Restriction of DNA replication to the reductive phase of the metabolic cycle protects genome integrity

When prototrophic yeast cells are cultured under nutrient-limited conditions that mimic growth in the wild, rather than in the high-glucose solutions used in most laboratory studies, they exhibit a robustly periodic metabolic cycle. Over a cycle of 4 to 5 hours, yeast cells rhythmically alternate between glycolysis and respiration. The cell division cycle is tightly constrained to the reductive phase of this yeast metabolic cycle, with DNA replication taking place only during the glycolytic phase. We show that cell cycle mutants impeded in metabolic cycle-directed restriction of cell division exhibit substantial increases in spontaneous mutation rate. In addition, disruption of the gene encoding a DNA checkpoint kinase that couples the cell division cycle to the circadian cycle abolishes synchrony of the metabolic and cell cycles. Thus, circadian, metabolic, and cell division cycles may be coordinated similarly as an evolutionarily conserved means of preserving genome integrity.     

Cultural styles of participation in farmers’ discussions of seasonal climate forecasts in Uganda

Climate change is confronting African farmers with growing uncertainties. Advances in seasonal climate predictions offer potential for assisting farmers in dealing with climate risk. Experimental cases of forecast dissemination to African rural communities suggest that participatory approaches can facilitate understanding and use of uncertain climate information. But few of these studies integrate critical reflections on participation that have emerged in the last decade which reveal how participatory approaches can miss social dynamics of power at the community level and in the broader context. Furthermore, neither climate application research nor theoretical critiques of participation fully examine the culturally constructed nature of participation. Drawing on sociolinguistic analysis, in-depth interviews, and ethnographic observation, this paper examines how Ugandan farmers engage in participation in the context of discussions of seasonal climate forecasts. Forecasts were presented to farmers groups whose members were then asked to discuss the forecast among themselves. In doing so, groups sought to develop a common understanding of the forecast and consensual plans for response strategies. Focusing on one particular group meeting as an example, we show how different cultural styles of participation affect the interpretation of the forecast and the formulation of response strategies. Group interaction is shown to be mostly structured around two styles of participation. On the one hand, there is the “Western” style advocated by NGOs and the government, which centers on ensuring that all individuals who are present have opportunities to speak during discussion and to vote on group decisions. On the other hand, a “Kiganda” style of participation emphasizes the importance of affirming ties to a collectivity, respect for social hierarchy, deployment of good manners, and consensus building. The case study illuminates how the performance of different styles of participation is grounded in localized frameworks of language and culture but also draw on political and policy discourses at the national level. Although a cultural high value on consensus may work in favor of prominent members, the availability of multiple styles of participation also enables group members to exercise their agency in positive ways. Attention to the interplay of different styles of participation throws light on the subtle social processes that shape how knowledge is assessed, which sources are trusted, which and whose interpretations prevail, what options are deemed viable, how costs and benefits are calculated, and whose resources are mobilized in the effort to reduce vulnerability to climate risk. These are key questions for an assessment of the role of boundary organizations, such as farmer associations, in the communication and application of climate forecasts in agriculture.     

Intestinal stem cell replacement follows a pattern of neutral drift

With the capacity for rapid self-renewal and regeneration, the intestinal epithelium is stereotypical of stem cell-supported tissues. Yet the pattern of stem cell turnover remains in question. Applying analytical methods from population dynamics and statistical physics to an inducible genetic labeling system, we showed that clone size distributions conform to a distinctive scaling behavior at short times. This result demonstrates that intestinal stem cells form an equipotent population in which the loss of a stem cell is compensated by the multiplication of a neighbor, leading to neutral drift dynamics in which clones expand and contract at random until they either take over the crypt or they are lost. Combined with long-term clonal fate data, we show that the rate of stem cell replacement is comparable to the cell division rate, implying that neutral drift and symmetrical cell divisions are central to stem cell homeostasis.     

Energetics of hydrogen bond network rearrangements in liquid water

A strong temperature dependence of oxygen K-edge x-ray absorption fine structure features was observed for supercooled and normal liquid water droplets prepared from the breakup of a liquid microjet. Analysis of the data over the temperature range 251 to 288 kelvin (-22 degrees to +15 degrees C) yields a value of 1.5 +/- 0.5 kilocalories per mole for the average thermal energy required to effect an observable rearrangement between the fully coordinated ("ice-like") and distorted ("broken-donor") local hydrogen-bonding configurations responsible for the pre-edge and post-edge features, respectively. This energy equals the latent heat of melting of ice with hexagonal symmetry (ice Ih) and is consistent with the distribution of hydrogen bond strengths obtained for the "overstructured" ST2 model of water.     

