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Abstract In esophageal adenocarcinoma, the presence of lymph node metastases predicts patients' survival even after curative resection. Currently, there is no highly accurate marker for detecting the presence of lymph node metastasis. The SEMA3F/NRP2 axis was initially characterized in axon guidance and recent evidence has revealed its significant involvement in lymphangiogenesis, angiogenesis, and carcinogenesis. Hence, the objective of this study was to elucidate the roles of SEMA3F and its receptor NRP2 in esophageal adenocarcinoma. We conducted an immunohistochemical evaluation of SEMA3F and NRP2 protein expression in 776 patients with esophageal adenocarcinoma who underwent Ivor-Lewis esophagectomy at the University Hospital of Cologne. Total and positive cancer cell counts were digitally analyzed using QuPath and verified by experienced pathologists to ensure accuracy. Positive expression was determined as a cell percentage exceeding the 50th percentile threshold. In our cohort, patients exhibiting SEMA3F positive expression experience significantly lower pT- and pN-stages. In contrast, positive NRP2 expression is associated with the presence of lymph node metastases. Survival analyses showed that the expression status of NRP2 had no impact on patient survival. However, SEMA3F positivity was associated with a favorable patient survival outcome (median OS: 38.9 vs. 26.5 months). Furthermore, SEMA3F could be confirmed as an independent factor for better patient survival in patients with early tumor stage (pT1N0-3: HR = 0.505, p = 0.014, pT1-4N0: HR = 0.664, p = 0.024, pT1N0: HR = 0.483, p = 0.040). In summary, SEMA3F emerges as an independent predictor for a favorable prognosis in patients with early-stage esophageal adenocarcinoma. Additionally, NRP2 expression is linked to a higher risk of lymph node metastases occurrence. We hypothesize that low SEMA3F expression could identify patients with early-stage tumors who might benefit from more aggressive treatment options or intensified follow-up. Furthermore, SEMA3F and its associated pathways should be explored as potential tumor-suppressing agents.

Abstract With the beginning of the Early Bronze Age in Central Europe ~ 2200 BC, a regional and supra-regional hierarchical social organization emerged with few individuals in positions of power (chiefs), set apart by rich graves with extensive burial constructions. However, the social organization and stratification within the majority of people, who represent the non-elite, remain unclear. Here, we present genome-wide data of 46 individuals from the Early Bronze Age burial ground of Leubingen in today’s Germany, integrating archaeological, genetic and strontium isotope data to gain new insights into Early Bronze Age societies. We were able to reconstruct five pedigrees which constitute the members of close biological kinship groups (parents and their offspring), and also identify individuals who are not related to individuals buried at the site. Based on combined lines of evidence, we observe that the kinship structure of the burial community was predominantly patrilineal/virilocal involving female exogamy. Further, we detect a difference in the amount of grave goods among the individuals buried at Leubingen based on genetic sex, age at death and locality but see no difference in the types of grave goods.

Abstract Esophageal adenocarcinoma exhibits one of the highest mortality rates among all cancer entities. Multimodal therapy strategies have improved patients’ survival significantly. However, patients in early stages are currently limited to receiving only local therapies, even though some patients within this group showcase short survival periods. Until now, there has been no widely established clinically used biomarker to detect these high-risk patients. Telomerase reverse transcriptase (TERT), a gene encoding a crucial subunit of the telomerase enzyme, plays a significant role in establishing cancer cell immortality and is under suspicion for its potential contribution to tumor progression. Therefore, we aimed to evaluate the clinical relevance of the TERT amplification status. We included 643 patients with esophageal adenocarcinoma, who underwent Ivor-Lewis esophagectomy at the University Hospital of Cologne. The TERT amplification status was characterized using fluorescence in situ hybridization. Clinicopathological values and patients’ overall survival were compared between patients with and without TERT amplification. Further sub-cohort analyses were conducted for patients with pT1N0-3 tumor stage. Eighty-One patients (12.6%) exhibited TERT amplification. Patients with amplified TERT showed significantly worse overall survival (median OS: 22.6 vs. 36.8 months, p = 0.009). Interestingly, TERT amplification could be characterized as an independent risk factor for worse overall survival in multivariate analysis in patients with pT1N0-3 tumor stage (HR = 2.440, 95% CI 1.095–5.440, p = 0.029). In this study, we describe the TERT amplification status as an independent risk factor for worse survival in patients diagnosed with esophageal adenocarcinoma at pT1N0-3 tumor stage, encompassing cases involving tumor infiltration of the lamina propria, muscularis mucosae, and/or submucosa. Based on our findings, we put forth the proposition that evaluating the TERT amplification status may serve as a valuable tool in identifying a specific subgroup of patients, namely those with TERT amplification and pT1N0-3 tumor-stage esophageal adenocarcinoma. The patients of this subgroup could potentially benefit from enhanced follow-up protocols, more aggressive treatment approaches, or possible targeted TERT inhibition therapies, all aimed at improving their overall clinical outcomes.

Summary: The key auditory signature that may associate peripheral hearing with central auditory cognitive defects remains elusive. Suggesting the involvement of stress receptors, we here deleted the mineralocorticoid and glucocorticoid receptors (MR and GR) using a CaMKIIα-based tamoxifen-inducible CreERT2/loxP approach to generate mice with single or double deletion of central but not cochlear MR and GR. Hearing thresholds of MRGRCaMKIIαCreERT2 conditional knockouts (cKO) were unchanged, whereas auditory nerve fiber (ANF) responses were larger and faster and auditory steady state responses were improved. Subsequent analysis of single MR or GR cKO revealed discrete roles for both, central MR and GR on cochlear functions. Limbic MR deletion reduced inner hair cell (IHC) ribbon numbers and ANF responses. In contrast, GR deletion shortened the latency and improved the synchronization to amplitude-modulated tones without affecting IHC ribbon numbers. These findings imply that stress hormone-dependent functions of central MR/GR contribute to “precognitive” sound processing in the cochlea.

