@article{14938, abstract = {High elevation headwater catchments are complex hydrological systems that seasonally buffer water and release it in the form of snow and ice melt, modulating downstream runoff regimes and water availability. In High Mountain Asia (HMA), where a wide range of climates from semi-arid to monsoonal exist, the importance of the cryospheric contributions to the water budget varies with the amount and seasonal distribution of precipitation. Losses due to evapotranspiration and sublimation are to date largely unquantified components of the water budget in such catchments, although they can be comparable in magnitude to glacier melt contributions to streamflow. 
Here, we simulate the hydrology of three high elevation headwater catchments in distinct climates in HMA over 10 years using an ecohydrological model geared towards high-mountain areas including snow and glaciers, forced with reanalysis data. 
Our results show that evapotranspiration and sublimation together are most important at the semi-arid site, Kyzylsu, on the northernmost slopes of the Pamir mountain range. Here, the evaporative loss amounts to 28% of the water throughput, which we define as the total water added to, or removed from the water balance within a year. In comparison, evaporative losses are 19% at the Central Himalayan site Langtang and 13% at the wettest site, 24K, on the Southeastern Tibetan Plateau. At the three sites, respectively, sublimation removes 15%, 13% and 6% of snowfall, while evapotranspiration removes the equivalent of 76%, 28% and 19% of rainfall. In absolute terms, and across a comparable elevation range, the highest ET flux is 413 mm yr-1 at 24K, while the highest sublimation flux is 91 mm yr-1 at Kyzylsu. During warm and dry years, glacier melt was found to only partially compensate for the annual supply deficit.}, author = {Fugger, Stefan and Shaw, Thomas and Jouberton, Achille and Miles, Evan and Buri, Pascal and McCarthy, Michael and Fyffe, Catriona Louise and Fatichi, Simone and Kneib, Marin and Molnar, Peter and Pellicciotti, Francesca}, issn = {1748-9326}, journal = {Environmental Research Letters}, keywords = {Public Health, Environmental and Occupational Health, General Environmental Science, Renewable Energy, Sustainability and the Environment}, publisher = {IOP Publishing}, title = {{Hydrological regimes and evaporative flux partitioning at the climatic ends of High Mountain Asia}}, doi = {10.1088/1748-9326/ad25a0}, year = {2024}, } @inproceedings{14862, author = {Rella, Simon and Kulikova, Y and Minnegalieva, Aygul and Kondrashov, Fyodor}, booktitle = {European Journal of Public Health}, issn = {1464-360X}, keywords = {Public Health, Environmental and Occupational Health}, number = {Supplement_2}, publisher = {Oxford University Press}, title = {{Complex vaccination strategies prevent the emergence of vaccine resistance}}, doi = {10.1093/eurpub/ckad160.597}, volume = {33}, year = {2023}, } @article{11460, abstract = {Background: Proper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous work demonstrated focal neuronal migration defects in mice carrying loss-of-function alleles of the recognized autism risk gene WDFY3. However, the cellular origins of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide critical insight into WDFY3-dependent disease pathology. Methods: Here, in an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic analysis with double markers (MADM). MADM technology enabled us to genetically distinctly track and phenotypically analyze mutant and wild-type cells concomitantly in vivo using immunofluorescent techniques. Results: We revealed a cell autonomous requirement of WDFY3 for accurate laminar positioning of cortical projection neurons and elimination of mispositioned cells during early postnatal life. In addition, we identified significant deviations in dendritic arborization, as well as synaptic density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant neurons in Wdfy3-MADM reporter mice at postnatal stages. Limitations: While Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD pathology that remain inaccessible to investigation in humans, like most animal models, they do not a perfectly replicate all aspects of human ASD biology. The lack of human data makes it indeterminate whether morphological deviations described here apply to ASD patients or some of the other neurodevelopmental conditions associated with WDFY3 mutation. Conclusions: Our genetic approach revealed several cell autonomous requirements of WDFY3 in neuronal development that could underlie the pathogenic mechanisms of WDFY3-related neurodevelopmental conditions. The results are also consistent with findings in other ASD animal models and patients and suggest an important role for WDFY3 in regulating neuronal function and interconnectivity in postnatal life.