Filtyp
Methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) is a new drug target that is expressed in cancer cells but not in normal adult cells, which provides an Achilles heel to selectively kill cancer cells. Despite the availability of crystal structures of MTHFD2 in the inhibitor- and cofactor-bound forms, key information is missing due to technical limitations, including (a) the location
Our overall understanding of long-term climate dynamics is largely based on proxy data generated from archives such as ice cores, ocean sediments, tree rings, speleothems, and corals, whereas reconstructions of long-term changes in vegetation and associated climate during the Holocene are largely based on paleoecological records from peat and lake sequences, primarily pollen and plant macrofossil
Many studies have used the relative activities of extracellular enzymes associated with microbial carbon (C), nitrogen (N) and phosphorus (P) acquisition to infer the relative C vs. nutrient limitation of the microbial community. However, recent experimental and theoretical evidence has shown that the use of ecoenzymatic ratio to infer limiting microbial resources may be invalid. We added the two
Since it is currently not understood how changes in 14C production rate (Q), and in the carbon cycle, can be combined to explain the reconstructed atmospheric Δ14C record, we discuss possible reasons for this knowledge gap. Reviewing the literature, we exclude that changes in the content of atoms in the atmosphere, which produce cosmogenic 14C after being hit by galactic cosmic rays, might be resp
Significance This project describes the existence of previously unknown non-GPI-anchored CD59 isoforms required for insulin secretion, named CD59-IRIS-1 and CD59-IRIS-2, and finds reduced expression of CD59-IRIS isoforms in human diabetic islets, showing a link between dysregulation of IRIS isoforms and defects in insulin secretion in diabetic patients. These data open a path for future studies in
Cannabis sativa var. Kompolti, a variety routinely used for food production purposes, is characterized by a low concentration of psychoactive molecules, although containing many other biologically attractive metabolites in all parts of the plant, including the roots. In the present work, we evaluate the specific biological activities of the roots’ extract from plants cultivated through aeroponics,
Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolutio
The influence of climate on soil microorganisms governs the input and output fluxes of carbon (C) from soils. The study of the drastic responses to drying-rewetting offers an opportunity to assess an aspect of ‘soil health’ via evaluating the role of microbes in soil biochemistry and C cycling. Recent evidence has consistently shown that communities exposed to extreme moisture fluctuations recurre
Accelerated epigenetic ageing, a promising marker of disease risk, has been detected in peripheral blood cells of atherosclerotic patients, but evidence in the vascular wall is lacking. Understanding the trends of epigenetic ageing in the atheroma may provide insights into mechanisms of atherogenesis or identify targets for molecular therapy. We surveyed DNA methylation age in two human artery sam
Who are the guardians of separatism in Abkhazia and South Ossetia? These de facto states can be seen as self-determination movements or as outgrowths of Russian imperialism. We arbitrate between these competing scripts using a dataset that profiles officials in charge of high politics decision-making inside Georgia’s separatist entities from 1992 through 2020 (N=608). We find that most are sons of
Future climate warming in the Arctic will likely increase the vulnerability of soil carbon stocks to microbial decomposition. However, it remains uncertain to what extent decomposition rates will change in a warmer Arctic, because extended soil warming could induce temperature adaptation of bacterial communities. Here we show that experimental warming induces shifts in the temperature–growth relat
One novel option for treating metastatic castration resistant prostate cancer is radionuclide therapy targeting prostate-specific membrane antigen (PSMA), e.g. [177Lu]Lu-PSMA-617. Overexpression of HER2 has been found in 80% of metastatic cases of prostate cancer. Previous research showed that HER2 is elevated post irradiation in PC-3 prostate cancer cells. Co-treating with anti-HER2 antibody Tras
The immune system is integral to cardiovascular health and disease. Targeting inflammation ameliorates adverse cardiovascular outcomes. Atherosclerosis, a major underlying cause of cardiovascular disease, is conceptualized as lipid-driven inflammation in which macrophages play a nonredundant role. However, evidence emerging so far from single-cell atlases suggests a dichotomy between lipid-associa
Purpose: Added sugar is associated with a variety of adverse health outcomes, but its association with kidney stones is unclear. This study was to determine whether added sugar is associated with kidney stones. Materials and methods: This nationally representative study used National Health and Nutrition Examination Survey (NHANES) datasets from 2007 to 2018 for analysis. People aged ≥20 years who
Soil microbes perceive drying and rewetting (DRW) events as more or less harsh depending on the previous soil moisture history. If a DRW event is not perceived as harsh, microbial growth recovers rapidly after rewetting (referred to as ‘type 1’ response), while a harsh DRW will be followed by a delayed growth recovery (‘type 2’ response). Predicting these responses based on pedoclimatic factors is
Aims: Despite metformin being used as first-line pharmacological therapy for type 2 diabetes, its underlying mechanisms remain unclear. We aimed to determine whether metformin altered DNA methylation in newly-diagnosed individuals with type 2 diabetes. Methods and Results: We found that metformin therapy is associated with altered methylation of 26 sites in blood from Scandinavian discovery and re
The current war in Ukraine has severely disrupted global food supply chains due to the significant decline in the production of grain commodities, of which Ukraine and Russia are major global suppliers. This creates problems in today’s globalised food systems. In particular, a number of countries are heavily dependent on food imports from Ukraine and/or Russia, particularly some developing nations
In 2015, the United Nations (UN) General Assembly agreed on 17 Sustainable Development Goals (SDGs) with 169 targets as part of the 2030 Agenda for Sustainable Development. Although the SDGs, which are to be achieved by 2030, are not the first attempt to guide policy actors through global goals, they go far beyond earlier agreements in their detail, comprehensiveness, and ambition. Yet the 2022 SD
The concept of prefiguration is drawing increasing interest as a lens to study the collective dynamic and transformative potential of alternative organizing. We introduce an analytical distinction between two modes of prefiguration. Situated prefiguration emphasizes affective bonds and direct struggle taking place in bounded organizational spaces, while distributed prefiguration manifests in wider
