Dispersion, rehybridization, and pentacoordination: keys to understand clustering of boron and aluminum hydrides and halides

The structure, stability, and bonding characteristics of dimers and trimers involving BX3 and AlX3 (X = H, F, Cl) in the gas phase, many of them explored for the first time, were investigated using different DFT (B3LYP, B3LYP/D3BJ, and M06-2X) and ab initio (MP2 and G4) methods together with different energy decomposition formalisms, namely, many-body interaction-energy and localized molecular orbital energy decomposition analysis. The electron density of the clusters investigated was analyzed with QTAIM, electron localization function, NCIPLOT, and adaptive natural density partitioning approaches. Our results for triel hydride dimers and Al2X6 (X = F, Cl) clusters are in good agreement with previous studies in the literature, but in contrast with the general accepted idea that B2F6 and B2Cl6 do not exist, we have found that they are predicted to be weakly bound systems if dispersion interactions are conveniently accounted for in the theoretical schemes used. Dispersion interactions are also dominant in both homo- and heterotrimers involving boron halide monomers. Surprisingly, B3F9 and B3Cl9 C3v cyclic trimers, in spite of exhibiting rather strong B-X (X = F, Cl) interactions, were found to be unstable with respect to the isolated monomers due to the high energetic cost of the rehybridization of the B atom, which is larger than the two- and three-body stabilization contributions when the cyclic is formed. Another important feature is the enhanced stability of both homo- and heterotrimers in which Al is the central atom because Al is systematically pentacoordinated, whereas this is not the case when the central atom is B, which is only tri- or tetra-coordinatedPID2021-125207NB-C31, PID2021-125207NB-C32, PID2019-110091GB-I0

El análisis proteómico del interactoma intracelular revela que las tetraspaninas modulan el repertorio de proteínas que forman parte de los exosomas de linfocitos T humanos

Comunicaciones a congreso

Biological and functional analysis of interactions among tetraspanin-associated proteins in human T lymphocites by high-throuchput methods using second generation proteomics techniques

Comunicaciones a congreso

Characterization of intracellular interactome CD81 and EWI-2 in human T-Limphocytes

Comunicaciones a congreso

Human Endometrial CD98 Is Essential for Blastocyst Adhesion

BACKGROUND: Understanding the molecular basis of embryonic implantation is of great clinical and biological relevance. Little is currently known about the adhesion receptors that determine endometrial receptivity for embryonic implantation in humans. METHODS AND PRINCIPAL FINDINGS: Using two human endometrial cell lines characterized by low and high receptivity, we identified the membrane receptor CD98 as a novel molecule selectively and significantly associated with the receptive phenotype. In human endometrial samples, CD98 was the only molecule studied whose expression was restricted to the implantation window in human endometrial tissue. CD98 expression was restricted to the apical surface and included in tetraspanin-enriched microdomains of primary endometrial epithelial cells, as demonstrated by the biochemical association between CD98 and tetraspanin CD9. CD98 expression was induced in vitro by treatment of primary endometrial epithelial cells with human chorionic gonadotropin, 17-β-estradiol, LIF or EGF. Endometrial overexpression of CD98 or tetraspanin CD9 greatly enhanced mouse blastocyst adhesion, while their siRNA-mediated depletion reduced the blastocyst adhesion rate. CONCLUSIONS: These results indicate that CD98, a component of tetraspanin-enriched microdomains, appears to be an important determinant of human endometrial receptivity during the implantation window

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

ChemInform Abstract: Gas-Phase Basicities of β-Lactams and Azetidines. Cyclization Effects. An Experimental and Theoretical Study.

The gas-phase proton affinities of selected 0-lactams, amides, cyclic and acyclic ketones, azetidine, and acyclic amines were measured by FTICRMS techniques. SCF and MP2 calculations at different levels of accuracy have been performed for the different neutral and protonated species, as well as a topological analysis of the electronic charge density. Our results, both experimental and theoretical, show that 0-lactams are weaker bases, in the gas phase, than acyclic amides. The attenuation of basicity upon cyclization of 2-azetidinone is stronger than that found for cyclic ketones of similar size due to the existence of a negative hyperconjugation effect. Our ab initio calculations indicate that both 0-lactams and acyclic amides are oxygen bases, but the gap between the oxygen and nitrogen intrinsic basicities is much smaller in the former due to the aforementioned cyclization effects. This is the result of charge redistributions due to the hybridization changes at the carbonyl carbon, which are very well described by a topological analysis of the corresponding electronic charge densities. On the contrary the cyclization effects on the gas-phase basicities of amines are almost negligible, and azetidine presents a gas-phase basicity practically equal to that of /V-methylethanamine. Our topological analysis of bond activations of these species upon protonation reveals that for 2-azetidinone these effects are not dramatic when protonation takes place at the oxygen atom, whereas they are quite significant if protonation takes place at the ring nitrogen. Bond activations are also important in protonated azetidine and, in general, are slightly attenuated in the corresponding iV-methyl derivatives.This work was partially supported by the DGICYT (Projects PB90-0228-C02-01 and PB87-0357).Peer reviewe

Gas-phase basicities of β-lactams and azetidines. Cyclization effects. An experimental and theoretical study

The gas-phase proton affinities of selected 0-lactams, amides, cyclic and acyclic ketones, azetidine, and acyclic amines were measured by FTICRMS techniques. SCF and MP2 calculations at different levels of accuracy have been performed for the different neutral and protonated species, as well as a topological analysis of the electronic charge density. Our results, both experimental and theoretical, show that 0-lactams are weaker bases, in the gas phase, than acyclic amides. The attenuation of basicity upon cyclization of 2-azetidinone is stronger than that found for cyclic ketones of similar size due to the existence of a negative hyperconjugation effect. Our ab initio calculations indicate that both 0-lactams and acyclic amides are oxygen bases, but the gap between the oxygen and nitrogen intrinsic basicities is much smaller in the former due to the aforementioned cyclization effects. This is the result of charge redistributions due to the hybridization changes at the carbonyl carbon, which are very well described by a topological analysis of the corresponding electronic charge densities. On the contrary the cyclization effects on the gas-phase basicities of amines are almost negligible, and azetidine presents a gas-phase basicity practically equal to that of /V-methylethanamine. Our topological analysis of bond activations of these species upon protonation reveals that for 2-azetidinone these effects are not dramatic when protonation takes place at the oxygen atom, whereas they are quite significant if protonation takes place at the ring nitrogen. Bond activations are also important in protonated azetidine and, in general, are slightly attenuated in the corresponding iV-methyl derivatives.This work was partially supported by the DGICYT (Projects PB90-0228-C02-01 and PB87-0357).Peer reviewe