Effect of breed of cow and calf on recorded milk yield in a dairy ranching herd in Costa Rica

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Co-transport-induced instability of membrane voltage in tip-growing cells

A salient feature of stationary patterns in tip-growing cells is the key role played by the symports and antiports, membrane proteins that translocate two ionic species at the same time. It is shown that these co-transporters destabilize generically the membrane voltage if the two translocated ions diffuse differently and carry a charge of opposite (same) sign for symports (antiports). Orders of magnitude obtained for the time and lengthscale are in agreement with experiments. A weakly nonlinear analysis characterizes the bifurcation

Nonparametric relevance-shifted multiple testing procedures for the analysis of high-dimensional multivariate data with small sample sizes

<p>Abstract</p> <p>Background</p> <p>In many research areas it is necessary to find differences between treatment groups with several variables. For example, studies of microarray data seek to find a significant difference in location parameters from zero or one for ratios thereof for each variable. However, in some studies a significant deviation of the difference in locations from zero (or 1 in terms of the ratio) is biologically meaningless. A relevant difference or ratio is sought in such cases.</p> <p>Results</p> <p>This article addresses the use of relevance-shifted tests on ratios for a multivariate parallel two-sample group design. Two empirical procedures are proposed which embed the relevance-shifted test on ratios. As both procedures test a hypothesis for each variable, the resulting multiple testing problem has to be considered. Hence, the procedures include a multiplicity correction. Both procedures are extensions of available procedures for point null hypotheses achieving exact control of the familywise error rate. Whereas the shift of the null hypothesis alone would give straight-forward solutions, the problems that are the reason for the empirical considerations discussed here arise by the fact that the shift is considered in both directions and the whole parameter space in between these two limits has to be accepted as null hypothesis.</p> <p>Conclusion</p> <p>The first algorithm to be discussed uses a permutation algorithm, and is appropriate for designs with a moderately large number of observations. However, many experiments have limited sample sizes. Then the second procedure might be more appropriate, where multiplicity is corrected according to a concept of data-driven order of hypotheses.</p

Guiding cities under increased droughts: The limits to sustainable urban futures

Climate change is likely to increase droughts. The vulnerability of cities to droughts is increasing worldwide. Policy responses from cities to droughts lack consideration of long-term climatic and socio-economic scenarios, and focus on short-term emergency actions that disregard sustainability in the connected regional and river basin systems. We aim to explore the dynamics of the water-energy-land nexus in urban systems suffering increased climate change-related droughts, and their implications for sustainability. We complement a case study with a literature review providing cross-regional insights, and detail pervasive knowledge, policy and ambition gaps in the interaction between cities and droughts. We show that water availability with low emissions, without compromising ecosystems and with low costs to society, poses a local-scale limit to sustainable urban growth, a new concept delineating the limits to growth in cities. We conclude that urban and river basin planners need to institutionalize transparency and cross-sectoral integration in multi-sector partnerships, to consider long-term land use planning together with water and energy, and to apply integrated climate services to cities. Our study reveals the importance of including land, water and energy in long-term urban planning, and to connect them with the county, region, river basin and global scales. © 2021 The Author(s)The authors would like to express their gratitude for limited contributions, comments and discussions that helped to improve the manuscript to Muhamad Bahri, Jörg Cortekar, Mirabela Marin, Serban Octavian Davidescu, Iñaki Torres Cobián, and to two anonymous reviewers that helped to substantially improve the manuscript. Valuable feedback obtained in two conference sessions co‑lead by some of the authors (at Adaptation Futures 2018 in Cape Town, and at the 4th European Climate Change Adaptation conference, in Lisbon in 2019) is acknowledged. The authors acknowledge financial support from the project CLISWELN funded by ERA4CS. ERA4CS is an ERA-NET initiated by JPI Climate, and CLISWELN is funded by BMBF (DE), UEFISCDI (RO), BMBWF and FFG (AT), and MINECO (ES), with co-funding from the European Union (Grant 690462 ). This paper and the content included in it do not represent the opinion of the European Union, and the European Union is not responsible for any use that might be made of its content. Marta OlazabalThe authors would like to express their gratitude for limited contributions, comments and discussions that helped to improve the manuscript to Muhamad Bahri, Jörg Cortekar, Mirabela Marin, Serban Octavian Davidescu, Iñaki Torres Cobián, and to two anonymous reviewers that helped to substantially improve the manuscript. Valuable feedback obtained in two conference sessions co‑lead by some of the authors (at Adaptation Futures 2018 in Cape Town, and at the 4th European Climate Change Adaptation conference, in Lisbon in 2019) is acknowledged. The authors acknowledge financial support from the project CLISWELN funded by ERA4CS. ERA4CS is an ERA-NET initiated by JPI Climate, and CLISWELN is funded by BMBF (DE), UEFISCDI (RO), BMBWF and FFG (AT), and MINECO (ES), with co-funding from the European Union (Grant 690462 ). This paper and the content included in it do not represent the opinion of the European Union, and the European Union is not responsible for any use that might be made of its content. Marta Olazaba

Phosphatidylinositol 3-kinase activity and asymmetrical accumulation of F-actin are necessary for establishment of cell polarity in the early development of monospores from the marine red alga Porphyra yezoensis

