ALBERT

Beschreibung: The concept of cloud radiative forcing (CRF) is commonly applied to quantify the impact of clouds on the surface radiative energy budget (REB). In the Arctic, specific radiative interactions between microphysical and macrophysical properties of clouds and the surface strongly modify the warming or cooling effect of clouds, complicating the estimate of CRF obtained from observations or models. Clouds tend to increase the broadband surface albedo over snow or sea ice surfaces compared to cloud-free conditions. However, this effect is not adequately considered in the derivation of CRF in the Arctic so far. Therefore, we have quantified the effects caused by surface-albedo–cloud interactions over highly reflective snow or sea ice surfaces on the CRF using radiative transfer simulations and below-cloud airborne observations above the heterogeneous springtime marginal sea ice zone (MIZ) during the Arctic CLoud Observations Using airborne measurements during polar Day (ACLOUD) campaign. The impact of a modified surface albedo in the presence of clouds, as compared to cloud-free conditions, and its dependence on cloud optical thickness is found to be relevant for the estimation of the shortwave CRF. A method is proposed to consider this surface albedo effect on CRF estimates by continuously retrieving the cloud-free surface albedo from observations under cloudy conditions, using an available snow and ice albedo parameterization. Using ACLOUD data reveals that the estimated average shortwave cooling by clouds almost doubles over snow- and ice-covered surfaces (−62 W m−2 instead of −32 W m−2), if surface-albedo–cloud interactions are considered. As a result, the observed total (shortwave plus longwave) CRF shifted from a warming effect to an almost neutral one. Concerning the seasonal cycle of the surface albedo, it is demonstrated that this effect enhances shortwave cooling in periods when snow dominates the surface and potentially weakens the cooling by optically thin clouds during the summertime melting season. These findings suggest that the surface-albedo–cloud interaction should be considered in global climate models and in long-term studies to obtain a realistic estimate of the shortwave CRF to quantify the role of clouds in Arctic amplification.

Beschreibung: The evaluation of potential landslides in mountain areas is a very complex process. Currently, event understanding is scarce due to information limitations. Identifying the whole chain of events is not a straightforward task, and the impacts of mass-wasting processes depend on the conditions downstream of the origin. In this paper, we present an example that illustrates the complexities in the evaluation of the chain of events that may lead to a natural disaster. On 16 December 2017, a landslide occurred in the Yelcho mountain range (southern Chile). In that event, 7 million m3 of rocks and soil fell on the Yelcho glacier, depositing 2 million m3 on the glacier terminal, and the rest continued downstream, triggering a mudflow that hit Villa Santa Lucía in Chilean Patagonia and killing 22 people. The complex event was anticipated in the region by the National Geological and Mining Survey (Sernageomin in Spanish). However, the effects of the terrain characteristics along the run-out area were more significant than anticipated. In this work, we evaluate the conditions that enabled the mudflow that hit Villa Santa Lucía. We used the information generated by Sernageomin's professionals after the mudflow. We carried out geotechnical tests to characterize the soil. We simulated the mudflow using two hydrodynamic programs (r.avaflow and Flo-2D) that can handle the rheology of the water–soil mixture. Our results indicate that the soil is classified as volcanic pumices. This type of soil can be susceptible to the collapse of the structure when subjected to shearing (molding), flowing as a viscous liquid. From the numerical modeling, we concluded that r.avaflow performs better than Flo-2D. The mudflow was satisfactorily simulated using a water content in the mixture ranging from 30 % to 40 %, which would have required a source of about 3 million m3 of water. Coupling the simulations and the soil tests that we performed, we estimated that in the area scoured by the mudflow, there were probably around 2 800 000 m3 of water within the soil. Therefore, the conditions of the valley were crucial to enhancing the impacts of the landslide. This result is relevant because it highlights the importance of evaluating the complete chain of events to map hazards. We suggest that in future hazard mapping, geotechnical studies in combination with hydrodynamic simulation should be included, in particular when human lives are at risk.

Beschreibung: Production and reduction of nitrous oxide (N2O) by soil denitrifiers influence atmospheric concentrations of this potent greenhouse gas. Accurate projections of the net N2O flux have three key uncertainties: (1) short- vs. long-term responses to warming, (2) interactions among soil horizons, and (3) temperature responses of different steps in the denitrification pathway. We addressed these uncertainties by sampling soil from a boreal forest climate transect encompassing a 5.2 ∘C difference in the mean annual temperature and incubating the soil horizons in isolation and together at three ecologically relevant temperatures in conditions that promote denitrification. Both short-term exposure to warmer temperatures and long-term exposure to a warmer climate increased N2O emissions from organic and mineral soils; an isotopic tracer suggested that an increase in N2O production was more important than a decline in N2O reduction. Short-term warming promoted the reduction of organic horizon-derived N2O by mineral soil when these horizons were incubated together. The abundance of nirS (a precursor gene for N2O production) was not sensitive to temperature, whereas that of nosZ clade I (a gene for N2O reduction) decreased with short-term warming in both horizons and was higher from a warmer climate. These results suggest a decoupling of gene abundance and process rates in these soils that differs across horizons and timescales. In spite of these variations, our results suggest a consistent, positive response of denitrifier-mediated net N2O efflux rates to temperature across timescales in these boreal forests. Our work also highlights the importance of understanding cross-horizon N2O fluxes for developing a predictive understanding of net N2O efflux from soils.

Beschreibung: Wetlands are the largest and most uncertain natural sources of atmospheric methane (CH4). Several process-based models have been developed to quantify the magnitude and estimate spatial and temporal variations in CH4 emissions from global wetlands. Reliable models are required to estimate global wetland CH4 emissions. This study aimed to test two process-based models, CH4MODwetland and Terrestrial Ecosystem Model (TEM), against the CH4 flux measurements of marsh, swamp, peatland and coastal wetland sites across the world; specifically, model accuracy and generality were evaluated for different wetland types and in different continents, and then the global CH4 emissions from 2000 to 2010 were estimated. Both models showed similar high correlations with the observed seasonal/annual total CH4 emissions, and the regression of the observed versus computed total seasonal/annual CH4 emissions resulted in R2 values of 0.81 and 0.68 for CH4MODwetland and TEM, respectively. The CH4MODwetland produced accurate predictions for marshes, peatlands, swamps and coastal wetlands, with model efficiency (EF) values of 0.22, 0.52, 0.13 and 0.72, respectively. TEM produced good predictions for peatlands and swamps, with EF values of 0.69 and 0.74, respectively, but it could not accurately simulate marshes and coastal wetlands (EF 