The consumption of raw milk from dairy cows has caused multiple food-borne outbreaks of campylobacteriosis in the European Union (EU) since 2011. Cross-contamination of raw milk through faeces is an important vehicle for transmission of Campylobacter to consumers. This systematic review and meta-analysis, aimed to summarize data on the prevalence and concentration of Campylobacter in faeces of dairy cows. Suitable scientific articles published up to July 2021 were identified through a systematic literature search and subjected to screening and quality assessment. Fifty-three out of 1338 identified studies were eligible for data extraction and 44 were further eligible for meta-analysis. The pooled prevalence was calculated in two different meta-analytic models: a simple model based on one average prevalence estimate per study and a multilevel meta-analytic model that included all prevalence outcomes reported in each study (including different subgroups of e.g. health status and age of dairy cows). The results of the two models were significantly different with a pooled prevalence estimate of 29%, 95% CI [23–36%] and 51%, 95% CI [44–57%], respectively. The effect of sub-groups on prevalence were analyzed with a multilevel mixed-effect model which showed a significant effect of the faecal collection methods and Campylobacter species on the prevalence. A meta-analysis on concentration data could not be performed due to the limited availability of data. This systematic review highlights important data gaps and limitations in current studies and variation of prevalence outcomes between available studies. The included studies used a variety of methods for sampling, data collection and analysis of Campylobacter that added uncertainty to the pooled prevalence estimates. Nevertheless, the performed meta-analysis improved our understanding of Campylobacter prevalence in faeces of dairy cows and is considered a valuable basis for the further development of quantitative microbiological risk assessment models for Campylobacter in (raw) milk and food products thereof.

The consumption of raw milk from dairy cows has caused multiple food-borne outbreaks of campylobacteriosis in the European Union (EU) since 2011. Cross-contamination of raw milk through faeces is an important vehicle for transmission of Campylobacter to consumers. This systematic review and meta-analysis, aimed to summarize data on the prevalence and concentration of Campylobacter in faeces of dairy cows. Suitable scientific articles published up to July 2021 were identified through a systematic literature search and subjected to screening and quality assessment. Fifty-three out of 1338 identified studies were eligible for data extraction and 44 were further eligible for meta-analysis. The pooled prevalence was calculated in two different meta-analytic models: a simple model based on one average prevalence estimate per study and a multilevel meta-analytic model that included all prevalence outcomes reported in each study (including different subgroups of e.g. health status and age of dairy cows). The results of the two models were significantly different with a pooled prevalence estimate of 29%, 95% CI [23-36%] and 51%, 95% CI [44-57%], respectively. The effect of sub-groups on prevalence were analyzed with a multilevel mixed-effect model which showed a significant effect of the faecal collection methods and Campylobacter species on the prevalence. A meta-analysis on concentration data could not be performed due to the limited availability of data. This systematic review highlights important data gaps and limitations in current studies and variation of prevalence outcomes between available studies. The included studies used a variety of methods for sampling, data collection and analysis of Campylobacter that added uncertainty to the pooled prevalence estimates. Nevertheless, the performed meta-analysis improved our understanding of Campylobacter prevalence in faeces of dairy cows and is considered a valuable basis for the further development of quantitative microbiological risk assessment models for Campylobacter in (raw) milk and food products thereof.

Evapotranspiration (ET) is a crucial part of commercial grapevine production in California, and the partitioning of this quantity allows the separate assessment of soil and vine water and energy fluxes. This partitioning has an important role in agriculture since it is related to grapevine stress, yield quality, irrigation efficiency, and growth. Satellite remote sensing-based methods provide an opportunity for ET partitioning at a subfield scale. However, medium-resolution satellite imagery from platforms such as Landsat is often insufficient for precision agricultural management at the plant scale. Small, unmanned aerial systems (sUAS) such as the AggieAir platform from Utah State University enable ET estimation and its partitioning over vineyards via the two-source energy balance (TSEB) model. This study explores the assessment of ET and ET partitioning (i.e., soil water evaporation and plant transpiration), considering three different resistance models using ground-based information and aerial high-resolution imagery from the Grape Remote sensing Atmospheric Profile and Evapotranspiration eXperiment (GRAPEX). We developed a new method for temperature partitioning that incorporated a quantile technique separation (QTS) and high-resolution sUAS information. This new method, coupled with the TSEB model (called TSEB-2TQ), improved sensible heat flux (H) estimation, regarding the bias, with around 61% and 35% compared with the H from the TSEB-PT and TSEB-2T, respectively. Comparisons among ET partitioning estimates from three different methods (Modified Relaxed Eddy Accumulation—MREA; Flux Variance Similarity—FVS; and Conditional Eddy Covariance—CEC) based on EC flux tower data show that the transpiration estimates obtained from the FVS method are statistically different from the estimates from the MREA and the CEC methods, but the transpiration from the MREA and CEC methods are statistically the same. By using the transpiration from the CEC method to compare with the transpiration modeled by different TSEB models, the TSEB-2TQ shows better agreement with the transpiration obtained via the CEC method. Additionally, the transpiration estimation from TSEB-2TQ coupled with different resistance models resulted in insignificant differences. This comparison is one of the first for evaluating ET partitioning estimation from sUAS imagery based on eddy covariance-based partitioning methods.

Accurate characterization of evapotranspiration (ET) is imperative in water-limited cropping systems such as California vineyards and almond orchards. Satellite-based ET modeling techniques, including the atmosphere–land exchange inverse model (ALEXI) and associated flux disaggregation technique (DisALEXI), have proven reliable in determining field scale ET. However, validation efforts typically focus on ET and omit an evaluation of partitioned evaporation (E) and transpiration (T). ALEXI/DisALEXI is based on the two-source energy balance (TSEB) model, making it uniquely qualified to derive E and T individually. The current study evaluated E and T estimates derived using two formulations of DisALEXI; one based on Priestley-Taylor (DisALEXI-PT) and the other on Penman-Monteith (DisALEXI-PM). The modeled values were validated against partitioned fluxes derived from the conditional eddy covariance (CEC) approach using EC flux towers in three wine grape vineyards and three almond orchards for the year 2021. Modeled estimates were derived using Landsat 8 Collection 2 thermal infrared and surface reflectance imagery as well as Harmonized Landsat and Sentinel-2 surface reflectance datasets as input into DisALEXI. The results indicated that the modeled total ET fluxes were similar between the two methods, but the partitioned values diverged, with DisALEXI-PT overestimating E and slightly underestimating T when compared to CEC estimates. Conversely, DisALEXI-PM agreed better with CEC-derived E and overestimated T estimates under non-advective conditions. Compared to one another, DisALEXI-PM estimated canopy temperatures ~5 °C cooler and soil temperatures ~5 °C warmer than DisALEXI-PT, causing differences in E and T of −2.6 mm day−1 and +2.6 mm day−1, respectively. The evaluation of the iterative process required for DisALEXI indicates DisALEXI-PM ET values converge on ALEXI ET with proportionate adjustments to E and T, while DisALEXI-PT convergence is driven by adjustments to E. The analysis presented here can potentially drive improvements in the modeling framework to provide specific soil and canopy consumptive water use information in unique canopy structures, allowing for improved irrigation and water use efficiencies in these water-limited systems.

