Molecular basis for the interactions of eIF2β with eIF5, eIF2B, and 5MP1 and their regulation by CK2.

The heterotrimeric GTPase eukaryotic translation initiation factor 2 (eIF2) delivers the initiator Met-tRNAi to the ribosomal translation preinitiation complex (PIC). eIF2β has three lysine-rich repeats (K-boxes), important for binding to the GTPase-activating protein eIF5, the guanine nucleotide exchange factor eIF2B, and the regulator eIF5-mimic protein (5MP). Here, we combine X-ray crystallography with NMR to understand the molecular basis and dynamics of these interactions.

The Translational Dermatology Initiative: Aiming at a New Disease Classification of Inflammatory Skin Diseases.

Although precision medicine is at least partially realized in dermato-oncology, the field of dermatoimmunology comprising inflammatory skin diseases is only at the step from traditional toward stratified medicine. This lack of innovation leaves clinically relevant questions unanswered, including predicting the personal likelihood of therapeutic success as well as the risk of drug-related adverse events or the development of comorbidities. The translational dermatology initiative hypothesizes that these shortcomings are due to the subjective nature of the current disease ontology, which does not address the heterogeneity and dynamics of diseases.

Effects of open-channel blocking peptides in Na1.5 ΔKPQ.

Resurgent sodium currents (INaRs) result from an unorthodox gating behavior of voltage-activated sodium channels (Na), allowing transient re-openings during repolarization from an apparently inactivated state. In both native cells not normally exhibiting INaR and in heterologous expression systems, intracellular delivery of small positively charged peptides through the recording pipette elicits robust INaRs, suggesting that INaRs arise from a peptide-mediated open-channel block that is relieved upon repolarization. Here we examined the hNa1.

A spatio-temporal analysis of environmental fate and transport processes of pesticides and their transformation products in agricultural landscapes dominated by subsurface drainage with SWAT.

Pesticides are detected in surface water and groundwater, endangering the environment. In lowland regions with subsurface drainage systems, drained depressions become hotspots for transport of pesticides and their transformation products (TPs). This study focuses on detailed modelling of the degradation and transport of pesticides with different physico-chemical properties.

Molecular basis for the interactions of eIF2β with eIF5, eIF2B, and 5MP1 and their regulation by CK2.

The heterotrimeric GTPase eukaryotic translation initiation factor 2 (eIF2) delivers the initiator Met-tRNA to the ribosomal translation preinitiation complex (PIC). eIF2β has three lysine-rich repeats (K-boxes), important for binding to the GTPase-activating protein eIF5, the guanine nucleotide exchange factor eIF2B, and the regulator eIF5-mimic protein (5MP). Here, we combine X-ray crystallography with NMR to understand the molecular basis and dynamics of these interactions.

Examining characteristics and sampling methods of phosphor dynamics in lowland catchments.

Despite over two decades since the EU Water Framework Directive have passed, achieving the desired water quality in German surface waters remains challenging, regardless of efforts to reduce phosphorus inputs and associated environmental impacts. This study aims at analyzing the characteristics governing the concentrations of four key water quality parameters (total phosphorus, orthophosphate, particulate phosphate, and suspended solids) in two lowland catchments: the 50 km catchment of the Kielstau, Germany, and its 7 km tributary, the Moorau, which are dominated by agricultural land use. To this end, different sampling methods, particularly high-resolution precipitation event-based sampling and daily mixed samples, are conducted and evaluated, and their effectiveness is compared.

Spatial expression of claudin 18.2 in matched primaries and metastases of tubo-ovarian carcinoma of all subtypes.

Physiologically, claudin 18 splice variant 2 (CLDN18.2) expression is restricted to the gastric epithelium, but its expression has been detected in solid cancers. Zolbetuximab, a chimeric IgG1 antibody targeting CLDN18.

Proposal for a Novel Histological Scoring System as a Potential Grading Approach for Muscle-invasive Urothelial Bladder Cancer Correlating with Disease Aggressiveness and Patient Outcomes.

Background: Grading of muscle-invasive bladder cancer (MIBC) according to the current World Health Organization (WHO) criteria is controversial due to its limited prognostic value. All MIBC cases except a tiny minority are of high grade.

Objective: To develop a prognostic histological scoring system for MIBC integrating histomorphological phenotype, stromal tumor-infiltrating lymphocytes (sTILs), tumor budding, and growth and spreading patterns.

PreCancer Atlas: Present and Future.

Precancer atlases have the potential to revolutionize how we think about the topographic and morphologic structures of precancerous lesions in relation to cellular, molecular, genetic, and pathophysiologic states. This mini review uses the Human Tumor Atlas Network (HTAN), established by the National Cancer Institute (NCI), to illustrate the construction of cellular and molecular three-dimensional atlases of human cancers as they evolve from precancerous lesions to advanced disease. We describe the collaborative nature of the network and the research to determine how and when premalignant lesions progress to invasive cancer, regress or obtain a state of equilibrium.

Integrated modeling of global change impacts on land and water resources.

There is a common scientific understanding that global change impact analysis, mitigation, and adaptation require interdisciplinary work. Integrated modeling could help to address the challenges associated with the impacts of global change. Particularly, integrated modeling that takes feedback effects into account will allow for the derivation of climate resilient land use and land management.

National Cancer Institute's early detection research network: a model organization for biomarker research.

For many cancers a primary cause of poor survival is that they are detected at a late stage when therapies are less effective. Although screening methods exist to detect some types of cancer at an early stage, there are currently no effective methods to screen for most types of cancer. Biomarkers have the potential to improve detection of early-stage cancers, risk stratification, and prediction of which pre-cancerous lesions are likely to progress and to make screening tests less invasive.

Spatial and temporal assessment of human-water interactions at the Inle Lake, Myanmar: a socio-hydrological DPSIR analysis.