Conserved eukaryotic fusogens can fuse viral envelopes to cells

Caenorhabditis elegans proteins AFF-1 and EFF-1 [C. elegans fusion family (CeFF) proteins] are essential for developmental cell-to-cell fusion and can merge insect cells. To study the structure and function of AFF-1, we constructed vesicular stomatitis virus (VSV) displaying AFF-1 on the viral envelope, substituting the native fusogen VSV glycoprotein. Electron microscopy and tomography revealed that AFF-1 formed distinct supercomplexes resembling pentameric and hexameric "flowers" on pseudoviruses. Viruses carrying AFF-1 infected mammalian cells only when CeFFs were on the target cell surface. Furthermore, we identified fusion family (FF) proteins within and beyond nematodes, and divergent members from the human parasitic nematode Trichinella spiralis and the chordate Branchiostoma floridae could also fuse mammalian cells. Thus, FF proteins are part of an ancient family of cellular fusogens that can promote fusion when expressed on a viral particle.     

Extracellular proteins limit the dispersal of biogenic nanoparticles

High-spatial-resolution secondary ion microprobe spectrometry, synchrotron radiation-based Fourier-transform infrared spectroscopy, and polyacrylamide gel analysis demonstrated the intimate association of proteins with spheroidal aggregates of biogenic zinc sulfide nanocrystals, an example of extracellular biomineralization. Experiments involving synthetic zinc sulfide nanoparticles and representative amino acids indicated a driving role for cysteine in rapid nanoparticle aggregation. These findings suggest that microbially derived extracellular proteins can limit the dispersal of nanoparticulate metal-bearing phases, such as the mineral products of bioremediation, that may otherwise be transported away from their source by subsurface fluid flow.     

Regulation of integrin adhesions by varying the density of substrate-bound epidermal growth factor

Substrates coated with specific bioactive ligands are important for tissue engineering, enabling the local presentation of extracellular stimulants at controlled positions and densities. In this study, we examined the cross-talk between integrin and epidermal growth factor (EGF) receptors following their interaction with surface-immobilized Arg-Gly-Asp (RGD) and EGF ligands, respectively. Surfaces of glass coverslips, modified with biotinylated silane-polyethylene glycol, were functionalized by either biotinylated RGD or EGF (or both) via the biotin-NeutrAvidin interaction. Fluorescent labeling of the adhering A431 epidermoid carcinoma cells for zyxin or actin indicated that EGF had a dual effect on focal adhesions (FA) and stress fibers: at low concentrations (0.1; 1 ng/ml), it stimulated their growth; whereas at higher concentrations, on surfaces with low to intermediate RGD densities, it induced their disassembly, leading to cell detachment. The EGF-dependent dissociation of FAs was, however, attenuated on higher RGD density surfaces. Simultaneous stimulation by both immobilized RGD and EGF suggest a strong synergy between integrin and EGFR signaling, in FA induction and cell spreading. A critical threshold level of EGF was required to induce significant variation in cell adhesion; beyond this critical density, the immobilized molecule had a considerably stronger effect on cell adhesion than did soluble EGF. The mechanisms underlying this synergy between the adhesion ligand and EGF are discussed.     

Modelling and mapping natural hazard regulating ecosystem services in Sapa,Lao Cai province,Vietnam

Land use change due to the development of agriculture and community-based tourism has resulted in an increase in natural hazards (e.g. erosion and landslides) that affect sustainability in the Sapa mountainous area in northern Vietnam. Natural hazard regulating ecosystem services have protected the local people from the destruction of their villages, goods and natural resources, especially in the rainy season. However, it is difficult to identify which kinds of anthropogenic constructions support a co-production of regulating services in human-influenced social–ecological systems and in which specific types of land use and land cover the supply of such services takes place, especially in heterogeneous mountainous areas. Therefore, this research attempts to (1) distinguish between the potential and actual use (flow) of natural hazard regulating ecosystem services and (2) understand how soil erosion and landslide regulating ecosystem services can contribute to a sustainable management of different ecosystems, especially in rice fields and forest areas. Two models (InVEST for soil erosion, Analytic Hierarchy Process for landslide analysis) were used to analyze and map the contributions of natural versus anthropogenic components for regulating natural hazards in Sapa. The results show the incoherent distribution of erosion regulating services and low capacities of landslide regulating services in areas that have seriously been affected by human activities, especially forestry and agricultural development. The contribution of rice ecosystems to soil erosion mitigation is higher than in the case of landslides. Nevertheless, one-third of the area of paddy fields in the case study area have “no” capacity to supply natural hazard regulating ecosystem services and should therefore be re-forested.