Genetic diversity is the amount of variation observed between DNA sequences from distinct individuals of a given species. This pivotal concept of population genetics has implications for species ...health, domestication, management and conservation. Levels of genetic diversity seem to vary greatly in natural populations and species, but the determinants of this variation, and particularly the relative influences of species biology and ecology versus population history, are still largely mysterious. Here we show that the diversity of a species is predictable, and is determined in the first place by its ecological strategy. We investigated the genome-wide diversity of 76 non-model animal species by sequencing the transcriptome of two to ten individuals in each species. The distribution of genetic diversity between species revealed no detectable influence of geographic range or invasive status but was accurately predicted by key species traits related to parental investment: long-lived or low-fecundity species with brooding ability were genetically less diverse than short-lived or highly fecund ones. Our analysis demonstrates the influence of long-term life-history strategies on species response to short-term environmental perturbations, a result with immediate implications for conservation policies.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Molecular alterations in malignant disease result in the expression or upregulations of various targets that can be used for imaging and treatment with radiopharmaceuticals. This theranostic ...principle has acquired greater importance in personalized medicine in recent years, particularly in oncology, where advanced tumors can be treated effectively with low side effects. Since the pioneering use of
I in differentiated thyroid cancer in the 1940s, remarkable achievements in nuclear medicine endoradiotherapy have been demonstrated, mainly in the treatment of neuroendocrine neoplasms by using
Lu-labeled somatostatin analogs or in the treatment of advanced prostate cancer using prostate-specific membrane antigen-directed radionuclide therapy. Besides that, this review focuses on promising novel radiopharmaceuticals and describes their preclinical and clinical status. Radiolabeled antibodies, such as
I-omburtamab directed against the B7-H3 protein on the surface of neuroblastoma cells; HuMab-5B1, a
Zr/
Lu-labeled antibody for the treatment of CA19-9-expressing malignancies; and
Lu-lilotomab, a CD37 antibody for the treatment of B-cell lymphomas, are being highlighted. The neurotensin receptor ligand
In/
Lu-3B-227 has demonstrated high potential in imaging and therapy for several malignancies (e.g., pancreatic adenocarcinomas). Targeting of the fibroblast activation protein is currently being explored for different tumor entities using PET imaging with the fibroblast activation protein inhibitor (FAPI)
Ga-FAPI-04, and the first therapeutic applications of
Y-FAPI-04 have been applied. After 2 decades of rapid development in theranostics, a variety of new targets are available for further clinical investigation.
Liquid-liquid phase separation in biology Hyman, Anthony A; Weber, Christoph A; Jülicher, Frank
Annual review of cell and developmental biology,
01/2014, Volume:
30
Journal Article
Peer reviewed
Open access
Cells organize many of their biochemical reactions in non-membrane compartments. Recent evidence has shown that many of these compartments are liquids that form by phase separation from the ...cytoplasm. Here we discuss the basic physical concepts necessary to understand the consequences of liquid-like states for biological functions.
In the pursuit for future mobility, solid-state batteries open a wide field of promising battery concepts with a variety of advantages, ranging from energy density to power capability. However, ...trade-offs need to be addressed, especially for large-scale, cost-effective processing, which implies the use of a polymeric binder in the composite electrodes. Here, we investigate three-dimensional microstructure models of the active material, solid electrolyte, and binder to link cathode design and binder content with electrode performance. Focusing on lithium-ion transport, we evaluate the effective ionic conductivity and tortuosity in a flux-based simulation. Therein, we address the influence of electrode composition and active material particle size as well as the process-controlled design parameters of the void space and binder content. Even though added in small amounts, the latter has a strong negative influence on the ion transport paths and the active surface area. The simulation of ion transport within four-phase composites is supplemented by an estimation of the limiting current densities, illustrating that application-driven cell design starts at the microstructure level.
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IJS, KILJ, NUK, PNG, UL, UM
When it comes to energy density, all-solid-state batteries are seen as a promising technology for next-generation electrochemical storage devices. Nevertheless, the performance of all-solid-state ...cells is still very limited. The reasons are manifold, with insufficient ionic and electronic percolation within the composite cathode being a crucial one. In this work, we investigate percolation characteristics by three-dimensional microstructural modeling with the aim to define and understand boundary conditions for well-percolating networks. Utilizing spherical active material particles together with convex polyhedra as the solid electrolyte, ionic and electronic conduction clusters are determined and analyzed by means of percolation theory for varying macroscopic parameters, such as composition, porosity, particle size, and electrode thickness. Small active material particles turn out to enhance the effective electronic conductivity, offering high surface areas and thus more possibilities to connect particles, while porosity crucially affects ionic and electronic conduction capabilities. An impact of electrode thickness on the effective electronic conductivity is observed exclusively in thin electrodes, where percolation effects are suppressed implying favorable electrode properties. From microstructural modeling, ideal compositions are derived and guidelines for electrode design are developed at a given porosity and particle size of active material and solid electrolyte.