The Caucasus mountain range has impacted on the culture and genetics of the wider region. Here, the authors generate genome-wide SNP data for 45 Eneolithic and Bronze Age individuals across the Caucasus, and find distinct genetic clusters between mountain and steppe zones as well as occasional gene-flow.

Evapotranspiration (ET) represents crop water use and is a key indicator of crop health. Accurate estimation of ET is critical for agricultural irrigation and water resource management. ET retrieval using energy balance methods with remotely sensed thermal infrared data as the key input has been widely applied for irrigation scheduling, yield prediction, drought monitoring and so on. However, limitations on the spatial and temporal resolution of available thermal satellite data combined with the effects of cloud contamination constrain the amount of detail that a single satellite can provide. Fusing satellite data from different satellites with varying spatial and temporal resolutions can provide a more continuous estimation of daily ET at field scale. In this study, we applied an ET fusion modeling system, which uses a surface energy balance model to retrieve ET using both Landsat and Moderate Resolution Imaging Spectroradiometer (MODIS) data and then fuses the Landsat and MODIS ET retrieval timeseries using the Spatial-Temporal Adaptive Reflectance Fusion Model (STARFM). In this paper, we compared different STARFM ET fusion implementation strategies over various crop lands in the central California. In particular, the use of single versus two Landsat-MODIS pair images to constrain the fusion is explored in cases of rapidly changing crop conditions, as in frequently harvested alfalfa fields, as well as an improved dual-pair method. The daily 30 m ET retrievals are evaluated with flux tower observations and analyzed based on land cover type. This study demonstrates improvement using the new dual-pair STARFM method compared with the standard one-pair STARFM method in estimating daily field scale ET for all the major crop types in the study area.

The El Argar society of the Bronze Age in the southeast of the Iberian Peninsula (2200-1550 cal BCE) was among the first complex societies in Europe. Its economy was based on cereal cultivation and metallurgy, it was organized hierarchically, and successively expanded its territory. Most of the monumentally fortified settlements lay on steeply sloped mountains, separated by fertile plains, and allowed optimal control of the area. Here, we explore El Argar human diets, animal husbandry strategies, and food webs using stable carbon and nitrogen isotope analysis of charred cereal grains as well as human and animal bone collagen. The sample comprised 75 human individuals from the sites of La Bastida (n = 52) and Gatas (n = 23), 32 domesticated and wild animals as well as 76 barley and 29 wheat grains from two chronological phases of a total time span of ca. 650 years. The grains indicate extensive cereal cultivation under rain-fed conditions with little to moderate application of manure. Especially at La Bastida, crops and their by-products contributed significantly to the forage of the domesticated animals, which attests to a strong interrelation of cultivation and animal husbandry. Trophic level spacing and Bayesian modelling confirm that human diets were largely based on barley with some contribution of meat or dairy products. A cross-sectional analysis of bone collagen suggests that children were breastfed until about 1.5-2 years old, and infants from Gatas may have suffered from more metabolic stress than those at La Bastida. Adults of both sexes consumed similar diets that reflect social and chronological variation to some extent. Despite significantly higher δ13C and δ15N values at La Bastida than at Gatas, the isotopic data of the staple crops and domestic animals from both sites indicate that such differences do not necessarily correspond to different average human diets, but to agricultural strategies. These results urge for a reassessment of previous isotope studies in which only human remains have been taken into account. The study highlights that disentangling the complex influences on human isotope compositions requires a firm set of comparative data.

The decline of the Roman rule caused significant political instability and led to the emergence of various 'Barbarian' powers. While the names of the involved groups appeared in written sources, it is largely unknown how these changes affected the daily lives of the people during the 5th century AD. Did late Roman traditions persist, did new customs emerge, and did both amalgamate into new cultural expressions? A prime area to investigate these population and settlement historical changes is the Carpathian Basin (Hungary). Particularly, we studied archaeological and anthropological evidence, as well as radiogenic and stable isotope ratios of strontium, carbon, and nitrogen of human remains from 96 graves at the cemetery of Mözs-Icsei dűlő. Integrated data analysis suggests that most members of the founder generation at the site exhibited burial practises of late Antique traditions, even though they were heterogeneous regarding their places of origin and dietary habits. Furthermore, the isotope data disclosed a nonlocal group of people with similar dietary habits. According to the archaeological evidence, they joined the community a few decades after the founder generation and followed mainly foreign traditions with artificial skull modification as their most prominent characteristic. Moreover, individuals with modified skulls and late Antique grave attributes attest to deliberate cultural amalgamation, whereas burials of largely different isotope ratios underline the recipient habitus of the community. The integration of archaeological and bioarchaeological information at the individual level discloses the complex coalescence of people and traditions during the 5th century.

