A minimal receptor-Ig chimera of human FcepsilonRI alpha-chain efficiently binds secretory and membrane IgE

We constructed a soluble minimal receptor-Ig chimera in which the two extracellular domains of human Fcepsilonhain (D1 and D2) were fused to the dimerizing C-terminal domain of human IgG1 heavy chain (gamma1-CH3). The protein was expressed and actively secreted by Chinese hamster ovary (CHO) cells as a fully glycosylated soluble dimeric protein. It showed efficient binding both to human membrane-bound IgE isoforms and to the two secretory IgE isoforms. Moreover, the dimeric receptor binds IgE with the expected 1:2 stoichiometry. The receptor-Ig chimera, in 2-fold molar excess, inhibited engagement of secretory IgE to rat basophilic leukemia cells expressing the human alphabetagamma receptor. Full self-nature and inability to bind Fcgamma receptors make this protein an attractive candidate for clinical applications and a novel biotechnological tool for atopic allergy research.     

Trophic ecology of tadpoles in floodplain wetlands: combining gut contents,selectivity, and stable isotopes to study feeding segregation of syntopic species

Hydrobiologia - Little consensus exists on the role of food partitioning in the organization of tadpole assemblages. We studied trophic ecology of syntopic tadpoles through the analysis of gut...     

Paleoecological and isotopic analysis of fossil continental mollusks of Sandelzhausen (Miocene,Germany)

The fossil molluscan fauna of Sandelzhausen (Early/Middle Miocene, SE Germany) comprises a total of 44 species, mostly terrestrial pulmonate snails. Herein we present a paleoecological analysis of this fauna based on an actualistic approach and on data on stable isotopes of carbon and oxygen (assessed from specimens of the freshwater lymnaeid snail Galba dupuyiana and the terrestrial clausiliid snail Pseudidyla moersingensis). The paleoecological reconstruction achieved here is in line with previous works, with some novelties and minor modifications. The basal sediment layers point to a swampy area with ponds and/or oxbow lakes (closed system, as indicated by the covariation between oxygen and carbon isotopic signals of G. dupuyiana), prone to seasonal flooding events. This environment would then gradually transition into a perennial lake, as indicated by: the proportion of planorbids, the appearance of aquatic species intolerant to desiccation, and the decoupling of the covariation between oxygen and carbon isotopic signals of G. dupuyiana. The terrestrial habitat would have developed from a more open environment (semi-arid/sub-humid scrubland) to a sub-humid/humid denser forest afterwards. Still, species from drier and more open environments are present throughout all the layers, suggesting that these habitats persisted in the lake’s hinterland. The mean annual temperature, calculated from the oxygen isotopic composition of P. moersingensis, ranges from 18.5 to 20.5 °C, but with no significant trend of change throughout the layers.     

Supramolecular zippers elicit interbilayer adhesion of membranes producing cell death

Background

The fluorescent dye 10-N-nonyl acridine orange (NAO) is widely used as a mitochondrial marker. NAO was reported to have cytotoxic effects in cultured eukaryotic cells when incubated at high concentrations. Although the biochemical response of NAO-induced toxicity has been well identified, the underlying molecular mechanism has not yet been explored in detail.

Effect of aging on mechanical stresses,deformations, and hemodynamics in human femoropopliteal artery due to limb flexion

Femoropopliteal artery (FPA) reconstructions are notorious for poor clinical outcomes. Mechanical and flow conditions that occur in the FPA with limb flexion are thought to play a significant role, but are poorly characterized. FPA deformations due to acute limb flexion were quantified using a human cadaver model and used to build a finite element model that simulated surrounding tissue forces associated with limb flexion-induced deformations. Strains and intramural principal mechanical stresses were determined for seven age groups. Computational fluid dynamics analysis was performed to assess hemodynamic variables. FPA shape, stresses, and hemodynamics significantly changed with age. Younger arteries assumed straighter positions in the flexed limb with less pronounced bends and more uniform stress distribution along the length of the artery. Even in the flexed limb posture, FPAs younger than 50 years of age experienced tension, while older FPAs experienced compression. Aging resulted in localization of principal mechanical stresses to the adductor hiatus and popliteal artery below the knee that are typically prone to developing vascular pathology. Maximum principal stresses in these areas increased threefold to fivefold with age with largest increase observed at the adductor hiatus. Atheroprotective wall shear stress reduced after 35 years of age, and atheroprone and oscillatory shear stresses increased after the age of 50. These data can help better understand FPA pathophysiology and can inform the design of targeted materials and devices for peripheral arterial disease treatments.     