Freshwater resources as a key aspect of socio-economic development, provide a large number of services in human and environmental systems. Nevertheless, human appropriation of these water resources and the modification of landscapes lead to potential threats on water availability and quality from local to global scales. The Inle Lake in Myanmar is an economically, traditionally, and ecologically important freshwater ecosystem that faced severe degradation from the 2000s.

Land use change and climate dynamics in the Rift Valley Lake Basin, Ethiopia.

Land use and climate dynamics have a pronounced impact on water resources, biodiversity, land degradation, and productivity at all scales. Thus, in this study, we present the spatio-temporal dynamics of land use change and climate aiming to provide a scientific evidence about gains and losses in major land use categories and associated drivers and significancy and homogeneity of climate change. To this end, Landsat images and historical climate data have been used to determine the dynamics.

A method for detecting the non-stationarity during high flows under global change.

The sustainability of existing water resources is influenced by extreme streamflow, and climate variability and human activities are generally the major factors controlling these dynamics. However, most of previously proposed methods to determine the effects of these factors have only been developed under the assumption of stationarity. Therefore, to overcome the existing research gap, an innovative method was proposed in this study to analyze and distinguish the effects of climate variability and human activities on extreme streamflow based on the non-stationarity theory.

Effects of Diets Enriched with Conventional or High-Oleic Canola Oils on Vascular Endothelial Function: A Sub-Study of the Canola Oil Multi-Centre Intervention Trial 2 (COMIT-2), a Randomized Crossover Controlled Feeding Study.

Partial replacement of saturated fatty acids (SFA) with unsaturated fatty acids is recommended to reduce cardiovascular disease (CVD) risk. Monounsaturated fatty acids (MUFA), including oleic acid, are associated with lower CVD risk. Measurement of flow-mediated dilation of the brachial artery (FMD) is the gold standard for measuring endothelial function and predicts CVD risk.

Impacts of hydrological alteration on ecosystem services changes of a large river-connected lake (Poyang Lake), China.

Large lakes provide various types of ecosystem services (ESs), of which stocks and variations induced by hydrological alterations are largely unquantified. The present study investigates the long-term changes of five key ESs (i.e.

Elucidating the combinatorial effect of substrate stiffness and surface viscoelasticity on cellular phenotype.

Cells maintain tensional homeostasis by monitoring the mechanics of their microenvironment. In order to understand this mechanotransduction phenomenon, hydrogel materials have been developed with either controllable linear elastic or viscoelastic properties. Native biological tissues, and biomaterials used for medical purposes, often have complex mechanical properties.

LARAMOTIONS: a conceptual study on laser networks for near-term collision avoidance for space debris in the low Earth orbit.

A conceptual study has been carried out on laser station networks to enhance Space Situational Awareness and contribute to collision avoidance in the low Earth orbit by high-precision laser tracking of debris objects and momentum transfer via photon pressure from ground-based high-power lasers. Depending on the network size, geographical distribution of stations, orbit parameters, and remaining time to conjunction, multipass irradiation enhances the efficiency of photon momentum coupling by 1-2 orders of magnitude and has the potential to eventually yield a promisingly significant reduction of the collision rate in low Earth orbit.

APPARILLO: a fully operational and autonomous staring system for LEO debris detection.

For safe operation of active space crafts, the space debris population needs to be continuously scanned, to avoid collisions of active satellites with space debris. Especially the low Earth orbit (LEO) shows higher risks of collisions due to the highest density of orbital debris. Laser ranging stations can deliver highly accurate distance measurements of debris objects allowing precise orbit determination and more effective collision avoidance.

Twenty years of change: Land and water resources in the Chindwin catchment, Myanmar between 1999 and 2019.

Since 2011, Myanmar has undergone a more rapid socio-economic development, which may substantially have affected land use and land cover (LULC) and water resources. This study investigates the changes in land and water resources of the Chindwin River catchment (114,686.9 km) in Myanmar over a twenty-year timespan from 1999 to 2019.

Equity for and Inclusion of Non-Tenure-Track Pharmacy Faculty Within Academia.

Although there are at least twice as many non-tenure-track first-time pharmacy faculty as tenured and tenure-track first-time pharmacy faculty entering academia based on data collected from 2013 to 2019, there are ongoing equity, inclusion, and advancement issues between these categories of faculty that require consideration. Contracts with clear descriptions of responsibilities are needed along with regular evaluations and promotion opportunities based on the faculty member's performance of the assigned responsibilities, appropriate compensation including fringe benefits, inclusion in institutional voting and governance, and due process protections against abrupt termination. Further, universities and schools and colleges of pharmacy should foster a culture that values all faculty regardless of rank or position.

The Early Detection Research Network: A National Infrastructure to Support the Discovery, Development, and Validation of Cancer Biomarkers.

In 2000, the NCI (Rockville, MD) established the Early Detection Research Network (EDRN) to identify, develop, and validate biomarkers to improve the detection of early-stage cancers and risk assessment. This consortium of more than 300 investigators at academic institutions and in the private sector is working collaboratively to bring biomarkers and imaging methods to clinical fruition. Although significant roadblocks have hindered the field of biomarker discovery and validation, the EDRN has helped overcome many of them by setting well-defined strategies and milestones focused on solving defined unmet clinical needs.

Effects of dynamic land use/land cover change on water resources and sediment yield in the Anzali wetland catchment, Gilan, Iran.

Land use/land cover (LULC) changes strongly affect catchment hydrology and sediment yields. The current study aims at analyzing the hydrological consequences of dynamic LULC changes in the Anzali wetland catchment, Iran. The Soil and Water Assessment Tool (SWAT 2012) model was used to assess impacts on evapotranspiration, water yield, and sediment yield.