areas. We compared temperature trends to temperatures reconstructed from plant assemblages (observed in 76,634 surveys) over a 44-year period in France (1965-2008). Here we report that forest plant communities had responded to 0.54 °C of the effective increase of 1.07 °C in highland areas (500-2,600 m above sea level), while they had responded to only 0.02 °C of the 1.11 °C warming trend in lowland areas. There was a larger temperature lag (by 3.1 times) between the climate and plant community composition in lowland forests than in highland forests. The explanation of such disparity lies in the following properties of lowland, as compared to highland, forests: the higher proportion of species with greater ability for local persistence as the climate warms, the reduced opportunity for short-distance escapes, and the greater habitat fragmentation. Although mountains are currently considered to be among the ecosystems most threatened by climate change (owing to mountaintop extinction), the current inertia of plant communities in lowland forests should also be noted, as it could lead to lowland biotic attrition.     

Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase

Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients.     

IT Diffusion,Implementation and Assimilation in Micro-Businesses – an Exploratory Study Based on a Process Approach

An important limitation of the management information systems (MIS) literature concerns the lack of a process model to understand how a system is assimilated by the organization. We seek to contribute to this topic through studying ERP adoption in two Chilean restaurants. In this paper is proposed that adoption occurs as a process composed of four stages and, therefore, it is presented findings from three of them. We used action-research (AR) as a methodological framework. Two AR cycles were performed in each case. Qualitative data was collected from the field through video recording, interviews, observation and social network analysis. Analysis data was analyzed by comparing results within-cases and between-cases. Three conclusions were reached: (1) during the implementation, a user-system negotiation cycle occurs; (2) after assimilating, the system must be constantly confirmed, otherwise can be abandoned; (3) speed of assimilation by group users depends of degree of influence in the social group of early adopters. Interestingly, an innovative micro-business owner could become a barrier to successful assimilation of a system. Findings introduce a dissenting view to most studies that have found that involvement of management is always beneficial to the success of a technology project. Our findings show involvement of owner impacts a successful adoption, but this impact is not because that person is the owner, but because of their degree of influence on the social group. Conclusions of this study will be of interest to micro, small and medium-business owners because it shows the value of social structure of the organization as a determinant of the success of a technological project.