A
bstract
We present the results of a global fit to the Aligned Two-Higgs Doublet Model, assuming that there are no new sources of CP violation beyond the quark mixing matrix. We use the most ...constraining flavour observables, electroweak precision measurements and the available data on Higgs signal strengths and collider searches for heavy scalars, together with the theoretical requirements of perturbativity and positivity of the scalar potential. The combination of all these constraints restricts the values of the scalar masses, the couplings of the scalar potential and the flavour-alignment parameters. The numerical fits have been performed using the open-source HEPfit package.
Premise
Capsicum annuum (Solanaceae) was originally domesticated in Mexico, where wild (C. annuum var. glabriusculum) and cultivated (C. annuum var. annuum) chile pepper populations (>60 landraces) ...are common, and wild‐resembling individuals (hereafter semiwild) grow spontaneously in anthropogenic environments. Here we analyze the role of elevation and domestication gradients in shaping the genetic diversity in C. annuum from the state of Oaxaca, Mexico.
Methods
We collected samples of 341 individuals from 28 populations, corresponding to wild, semiwild (C. annuum var. glabriusculum) and cultivated C. annuum, and closely related species Capsicum frutescens and C. chinense. From the genetic variation of 10 simple sequence repeat (SSR) loci, we assessed the population genetic structure, inbreeding, and gene flow through variance distribution analyses, genetic clustering, and connectivity estimations.
Results
Genetic diversity (HE) did not differ across domestication levels. However, inbreeding coefficients were higher in semiwild and cultivated chiles than in wild populations. We found evidence for gene flow between wild populations and cultivated landraces along the coast. Genetic structure analysis revealed strong differentiation between most highland and lowland landraces.
Conclusions
Gene flow between wild and domesticated populations may be mediated by backyards and smallholder farms, while mating systems may facilitate gene flow between landraces and semiwild populations. Domestication and elevation may overlap in their influence on genetic differentiation. Lowland Gui'ña dani clustered with highland landraces perhaps due to the social history of the Zapotec peoples. In situ conservation may play an important role in preserving semiwild populations and private alleles found in landraces.
High-glycemic-index diets, as well as a sedentary lifestyle are considered as determinant factors for the development of obesity, type 2 diabetes, and cardiovascular diseases in humans. These diets ...have been shown to shorten the life span of C. elegans in a manner that is dependent on insulin signaling, but the participation of other signaling pathways have not been addressed. In this study, we have determined that worms fed with high-glucose diets show alterations in glucose content and uptake, triglyceride content, body size, number of eggs laid, egg-laying defects, and signs of oxidative stress and accelerated aging. Additionally, we analyzed the participation of different key regulators of carbohydrate and lipid metabolism, oxidative stress and longevity such as SKN-1/NRF2, HIF-1/HIF1α, SBP-1/SREBP, CRH-1/CREB, CEP-1/p53, and DAF-16/FOXO, in the reduction of lifespan in glucose-fed worms.
A novel DNA‐based hybrid catalyst comprised of salmon testes DNA and an iron(III) complex of a cationic meso‐tetrakis(N‐alkylpyridyl)porphyrin was developed. When the N‐methyl substituents were ...placed at the ortho position with respect to the porphyrin ring, high reactivity in catalytic carbene‐transfer reactions was observed under mild conditions, as demonstrated in the catalytic enantioselective cyclopropanation of styrene derivatives with ethyl diazoacetate (EDA) as the carbene precursor. A remarkable feature of this catalytic system is the large DNA‐induced rate acceleration observed in this reaction and the related dimerization of EDA. It is proposed that high effective molarity of all components of the reaction in or near the DNA is one of the key contributors to this unique reactivity. This study demonstrates that the concept of DNA‐based asymmetric catalysis can be expanded into the realm of organometallic chemistry.
DNA shows the way: DNA‐based catalysis by cationic iron porphyrins enabled efficient carbene transfer in the enantioselective cyclopropanation of styrenes with diazo compounds. High effective molarity of all reaction components in or near the DNA is believed to be key to this unique reactivity (see picture).
•Reversible single-crystal to single-crystal transformations (SCSC) in Coordination Compounds.•Reversible Structural transformations can be followed via single cristal X-ray diffraction.•SCSC leads ...to the formation of new products that could not be designed by conventional methods.