The flanks of the Caucasus Mountains and the steppe landscape to their north offered highly productive grasslands for Bronze Age herders and their flocks of sheep, goat, and cattle. While the archaeological evidence points to a largely pastoral lifestyle, knowledge regarding the general composition of human diets and their variation across landscapes and during the different phases of the Bronze Age is still restricted. Human and animal skeletal remains from the burial mounds that dominate the archaeological landscape and their stable isotope compositions are major sources of dietary information. Here, we present stable carbon and nitrogen isotope data of bone collagen of 105 human and 50 animal individuals from the 5th millennium BC to the Sarmatian period, with a strong focus on the Bronze Age and its cultural units including Maykop, Yamnaya, Novotitorovskaya, North Caucasian, Catacomb, post-Catacomb and late Bronze Age groups. The samples comprise all inhumations with sufficient bone preservation from five burial mound sites and a flat grave cemetery as well as subsamples from three further sites. They represent the Caucasus Mountains in the south, the piedmont zone and Kuban steppe with humid steppe and forest vegetation to its north, and more arid regions in the Caspian steppe. The stable isotope compositions of the bone collagen of humans and animals varied across the study area and reflect regional diversity in environmental conditions and diets. The data agree with meat, milk, and/or dairy products from domesticated herbivores, especially from sheep and goats having contributed substantially to human diets, as it is common for a largely pastoral economy. This observation is also in correspondence with the faunal remains observed in the graves and offerings of animals in the mound shells. In addition, foodstuffs with elevated carbon and nitrogen isotope values, such as meat of unweaned animals, fish, or plants, also contributed to human diets, especially among communities living in the more arid landscapes. The regional distinction of the animal and human data with few outliers points to mobility radii that were largely concentrated within the environmental zones in which the respective sites are located. In general, dietary variation among the cultural entities as well as regarding age, sex and archaeologically indicated social status is only weakly reflected. There is, however, some indication for a dietary shift during the Early Bronze Age Maykop period.

Prehistoric warfare and massacres of Linearbandkeramik (LBK) communities are evidenced by mass graves from the Early Neolithic of Central Europe. Here, Meyer et al. describe a newly discovered mass grave from Germany revealing the execution of a predominantly adult male group of non-local individuals.

A new approach is proposed to derive evapotranspiration (E) and irrigation requirements by implementing the combination equation models of Penman–Monteith and Shuttleworth and Wallace with surface parameters and resistances derived from Sentinel-2 data. Surface parameters are derived from Sentinel-2 and used as an input in these models; namely: the hemispherical shortwave albedo, leaf area index and water status of the soil and canopy ensemble evaluated by using a shortwave infrared-based index. The proposed approach has been validated with data acquired during the GRAPEX (Grape Remote-sensing Atmospheric Profile and Evapotranspiration eXperiment) in California irrigated vineyards. The E products obtained with the combination equation models are evaluated by using eddy covariance flux tower measurements and are additionally compared with surface energy balance models with Landsat-7 and -8 thermal infrared data. The Shuttleworth and Wallace (S-W S-2) model provides an accuracy comparable to thermal-based methods when using local meteorological data, with daily E errors < 1 mm/day, which increased from 1 to 1.5 mm/day using meteorological forcing data from atmospheric models. The advantage of using the S-W S-2 modeling approach for monitoring ET is the high temporal revisit time of the Sentinel-2 satellites and the finer pixel resolution. These results suggest that, by integrating the thermal-based data fusion approach with the S-W S-2 modeling scheme, there is the potential to increase the frequency and reliability of satellite-based daily evapotranspiration products.

Accurate and frequent monitoring of evapotranspiration (ET) at sub-field scales can provide valuable information for agricultural water management, quantifying crop water use and stress toward the goal of increasing crop water use efficiency and production. Using land-surface temperature (LST) data retrieved from Landsat thermal infrared (TIR) imagery, along with surface reflectance data describing albedo and vegetation cover fraction, surface energy balance models can generate ET maps down to a 30 m spatial resolution. However, the temporal sampling by such maps can be limited by the relatively infrequent revisit period of Landsat data (8 days for combined Landsats 7 and 8), especially in cloudy areas experiencing rapid changes in moisture status. The Sentinel-2 (S2) satellites, as a good complement to the Landsat system, provide surface reflectance data at 10–20 m spatial resolution and 5 day revisit period but do not have a thermal sensor. On the other hand, the Visible Infrared Imaging Radiometer Suite (VIIRS) provides TIR data on a near-daily basis with 375 m resolution, which can be refined through thermal sharpening using S2 reflectances. This study assesses the utility of augmenting the Harmonized Landsat and Sentinel-2 (HLS) dataset with S2-sharpened VIIRS as a thermal proxy source on S2 overpass days, enabling 30 m ET mapping at a potential combined frequency of 2–3 days (including Landsat). The value added by including VIIRS-S2 is assessed both retrospectively and operationally in comparison with flux tower observations collected from several U.S. agricultural sites covering a range of crop types. In particular, we evaluate the performance of VIIRS-S2 ET estimates as a function of VIIRS view angle and cloud masking approach. VIIRS-S2 ET retrievals (MAE of 0.49 mm d−1 against observations) generally show comparable accuracy to Landsat ET (0.45 mm d−1) on days of commensurate overpass, but with decreasing performance at large VIIRS view angles. Low-quality VIIRS-S2 ET retrievals linked to imperfect VIIRS/S2 cloud masking are also discussed, and caution is required when applying such data for generating ET timeseries. Fused daily ET time series benefited during the peak growing season from the improved multi-source temporal sampling afforded by VIIRS-S2, particularly in cloudy regions and over surfaces with rapidly changing vegetation conditions, and value added for real-time monitoring applications is discussed. This work demonstrates the utility and feasibility of augmenting the HLS dataset with sharpened VIIRS TIR imagery on S2 overpass dates for generating high spatiotemporal resolution ET products.

In 2016, an extraordinary burial of a young adult individual was discovered at the Late Pre-Pottery Neolithic B (LPPNB, 7,500-6,900 BCE) settlement of Ba'ja in southern Jordan. This burial has exceptional grave goods and an elaborate grave construction. It suggests discussing anew reconstructions of early Neolithic social structures. In this article, we will summarize former theories on the emergence of leadership and hierarchies and present a multivariate model according to which anthropological and archaeological data of the burial will be analyzed. In conclusion, we surmise that early Neolithic hierarchization in southern Jordan was based on corporate pathways to power rather than self-interested aggrandizers. However, some aspects of the burial point to regional exchange networks of prestige goods, a trait considered characteristic of network based leadership. In line with anthropological and sociological research, we argue that pathways to power should be considered as relational processes that can be understood only when comparing traits of the outstanding person to her/his social environment.