Beschreibung: As knowledge about the cirrus clouds in the lower stratosphere is limited, reliable long-term measurements are needed to assess their characteristics, radiative impact and important role in upper troposphere and lower stratosphere (UTLS) chemistry. We used 6 years (2006–2012) of Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) measurements to investigate the global and seasonal distribution of stratospheric cirrus clouds and compared the MIPAS results with results derived from the latest version (V4.x) of the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) data. For the identification of stratospheric cirrus clouds, precise information on both the cloud top height (CTH) and the tropopause height is crucial. Here, we used lapse rate tropopause heights estimated from the ERA-Interim global reanalysis. Considering the uncertainties of the tropopause heights and the vertical sampling grid, we define CTHs more than 0.5 km above the tropopause as stratospheric for CALIPSO data. For MIPAS data, we took into account the coarser vertical sampling grid and the broad field of view so that we considered cirrus CTHs detected more than 0.75 km above the tropopause as stratospheric. Further sensitivity tests were conducted to rule out sampling artefacts in MIPAS data. The global distribution of stratospheric cirrus clouds was derived from night-time measurements because of the higher detection sensitivity of CALIPSO. In both data sets, MIPAS and CALIPSO, the stratospheric cirrus cloud occurrence frequencies are significantly higher in the tropics than in the extra-tropics. Tropical hotspots of stratospheric cirrus clouds associated with deep convection are located over equatorial Africa, South and Southeast Asia, the western Pacific, and South America. Stratospheric cirrus clouds were more often detected in December–February (15 %) than June–August (8 %) in the tropics (±20∘). At northern and southern middle latitudes (40–60∘), MIPAS observed about twice as many stratospheric cirrus clouds (occurrence frequencies of 4 %–5 % for MIPAS rather than about 2 % for CALIPSO). We attribute more frequent observations of stratospheric cirrus clouds with MIPAS to the higher detection sensitivity of the instrument to optically thin clouds. In contrast to the difference between daytime and night-time occurrence frequencies of stratospheric cirrus clouds by a factor of about 2 in zonal means in the tropics (4 % and 10 %, respectively) and at middle latitudes for CALIPSO data, there is little diurnal cycle in MIPAS data, in which the difference of occurrence frequencies in the tropics is about 1 percentage point in zonal mean and about 0.5 percentage point at middle latitudes. The difference between CALIPSO day and night measurements can also be attributed to their differences in detection sensitivity. Future work should focus on better understanding the origin of the stratospheric cirrus clouds and their impact on radiative forcing and climate.

Beschreibung: Air quality on our planet has been changing in particular since the industrial revolution (1750s) because of anthropogenic emissions. It is becoming increasingly important to realize air cleanliness, since clean air is as valuable a resource as clean water. A global standard for quantifying the level of air cleanliness is swiftly required, and we defined a novel concept, namely the Clean aIr Index (CII). The CII is a simple index defined by the normalization of the amount of a set of individual air pollutants. A CII value of 1 indicates completely clean air (no air pollutants), and 0 indicates the presence of air pollutants that meet the numerical environmental criteria for the normalization. In this time, the air pollutants used in the CII were taken from the Air Quality Guidelines (AQG) set by the World Health Organization (WHO), namely O3, particulate matters, NO2, and SO2. We chose Japan as a study area to evaluate CII because of the following reasons: (i) accurate validation data, as the in situ observation sites of the Atmospheric Environmental Regional Observation System (AEROS) provide highly accurate values of air pollutant amounts, and (ii) fixed numerical criteria from the Japanese Environmental Quality Standards (JEQS) as directed by the Ministry of the Environment (MOE) of Japan. We quantified air cleanliness in terms of the CII for the all 1896 municipalities in Japan and used data from Seoul and Beijing to evaluate Japanese air cleanliness. The amount of each air pollutant was calculated using a model that combined the Weather Research and Forecasting (WRF) and Community Multiscale Air Quality (CMAQ) models for 1 April 2014 to 31 March 2017. The CII values calculated by the WRF–CMAQ model and the AEROS measurements showed good agreement. The mean of the correlation coefficient for the CII values of 498 municipalities where the AEROS measurements operated was 0.66±0.05, which was higher than that of the Air Quality Index (AQI) of 0.57±0.06. The CII values averaged for the study period were 0.67, 0.52, and 0.24 in Tokyo, Seoul, and Beijing, respectively; thus, the air in Tokyo was 1.5 and 2.3 times cleaner, i.e., lower amounts of air pollutants, than the air in Seoul and Beijing, respectively. The average CII value for the all Japanese municipalities was 0.72 over the study period. The extremely clean air, CII ≈0.90, occurred in the southern remote islands of Tokyo and to the west of the Pacific coast, i.e., Kochi, Mie, and Wakayama prefectures during summer, with the transport of clean air from the ocean. We presented the top 100 clean air cities in Japan as one example of an application of CII in society. We confirmed that the CII enabled the quantitative evaluation of air cleanliness. The CII can be useful and valuable in various scenarios such as encouraging sightseeing and migration, investment and insurance business, and city planning. The CII is a simple and fair index that can be applied to all nations.

Beschreibung: Calculating a multi-model mean, a commonly used method for ensemble averaging, assumes model independence and equal model skill. Sharing of model components amongst families of models and research centres, conflated by growing ensemble size, means model independence cannot be assumed and is hard to quantify. We present a methodology to produce a weighted-model ensemble projection, accounting for model performance and model independence. Model weights are calculated by comparing model hindcasts to a selection of metrics chosen for their physical relevance to the process or phenomena of interest. This weighting methodology is applied to the Chemistry–Climate Model Initiative (CCMI) ensemble to investigate Antarctic ozone depletion and subsequent recovery. The weighted mean projects an ozone recovery to 1980 levels, by 2056 with a 95 % confidence interval (2052–2060), 4 years earlier than the most recent study. Perfect-model testing and out-of-sample testing validate the results and show a greater projective skill than a standard multi-model mean. Interestingly, the construction of a weighted mean also provides insight into model performance and dependence between the models. This weighting methodology is robust to both model and metric choices and therefore has potential applications throughout the climate and chemistry–climate modelling communities.

Beschreibung: Connections between vegetation and soil thermal dynamics are critical for estimating the vulnerability of permafrost to thaw with continued climate warming and vegetation changes. The interplay of complex biophysical processes results in a highly heterogeneous soil temperature distribution on small spatial scales. Moreover, the link between topsoil temperature and active layer thickness remains poorly constrained. Sixty-eight temperature loggers were installed at 1–3 cm depth to record the distribution of topsoil temperatures at the Trail Valley Creek study site in the northwestern Canadian Arctic. The measurements were distributed across six different vegetation types characteristic for this landscape. Two years of topsoil temperature data were analysed statistically to identify temporal and spatial characteristics and their relationship to vegetation, snow cover, and active layer thickness. The mean annual topsoil temperature varied between −3.7 and 0.1 ∘C within 0.5 km2. The observed variation can, to a large degree, be explained by variation in snow cover. Differences in snow depth are strongly related with vegetation type and show complex associations with late-summer thaw depth. While cold winter soil temperature is associated with deep active layers in the following summer for lichen and dwarf shrub tundra, we observed the opposite beneath tall shrubs and tussocks. In contrast to winter observations, summer topsoil temperature is similar below all vegetation types with an average summer topsoil temperature difference of less than 1 ∘C. Moreover, there is no significant relationship between summer soil temperature or cumulative positive degree days and active layer thickness. Altogether, our results demonstrate the high spatial variability of topsoil temperature and active layer thickness even within specific vegetation types. Given that vegetation type defines the direction of the relationship between topsoil temperature and active layer thickness in winter and summer, estimates of permafrost vulnerability based on remote sensing or model results will need to incorporate complex local feedback mechanisms of vegetation change and permafrost thaw.