The polarized distribution of F-actin is important in providing the driving force for directional migration in mammalian leukocytes and Dictyostelium cells, in which compartmentation of phosphatidylinositol 3-kinase (PI3K) and phosphatidylinositol phosphatase is critical for the establishment of cell polarity. Since monospores from the red alga Porphyra yezoensis are a real example of migrating plant cells, the involvement of the cytoskeleton and PI3K was investigated during their early development. Our results indicate that the asymmetrical localization of F-actin at the leading edge is fixed by the establishment of the anterior–posterior axis in migrating monospores, which is PI3K-dependent and protein synthesis-independent. After migration, monospores adhere to the substratum and then become upright, developing into multicellular thalli via the establishment of the apical–basal axis. In this process, F-actin usually accumulates at the bottom of the basal cell and development after migration requires new protein synthesis. These findings suggest that the establishment of anterior–posterior and apical–basal axes are differentially regulated during the early development of monospores. Our results also indicate that PI3K-dependent F-actin asymmetry is evolutionally conserved in relation to the establishment of cell polarity in migrating eukaryotic cells

Large-scale risk assessment on snow avalanche hazard in alpine regions

Snow avalanches are recurring natural hazards that affect the population and infrastructure in mountainous regions, such as in the recent avalanche winters of 2018 and 2019, when considerable damage was caused by avalanches throughout the Alps. Hazard decision makers need detailed information on the spatial distribution of avalanche hazards and risks to prioritize and apply appropriate adaptation strategies and mitigation measures and thus minimize impacts. Here, we present a novel risk assessment approach for assessing the spatial distribution of avalanche risk by combining large-scale hazard mapping with a state-of-the-art risk assessment tool, where risk is understood as the product of hazard, exposure and vulnerability. Hazard disposition is modeled using the large-scale hazard indication mapping method RAMMS::LSHIM (Rapid Mass Movement Simulation::Large-Scale Hazard Indication Mapping), and risks are assessed using the probabilistic Python-based risk assessment platform CLIMADA, developed at ETH Zürich. Avalanche hazard mapping for scenarios with a 30-, 100- and 300-year return period is based on a high-resolution terrain model, 3 d snow depth increase, automatically determined potential release areas and protection forest data. Avalanche hazard for 40 000 individual snow avalanches is expressed as avalanche intensity, measured as pressure. Exposure is represented by a detailed building layer indicating the spatial distribution of monetary assets. The vulnerability of buildings is defined by damage functions based on the software EconoMe, which is in operational use in Switzerland. The outputs of the hazard, exposure and vulnerability analyses are combined to quantify the risk in spatially explicit risk maps. The risk considers the probability and intensity of snow avalanche occurrence, as well as the concentration of vulnerable, exposed buildings. Uncertainty and sensitivity analyses were performed to capture inherent variability in the input parameters. This new risk assessment approach allows us to quantify avalanche risk over large areas and results in maps displaying the spatial distribution of risk at specific locations. Large-scale risk maps can assist decision makers in identifying areas where avalanche hazard mitigation and/or adaption is needed.</p

Local Suppression of T Cell Responses by Arginase-Induced L-Arginine Depletion in Nonhealing Leishmaniasis

The balance between T helper (Th) 1 and Th2 cell responses is a major determinant of the outcome of experimental leishmaniasis, but polarized Th1 or Th2 responses are not sufficient to account for healing or nonhealing. Here we show that high arginase activity, a hallmark of nonhealing disease, is primarily expressed locally at the site of pathology. The high arginase activity causes local depletion of L-arginine, which impairs the capacity of T cells in the lesion to proliferate and to produce interferon-γ, while T cells in the local draining lymph nodes respond normally. Healing, induced by chemotherapy, resulted in control of arginase activity and reversal of local immunosuppression. Moreover, competitive inhibition of arginase as well as supplementation with L-arginine restored T cell effector functions and reduced pathology and parasite growth at the site of lesions. These results demonstrate that in nonhealing leishmaniasis, arginase-induced L-arginine depletion results in impaired T cell responses. Our results identify a novel mechanism in leishmaniasis that contributes to the failure to heal persistent lesions and suggest new approaches to therapy

Age-Related Alteration of Arginase Activity Impacts on Severity of Leishmaniasis

It is well documented that ageing alters many aspects of immune responses; however, a causal relation between impaired immune functions in ageing individuals and the response to infection has not been established. Experimental leishmaniasis is an excellent model to analyse protective and pathological immune responses. Leishmania parasites are obligate intracellular pathogens and invade mainly macrophages, which have dual function: they can kill the parasites or promote their growth. We have recently shown that arginase, an enzyme induced in infected macrophages, is a key factor for parasite survival. Here, we show that ageing reduces the expression levels of arginase in macrophages, resulting in more efficient control of parasite growth. Our results suggest that age-related differences in the metabolism of arginase in macrophages might contribute to the higher susceptibility of children to leishmaniasis

Local Increase of Arginase Activity in Lesions of Patients with Cutaneous Leishmaniasis in Ethiopia

The leishmaniases are a complex of diseases caused by Leishmania parasites. Currently, the diseases affect an estimated 12 million people in 88 countries, and approximately 350 million more people are at risk. The leishmaniases belong to the most neglected tropical diseases, affecting the poorest populations, for whom access to diagnosis and effective treatment are often not available. Leishmania parasites infect cells of the immune system called macrophages, which have the capacity to eliminate the intracellular parasites when they receive the appropriate signals from other cells of the immune system. In nonhealing persistent leishmaniasis, lymphocytes are unable to transmit the signals to macrophages required to kill the intracellular parasites. The local upregulation of the enzyme arginase has been shown to impair lymphocyte effector functions at the site of pathology. In this study, we tested the activity of this enzyme in skin lesions of patients presenting with localized cutaneous leishmaniasis. Our results show that arginase is highly upregulated in these lesions. This increase in arginase activity coincides with lower expression of a signalling molecule in lymphocytes, which is essential for efficient activation of these cells. These results suggest that increased arginase expression in the localized cutaneous lesions might contribute to persistent disease in patients presenting with cutaneous leishmaniasis