A well-planned irrigation management strategy is crucial for successful wine grape production and is highly dependent on accurate assessments of water stress. Precision irrigation practices may benefit from the quantification of within-field spatial variability and temporal patterns of evapotranspiration (ET). A spatiotemporal modeling framework is proposed to delineate the vineyard into homogeneous areas (i.e., management zones) according to their ET patterns. The dataset for this study relied on ET retrievals from multiple satellite platforms, generating estimates at high spatial (30 m) and temporal (daily) resolutions for a Vitis vinifera Pinot noir vineyard in the Central Valley of California during the growing seasons of 2015-2018. Time-series decomposition was used to deconstruct the time series of each pixel into three components: long-term trend, seasonality, and remainder, which indicates daily fluctuations. For each time-series component, a time-series clustering (TSC) algorithm was applied to partition the time series of all pixels into homogeneous groups and generate TSC maps. The TSC maps were compared for spatial similarities using the V-measure statistic. A random forest (RF) classification algorithm was used for each TSC map against six environmental variables (elevation, slope, northness, lithology, topographic wetness index, and soil type) to check for spatial association between ET-TSC maps and the local characteristics in the vineyard. Finally, the TSC maps were used as independent variables against yield (ton ha-1) using analysis of variance (ANOVA) to assess whether the TSC maps explained yield variability. The trend and seasonality TSC maps had a moderate spatial association (V = 0.49), while the remainder showed dissimilar spatial patterns to seasonality and trend. The RF model showed high error matrix-based prediction accuracy levels ranging between 86% and 90%. For the trend and seasonality models, the most important predictor was soil type, followed by elevation, while the remainder TSC was strongly linked with northness spatial variability. The yield levels corresponding to the two clusters in all TSC were significantly different. These findings enabled spatial quantification of ET time series at different temporal scales that may benefit within-season decision-making regarding the amounts, timing, intervals, and location of irrigation. The proposed framework may be applicable to other cases in both agricultural systems and environmental modeling.

Both TH2-dependent helminth killing and suppression of the TH2 effector response have been attributed to macrophages (MΦ) activated by IL-4 (M(IL-4)). To investigate how M(IL-4) contribute to diverse infection outcomes, the MΦ compartment of susceptible BALB/c mice and more resistant C57BL/6 mice was profiled during infection of the pleural cavity with the filarial nematode, Litomosoides sigmodontis. C57BL/6 mice exhibited a profoundly expanded resident MΦ (resMΦ) population, which was gradually replenished from the bone marrow in an age-dependent manner. Infection status did not alter the bone-marrow derived contribution to the resMΦ population, confirming local proliferation as the driver of resMΦ expansion. Significantly less resMΦ expansion was observed in the susceptible BALB/c strain, which instead exhibited an influx of monocytes that assumed an immunosuppressive PD-L2+ phenotype. Inhibition of monocyte recruitment enhanced nematode killing. Thus, the balance of monocytic vs. resident M(IL-4) numbers varies between inbred mouse strains and impacts infection outcome.

In viticulture, deficit irrigation strategies are often implemented to control vine canopy growth and to impose stress at critical stages of vine growth to improve wine grape quality. To support deficit irrigation scheduling, remote sensing technologies can be employed in the mapping of evapotranspiration (ET) at the field to sub-field scales, quantifying time-varying vineyard water requirements and actual water use. In the current study, we investigate the utility of ET maps derived from thermal infrared satellite imagery over a vineyard in the Central Valley of California equipped with a variable rate drip irrigation (VRDI) system which enables differential water applications at the 30 × 30 m scale. To support irrigation management at that scale, we utilized a thermal-based multi-sensor data fusion approach to generate weekly total actual ET (ETa) estimates at 30 m spatial resolution, coinciding with the resolution of the Landsat reflectance bands. Crop water requirements (ETc) were defined with a vegetative index (VI)-based approach. To test capacity to capture stress signals, the vineyard was sub-divided into four blocks with different irrigation management strategies and goals, inducing varying degrees of stress during the growing season. Results indicate derived weekly total ET from the thermal-based data fusion approach match well with observations. The thermal-based method was also able to capture the spatial heterogeneity in ET over the vineyard due to a water stress event imposed on two of the four vineyard blocks. This transient stress event was not reflected in the VI-based ETc estimate, highlighting the value of thermal band imaging. While the data fusion system provided valuable information, latency in current satellite data availability, particularly from Landsat, impacts operational applications over the course of a growing season.

The energy delivered to the land surface via insolation is a primary driver of evapotranspiration (ET)—the exchange of water vapor between the land and atmosphere. Spatially distributed ET products are in great demand in the water resource management community for real-time operations and sustainable water use planning. The accuracy and deliverability of these products are determined in part by the characteristics and quality of the insolation data sources used as input to the ET models. This paper investigates the practical utility of three different insolation datasets within the context of a satellite-based remote sensing framework for mapping ET at high spatiotemporal resolution, in an application over the Sacramento⁻San Joaquin Delta region in California. The datasets tested included one reanalysis product: The Climate System Forecast Reanalysis (CFSR) at 0.25° spatial resolution, and two remote sensing insolation products generated with geostationary satellite imagery: a product for the continental United States at 0.2°, developed by the University of Wisconsin Space Sciences and Engineering Center (SSEC) and a coarser resolution (1°) global Clouds and the Earth’s Radiant Energy System (CERES) product. The three insolation data sources were compared to pyranometer data collected at flux towers within the Delta region to establish relative accuracy. The satellite products significantly outperformed CFSR, with root-mean square errors (RMSE) of 2.7, 1.5, and 1.4 MJ·m−2·d−1 for CFSR, CERES, and SSEC, respectively, at daily timesteps. The satellite-based products provided more accurate estimates of cloud occurrence and radiation transmission, while the reanalysis tended to underestimate solar radiation under cloudy-sky conditions. However, this difference in insolation performance did not translate into comparable improvement in the ET retrieval accuracy, where the RMSE in daily ET was 0.98 and 0.94 mm d−1 using the CFSR and SSEC insolation data sources, respectively, for all the flux sites combined. The lack of a notable impact on the aggregate ET performance may be due in part to the predominantly clear-sky conditions prevalent in central California, under which the reanalysis and satellite-based insolation data sources have comparable accuracy. While satellite-based insolation data could improve ET retrieval in more humid regions with greater cloud-cover frequency, over the California Delta and climatologically similar regions in the western U.S., the CFSR data may suffice for real-time ET modeling efforts.