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IJS, KILJ, NUK, PNG, UL, UM
It has been proposed that during the early steps in the origin of life, small droplets could have formed via the segregation of molecules from complex mixtures by phase separation. These droplets ...could have provided chemical reaction centres. However, whether these droplets could divide and propagate is unclear. Here we examine the behaviour of droplets in systems that are maintained away from thermodynamic equilibrium by an external supply of energy. In these systems, droplets grow by the addition of droplet material generated by chemical reactions. Surprisingly, we find that chemically driven droplet growth can lead to shape instabilities that trigger the division of droplets into two smaller daughters. Therefore, chemically active droplets can exhibit cycles of growth and division that resemble the proliferation of living cells. Dividing active droplets could serve as a model for prebiotic protocells, where chemical reactions in the droplet play the role of a prebiotic metabolism.
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IJS, NUK, SBMB, UL, UM, UPUK
Cancer cells rewire their metabolism and rely on endogenous antioxidants to mitigate lethal oxidative damage to lipids. However, the metabolic processes that modulate the response to lipid ...peroxidation are poorly defined. Using genetic screens, we compared metabolic genes essential for proliferation upon inhibition of cystine uptake or glutathione peroxidase-4 (GPX4). Interestingly, very few genes were commonly required under both conditions, suggesting that cystine limitation and GPX4 inhibition may impair proliferation via distinct mechanisms. Our screens also identify tetrahydrobiopterin (BH4) biosynthesis as an essential metabolic pathway upon GPX4 inhibition. Mechanistically, BH4 is a potent radical-trapping antioxidant that protects lipid membranes from autoxidation, alone and in synergy with vitamin E. Dihydrofolate reductase catalyzes the regeneration of BH4, and its inhibition by methotrexate synergizes with GPX4 inhibition. Altogether, our work identifies the mechanism by which BH4 acts as an endogenous antioxidant and provides a compendium of metabolic modifiers of lipid peroxidation.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Silicones are usually considered to be inert and, thus, not reactive with surfaces. Here we show that the most common silicone, methyl-terminated polydimethylsiloxane, spontaneously and stably bonds ...on glassand any other material with silicon oxide surface chemistryeven at room temperature. As a result, a 2–5 nm thick and transparent coating, which shows extraordinary nonstick properties toward polar and nonpolar liquids, ice, and even super glue, is formed. Ten microliter drops of various liquids slide off a coated glass when the sample is inclined by less than 10°. Ice adhesion strength on a coated glass is only 2.7 ± 0.6 kPa, that is, more than 98% less than ice adhesion on an uncoated glass. The mechanically stable coating can be easily applied by painting, spraying, or roll-coating. Notably, the reaction does not require any excess energy or solvents, nor does it induce hazardous byproducts, which makes it an ideal option for environmentally sustainable surface modification in a myriad of technological applications.
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IJS, KILJ, NUK, PNG, UL, UM
Abstract
The growth of lithium dendrites in inorganic solid electrolytes is an essential drawback that hinders the development of reliable all-solid-state lithium metal batteries. Generally, ex situ ...post mortem measurements of battery components show the presence of lithium dendrites at the grain boundaries of the solid electrolyte. However, the role of grain boundaries in the nucleation and dendritic growth of metallic lithium is not yet fully understood. Here, to shed light on these crucial aspects, we report the use of operando Kelvin probe force microscopy measurements to map locally time-dependent electric potential changes in the Li
6.25
Al
0.25
La
3
Zr
2
O
12
garnet-type solid electrolyte. We find that the Galvani potential drops at grain boundaries near the lithium metal electrode during plating as a response to the preferential accumulation of electrons. Time-resolved electrostatic force microscopy measurements and quantitative analyses of lithium metal formed at the grain boundaries under electron beam irradiation support this finding. Based on these results, we propose a mechanistic model to explain the preferential growth of lithium dendrites at grain boundaries and their penetration in inorganic solid electrolytes.
Closely related species with divergent life history traits are excellent models to infer the role of such traits in genetic diversity and connectivity. Ophioderma longicauda is a brittle star species ...complex composed of different genetic clusters, including brooders and broadcasters. These species diverged very recently and some of them are sympatric and ecologically syntopic, making them particularly suitable to study the consequences of their trait differences. At the scale of the geographic distribution of the broadcasters (Mediterranean Sea and northeastern Atlantic), we sequenced the mitochondrial marker COI and genotyped an intron (i51) for 788 individuals. In addition, we sequenced 10 nuclear loci newly developed from transcriptome sequences, for six sympatric populations of brooders and broadcasters from Greece. At the large scale, we found a high genetic structure within the brooders (COI: 0.07 < FST < 0.65) and no polymorphism at the nuclear locus i51. In contrast, the broadcasters displayed lower genetic structure (0 < FST < 0.14) and were polymorphic at locus i51. At the regional scale, the multilocus analysis confirmed the contrasting genetic structure between species, with no structure in the broadcasters (global FST < 0.001) and strong structure in the brooders (global FST = 0.49), and revealed a higher genetic diversity in broadcasters. Our study showed that the lecithotrophic larval stage allows on average a 50‐fold increase in migration rates, a 280‐fold increase in effective size and a threefold to fourfold increase in genetic diversity. Our work, investigating complementary genetic markers on sympatric and syntopic taxa, highlights the strong impact of the larval phase on connectivity and genetic diversity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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