Beschreibung: Evapotranspiration (ET) from tropical forests serves as a critical moisture source for regional and global climate cycles. However, the magnitude, seasonality, and interannual variability of ET in the Congo Basin remain poorly constrained due to a scarcity of direct observations, despite the Congo being the second-largest river basin in the world and containing a vast region of tropical forest. In this study, we applied a water balance model to an array of remotely sensed and in situ datasets to produce monthly, basin-wide ET estimates spanning April 2002 to November 2016. Data sources include water storage changes estimated from the Gravity Recovery and Climate Experiment (GRACE) satellites, in situ measurements of river discharge, and precipitation from several remotely sensed and gauge-based sources. An optimal precipitation dataset was determined as a weighted average of interpolated data by Nicholson et al. (2018), Climate Hazards InfraRed Precipitation with Station data version 2 (CHIRPS2) , and the Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks–Climate Data Record product (PERSIANN-CDR), with the relative weights based on the error magnitudes of each dataset as determined by triple collocation. The resulting water-balance-derived ET (ETwb) features a long-term average that is consistent with previous studies (117.2±3.5 cm yr−1) but displays greater seasonal and interannual variability than seven global ET products. The seasonal cycle of ETwb generally tracks that of precipitation over the basin, with the exception that ETwb is greater in March–April–May (MAM) than in the relatively wetter September–October–November (SON) periods. This pattern appears to be driven by seasonal variations in the diffuse photosynthetically active radiation (PAR) fraction, net radiation (Rn), and soil water availability. From 2002 to 2016, Rn, PAR, and vapor-pressure deficit (VPD) all increased significantly within the Congo Basin; however, no corresponding trend occurred in ETwb. We hypothesize that the stability of ETwb over the study period despite sunnier and less humid conditions may be due to increasing atmospheric CO2 concentrations that offset the impacts of rising VPD and irradiance on stomatal water use efficiency (WUE).

Beschreibung: A range of future climate scenarios are projected for high atmospheric CO2 concentrations, given uncertainties over future human actions as well as potential environmental and climatic feedbacks. The geological record offers an opportunity to understand climate system response to a range of forcings and feedbacks which operate over multiple temporal and spatial scales. Here, we examine a single interglacial during the late Pliocene (KM5c, ca. 3.205±0.01 Ma) when atmospheric CO2 exceeded pre-industrial concentrations, but were similar to today and to the lowest emission scenarios for this century. As orbital forcing and continental configurations were almost identical to today, we are able to focus on equilibrium climate system response to modern and near-future CO2. Using proxy data from 32 sites, we demonstrate that global mean sea-surface temperatures were warmer than pre-industrial values, by ∼2.3 ∘C for the combined proxy data (foraminifera Mg∕Ca and alkenones), or by ∼3.2–3.4 ∘C (alkenones only). Compared to the pre-industrial period, reduced meridional gradients and enhanced warming in the North Atlantic are consistently reconstructed. There is broad agreement between data and models at the global scale, with regional differences reflecting ocean circulation and/or proxy signals. An uneven distribution of proxy data in time and space does, however, add uncertainty to our anomaly calculations. The reconstructed global mean sea-surface temperature anomaly for KM5c is warmer than all but three of the PlioMIP2 model outputs, and the reconstructed North Atlantic data tend to align with the warmest KM5c model values. Our results demonstrate that even under low-CO2 emission scenarios, surface ocean warming may be expected to exceed model projections and will be accentuated in the higher latitudes.

Beschreibung: The meridional heat transport (MHT) in the North Atlantic is critically important to climate variability and the global overturning circulation. A wide range of ocean processes contribute to North Atlantic MHT, ranging from basin-scale overturning and gyre motions to mesoscale instabilities (such as eddies). However, previous analyses of “eddy” MHT in the region have mostly focused on the contributions of time-variable velocity and temperature, rather than considering the association of MHT with distinct spatial scales within the basin. In this study, a zonal spatial-scale decomposition separates large-scale from mesoscale velocity and temperature contributions to MHT, in order to characterize the physical processes driving MHT. Using this approach, we found that the mesoscale contributions to the time-mean and interannual/decadal (ID) variability of MHT in the latitude range 39–45∘ N are larger than large-scale horizontal contributions, though smaller than the overturning contributions. Considering the 40∘ N transect as a case study, large-scale ID variability is mostly generated close to the western boundary. In contrast, most ID MHT variability associated with mesoscales originates in two distinct regions: a western boundary region (70–60∘ W) associated with 1- to 4-year interannual variations and an interior region (50–35∘ W) associated with decadal variations. Surface eddy kinetic energy is not a reliable indicator of high MHT episodes, but the large-scale meridional temperature gradient is an important factor, by influencing the local temperature variance as well as the local correlation of velocity and temperature. Most of the mesoscale contribution to MHT at 40∘ N is associated with transient and propagating processes, but stationary mesoscale structures explain most of the mesoscale MHT south of the Gulf Stream separation, highlighting the differences between the temporal and spatial decomposition of meridional temperature fluxes.

Beschreibung: Accurate reference spectroscopic information for the water molecule from the microwave to the near-ultraviolet is of paramount importance in atmospheric research. A semi-empirical potential energy surface for the ground electronic state of H216O has been created by refining almost 4000 experimentally determined energy levels. These states extend into regions with large values of rotational and vibrational excitation. For all states considered in our refinement procedure, which extend to 37 000 cm−1 and J=20 (total angular momentum), the average root-mean-square deviation is approximately 0.05 cm−1. This potential energy surface offers significant improvements when compared to recent models by accurately predicting states possessing high values of J. This feature will offer significant improvements in calculated line positions for high-temperature spectra where transitions between high J states become more prominent. Combining this potential with the latest dipole moment surface for water vapour, a line list has been calculated which extends reliably to 37 000 cm−1. Obtaining reliable results in the ultraviolet is of special importance as it is a challenging spectral region for the water molecule both experimentally and theoretically. Comparisons are made against several experimental sources of cross sections in the near-ultraviolet and discrepancies are observed. In the near-ultraviolet our calculations are in agreement with recent atmospheric retrievals and the upper limit obtained using broadband spectroscopy by Wilson et al. (2016, p. 194), but they do not support recent suggestions of very strong absorption in this region.

Beschreibung: Various studies investigated the fate of evaporation and the origin of precipitation. The more recent studies among them were often carried out with the help of numerical moisture tracking. Many research questions could be answered within this context, such as dependencies of atmospheric moisture transfers between different regions, impacts of land cover changes on the hydrological cycle, sustainability-related questions, and questions regarding the seasonal and interannual variability of precipitation. In order to facilitate future applications, global datasets on the fate of evaporation and the sources of precipitation are needed. Since most studies are on a regional level and focus more on the sources of precipitation, the goal of this study is to provide a readily available global dataset on the fate of evaporation for a fine-meshed grid of source and receptor cells. The dataset was created through a global run of the numerical moisture tracking model Water Accounting Model-2layers (WAM-2layers) and focused on the fate of land evaporation. The tracking was conducted on a 1.5∘×1.5∘ grid and was based on reanalysis data from the ERA-Interim database. Climatic input data were incorporated in 3- to 6-hourly time steps and represent the time period from 2001 to 2018. Atmospheric moisture was tracked forward in time and the geographical borders of the model were located at ±79.5∘ latitude. As a result of the model run, the annual, the monthly and the interannual average fate of evaporation were determined for 8684 land grid cells (all land cells except those located within Greenland and Antarctica) and provided via source–receptor matrices. The gained dataset was complemented via an aggregation to country and basin scales in order to highlight possible usages for areas of interest larger than grid cells. This resulted in data for 265 countries and 8223 basins. Finally, five types of source–receptor matrices for average moisture transfers were chosen to build the core of the dataset: land grid cell to grid cell, country to grid cell, basin to grid cell, country to country, basin to basin. The dataset is, to our knowledge, the first ready-to-download dataset providing the overall fate of evaporation for land cells of a global fine-meshed grid in monthly resolution. At the same time, information on the sources of precipitation can be extracted from it. It could be used for investigations into average annual, seasonal, and interannual sink and source regions of atmospheric moisture from land masses for most of the regions in the world and shows various application possibilities for studying interactions between people and water, such as land cover changes or human water consumption patterns. The dataset is accessible under https://doi.org/10.1594/PANGAEA.908705 (Link et al., 2019a) and comes along with example scripts for reading and plotting the data.