The ability to accurately monitor and anticipate changes in consumptive water use associated with changing land use and land management is critical to developing sustainable water management strategies in water-limited climatic regions. In this paper, we present an application of a remote sensing data fusion technique for developing high spatiotemporal resolution maps of evapotranspiration (ET) at scales that can be associated with changes in land use. The fusion approach combines ET map timeseries developed using an multi-scale energy balance algorithm applied to thermal data from Earth observation platforms with high spatial but low temporal resolution (e.g., Landsat) and with moderate resolution but frequent temporal coverage (e.g., MODIS (Moderate Resolution Imaging Spectroradiometer)). The approach is applied over the Sacramento-San Joaquin Delta region in California—an area critical to both agricultural production and drinking water supply within the state that has recently experienced stresses on water resources due to a multi-year (2012–2017) extreme drought. ET “datacubes” with 30-m resolution and daily timesteps were constructed for the 2015–2016 water years and related to detailed maps of land use developed at the same spatial scale. The ET retrievals are evaluated at flux sites over multiple land covers to establish a metric of accuracy in the annual water use estimates, yielding root-mean-square errors of 1.0, 0.8, and 0.3 mm day−1 at daily, monthly, and yearly timesteps, respectively, for all sites combined. Annual ET averaged over the Delta changed only 3 mm year−1 between water years, from 822 to 819 mm year−1, translating to an area-integrated total change in consumptive water use of seven thousand acre-feet (TAF). Changes were largest in areas with recorded land-use change between water years—most significantly, fallowing of crop land presumably in response to reductions in water availability and allocations due to the drought. Moreover, the time evolution in water use associated with wetland restoration—an effort aimed at reducing subsidence and carbon emissions within the inner Delta—is assessed using a sample wetland chronosequence. Region-specific matrices of consumptive water use associated with land use changes may be an effective tool for policymakers and farmers to understand how land use conversion could impact consumptive use and demand.

Evapotranspiration (ET) is a key component of the water balance, especially in arid and semiarid regions. The current study takes advantage of spatially-distributed, near real-time information provided by satellite remote sensing to develop a regional scale ET product derived from remotely-sensed observations. ET is calculated by scaling PET estimated from Moderate Resolution Imaging Spectroradiometer (MODIS) products with downscaled soil moisture derived using the Soil Moisture Ocean Salinity (SMOS) satellite and a second order polynomial regression formula. The MODis-Soil Moisture ET (MOD-SMET) estimates are validated using four flux tower sites in southern Arizona USA, a calibrated empirical ET model, and model output from Version 2 of the North American Land Data Assimilation System (NLDAS-2). Validation against daily eddy covariance ET indicates correlations between 0.63 and 0.83 and root mean square errors (RMSE) between 40 and 96 W/m2. MOD-SMET estimates compare well to the calibrated empirical ET model, with a −0.14 difference in correlation between sites, on average. By comparison, NLDAS-2 models underestimate daily ET compared to both flux towers and MOD-SMET estimates. Our analysis shows the MOD-SMET approach to be effective for estimating ET. Because it requires limited ancillary ground-based data and no site-specific calibration, the method is applicable to regions where ground-based measurements are not available.

The inland area of southwestern Sweden is well known for its well-preserved archaeological animal and human remains dating back to the Mesolithic and Neolithic (10000-4000 and 4000-1700 BC). They allow application of multiple bioarchaeological methods, giving insights into various and complementary aspects of prehistoric human life, as well as economic and social structures. One important aspect concerns human mobility and its relation to social networks and to circulation of objects. Here, strontium isotope analysis plays a crucial role. The present study aims to construct a strontium isotope baseline of southwestern Sweden with considerably greater coverage and higher resolution than previously published data. As the region has been affected by glacial events, the relation between bedrock geology and isotope signals of the bioavailable strontium in such areas is given special attention. We determined strontium isotope ratios for 61 water and five archaeological animal samples, and combined the data with previous measurements of two water and 21 non-domestic faunal samples. The results reveal a complex pattern. Several areas with distinct baseline ranges can be distinguished, although with overlaps between some of them. Overall, the bioavailable strontium isotope signals mirror the basement geology of the region. The highest ratios occur in the geologically oldest eastern parts of the Precambrian terrain, while lower ratios are found in the western part, and the lowest ratios occur in the youngest Paleozoic areas. At the same time, there are minor deviations compared to the underlying bedrock, due to glacial transport, overlying sediments, and local intrusions of younger rocks. The background data set now available allows for more nuanced and detailed interpretations of human and animal mobility in the region, in particular by identification of subregions with differing strontium isotope ratios within the Precambrian province. Also, we can now identify long distance mobility with greater confidence.

Investigation of human diet during the Neolithic has often been limited to a few archaeological cultures or single sites. In order to provide insight into the development of human food consumption and husbandry strategies, our study explores bone collagen carbon and nitrogen isotope data from 466 human and 105 faunal individuals from 26 sites in central Germany. It is the most extensive data set to date from an enclosed geographic microregion, covering 4,000 years of agricultural history from the Early Neolithic to the Early Bronze Age. The animal data show that a variety of pastures and dietary resources were explored, but that these changed remarkably little over time. In the human δ15N however we found a significant increase with time across the different archaeological cultures. This trend could be observed in all time periods and archaeological cultures (Bell Beaker phenomenon excluded), even on continuously populated sites. Since there was no such trend in faunal isotope values, we were able largely to exclude manuring as the cause of this effect. Based on the rich interdisciplinary data from this region and archaeological period we can argue that meat consumption increased with the increasing duration of farming subsistence. In δ13C, we could not observe any clear increasing or decreasing trends during the archaeological time periods, either for humans or for animals, which would have suggested significant changes in the environment and landscape use. We discovered sex-related dietary differences, with males of all archaeological periods having higher δ15N values than females, and an age-related increasing consumption of animal protein. An initial decrease of δ15N-values at the age of 1-2 years reveals partial weaning, while complete weaning took place at the age of 3-4 years.

