A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance

Mitochondrial energy metabolism plays an important role in the pathophysiology of insulin resistance. Recently, a missense N437S variant was identified in the MRPP3 gene, which encodes a mitochondrial RNA processing enzyme within the RNase P complex, with predicted impact on metabolism. We used CRISPR-Cas9 genome editing to introduce this variant into the mouse Mrpp3 gene and show that the variant causes insulin resistance on a high-fat diet. The variant did not influence mitochondrial gene expression markedly, but instead, it reduced mitochondrial calcium that lowered insulin release from the pancreatic islet β cells of the Mrpp3 variant mice. Reduced insulin secretion resulted in lower insulin levels that contributed to imbalanced metabolism and liver steatosis in the Mrpp3 variant mice on a high-fat diet. Our findings reveal that the MRPP3 variant may be a predisposing factor to insulin resistance and metabolic disease in the human population

Continuous symmetry of C60 fullerene and its derivatives

Conventionally, the Ih symmetry of fullerene C60 is accepted which is supported by numerous calculations. However, this conclusion results from the consideration of the molecule electron system, of its odd electrons in particular, in a close-shell approximation without taking the electron spin into account. Passing to the open-shell approximation has lead to both the energy and the symmetry lowering up to Ci. Seemingly contradicting to a high-symmetry pattern of experimental recording, particularly concerning the molecule electronic spectra, the finding is considered in the current paper from the continuous symmetry viewpoint. Exploiting both continuous symmetry measure and continuous symmetry content, was shown that formal Ci symmetry of the molecule is by 99.99% Ih. A similar continuous symmetry analysis of the fullerene monoderivatives gives a reasonable explanation of a large variety of their optical spectra patterns within the framework of the same C1 formal symmetry exhibiting a strong stability of the C60 skeleton.Comment: 11 pages. 5 figures. 6 table

Serra da Estrela cheeses free amino acids profiles by UPLC-DAD-MS/MS and their application for cheese origin assessment

Serra da Estrela cheese is a high-value Portuguese Protected Designation of Origin cheese, produced with raw ewe milk. Thus, information regarding its composition is of utmost relevance for both consumers and certified producers. In this work, the chromatographic profiles of free amino acids in cheeses (45 days of maturation, 6 producers located in 5 municipalities and produced from November 2017 to March 2018) were established by UPLC-DAD-MS/MS. The proposed method allowed detecting 19 free amino acids and cystine with overall limits of detection and quantification lower than 44 mol/L (1.4 mg/100 g cheese, wet matter) and then 134 mol/L (4.2 mg/100 g cheese, wet matter), respectively. In all cheeses, 17 free amino acids were quantified including 8 essential amino acids (histidine, leucine-isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine) and 9 non-essential amino acids (arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, proline, serine and tyrosine). The amounts of the free amino acids, essential free amino acids, branched chain free amino acids (leucine, isoleucine and valine) plus the free amino acids ratios (mg/g protein) were further used to identify the producer of Serra da Estrela cheeses. Linear discriminant analysis coupled with the simulated annealing variable selection algorithm was used allowing the correct classification of 96% and 90±8% of the samples, for leave-one-out and repeated K-fold cross-validation procedures, respectively. The satisfactory predictive performance pointed out the possibility of using cheeses amino acids profiles as origin biomarkers for authenticity control, warranting the correctness identification of the cheese producer/brand, which is quite relevant for ensuring the consumer confidence and satisfaction when purchasing this high-value dairy food.This work was financially supported by Associate Laboratory LSRELCM – UID/EQU/50020/2019, strategic funding UID/BIO/04469/2019-CEB and BioTecNorte operation (NORTE-01-0145-FEDER000004), and strategic project PEst-OE/AGR/UI0690/2014–CIMO funded by – funded by national funds through FCT/MCTES (PIDDAC). The authors would also like to acknowledge the funding provided by the approved Project, with reference 02/SAICT/ 2016/23290, entitled Characterization and Valorization of QSE PDO and its ability for health promotion (QCLASSE), financed by FCT. S. I. Falcão thanks National funding by FCT- Foundation for Science and Technology, P.I., through the institutional scientific employment program-contract.info:eu-repo/semantics/publishedVersio