Beschreibung: Antibody-mediated immune checkpoint blockade is a transformative immunotherapy for cancer. These same mechanisms can be repurposed for the control of destructive alloreactive immune responses in the transplantation setting. Here, we implement a synthetic biomaterial platform for the local delivery of a chimeric streptavidin/programmed cell death-1 (SA-PD-L1) protein to direct “reprogramming” of local immune responses to transplanted pancreatic islets. Controlled presentation of SA-PD-L1 on the surface of poly(ethylene glycol) microgels improves local retention of the immunomodulatory agent over 3 weeks in vivo. Furthermore, local induction of allograft acceptance is achieved in a murine model of diabetes only when receiving the SA-PD-L1–presenting biomaterial in combination with a brief rapamycin treatment. Immune characterization revealed an increase in T regulatory and anergic cells after SA-PD-L1-microgel delivery, which was distinct from naïve and biomaterial alone microenvironments. Engineering the local microenvironment via biomaterial delivery of checkpoint proteins has the potential to advance cell-based therapies, avoiding the need for systemic chronic immunosuppression.

Beschreibung: Human genome-wide association studies have linked single-nucleotide polymorphisms (SNPs) in NEMP1 (nuclear envelope membrane protein 1) with early menopause; however, it is unclear whether NEMP1 has any role in fertility. We show that whole-animal loss of NEMP1 homologs in Drosophila, Caenorhabditis elegans, zebrafish, and mice leads to sterility or early loss of fertility. Loss of Nemp leads to nuclear shaping defects, most prominently in the germ line. Biochemical, biophysical, and genetic studies reveal that NEMP proteins support the mechanical stiffness of the germline nuclear envelope via formation of a NEMP-EMERIN complex. These data indicate that the germline nuclear envelope has specialized mechanical properties and that NEMP proteins play essential and conserved roles in fertility.

Beschreibung: Overuse injuries to dense collagenous tissues are common, but their etiology is poorly understood. The predominant hypothesis that micro-damage accumulation exceeds the rate of biological repair is missing a mechanistic explanation. Here, we used collagen hybridizing peptides to measure collagen molecular damage during tendon cyclic fatigue loading and computational simulations to identify potential explanations for our findings. Our results revealed that triple-helical collagen denaturation accumulates with increasing cycles of fatigue loading, and damage is correlated with creep strain independent of the cyclic strain rate. Finite-element simulations demonstrated that biphasic fluid flow is a possible fascicle-level mechanism to explain the rate dependence of the number of cycles and time to failure. Molecular dynamics simulations demonstrated that triple-helical unfolding is rate dependent, revealing rate-dependent mechanisms at multiple length scales in the tissue. The accumulation of collagen molecular denaturation during cyclic loading provides a long-sought “micro-damage” mechanism for the development of overuse injuries.

Beschreibung: Mounting evidence suggests that immunotherapies are a promising new class of anticancer therapies. However, the immunosuppressive tumor microenvironment (TME), poor immunogenicity, and off-target toxicity hinder the broader implementation of immunotherapies. Here, we describe a novel strategy combining chemotherapy and immunotherapy to modulate the TME by systemically and concurrently delivering the chemotherapeutic agent SN38 (7-ethyl-10-hydroxycamptothecin) and the STING agonist DMXAA (5,6-dimethylxanthenone-4-acetic acid) into tumors using triblock copolymer nanoparticles, named PS3D1@DMXAA, which enhances antigen cross-presentation and induces the conversion of the immunosuppressive TME to immunogenic TME through the newly found synergistic function between SN38 and STING activation. PS3D1@DMXAA thus shows potent therapeutic efficacy in three mice tumor models and elicits remarkable therapeutic benefit when combined with anti–PD-1 therapy. Our engineered nanosystem offers a rational design of an effective immunotherapy combination regimen to convert uninflamed “cold” tumors into “hot” tumors, addressing the major challenges immunotherapies faced.

Beschreibung: In the first days of embryogenesis, transposable element–embedded regulatory sequences (TEeRS) are silenced by Kruppel-associated box (KRAB) zinc finger proteins (KZFPs). Many TEeRS are subsequently co-opted in transcription networks, but how KZFPs influence this process is largely unknown. We identify ZNF417 and ZNF587 as primate-specific KZFPs repressing HERVK (human endogenous retrovirus K) and SVA (SINE-VNTR-Alu) integrants in human embryonic stem cells (ESCs). Expressed in specific regions of the human developing and adult brain, ZNF417/587 keep controlling TEeRS in ESC-derived neurons and brain organoids, secondarily influencing the differentiation and neurotransmission profile of neurons and preventing the induction of neurotoxic retroviral proteins and an interferon-like response. Thus, evolutionarily recent KZFPs and their TE targets partner up to influence human neuronal differentiation and physiology.

Beschreibung: Early embryonic arrest is a challenge for in vitro fertilization (IVF). No genetic factors were previously revealed in the sperm-derived arrest of embryonic development. Here, we reported two infertile brothers presenting normal in conventional semen analysis, but both couples had no embryos for transfer after several IVF and intracytoplasmic sperm injection (ICSI). Whole-exome sequencing identified a homozygous missense mutation of ACTL7A in both brothers. This mutation is deleterious and causes sperm acrosomal ultrastructural defects. The Actl7a knock-in mouse model was generated, and male mutated mice showed sperm acrosomal defects, which were completely consistent with the observations in patients. Furthermore, the sperm from ACTL7A/Actl7a-mutated men and mice showed reduced expression and abnormal localization of PLCζ as a potential cause of embryonic arrest and failure of fertilization. Artificial oocyte activation could successfully overcome the Actl7a-mutated sperm-derived infertility, which is meaningful in the future practice of IVF/ICSI for the ACTL7A-associated male infertility.

Beschreibung: The gut microbiota affects tissue physiology, metabolism, and function of both the immune and nervous systems. We found that intrinsic enteric-associated neurons (iEAN) in mice are functionally adapted to the intestinal segment they occupy; ileal and colonic neurons are more responsive to microbial colonization than duodenal neurons. Specifically, a microbially-responsive subset of viscerofugal CART+ neurons, enriched in the ileum and colon, modulated feeding and glucose metabolism. These CART+ neurons send axons to the prevertebral ganglia and are poly-synaptically connected to the liver and pancreas. Microbiota depletion led to NLRP6– and Caspase 11-dependent loss of CART+ neurons, and impaired glucose regulation. Hence, iEAN subsets appear to be capable of regulating blood glucose levels independently from the central nervous system.

Beschreibung: Optimum management of irrigated crops in regions with shallow saline groundwater requires a careful balance between application of irrigation water and upward movement of salinity from the groundwater. Few field-validated surrogate models are available to aid in the management of irrigation water under shallow groundwater conditions. The objective of this research is to develop a model that can aid in the management using a minimum of input data that are field validated. In this paper a 2-year field experiment was carried out in the Hetao irrigation district in Inner Mongolia, China, and a physically based integrated surrogate model for arid irrigated areas with shallow groundwater was developed and validated with the collected field data. The integrated model that links crop growth with available water and salinity in the vadose zone is called Evaluation of the Performance of Irrigated Crops and Soils (EPICS). EPICS recognizes that field capacity is reached when the matric potential is equal to the height above the groundwater table and thus not by a limiting hydraulic conductivity. In the field experiment, soil moisture contents and soil salt conductivity at five depths in the top 100 cm, groundwater depth, crop height, and leaf area index were measured in 2017 and 2018. The field results were used for calibration and validation of EPICS. Simulated and observed data fitted generally well during both calibration and validation. The EPICS model that can predict crop growth, soil water, groundwater depth, and soil salinity can aid in optimizing water management in irrigation districts with shallow aquifers.