Terrestrial biosphere models need better representation of vegetation phenology: results from the North American Carbon Program Site Synthesis

Phenology, by controlling the seasonal activity of vegetation on the land surface, plays a fundamental role in regulating photosynthesis and other ecosystem processes, as well as competitive interactions and feedbacks to the climate system. We conducted an analysis to evaluate the representation of phenology, and the associated seasonality of ecosystem‐scale CO₂ exchange, in 14 models participating in the North American Carbon Program Site Synthesis. Model predictions were evaluated using long‐term measurements (emphasizing the period 2000–2006) from 10 forested sites within the AmeriFlux and Fluxnet‐Canada networks. In deciduous forests, almost all models consistently predicted that the growing season started earlier, and ended later, than was actually observed; biases of 2 weeks or more were typical. For these sites, most models were also unable to explain more than a small fraction of the observed interannual variability in phenological transition dates. Finally, for deciduous forests, misrepresentation of the seasonal cycle resulted in over‐prediction of gross ecosystem photosynthesis by +160 ± 145 g C m^?2 yr^?1 during the spring transition period and +75 ± 130 g C m^?2 yr^?1 during the autumn transition period (13% and 8% annual productivity, respectively) compensating for the tendency of most models to under‐predict the magnitude of peak summertime photosynthetic rates. Models did a better job of predicting the seasonality of CO₂ exchange for evergreen forests. These results highlight the need for improved understanding of the environmental controls on vegetation phenology and incorporation of this knowledge into better phenological models. Existing models are unlikely to predict future responses of phenology to climate change accurately and therefore will misrepresent the seasonality and interannual variability of key biosphere–atmosphere feedbacks and interactions in coupled global climate models.     

Development of user-friendly functional molecular markers for VvDXS gene conferring muscat flavor in grapevine

High fruit and wine quality combined with good climatic adaptation and disease resistance are essential objectives of grape breeding. While several molecular markers are available for pyramiding resistance to fungal pathogens, molecular tools for predicting fruit composition are still scarce. Muscat flavor, caused by the accumulation of monoterpenoids in the berry, is an important target trait for breeding, sought after in both table grapes and wine. Four missense mutations in the VvDXS gene in grape germplasm have been shown to be tightly linked to muscat flavor. Here we present highly reproducible and breeder-friendly functional markers for each of the targeted polymorphisms developed by using either the multiplexed minisequencing SNaPshot? method, the high-resolution melting (HRM) assay or the cleaved amplified polymorphic sequence system. A total of 242 grapevine accessions were analyzed to optimize these different genotyping methods and to provide allele-specific markers for accurate selection of muscat flavor at early stages of grape breeding programs. The HRM and the minisequencing SNaPshot multiplex assays allow for high-throughput automated screening and are suitable for large-scale breeding programs and germplasm characterization.     

Population Genetics and Signatures of Selection in Early Neolithic European Farmers

Human expansion in the course of the Neolithic transition in western Eurasia has been one of the major topics in ancient DNA research in the last 10 years. Multiple studies have shown that the spread of agriculture and animal husbandry from the Near East across Europe was accompanied by large-scale human expansions. Moreover, changes in subsistence and migration associated with the Neolithic transition have been hypothesized to involve genetic adaptation. Here, we present high quality genome-wide data from the Linear Pottery Culture site Derenburg-Meerenstieg II (DER) (N = 32 individuals) in Central Germany. Population genetic analyses show that the DER individuals carried predominantly Anatolian Neolithic-like ancestry and a very limited degree of local hunter-gatherer admixture, similar to other early European farmers. Increasing the Linear Pottery culture cohort size to ∼100 individuals allowed us to perform various frequency- and haplotype-based analyses to investigate signatures of selection associated with changes following the adoption of the Neolithic lifestyle. In addition, we developed a new method called Admixture-informed Maximum-likelihood Estimation for Selection Scans that allowed us test for selection signatures in an admixture-aware fashion. Focusing on the intersection of results from these selection scans, we identified various loci associated with immune function (JAK1, HLA-DQB1) and metabolism (LMF1, LEPR, SORBS1), as well as skin color (SLC24A5, CD82) and folate synthesis (MTHFR, NBPF3). Our findings shed light on the evolutionary pressures, such as infectious disease and changing diet, that were faced by the early farmers of Western Eurasia.