Reticular synthesis and the design of new materials

The long-standing challenge of designing and constructing new crystalline solid-state materials from molecular building blocks is just beginning to be addressed with success. A conceptual approach that requires the use of secondary building units to direct the assembly of ordered frameworks epitomizes this process: we call this approach reticular synthesis. This chemistry has yielded materials designed to have predetermined structures, compositions and properties. In particular, highly porous frameworks held together by strong metal-oxygen-carbon bonds and with exceptionally large surface area and capacity for gas storage have been prepared and their pore metrics systematically varied and functionalized.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62718/1/nature01650.pd

Cross-cultural regularities in the cognitive architecture of pride

Pride occurs in every known culture, appears early in development, is reliably triggered by achievements and formidability, and causes a characteristic display that is recognized everywhere. Here, we evaluate the theory that pride evolved to guide decisions relevant to pursuing actions that enhance valuation and respect for a person in the minds of others. By hypothesis, pride is a neurocomputational program tailored by selection to orchestrate cognition and behavior in the service of: (i) motivating the costeffective pursuit of courses of action that would increase others' valuations and respect of the individual, (ii) motivating the advertisement of acts or characteristics whose recognition by others would lead them to enhance their evaluations of the individual, and (iii) mobilizing the individual to take advantage of the resulting enhanced social landscape. To modulate how much to invest in actions that might lead to enhanced evaluations by others, the pride system must forecast the magnitude of the evaluations the action would evoke in the audience and calibrate its activation proportionally. We tested this prediction in 16 countries across 4 continents (n = 2,085), for 25 acts and traits. As predicted, the pride intensity for a given act or trait closely tracks the valuations of audiences, local (mean r = +0.82) and foreign (mean r = +0.75). This relationship is specific to pride and does not generalize to other positive emotions that coactivate with pride but lack its audience-recalibrating function

Cross cultural regularities in the cognitive architecture of pride

Pride occurs in every known culture, appears early in development, is reliably triggered by achievements and formidability, and causes a characteristic display that is recognized everywhere. Here, we evaluate the theory that pride evolved to guide decisions relevant to pursuing actions that enhance valuation and respect for a person in the minds of others. By hypothesis, pride is a neurocomputational program tailored by selection to orchestrate cognition and behavior in the service of: (i) motivating the cost-effective pursuit of courses of action that would increase others' valuations and respect of the individual, (ii) motivating the advertisement of acts or characteristics whose recognition by others would lead them to enhance their evaluations of the individual, and (iii) mobilizing the individual to take advantage of the resulting enhanced social landscape. To modulate how much to invest in actions that might lead to enhanced evaluations by others, the pride system must forecast the magnitude of the evaluations the action would evoke in the audience and calibrate its activation proportionally. We tested this prediction in 16 countries across 4 continents (n = 2,085), for 25 acts and traits. As predicted, the pride intensity for a given act or trait closely tracks the valuations of audiences, local (mean r = +0.82) and foreign (mean r = +0.75). This relationship is specific to pride and does not generalize to other positive emotions that coactivate with pride but lack its audience-recalibrating function

Structure of [4.4.4]propellane and [4.4.4]propellatriene by <i>X</i>-ray Analysis

The crystal structures of [4.4.4]propellane (monoclinic, a=12.053, b=7.832, c=13.001 Å, β=104.89°, space group C2/c, Z=4) and [4.4.4]propellatriene (monoclinic, a=7.876, b=12.651, c=13.164 Å, β=122.81°, space group P21/c,Z=4) have been determined by X-ray analysis. In propellane the six-membered rings are in the chair conformation, in propellatriene they adopt the ‘half-chair’ conformation with a twofold axis passing through the centre of each double bond. In both cases the observed parameters correspond to virtual D3(32) molecular symmetry. Corrections have been applied for the effect of molecular libration. Strain-minimization calculations based on semi-empirical potential functions have been carried out and the molecular parameters so derived are compared with the experimental values.</p