}, author = {Schaaf, Zachary A. and Tat, Lyvin and Cannizzaro, Noemi and Green, Ralph and Rülicke, Thomas and Hippenmeyer, Simon and Zarbalis, Konstantinos S.}, issn = {2040-2392}, journal = {Molecular Autism}, keywords = {Psychiatry and Mental health, Developmental Biology, Developmental Neuroscience, Molecular Biology}, publisher = {Springer Nature}, title = {{WDFY3 mutation alters laminar position and morphology of cortical neurons}}, doi = {10.1186/s13229-022-00508-3}, volume = {13}, year = {2022}, } @article{12051, abstract = {Transcription of the ribosomal RNA precursor by RNA polymerase (Pol) I is a major determinant of cellular growth, and dysregulation is observed in many cancer types. Here, we present the purification of human Pol I from cells carrying a genomic GFP fusion on the largest subunit allowing the structural and functional analysis of the enzyme across species. In contrast to yeast, human Pol I carries a single-subunit stalk, and in vitro transcription indicates a reduced proofreading activity. Determination of the human Pol I cryo-EM reconstruction in a close-to-native state rationalizes the effects of disease-associated mutations and uncovers an additional domain that is built into the sequence of Pol I subunit RPA1. This “dock II” domain resembles a truncated HMG box incapable of DNA binding which may serve as a downstream transcription factor–binding platform in metazoans. Biochemical analysis, in situ modelling, and ChIP data indicate that Topoisomerase 2a can be recruited to Pol I via the domain and cooperates with the HMG box domain–containing factor UBF. These adaptations of the metazoan Pol I transcription system may allow efficient release of positive DNA supercoils accumulating downstream of the transcription bubble.}, author = {Daiß, Julia L and Pilsl, Michael and Straub, Kristina and Bleckmann, Andrea and Höcherl, Mona and Heiss, Florian B and Abascal-Palacios, Guillermo and Ramsay, Ewan P and Tluckova, Katarina and Mars, Jean-Clement and Fürtges, Torben and Bruckmann, Astrid and Rudack, Till and Bernecky, Carrie A and Lamour, Valérie and Panov, Konstantin and Vannini, Alessandro and Moss, Tom and Engel, Christoph}, issn = {2575-1077}, journal = {Life Science Alliance}, keywords = {Health, Toxicology and Mutagenesis, Plant Science, Biochemistry, Genetics and Molecular Biology (miscellaneous), Ecology}, number = {11}, publisher = {Life Science Alliance}, title = {{The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans}}, doi = {10.26508/lsa.202201568}, volume = {5}, year = {2022}, } @article{12576, abstract = {Glacier health across High Mountain Asia (HMA) is highly heterogeneous and strongly governed by regional climate, which is variably influenced by monsoon dynamics and the westerlies. We explore four decades of glacier energy and mass balance at three climatically distinct sites across HMA by utilising a detailed land surface model driven by bias-corrected Weather Research and Forecasting meteorological forcing. All three glaciers have experienced long-term mass losses (ranging from −0.04 ± 0.09 to −0.59 ± 0.20 m w.e. a−1) consistent with widespread warming across the region. However, complex and contrasting responses of glacier energy and mass balance to the patterns of the Indian Summer Monsoon were evident, largely driven by the role snowfall timing, amount and phase. A later monsoon onset generates less total snowfall to the glacier in the southeastern Tibetan Plateau during May–June, augmenting net shortwave radiation and affecting annual mass balance (−0.5 m w.e. on average compared to early onset years). Conversely, timing of the monsoon’s arrival has limited impact for the Nepalese Himalaya which is more strongly governed by the temperature and snowfall amount during the core monsoon season. In the arid central Tibetan Plateau, a later monsoon arrival results in a 40 mm (58%) increase of May–June snowfall on average compared to early onset years, likely driven by the greater interaction of westerly storm events. Meanwhile, a late monsoon cessation at this site sees an average 200 mm (192%) increase in late summer precipitation due to monsoonal storms. A trend towards weaker intensity monsoon conditions in recent decades, combined with long-term warming patterns, has produced predominantly negative glacier mass balances for all sites (up to 1 m w.e. more mass loss in the Nepalese Himalaya compared to strong monsoon intensity years) but sub-regional variability in monsoon timing can additionally complicate this response.