Beschreibung: Recently, it has been established that interplanetary coronal mass ejections (ICMEs) can dramatically affect both trapped electron fluxes in the outer radiation belt and precipitating electron fluxes lost from the belt into the atmosphere. Precipitating electron fluxes and energies can vary over a range of timescales during these events. These variations depend on the initial energy and location of the electron population and the ICME characteristics and structures. One important factor controlling electron dynamics is the magnetic field orientation within the ejecta that is an integral part of the ICME. In this study, we examine Van Allen Probes (RBSPs) and Polar Orbiting Environmental Satellites (POESs) data to explore trapped and precipitating electron fluxes during two ICMEs. The ejecta in the selected ICMEs have magnetic cloud characteristics that exhibit the opposite sense of the rotation of the north–south magnetic field component (BZ). RBSP data are used to study trapped electron fluxes in situ, while POES data are used for electron fluxes precipitating into the upper atmosphere. The trapped and precipitating electron fluxes are qualitatively analysed to understand their variation in relation to each other and to the magnetic cloud rotation during these events. Inner magnetospheric wave activity was also estimated using RBSP and Geostationary Operational Environmental Satellite (GOES) data. In each event, the largest changes in the location and magnitude of both the trapped and precipitating electron fluxes occurred during the southward portion of the magnetic cloud. Significant changes also occurred during the end of the sheath and at the sheath–ejecta boundary for the cloud with south to north magnetic field rotation, while the ICME with north to south rotation had significant changes at the end boundary of the cloud. The sense of rotation of BZ and its profile also clearly affects the coherence of the trapped and/or precipitating flux changes, timing of variations with respect to the ICME structures, and flux magnitude of different electron populations. The differing electron responses could therefore imply partly different dominant acceleration mechanisms acting on the outer radiation belt electron populations as a result of opposite magnetic cloud rotation.

Beschreibung: In this paper, we quantify the CO2 and N2O emissions from denitrification over the Amazonian wetlands. The study concerns the entire Amazonian wetland ecosystem with a specific focus on three floodplain (FP) locations: the Branco FP, the Madeira FP and the FP alongside the Amazon River. We adapted a simple denitrification model to the case of tropical wetlands and forced it by open water surface extent products from the Soil Moisture and Ocean Salinity (SMOS) satellite. A priori model parameters were provided by in situ observations and gauging stations from the HYBAM Observatory. Our results show that the denitrification and the trace gas emissions present a strong cyclic pattern linked to the inundation processes that can be divided into three distinct phases: activation, stabilization and deactivation. We quantify the average yearly denitrification and associated emissions of CO2 and N2O over the entire watershed at 17.8 kgN ha−1 yr−1, 0.37 gC-CO2 m−2 yr−1 and 0.18 gN-N2O m−2 yr−1 respectively for the period 2011–2015. When compared to local observations, it was found that the CO2 emissions accounted for 0.01 % of the integrated ecosystem, which emphasizes the fact that minor changes to the land cover may induce strong impacts on the Amazonian carbon budget. Our results are consistent with the state of the art of global nitrogen models with a positive bias of 28 %. When compared to other wetlands in different pedoclimatic environments we found that the Amazonian wetlands have similar emissions of N2O with the Congo tropical wetlands and lower emissions than the temperate and tropical anthropogenic wetlands of the Garonne (France), the Rhine (Europe) and south-eastern Asia rice paddies. In summary our paper shows that a data-model-based approach can be successfully applied to quantify N2O and CO2 fluxes associated with denitrification over the Amazon basin. In the future, the use of higher-resolution remote sensing products from sensor fusion or new sensors like the Surface Water and Ocean Topography (SWOT) mission will permit the transposition of the approach to other large-scale watersheds in tropical environments.

Beschreibung: In the framework of the EU Copernicus programme, the European Centre for Medium-Range Weather Forecasts (ECMWF) on behalf of the Joint Research Centre (JRC) is forecasting daily fire weather indices using its medium-range ensemble prediction system. The use of weather forecasts in place of local observations can extend early warnings by up to 1–2 weeks, allowing for greater proactive coordination of resource-sharing and mobilization within and across countries. Using 1 year of pre-operational service in 2017 and the Fire Weather Index (FWI), here we assess the capability of the system globally and analyse in detail three major events in Chile, Portugal and California. The analysis shows that the skill provided by the ensemble forecast system extends to more than 10 d when compared to the use of mean climate, making a case for extending the forecast range to the sub-seasonal to seasonal timescale. However, accurate FWI prediction does not translate into accuracy in the forecast of fire activity globally. Indeed, when all fires detected in 2017 are considered, including agricultural- and human-induced burning, high FWI values only occur in 50 % of the cases and are limited to the Boreal regions. Nevertheless for very large events which were driven by weather conditions, FWI forecasts provide advance warning that could be instrumental in setting up management and containment strategies.

Beschreibung: North African dust reaches the southeastern United States every summer. Size-resolved dust mass measurements taken in Miami, Florida, indicate that more than one-half of the surface dust mass concentrations reside in particles with geometric diameters less than 2.1 µm, while vertical profiles of micropulse lidar depolarization ratios show dust reaching above 4 km during pronounced events. These observations are compared to the representation of dust in the Modern-Era Retrospective analysis for Research and Applications, version 2 (MERRA-2) aerosol reanalysis and closely related Goddard Earth Observing System model version 5 (GEOS-5) Forward Processing (FP) aerosol product, both of which assimilate satellite-derived aerosol optical depths using a similar protocol and inputs. These capture the day-to-day variability in aerosol optical depth well, in a comparison to an independent sun-photometer-derived aerosol optical depth dataset. Most of the modeled dust mass resides in diameters between 2 and 6 µm, in contrast to the measurements. Model-specified mass extinction efficiencies equate light extinction with approximately 3 times as much aerosol mass, in this size range, compared to the measured dust sizes. GEOS-5 FP surface-layer sea salt mass concentrations greatly exceed observed values, despite realistic winds and relative humidities. In combination, these observations help explain why, despite realistic total aerosol optical depths, (1) free-tropospheric model volume extinction coefficients are lower than those retrieved from the micro-pulse lidar, suggesting too-low model dust loadings in the free troposphere, and (2) model dust mass concentrations near the surface can be higher than those measured. The modeled vertical distribution of dust, when captured, is reasonable. Large, aspherical particles exceeding the modeled dust sizes are also occasionally present, but dust particles with diameters exceeding 10 µm contribute little to the measured total dust mass concentrations after such long-range transport. Remaining uncertainties warrant a further integrated assessment to confirm this study's interpretations.