Manganese oxides are one of the most important groups of materials in energy storage science. In order to fully leverage their application potential, precise control of their properties such as particle size, surface area and Mnx+ oxidation state is required. Here, Mn3O4 and Mn5O8 nanoparticles as well as mesoporous α-Mn2O3 particles were synthesized by calcination of Mn(II) glycolate nanoparticles obtained through an economical route based on a polyol synthesis. The preparation of the different manganese oxides via one route facilitates assigning actual structure–property relationships. The oxidation process related to the different MnOx species was observed by in situ X-ray diffraction (XRD) measurements showing time- and temperature-dependent phase transformations occurring during oxidation of the Mn(II) glycolate precursor to α-Mn2O3 via Mn3O4 and Mn5O8 in O2 atmosphere. Detailed structural and morphological investigations using transmission electron microscopy (TEM) and powder XRD revealed the dependence of the lattice constants and particle sizes of the MnOx species on the calcination temperature and the presence of an oxidizing or neutral atmosphere. Furthermore, to demonstrate the application potential of the synthesized MnOx species, we studied their catalytic activity for the oxygen reduction reaction in aprotic media. Linear sweep voltammetry revealed the best performance for the mesoporous α-Mn2O3 species.

Reconstructing stock herding strategies and land use is key to comprehending past human social organization and economy. We present laser-ablation strontium and carbon isotope data from 25 cattle (Bos taurus) to reconstruct mobility and infer herding management at the Swiss lakeside settlement of Arbon Bleiche 3, occupied for only 15 years (3384-3370 BC). Our results reveal three distinct isotopic patterns that likely reflect different herding strategies: 1) localized cattle herding, 2) seasonal movement, and 3) herding away from the site year-round. Different strategies of herding are not uniformly represented in various areas of the settlement, which indicates specialist modes of cattle management. The pressure on local fodder capacities and the need for alternative herding regimes must have involved diverse access to grazing resources. Consequently, the increasing importance of cattle in the local landscape was likely to have contributed to the progress of socio-economic differentiation in early agricultural societies in Europe.

The analysis of the human remains from the megalithic tomb at Alto de Reinoso represents the widest integrative study of a Neolithic collective burial in Spain. Combining archaeology, osteology, molecular genetics and stable isotope analysis (87Sr/86Sr, δ15N, δ13C) it provides a wealth of information on the minimum number of individuals, age, sex, body height, pathologies, mitochondrial DNA profiles, kinship relations, mobility, and diet. The grave was in use for approximately one hundred years around 3700 cal BC, thus dating from the Late Neolithic of the Iberian chronology. At the bottom of the collective tomb, six complete and six partial skeletons lay in anatomically correct positions. Above them, further bodies represented a subsequent and different use of the tomb, with almost all of the skeletons exhibiting signs of manipulation such as missing skeletal parts, especially skulls. The megalithic monument comprised at least 47 individuals, including males, females, and subadults, although children aged 0-6 years were underrepresented. The skeletal remains exhibited a moderate number of pathologies, such as degenerative joint diseases, healed fractures, cranial trauma, and a low intensity of caries. The mitochondrial DNA profiles revealed a pattern pointing to a closely related local community with matrilineal kinship patterns. In some cases adjacent individuals in the bottom layer showed familial relationships. According to their strontium isotope ratios, only a few individuals were likely to have spent their early childhood in a different geological environment, whilst the majority of individuals grew up locally. Carbon and nitrogen isotope analysis, which was undertaken to reconstruct the dietary habits, indicated that this was a homogeneous group with egalitarian access to food. Cereals and small ruminants were the principal sources of nutrition. These data fit in well with a lifestyle typical of sedentary farming populations in the Spanish Meseta during this period of the Neolithic.

The transition from the Neolithic to the Early Bronze Age in Central Europe has often been considered as a supra-regional uniform process, which led to the growing mastery of the new bronze technology. Since the 1920s, archaeologists have divided the Early Bronze Age into two chronological phases (Bronze A1 and A2), which were also seen as stages of technical progress. On the basis of the early radiocarbon dates from the cemetery of Singen, southern Germany, the beginning of the Early Bronze Age in Central Europe was originally dated around 2300/2200 BC and the transition to more complex casting techniques (i.e., Bronze A2) around 2000 BC. On the basis of 140 newly radiocarbon dated human remains from Final Neolithic, Early and Middle Bronze Age cemeteries south of Augsburg (Bavaria) and a re-dating of ten graves from the cemetery of Singen, we propose a significantly different dating range, which forces us to re-think the traditional relative and absolute chronologies as well as the narrative of technical development. We are now able to date the beginning of the Early Bronze Age to around 2150 BC and its end to around 1700 BC. Moreover, there is no transition between Bronze (Bz) A1 and Bronze (Bz) A2, but a complete overlap between the type objects of the two phases from 1900-1700 BC. We thus present a revised chronology of the assumed diagnostic type objects of the Early Bronze Age and recommend a radiocarbon-based view on the development of the material culture. Finally, we propose that the traditional phases Bz A1 and Bz A2 do not represent a chronological sequence, but regionally different social phenomena connected to the willingness of local actors to appropriate the new bronze technology.

In 2005 to 2007 45 skeletons of adults and subadults were excavated at the Lombard period cemetery at Szólád (6th century A.D.), Hungary. Embedded into the well-recorded historical context, the article presents the results obtained by an integrative investigation including anthropological, molecular genetic and isotopic (δ(15)N, δ(13)C, (87)Sr/(86)Sr) analyses. Skeletal stress markers as well as traces of interpersonal violence were found to occur frequently. The mitochondrial DNA profiles revealed a heterogeneous spectrum of lineages that belong to the haplogroups H, U, J, HV, T2, I, and K, which are common in present-day Europe and in the Near East, while N1a and N1b are today quite rare. Evidence of possible direct maternal kinship was identified in only three pairs of individuals. According to enamel strontium isotope ratios, at least 31% of the individuals died at a location other than their birthplace and/or had moved during childhood. Based on the peculiar 87 Sr/86 Sr ratio distribution between females, males, and subadults in comparison to local vegetation and soil samples, we propose a three-phase model of group movement. An initial patrilocal group with narrower male but wider female Sr isotope distribution settled at Szólád, whilst the majority of subadults represented in the cemetery yielded a distinct Sr isotope signature. Owing to the virtual absence of Szólád-born adults in the cemetery, we may conclude that the settlement was abandoned after approx. one generation. Population heterogeneity is furthermore supported by the carbon and nitrogen isotope data. They indicate that a group of high-ranking men had access to larger shares of animal-derived food whilst a few individuals consumed remarkable amounts of millet. The inferred dynamics of the burial community are in agreement with hypotheses of a highly mobile lifestyle during the Migration Period and a short-term occupation of Pannonia by Lombard settlers as conveyed by written sources.