}, author = {Shaw, T E and Miles, E S and Chen, D and Jouberton, A and Kneib, M and Fugger, S and Ou, T and Lai, H-W and Fujita, K and Yang, W and Fatichi, S and Pellicciotti, Francesca}, issn = {1748-9326}, journal = {Environmental Research Letters}, keywords = {Public Health, Environmental and Occupational Health, General Environmental Science, Renewable Energy, Sustainability and the Environment}, number = {10}, publisher = {IOP Publishing}, title = {{Multi-decadal monsoon characteristics and glacier response in High Mountain Asia}}, doi = {10.1088/1748-9326/ac9008}, volume = {17}, year = {2022}, } @article{12582, abstract = {Supraglacial debris covers 7% of mountain glacier area globally and generally reduces glacier surface melt. Enhanced energy absorption at ice cliffs and supraglacial ponds scattered across the debris surface leads these features to contribute disproportionately to glacier-wide ablation. However, the degree to which cliffs and ponds actually increase melt rates remains unclear, as these features have only been studied in a detailed manner for selected locations, almost exclusively in High Mountain Asia. In this study we model the surface energy balance for debris-covered ice, ice cliffs, and supraglacial ponds with a set of automatic weather station records representing the global prevalence of debris-covered glacier ice. We generate 5000 random sets of values for physical parameters using probability distributions derived from literature, which we use to investigate relative melt rates and to isolate the melt responses of debris, cliffs and ponds to the site-specific meteorological forcing. Modelled sub-debris melt rates are primarily controlled by debris thickness and thermal conductivity. At a reference thickness of 0.1 m, sub-debris melt rates vary considerably, differing by up to a factor of four between sites, mainly attributable to air temperature differences. We find that melt rates for ice cliffs are consistently 2–3× the melt rate for clean glacier ice, but this melt enhancement decays with increasing clean ice melt rates. Energy absorption at supraglacial ponds is dominated by latent heat exchange and is therefore highly sensitive to wind speed and relative humidity, but is generally less than for clean ice. Our results provide reference melt enhancement factors for melt modelling of debris-covered glacier sites, globally, while highlighting the need for direct measurement of debris-covered glacier surface characteristics, physical parameters, and local meteorological conditions at a variety of sites around the world.}, author = {Miles, E S and Steiner, J F and Buri, P and Immerzeel, W W and Pellicciotti, Francesca}, issn = {1748-9326}, journal = {Environmental Research Letters}, keywords = {Public Health, Environmental and Occupational Health, General Environmental Science, Renewable Energy, Sustainability and the Environment}, number = {6}, publisher = {IOP Publishing}, title = {{Controls on the relative melt rates of debris-covered glacier surfaces}}, doi = {10.1088/1748-9326/ac6966}, volume = {17}, year = {2022}, } @article{11058, abstract = {Nucleoporin 93 (Nup93) expression inversely correlates with the survival of triple-negative breast cancer patients. However, our knowledge of Nup93 function in breast cancer besides its role as structural component of the nuclear pore complex is not understood. Combination of functional assays and genetic analyses suggested that chromatin interaction of Nup93 partially modulates the expression of genes associated with actin cytoskeleton remodeling and epithelial to mesenchymal transition, resulting in impaired invasion of triple-negative, claudin-low breast cancer cells. Nup93 depletion induced stress fiber formation associated with reduced cell migration/proliferation and impaired expression of mesenchymal-like genes. Silencing LIMCH1, a gene responsible for actin cytoskeleton remodeling and up-regulated upon Nup93 depletion, partially restored the invasive phenotype of cancer cells. Loss of Nup93 led to significant defects in tumor establishment/propagation in vivo, whereas patient samples revealed that high Nup93 and low LIMCH1 expression correlate with late tumor stage. Our approach identified Nup93 as contributor of triple-negative, claudin-low breast cancer cell invasion and paves the way to study the role of nuclear envelope proteins during breast cancer tumorigenesis.}, author = {Bersini, Simone and Lytle, Nikki K and Schulte, Roberta and Huang, Ling and Wahl, Geoffrey M and HETZER, Martin W}, issn = {2575-1077}, journal = {Life Science Alliance}, keywords = {Health, Toxicology and Mutagenesis, Plant Science, Biochemistry, Genetics and Molecular Biology (miscellaneous), Ecology}, number = {1}, publisher = {Life Science Alliance}, title = {{Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling}}, doi = {10.26508/lsa.201900623}, volume = {3}, year = {2020}, } @article{9128, abstract = {This paper reviews recent important advances in our understanding of the response of precipitation extremes to warming from theory and from idealized cloud-resolving simulations. A theoretical scaling for precipitation extremes has been proposed and refined in the past decades, allowing to address separately the contributions from the thermodynamics, the dynamics and the microphysics. Theoretical