Beschreibung: Anaerobic nitrate-dependent Fe(II) oxidation (NDFeO) is widespread in various aquatic environments and plays a major role in iron and nitrogen redox dynamics. However, evidence for truly enzymatic, autotrophic NDFeO remains limited, with alternative explanations involving the coupling of heterotrophic denitrification with the abiotic oxidation of structurally bound or aqueous Fe(II) by reactive intermediate nitrogen (N) species (chemodenitrification). The extent to which chemodenitrification is caused (or enhanced) by ex vivo surface catalytic effects has not been directly tested to date. To determine whether the presence of either an Fe(II)-bearing mineral or dead biomass (DB) catalyses chemodenitrification, two different sets of anoxic batch experiments were conducted: 2 mM Fe(II) was added to a low-phosphate medium, resulting in the precipitation of vivianite (Fe3(PO4)2), to which 2 mM nitrite (NO2-) was later added, with or without an autoclaved cell suspension (∼1.96×108 cells mL−1) of Shewanella oneidensis MR-1. Concentrations of nitrite (NO2-), nitrous oxide (N2O), and iron (Fe2+, Fetot) were monitored over time in both set-ups to assess the impact of Fe(II) minerals and/or DB as catalysts of chemodenitrification. In addition, the natural-abundance isotope ratios of NO2- and N2O (δ15N and δ18O) were analysed to constrain the associated isotope effects. Up to 90 % of the Fe(II) was oxidized in the presence of DB, whereas only ∼65 % of the Fe(II) was oxidized under mineral-only conditions, suggesting an overall lower reactivity of the mineral-only set-up. Similarly, the average NO2- reduction rate in the mineral-only experiments (0.004±0.003 mmol L−1 d−1) was much lower than in the experiments with both mineral and DB (0.053±0.013 mmol L−1 d−1), as was N2O production (204.02±60.29 nmol L−1 d−1). The N2O yield per mole NO2- reduced was higher in the mineral-only set-ups (4 %) than in the experiments with DB (1 %), suggesting the catalysis-dependent differential formation of NO. N-NO2- isotope ratio measurements indicated a clear difference between both experimental conditions: in contrast to the marked 15N isotope enrichment during active NO2- reduction (15εNO2=+10.3 ‰) observed in the presence of DB, NO2- loss in the mineral-only experiments exhibited only a small N isotope effect (

Beschreibung: The Mediterranean (MED) Basin is a climate change hotspot that has seen drying and a pronounced increase in heatwaves over the last century. At the same time, it is experiencing increased heavy precipitation during wintertime cold spells. Understanding and quantifying the risks from compound events over the MED is paramount for present and future disaster risk reduction measures. Here, we apply a novel method to study compound events based on dynamical systems theory and analyse compound temperature and precipitation events over the MED from 1979 to 2018. The dynamical systems analysis quantifies the strength of the coupling between different atmospheric variables over the MED. Further, we consider compound warm–dry anomalies in summer and cold–wet anomalies in winter. Our results show that these warm–dry and cold–wet compound days are associated with large values of the temperature–precipitation coupling parameter of the dynamical systems analysis. This indicates that there is a strong interaction between temperature and precipitation during compound events. In winter, we find no significant trend in the coupling between temperature and precipitation. However in summer, we find a significant upward trend which is likely driven by a stronger coupling during warm and dry days. Thermodynamic processes associated with long-term MED warming can best explain the trend, which intensifies compound warm–dry events.

Beschreibung: Topology and strong electron correlations are crucial ingredients in emerging quantum materials, yet their intersection in experimental systems has been relatively limited to date. Strongly correlated Weyl semimetals, particularly when magnetism is incorporated, offer a unique and fertile platform to explore emergent phenomena in novel topological matter and topological spintronics. The antiferromagnetic Weyl semimetal Mn3Sn exhibits many exotic physical properties such as a large spontaneous Hall effect and has recently attracted intense interest. In this work, we report synthesis of epitaxial Mn3+xSn1−x films with greatly extended compositional range in comparison with that of bulk samples. As Sn atoms are replaced by magnetic Mn atoms, the Kondo effect, which is a celebrated example of strong correlations, emerges, develops coherence, and induces a hybridization energy gap. The magnetic doping and gap opening lead to rich extraordinary properties, as exemplified by the prominent DC Hall effects and resonance-enhanced terahertz Faraday rotation.

Beschreibung: Andean uplift played a fundamental role in shaping South American climate and species distribution, but the relationship between the rise of the Andes, plant composition, and local climatic evolution is poorly known. We investigated the fossil record (pollen, leaves, and wood) from the Neogene of the Central Andean Plateau and documented the earliest evidence of a puna-like ecosystem in the Pliocene and a montane ecosystem without modern analogs in the Miocene. In contrast to regional climate model simulations, our climate inferences based on fossil data suggest wetter than modern precipitation conditions during the Pliocene, when the area was near modern elevations, and even wetter conditions during the Miocene, when the cordillera was around ~1700 meters above sea level. Our empirical data highlight the importance of the plant fossil record in studying past, present, and future climates and underscore the dynamic nature of high elevation ecosystems.

Beschreibung: The phospholipid cardiolipin has pleiotropic structural and functional roles that are collectively essential for mitochondrial biology. Yet, the molecular details of how this lipid supports the structure and function of proteins and protein complexes are poorly understood. To address this property of cardiolipin, we use the mitochondrial adenosine 5′-diphosphate/adenosine 5′-triphosphate carrier (Aac) as a model. Here, we have determined that cardiolipin is critical for both the tertiary and quaternary assembly of the major yeast Aac isoform Aac2 as well as its conformation. Notably, these cardiolipin-provided structural roles are separable. In addition, we show that multiple copies of Aac2 engage in shared complexes that are largely dependent on the presence of assembled respiratory complexes III and IV or respiratory supercomplexes. Intriguingly, the assembly state of Aac2 is sensitive to its transport-related conformation. Together, these results expand our understanding of the numerous structural roles provided by cardiolipin for mitochondrial membrane proteins.

Beschreibung: Connexin family proteins assemble into hexameric channels called hemichannels/connexons, which function as transmembrane channels or dock together to form gap junction intercellular channels (GJIChs). We determined the cryo–electron microscopy structures of human connexin 31.3 (Cx31.3)/GJC3 hemichannels in the presence and absence of calcium ions and with a hearing-loss mutation R15G at 2.3-, 2.5-, and 2.6-Å resolutions, respectively. Compared with available structures of GJICh in open conformation, Cx31.3 hemichannel shows substantial structural changes of highly conserved regions in the connexin family, including opening of calcium ion–binding tunnels, reorganization of salt-bridge networks, exposure of lipid-binding sites, and collocation of amino-terminal helices at the cytoplasmic entrance. We also found that the hemichannel has a pore with a diameter of ~8 Å and selectively transports chloride ions. Our study provides structural insights into the permeant selectivity of Cx31.3 hemichannel.

Beschreibung: Implantable drug release platforms that offer wirelessly programmable control over pharmacokinetics have potential in advanced treatment protocols for hormone imbalances, malignant cancers, diabetic conditions, and others. We present a system with this type of functionality in which the constituent materials undergo complete bioresorption to eliminate device load from the patient after completing the final stage of the release process. Here, bioresorbable polyanhydride reservoirs store drugs in defined reservoirs without leakage until wirelessly triggered valve structures open to allow release. These valves operate through an electrochemical mechanism of geometrically accelerated corrosion induced by passage of electrical current from a wireless, bioresorbable power-harvesting unit. Evaluations in cell cultures demonstrate the efficacy of this technology for the treatment of cancerous tissues by release of the drug doxorubicin. Complete in vivo studies of platforms with multiple, independently controlled release events in live-animal models illustrate capabilities for control of blood glucose levels by timed delivery of insulin.

Beschreibung: Sweat sensors targeting exercise or chemically induced sweat have shown promise for noninvasive health monitoring. Natural thermoregulatory sweat is an attractive alternative as it can be accessed during routine and sedentary activity without impeding user lifestyles and potentially preserves correlations between sweat and blood biomarkers. We present simple glove-based sensors to accumulate natural sweat with minimal evaporation, capitalizing on high sweat gland densities to collect hundreds of microliters in just 30 min without active sweat stimulation. Sensing electrodes are patterned on nitrile gloves and finger cots for in situ detection of diverse biomarkers, including electrolytes and xenobiotics, and multiple gloves or cots are worn in sequence to track overarching analyte dynamics. Direct integration of sensors into gloves represents a simple and low-overhead scheme for natural sweat analysis, enabling sweat-based physiological monitoring to become practical and routine without requiring highly complex or miniaturized components for analyte collection and signal transduction.