This review discusses recent advanced literature reported on crystalline Coordination Compounds with emphasis in Coordination Polymers (CPs) involving reversibility in single-crystal to single-crystal transformations (SCSC). The reversibility, characteristic of certain processes which can be reversed and restored to its initial state, can be a very important factor, but at the same time difficult to achieve without losing partially, or completely, the crystallinity of some molecular-based materials. Nevertheless, in recent times some outstanding examples of reversible SCSC transformation appear in the literature. These examples will be described, and the observed physicochemical properties variation (i.e. changes in dimensionality, polymerization, polymorphism, changes in colour and texture, etc.) due to external stimuli (mainly temperature, loss/uptake of solvent vapours) will be evaluated. Such alterations in the properties of these compounds mean that they can be used in various applications such as sensors, molecular machines and selective compounds storage, among others.
•Capillary LC (cLC) increases ionization efficiency and sensitivity.•The cLC-HRMS method showed superior sensitivity in the analysis of ciguatoxins.•The full ciguatoxin profile in fish from the ...eastern Atlantic Ocean was characterized.•C-CTX1 was the principal responsible for the contamination.•hydroxy- and didehydro- metabolites were first structurally characterized.
Ciguatera Poisoning is an emerging risk in the east Atlantic Ocean. Despite characterization efforts, the complete profile of ciguatoxin chemical species in these waters is still unknown. These efforts have been complicated by a lack of reference materials and scarcity of fish contaminated with high levels of ciguatoxins. Development and application of analytical methods with enhanced selectivity and sensitivity is essential for ciguatoxin characterization. Here, we developed an analytical characterization approach using capillary liquid chromatography coupled to high resolution mass spectrometry applied to reference materials obtained from ciguatoxin contaminated fish. Capillary LC coupled mass spectrometry resulted in increased sensitivity leading to the confirmation of C-CTX1 as the principal ciguatoxin present in these samples. We also detected and structurally characterized minor C-CTXs analogues consisting of C-CTX3/4, hydroxy-, didehydro-, and methoxy- metabolites.
Glioblastoma (GBM) is the most invasive and deadliest brain cancer in adults. Its inherent heterogeneity has been designated as the main cause of treatment failure. Thus, a deeper understanding of ...the diversity that shapes GBM pathobiology is of utmost importance. Single-cell RNA sequencing (scRNA-seq) technologies have begun to uncover the hidden composition of complex tumor ecosystems. Herein, a semi-systematic search of reference literature databases provided all existing publications using scRNA-seq for the investigation of human GBM. We compared and discussed findings from these works to build a more robust and unified knowledge base. All aspects ranging from inter-patient heterogeneity to intra-tumoral organization, cancer stem cell diversity, clonal mosaicism, and the tumor microenvironment (TME) are comprehensively covered in this report. Tumor composition not only differs across patients but also involves a great extent of heterogeneity within itself. Spatial and cellular heterogeneity can reveal tumor evolution dynamics. In addition, the discovery of distinct cell phenotypes might lead to the development of targeted treatment approaches. In conclusion, scRNA-seq expands our knowledge of GBM heterogeneity and helps to unravel putative therapeutic targets.
•GBM heterogeneity hampers treatment efficacy and requires high-resolution characterization by means of scRNA-seq.•All TCGA subtypes are represented in individual GBM tumors.•GBM cancer cells adopt 4 states in which every putatively transformed cell expresses dissimilar GSC markers.•TME subpopulations have been identified and proposed as promising therapeutic targets for GBM immunotherapy.
Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assessed the impact of gut microbial choline metabolism on bacterial fitness and host biology by ...engineering a microbial community that lacks a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites and recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria showed increased susceptibility to metabolic disease in the context of a high-fat diet. Furthermore, bacterially induced reduction of methyl-donor availability influenced global DNA methylation patterns in both adult mice and their offspring and engendered behavioral alterations. Our results reveal an underappreciated effect of bacterial choline metabolism on host metabolism, epigenetics, and behavior. This work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal nutrient intake requirements.
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•Gut bacteria compete with the host for choline, decreasing bioavailability•Microbial choline degradation depletes methyl-donor metabolites•Microbial choline utilization alters in utero epigenetic programming of the brain•Mice with choline-consuming gut microbiota display altered behavior
The gut microbiota is a dynamic metabolic organ associated with host health and disease phenotypes. Romano, Martinez-del Campo et al. report that choline-consuming gut bacteria reduce the bioavailability of this essential nutrient and deplete methyl-donor metabolites, resulting in alterations to host epigenetic programming and increased susceptibility to metabolic disease.
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