constraints, as well as remaining uncertainties, associated with each of these three contributions to precipitation extremes, are discussed. Notably, although to leading order precipitation extremes seem to follow the thermodynamic theoretical expectation in idealized simulations, considerable uncertainty remains regarding the response of the dynamics and of the microphysics to warming, and considerable departure from this theoretical expectation is found in observations and in more realistic simulations. We also emphasize key outstanding questions, in particular the response of mesoscale convective organization to warming. Observations suggest that extreme rainfall often comes from an organized system in very moist environments. Improved understanding of the physical processes behind convective organization is needed in order to achieve accurate extreme rainfall prediction in our current, and in a warming climate.}, author = {Muller, Caroline J and Takayabu, Yukari}, issn = {1748-9326}, journal = {Environmental Research Letters}, keywords = {Renewable Energy, Sustainability and the Environment, Public Health, Environmental and Occupational Health, General Environmental Science}, number = {3}, publisher = {IOP Publishing}, title = {{Response of precipitation extremes to warming: What have we learned from theory and idealized cloud-resolving simulations, and what remains to be learned?}}, doi = {10.1088/1748-9326/ab7130}, volume = {15}, year = {2020}, } @article{10815, abstract = {In the last several decades, developmental biology has clarified the molecular mechanisms of embryogenesis and organogenesis. In particular, it has demonstrated that the “tool-kit genes” essential for regulating developmental processes are not only highly conserved among species, but are also used as systems at various times and places in an organism to control distinct developmental events. Therefore, mutations in many of these tool-kit genes may cause congenital diseases involving morphological abnormalities. This link between genes and abnormal morphological phenotypes underscores the importance of understanding how cells behave and contribute to morphogenesis as a result of gene function. Recent improvements in live imaging and in quantitative analyses of cellular dynamics will advance our understanding of the cellular pathogenesis of congenital diseases associated with aberrant morphologies. In these studies, it is critical to select an appropriate model organism for the particular phenomenon of interest.}, author = {Hashimoto, Masakazu and Morita, Hitoshi and Ueno, Naoto}, issn = {0914-3505}, journal = {Congenital Anomalies}, keywords = {Developmental Biology, Embryology, General Medicine, Pediatrics, Perinatology, and Child Health}, number = {1}, pages = {1--7}, publisher = {Wiley}, title = {{Molecular and cellular mechanisms of development underlying congenital diseases}}, doi = {10.1111/cga.12039}, volume = {54}, year = {2014}, } @article{9146, abstract = {The factors governing the rate of change in the amount of atmospheric water vapor are analyzed in simulations of climate change. The global-mean amount of water vapor is estimated to increase at a differential rate of 7.3% K − 1 with respect to global-mean surface air temperature in the multi-model mean. Larger rates of change result if the fractional change is evaluated over a finite change in temperature (e.g., 8.2% K − 1 for a 3 K warming), and rates of change of zonal-mean column water vapor range from 6 to 12% K − 1 depending on latitude. Clausius–Clapeyron scaling is directly evaluated using an invariant distribution of monthly-mean relative humidity, giving a rate of 7.4% K − 1 for global-mean water vapor. There are deviations from Clausius–Clapeyron scaling of zonal-mean column water vapor in the tropics and mid-latitudes, but they largely cancel in the global mean. A purely thermodynamic scaling based on a saturated troposphere gives a higher global rate of 7.9% K − 1. Surface specific humidity increases at a rate of 5.7% K − 1, considerably lower than the rate for global-mean water vapor. Surface specific humidity closely follows Clausius–Clapeyron scaling over ocean. But there are widespread decreases in surface relative humidity over land (by more than 1% K − 1 in many regions), and it is argued that decreases of this magnitude could result from the land/ocean contrast in surface warming.}, author = {O’Gorman, P A and Muller, Caroline J}, issn = {1748-9326}, journal = {Environmental Research Letters}, keywords = {Renewable Energy, Sustainability and the Environment, Public Health, Environmental and Occupational Health, General Environmental Science}, number = {2}, publisher = {IOP Publishing}, title = {{How closely do changes in surface and column water vapor follow Clausius–Clapeyron scaling in climate change simulations?}}, doi = {10.1088/1748-9326/5/2/025207}, volume = {5}, year = {2010}, }