Beschreibung: Anhand von sedimentologischen und geländemorphologischen Untersuchungen wird die Abschmelzgeschichte des südöstlichen Chiemsee-Gletschers beschrieben. Mit dem Trockenfallen der Bad Adelholzen-Erlstätter Rinne im Verlaufe des Spätwürm entwickelt sich aus dem Abschmelzen des Eislappens in der Grabenstätter Bucht eine sich ständig tiefer legende konzentrische Abfolge von zunächst peripheren Entwässerungsrinnen, wobei die ältesten Rinnen dieser Phase bei Chieming, die jüngeren dann entsprechend weiter im Süden, in die zentripetale Richtung umschwenken. Die Entstehung des Tüttensee-Komplexes ist im Kontext dieser Entwicklung zu sehen. Er ist das Ergebnis der glazifluvialen und glazilakustrinen Sedimentation im Einflussbereich des sukzessiven Eisabbaus in der Grabenstätter Bucht in Kombination mit einer Toteisbildung im Bereich des heutigen Tüttensees. Dafür sprechen die stufenartige Abfolge der beschriebenen peripheren Abflussrinnen mit ihren immer tiefer liegenden Abflussniveaus, die Höhengleichheit von drei dieser Rinnen mit den Tüttensee-Terrassen sowie die für die jeweilige Terrassenentstehung typische glazifluviale bzw. delta-artige Sedimentstruktur und -reife. Dieses Ergebnis stellt ein Korrektiv zur Hypothese des Chiemgau-Impakts dar, wonach der Tüttensee ein Impaktkrater sein soll. Da diese nun falsifizierte Annahme vor allem im deutschsprachigen Raum von zahlreichen Medien propagiert wird, ist der folgende Artikel auf Deutsch verfasst, um einer breiten Leserschaft zugänglich zu sein.

Beschreibung: Temperature appears to be the best predictor of species composition of planktonic foraminifera communities, making it possible to use their fossil assemblages to reconstruct sea surface temperature (SST) variation in the past. However, the role of other environmental factors potentially modulating the spatial and vertical distribution of planktonic foraminifera species is poorly understood. This is especially relevant for environmental factors affecting the subsurface habitat. If such factors play a role, changes in the abundance of subsurface-dwelling species may not solely reflect SST variation. In order to constrain the effect of subsurface parameters on species composition, we here characterize the vertical distribution of living planktonic foraminifera community across an east–west transect through the subtropical South Atlantic Ocean, where SST variability was small, but the subsurface water mass structure changed dramatically. Four planktonic foraminifera communities could be identified across the top 700 m of the transect. Gyre and Agulhas Leakage surface faunas were predominantly composed of Globigerinoides ruber, Globigerinoides tenellus, Trilobatus sacculifer, Globoturborotalita rubescens, Globigerinella calida, Tenuitella iota, and Globigerinita glutinata, and these only differed in terms of relative abundances (community composition). Upwelling fauna was dominated by Neogloboquadrina pachyderma, Neogloboquadrina incompta, Globorotalia crassaformis, and Globorotalia inflata. Thermocline fauna was dominated by Tenuitella fleisheri, Globorotalia truncatulinoides, and Globorotalia scitula in the west and by G. scitula only in the east. The largest part of the standing stock was consistently found in the surface layer, but SST was not the main predictor of species composition either for the depth-integrated fauna across the stations or at individual depth layers. Instead, we identified a pattern of vertical stacking of different parameters controlling species composition, reflecting different aspects of the pelagic habitat. Whereas productivity appears to dominate in the mixed layer (0–60 m), physical properties (temperature, salinity) become important at intermediate depths and in the subsurface, a complex combination of factors including oxygen concentration is required to explain the assemblage composition. These results indicate that the seemingly straightforward relationship between assemblage composition and SST in sedimentary assemblages reflects vertically and seasonally integrated processes that are only indirectly linked to SST. It also implies that fossil assemblages of planktonic foraminifera should also contain a signature of subsurface processes, which could be used for paleoceanographic reconstructions.

Beschreibung: Disordered crystalline materials are used in a wide variety of energy-related technologies. Recent results from neutron total scattering experiments have shown that the atomic arrangements of many disordered crystalline materials are not random nor are they represented by the long-range structure observed from diffraction experiments. Despite the importance of disordered materials and the impact of disorder on the expression of physical properties, the underlying fundamental atomic-scale rules of disordering are not currently well understood. Here, we report that heterogeneous disordering (and associated structural distortions) can be understood by the straightforward application of Pauling’s rules (1929). This insight, corroborated by first principles calculations, can be used to predict the short-range, atomic-scale changes that result from structural disordering induced by extreme conditions associated with energy-related applications, such as high temperature, high pressure, and intense radiation fields.

Beschreibung: Neurodegeneration in mitochondrial disorders is considered irreversible because of limited metabolic plasticity in neurons, yet the cell-autonomous implications of mitochondrial dysfunction for neuronal metabolism in vivo are poorly understood. Here, we profiled the cell-specific proteome of Purkinje neurons undergoing progressive OXPHOS deficiency caused by disrupted mitochondrial fusion dynamics. We found that mitochondrial dysfunction triggers a profound rewiring of the proteomic landscape, culminating in the sequential activation of precise metabolic programs preceding cell death. Unexpectedly, we identified a marked induction of pyruvate carboxylase (PCx) and other anaplerotic enzymes involved in replenishing tricarboxylic acid cycle intermediates. Suppression of PCx aggravated oxidative stress and neurodegeneration, showing that anaplerosis is protective in OXPHOS-deficient neurons. Restoration of mitochondrial fusion in end-stage degenerating neurons fully reversed these metabolic hallmarks, thereby preventing cell death. Our findings identify a previously unappreciated pathway conferring resilience to mitochondrial dysfunction and show that neurodegeneration can be reversed even at advanced disease stages.

Beschreibung: Ingestible electronic devices enable noninvasive evaluation and diagnosis of pathologies in the gastrointestinal (GI) tract but generally cannot therapeutically interact with the tissue wall. Here, we report the development of an orally administered electrical stimulation device characterized in ex vivo human tissue and in in vivo swine models, which transiently anchored itself to the stomach by autonomously inserting electrically conductive, hooked probes. The probes provided stimulation to the tissue via timed electrical pulses that could be used as a treatment for gastric motility disorders. To demonstrate interaction with stomach muscle tissue, we used the electrical stimulation to induce acute muscular contractions. Pulses conductively signaled the probes’ successful anchoring and detachment events to a parenterally placed device. The ability to anchor into and electrically interact with targeted GI tissues controlled by the enteric nervous system introduces opportunities to treat a multitude of associated pathologies.

Beschreibung: Light-use efficiency defines the ability of primary producers to convert sunlight energy to primary production and is computed as the ratio between the gross primary production and the intercepted photosynthetic active radiation. While this measure has been applied broadly within terrestrial ecology to investigate habitat resource-use efficiency, it remains underused within the aquatic realm. This report provides a conceptual framework to compute hourly and daily light-use efficiency using underwater O2 eddy covariance, a recent technological development that produces habitat-scale rates of primary production under unaltered in situ conditions. The analysis, tested on two benthic flux datasets, documents that hourly light-use efficiency may approach the theoretical limit of 0.125 O2 per photon under low-light conditions, but it decreases rapidly towards the middle of the day and is typically 10-fold lower on a 24 h basis. Overall, light-use efficiency provides a useful measure of habitat functioning and facilitates site comparison in time and space.

