Cancer is widely considered a genetic disease involving nuclear mutations in oncogenes and tumor suppressor genes. This view persists despite the numerous inconsistencies associated with the somatic ...mutation theory. In contrast to the somatic mutation theory, emerging evidence suggests that cancer is a mitochondrial metabolic disease, according to the original theory of Otto Warburg. The findings are reviewed from nuclear cytoplasm transfer experiments that relate to the origin of cancer. The evidence from these experiments is difficult to reconcile with the somatic mutation theory, but is consistent with the notion that cancer is primarily a mitochondrial metabolic disease.
Parameters used to describe the electrical properties of organic field-effect transistors, such as mobility and threshold voltage, are commonly extracted from measured current-voltage characteristics ...and interpreted by using the classical metal oxide-semiconductor field-effect transistor model. However, in recent reports of devices with ultra-high mobility (>40 cm(2) V(-1) s(-1)), the device characteristics deviate from this idealized model and show an abrupt turn-on in the drain current when measured as a function of gate voltage. In order to investigate this phenomenon, here we report on single crystal rubrene transistors intentionally fabricated to exhibit an abrupt turn-on. We disentangle the channel properties from the contact resistance by using impedance spectroscopy and show that the current in such devices is governed by a gate bias dependence of the contact resistance. As a result, extracted mobility values from d.c. current-voltage characterization are overestimated by one order of magnitude or more.
FeRh attracts intensive interest in antiferromagnetic (AFM) spintronics due to its first-order phase transition between the AFM and ferromagnetic (FM) phase, which is unique for exploring spin ...dynamics in coexisting phases. Here, we report lateral spin pumping by which angular momentum is transferred from FM domains into the AFM matrix during the phase transition of ultrathin FeRh films. In addition, FeRh is verified to be both an efficient spin generator and an efficient spin sink, by electrically probing vertical spin pumping from FM-FeRh into Pt and from Py into FeRh, respectively. A dramatic enhancement of damping related to AFM-FeRh is observed during the phase transition, which we prove to be dominated by lateral spin pumping across the FM/AFM interface. The discovery of lateral spin pumping provides insight into the spin dynamics of magnetic thin films with mixed-phases, and the significantly modulated damping advances its potential applications, such as ultrafast spintronics.
Abstract
Plants often experience multiple stresses in a given day or season, and it is self-evident that given functional traits can provide tolerances of multiple stresses. Yet, the multiple ...functions of individual traits are rarely explicitly considered in ecology and evolution due to a lack of a quantitative framework. We present a theory for considering the combined importance of the several functions that a single trait can contribute to alleviating multiple stresses. We derive five inter-related general predictions: (1) that trait multifunctionality is overall highly beneficial to fitness; (2) that species possessing multifunctional traits should increase in abundance and in niche breadth; (3) that traits are typically optimized for multiple functions and thus can be far from optimal for individual functions; (4) that the relative importance of each function of a multifunctional trait depends on the environment; and (5) that traits will be often “co-opted” for additional functions during evolution and community assembly. We demonstrate how the theory can be applied quantitatively by examining the multiple functions of leaf trichomes (hairs) using heuristic model simulations, substantiating the general principles. We identify avenues for further development and applications of the theory of trait multifunctionality in ecology and evolution.
Sickle cell disease (SCD) is a single gene disorder causing a debilitating systemic syndrome characterised by chronic anaemia, acute painful episodes, organ infarction and chronic organ damage and by ...a significant reduction in life expectancy. The origin of SCD lies in the malarial regions of the tropics where carriers are protected against death from malaria and hence enjoy an evolutionary advantage. More recently, population migration has meant that SCD now has a worldwide distribution and that a substantial number of children are born with the condition in higher-income areas, including large parts of Europe and North and South America. Newborn screening, systematic clinical follow-up and prevention of sepsis and organ damage have led to an increased life expectancy among people with SCD in many such countries; however, in resource-limited settings where the majority continue to be born, most affected children continue to die in early childhood, usually undiagnosed, due to the lack of effective programmes for its early detection and treatment. As new therapies emerge, potentially leading to disease amelioration or cure, it is of paramount importance that the significant burden of SCD in resource-poor countries is properly recognised.
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•PBS is not miscible with PLA to any substantial extent, but compatibility is achieved at low addition levels (20wt%).•Elongation-to-break increased to over 250% with as little as ...10wt% of PBS added.•PLA and PBS formed a co-continuous phase in the composition range of 8–42wt% of PBS.•The theoretical value of the phase inversion point calculated from viscosity measurements was 8.4wt%.