Hearing relies on faithful signal transmission by cochlear inner hair cells (IHCs) onto auditory fibres over a wide frequency and intensity range. Exocytosis at IHC ribbon synapses is triggered by Ca(2+) inflow through Ca(V)1.3 (L-type) Ca(2+) channels. We investigated the macroscopic (whole-cell) and elementary (cell-attached) properties of Ca(2+) currents in IHCs positioned at the middle turn (frequency ∼ 2 kHz) of the adult gerbil cochlea, which is their most sensitive hearing region. Using near physiological recordings conditions (body temperature and a Na(+) based extracellular solution), we found that the macroscopic Ca(2+) current activates and deactivates very rapidly (time constant below 1 ms) and inactivates slowly and only partially. Single-channel recordings showed an elementary conductance of 15 pS, a sub-ms latency to first opening, and a very low steady-state open probability (Po: 0.024 in response to 500-ms depolarizing steps at ∼-18 mV). The value of Po was significantly larger (0.06) in the first 40 ms of membrane depolarization, which corresponds to the time when most Ca(2+) channel openings occurred clustered in bursts (mean burst duration: 19 ms). Both the Po and the mean burst duration were smaller than those previously reported in high-frequency basal IHCs. Finally, we found that middle turn IHCs are likely to express about 4 times more Ca(2+) channels per ribbon than basal cells. We propose that middle-turn IHCs finely-tune Ca(V)1.3 Ca(2+) channel gating in order to provide reliable information upon timing and intensity of lower-frequency sounds.

The transition from mobile to sedentary life was one of the greatest social challenges of the human past. Yet little is known about the impact of this fundamental change on social interactions amongst early Neolithic communities, which are best recorded in the Near East. The importance of social processes associated with these economic and ecological changes has long been underestimated. However, ethnographic observations demonstrate that generalized reciprocity - such as open access to resources and land - had to be reduced to a circumscribed group before regular farming and herding could be successfully established. Our aim was thus to investigate the role of familial relationships as one possible factor within this process of segregation as recorded directly in the skeletal remains, rather than based on hypothetical correlations such as house types and social units. Here we present the revealing results of the systematically recorded epigenetic characteristics of teeth and skulls of the late Pre-Pottery Neolithic community of Basta in Southern Jordan (Figure S1). Additionally, mobility was reconstructed via a systematic strontium (Sr) isotope analysis of tooth enamel of the Basta individuals. The frequency of congenitally missing maxillary lateral incisors in the 9,000-year-old community of Basta is exceptionally high (35.7%). Genetic studies and a worldwide comparison of the general rate of this dental anomaly in modern and historic populations show that the enhanced frequency can only be explained by close familial relationships akin to endogamy. This is supported by strontium isotope analyses of teeth, indicating a local origin of almost all investigated individuals. Yet, the accompanying archaeological finds document far-reaching economic exchange with neighboring groups and a population density hitherto unparalleled. We thus conclude that endogamy in the early Neolithic village of Basta was not due to geographic isolation or a lack of exogamous mating partners but a socio-cultural choice.

Tinnitus is proposed to be caused by decreased central input from the cochlea, followed by increased spontaneous and evoked subcortical activity that is interpreted as compensation for increased responsiveness of central auditory circuits. We compared equally noise exposed rats separated into groups with and without tinnitus for differences in brain responsiveness relative to the degree of deafferentation in the periphery. We analyzed (1) the number of CtBP2/RIBEYE-positive particles in ribbon synapses of the inner hair cell (IHC) as a measure for deafferentation; (2) the fine structure of the amplitudes of auditory brainstem responses (ABR) reflecting differences in sound responses following decreased auditory nerve activity and (3) the expression of the activity-regulated gene Arc in the auditory cortex (AC) to identify long-lasting central activity following sensory deprivation. Following moderate trauma, 30% of animals exhibited tinnitus, similar to the tinnitus prevalence among hearing impaired humans. Although both tinnitus and no-tinnitus animals exhibited a reduced ABR wave I amplitude (generated by primary auditory nerve fibers), IHCs ribbon loss and high-frequency hearing impairment was more severe in tinnitus animals, associated with significantly reduced amplitudes of the more centrally generated wave IV and V and less intense staining of Arc mRNA and protein in the AC. The observed severe IHCs ribbon loss, the minimal restoration of ABR wave size, and reduced cortical Arc expression suggest that tinnitus is linked to a failure to adapt central circuits to reduced cochlear input.

Inner hair cells (IHCs), the primary sensory receptors of the mammalian cochlea, fire spontaneous Ca(2+) action potentials before the onset of hearing. Although this firing activity is mainly sustained by a depolarizing L-type (Ca(V)1.3) Ca(2+) current (I(Ca)), IHCs also transiently express a large Na(+) current (I(Na)). We aimed to investigate the specific contribution of I(Na) to the action potentials, the nature of the channels carrying the current and whether the biophysical properties of I(Na) differ between low- and high-frequency IHCs. We show that I(Na) is highly temperature-dependent and activates at around -60 mV, close to the action potential threshold. Its size was larger in apical than in basal IHCs and between 5% and 20% should be available at around the resting membrane potential (-55 mV/-60 mV). However, in vivo the availability of I(Na) could potentially increase to >60% during inhibitory postsynaptic potential activity, which transiently hyperpolarize IHCs down to as far as -70 mV. When IHCs were held at -60 mV and I(Na) elicited using a simulated action potential as a voltage command, we found that I(Na) contributed to the subthreshold depolarization and upstroke of an action potential. We also found that I(Na) is likely to be carried by the TTX-sensitive channel subunits Na(V)1.1 and Na(V)1.6 in both apical and basal IHCs. The results provide insight into how the biophysical properties of I(Na) in mammalian cochlear IHCs could contribute to the spontaneous physiological activity during cochlear maturation in vivo.