Beschreibung: Breakdown of the blood-retinal barrier (BRB) causes retinal edema and vision loss. We investigated the role of Wnt signaling in maintaining the BRB by limiting transcytosis. Mice lacking either the Wnt co-receptor low-density lipoprotein receptor–related protein 5 (Lrp5−/−) or the Wnt ligand Norrin (Ndpy/−) exhibit increased retinal vascular leakage and enhanced endothelial transcytosis. Wnt signaling directly controls the transcription of an endothelium-specific transcytosis inhibitor, major facilitator superfamily domain–containing protein 2a (MFSD2A), in a β-catenin–dependent manner. MFSD2A overexpression reverses Wnt deficiency–induced transcytosis in endothelial cells and in retinas. Moreover, Wnt signaling mediates MFSD2A-dependent vascular endothelium transcytosis through a caveolin-1 (CAV-1)–positive caveolae pathway. In addition, levels of omega-3 fatty acids are also decreased in Wnt signaling–deficient retinas, reflecting the basic function of MFSD2A as a lipid transporter. Our findings uncovered the Wnt/β-catenin/MFSD2A/CAV-1 axis as a key pathway governing endothelium transcytosis and inner BRB integrity.

Beschreibung: Alzheimer’s disease (AD) manifests with progressive memory loss and spatial disorientation. Neuropathological studies suggest early AD pathology in the entorhinal cortex (EC) of young adults at genetic risk for AD (APOE ε4-carriers). Because the EC harbors grid cells, a likely neural substrate of path integration (PI), we examined PI performance in APOE ε4-carriers during a virtual navigation task. We report a selective impairment in APOE ε4-carriers specifically when recruitment of compensatory navigational strategies via supportive spatial cues was disabled. A separate fMRI study revealed that PI performance was associated with the strength of entorhinal grid-like representations when no compensatory strategies were available, suggesting grid cell dysfunction as a mechanistic explanation for PI deficits in APOE ε4-carriers. Furthermore, posterior cingulate/retrosplenial cortex was involved in the recruitment of compensatory navigational strategies via supportive spatial cues. Our results provide evidence for selective PI deficits in AD risk carriers, decades before potential disease onset.

Beschreibung: Minimally invasive surgeries have numerous advantages, yet complications may arise from limited knowledge about the anatomical site targeted for the delivery of therapy. Transcatheter aortic valve replacement (TAVR) is a minimally invasive procedure for treating aortic stenosis. Here, we demonstrate multimaterial three-dimensional printing of patient-specific soft aortic root models with internally integrated electronic sensor arrays that can augment testing for TAVR preprocedural planning. We evaluated the efficacies of the models by comparing their geometric fidelities with postoperative data from patients, as well as their in vitro hemodynamic performances in cases with and without leaflet calcifications. Furthermore, we demonstrated that internal sensor arrays can facilitate the optimization of bioprosthetic valve selections and in vitro placements via mapping of the pressures applied on the critical regions of the aortic anatomies. These models may pave exciting avenues for mitigating the risks of postoperative complications and facilitating the development of next-generation medical devices.

Beschreibung: Marine boundary layer clouds, including the transition from stratocumulus to cumulus, are poorly represented in numerical weather prediction and general circulation models. Further uncertainties in the cloud structure arise in the presence of biomass burning carbonaceous aerosol, as is the case over the southeast Atlantic Ocean, where biomass burning aerosol is transported from the African continent. As the aerosol plume progresses across the southeast Atlantic Ocean, radiative heating within the aerosol layer has the potential to alter the thermodynamic environment and therefore the cloud structure; however, limited work has been done to quantify this along the trajectory of the aerosol plume in the region. The deployment of the first Atmospheric Radiation Measurement (ARM) Mobile Facility (AMF1) in support of the Layered Atlantic Smoke Interactions with Clouds field campaign provided a unique opportunity to collect observations of cloud and aerosol properties during two consecutive biomass burning seasons during July through October of 2016 and 2017 over Ascension Island (7.96∘ S, 14.35∘ W). Using observed profiles of temperature, humidity, and clouds from the field campaign alongside aerosol optical properties from Modern-Era Retrospective analysis for Research and Applications, Version 2 (MERRA-2), as input for the Rapid Radiation Transfer Model (RRTM), profiles of the radiative heating rate due to aerosols and clouds were computed. Radiative heating is also assessed across the southeast Atlantic Ocean using an ensemble of back trajectories from the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model. Idealized experiments using the RRTM with and without aerosols and a range of values for the single-scattering albedo (SSA) demonstrate that shortwave (SW) heating within the aerosol layer above Ascension Island can locally range between 2 and 8 K d−1 depending on the aerosol optical properties, though impacts of the aerosol can be felt elsewhere in the atmospheric column. When considered under clear conditions, the aerosol has a cooling effect at the TOA, and based on the observed cloud properties at Ascension Island, the cloud albedo is not large enough to overcome this. Shortwave radiative heating due to biomass burning aerosol is not balanced by additional longwave (LW) cooling, and the net radiative impact results in a stabilization of the lower troposphere. However, these results are extremely sensitive to the single-scattering albedo assumptions in models.

Beschreibung: Information on global cropland distribution and agricultural production is critical for the world's agricultural monitoring and food security. We present datasets of cropland extent and agricultural production in a two-paper series of a cultivated planet in 2010. In the first part, we propose a new Self-adapting Statistics Allocation Model (SASAM) to develop the global map of cropland distribution. SASAM is based on the fusion of multiple existing cropland maps and multilevel statistics of the cropland area, which is independent of training samples. First, cropland area statistics are used to rank the input cropland maps, and then a scoring table is built to indicate the agreement among the input datasets. Secondly, statistics are allocated adaptively to the pixels with higher agreement scores until the cumulative cropland area is close to the statistics. The multilevel allocation results are then integrated to obtain the extent of cropland. We applied SASAM to produce a global cropland synergy map with a 500 m spatial resolution for circa 2010. The accuracy assessments show that the synergy map has higher accuracy than the input datasets and better consistency with the cropland statistics. The synergy cropland map is available via an open-data repository (https://doi.org/10.7910/DVN/ZWSFAA; Lu et al., 2020). This new cropland map has been used as an essential input to the Spatial Production Allocation Model (SPAM) for producing the global dataset of agricultural production for circa 2010, which is described in the second part of the two-paper series.

Beschreibung: Postmortem diagnosis of cantharidin-induced myocardial injury and postmortem interval estimation (PMI) are the challenges in forensic science. Cardiac biomarkers play an important role in the prediction and diagnosis of myocardial injury and can be used to determine the PMI. Based on the evidence, we aimed to explore the biomarkers which may be used for the postmortem diagnosis of cantharidin-induced myocardial injury and PMI estimation using the study of the proteins expression of TN-T, VEGF and HIF-1α by ELISA. Results of this study suggested that postmortem pathological changes were difficult to identify due to the autolysis of myocardium 72 h after death in cantharidin poisoning group. The plasma levels of TN-T and HIF-1α/TN-T are cardiac biomarkers with higher diagnostic accuracy for postmortem diagnosis of cantharidin-induced myocardial injury, VEGF/HIF-1α promises to be a biomarker for PMI estimation. Further studies are needed to verify these biomarkers, based on population, for being a useful tool in postmortem diagnosis of cantharidin-induced myocardial injury and PMI estimation.