Synergistic effects of blending two bio-based, bio-degradable polymers, poly(butylene succinate) (PBS) and poly(lactic acid) (PLA) are investigated. A series of melt-blended compounds were prepared at PBS/PLA weight ratios of 0/100, 10/90, 20/80, 40/60, 60/40, 80/20 and 100/0. Thermal properties, crystallinity, melt viscosities, mechanical properties and phase morphology were studied. There was found to be a dramatic improvement in ductility, over 250% elongation-to-break, with as little as 10wt% of PBS added. This was shown to be due to a co-continuous phase morphology, which was determined by the relative viscosities of the components.
The growing threat of antimicrobial resistance (AMR) calls for new epidemiological surveillance methods, as well as a deeper understanding of how antimicrobial resistance genes (ARGs) have been ...transmitted around the world. The large pool of sequencing data available in public repositories provides an excellent resource for monitoring the temporal and spatial dissemination of AMR in different ecological settings. However, only a limited number of research groups globally have the computational resources to analyze such data. We retrieved 442 Tbp of sequencing reads from 214,095 metagenomic samples from the European Nucleotide Archive (ENA) and aligned them using a uniform approach against ARGs and 16S/18S rRNA genes. Here, we present the results of this extensive computational analysis and share the counts of reads aligned. Over 6.76∙10
8
read fragments were assigned to ARGs and 3.21∙10
9
to rRNA genes, where we observed distinct differences in both the abundance of ARGs and the link between microbiome and resistome compositions across various sampling types. This collection is another step towards establishing global surveillance of AMR and can serve as a resource for further research into the environmental spread and dynamic changes of ARGs.
Vascular and nervous systems, two major networks in mammalian bodies, show a high degree of anatomical parallelism and functional crosstalk. During development, neurons guide and attract blood ...vessels, and consequently this parallelism is established. Here, we identified a noncanonical neurovascular interaction in eye development and disease. VEGFR2, a critical endothelial receptor for VEGF, was more abundantly expressed in retinal neurons than in endothelial cells, including endothelial tip cells. Genetic deletion of VEGFR2 in neurons caused misdirected angiogenesis toward neurons, resulting in abnormally increased vascular density around neurons. Further genetic experiments revealed that this misdirected angiogenesis was attributable to an excessive amount of VEGF protein around neurons caused by insufficient engulfment of VEGF by VEGFR2-deficient neurons. Moreover, absence of neuronal VEGFR2 caused misdirected regenerative angiogenesis in ischemic retinopathy. Thus, this study revealed neurovascular crosstalk and unprecedented cellular regulation of VEGF: retinal neurons titrate VEGF to limit neuronal vascularization.
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•Retinal neurons highly express VEGFR2 via a hemangioblast-specific enhancer, DMME•Loss of VEGFR2 in retinal neurons causes misdirected angiogenesis toward neurons•Deletion of neuronal VEGF normalizes vascular defects in neuronal VEGFR2 knockouts•Excessive VEGF due to poor engulfment by VEGFR2 null neurons misdirects angiogenesis
A critical endothelial receptor for VEGF is more abundantly expressed in retinal neurons than in endothelial cells. It titrates VEGF via endocytosis, thereby limiting angiogenesis and ensuring an appropriate level of vascular supply.
Itaconic acid (ITA), or methylenesuccinic acid, is not generally classified as a mammalian metabolite. Using NMR-based metabolomics and 13C-labeling, we have detected ITA in both macrophage-like ...VM-M3 and RAW 264.7 tumor cell lines as well as stimulated and unstimulated primary murine macrophages. Macrophage activation by addition of lipopolysaccharide and IFN-γ markedly increased ITA production and secretion. Crude cell extracts synthesize ITA via decarboxylation of cis-aconitate, indicative of a novel mammalian cis-aconitic decarboxylase activity. Our results highlight a previously unidentified biosynthetic pathway related to TCA cycle metabolism in mammalian cells and a novel metabolite that likely plays a role in macrophage-based immune response.
The success of health protection measures depends on public compliance. This paper aims to understand the influence of three different types of communication (i.e., news media, social media, and ...interpersonal communication) on people's engagement in health protective behavior during a public health crisis. Our C-ENT model of health protective behavior proposes that communication raises perceptions of efficacy, norms, and threat, which in turn influence health protective behavior (communication → efficacy, norms, threat: C-ENT). We test the model for the case of social distancing during the COVID-19 pandemic, based on a representative online survey during the first week of the lockdown in Switzerland (N = 1005). The results support the C-ENT model and illustrate the important role of communication engagement during a public health crisis. News media use was associated with perceptions of behavior-related efficacy and norms and disease-related threat, and these perceptions were positively associated with compliance with social distancing. Social media use and interpersonal communication were related with perceived norms. Social media use was negatively and interpersonal communication positively associated with health behavior-supporting normative perceptions. Our findings suggest taking the distinct pattern among communication types (i.e., news media, social media, and interpersonal communication), perceptions, and behavior into account in order to understand existing dependencies and design respective communication strategies.
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