Cysteine sulfinic acid or S-sulfinylation is an oxidative post-translational modification (OxiPTM) that is known to be involved in redox-dependent regulation of protein function but has been ...historically difficult to analyze biochemically. To facilitate the detection of S-sulfinylated proteins, we demonstrate that a clickable, electrophilic diazene probe (DiaAlk) enables capture and site-centric proteomic analysis of this OxiPTM. Using this workflow, we revealed a striking difference between sulfenic acid modification (S-sulfenylation) and the S-sulfinylation dynamic response to oxidative stress, which is indicative of different roles for these OxiPTMs in redox regulation. We also identified >55 heretofore-unknown protein substrates of the cysteine sulfinic acid reductase sulfiredoxin, extending its function well beyond those of 2-cysteine peroxiredoxins (2-Cys PRDX1-4) and offering new insights into the role of this unique oxidoreductase as a central mediator of reactive oxygen species-associated diseases, particularly cancer. DiaAlk therefore provides a novel tool to profile S-sulfinylated proteins and study their regulatory mechanisms in cells.
Improvement initiatives offer a valuable mechanism for delivering and testing innovations in healthcare settings. Many of these initiatives deliver meaningful and necessary changes to patient care ...and outcomes. However, many improvement initiatives fail to sustain to a point where their full benefits can be realised. This has led many researchers and healthcare practitioners to develop frameworks, models and tools to support and monitor sustainability. This work aimed to identify what approaches are available to assess and influence sustainability in healthcare and to describe the different perspectives, applications and constructs within these approaches to guide their future use.
A systematic review was carried out following PRISMA guidelines to identify publications that reported approaches to support or influence sustainability in healthcare. Eligibility criteria were defined through an iterative process in which two reviewers independently assessed 20% of articles to test the objectivity of the selection criteria. Data were extracted from the identified articles, and a template analysis was undertaken to identify and assess the sustainability constructs within each reported approach.
The search strategy identified 1748 publications with 227 articles retrieved in full text for full documentary analysis. In total, 62 publications identifying a sustainability approach were included in this review (32 frameworks, 16 models, 8 tools, 4 strategies, 1 checklist and 1 process). Constructs across approaches were compared and 40 individual constructs for sustainability were found. Comparison across approaches demonstrated consistent constructs were seen regardless of proposed interventions, setting or level of application with 6 constructs included in 75% of the approaches. Although similarities were found, no approaches contained the same combination of the constructs nor did any single approach capture all identified constructs. From these results, a consolidated framework for sustainability constructs in healthcare was developed.
Choosing a sustainability method can pose a challenge because of the diverse approaches reported in the literature. This review provides a valuable resource to researchers, healthcare professionals and improvement practitioners by providing a summary of available sustainability approaches and their characteristics.
This review was registered on the PROSPERO database: CRD42016040081 in June 2016.
Bcl-2-family proteins are central regulators of cell life and death. At least three major classes of Bcl-2-family proteins have been delineated, including proapoptotic proteins that contain several ...conserved regions of sequence similarity (termed 'multidomain'). In mammals, the multidomain proteins (MDPs) of the Bcl-2 family include Bax, Bak, and Bok. The founding member of the MDP group of Bcl-2-family proteins was discovered by Stanley Korsmeyer and co-workers, initiating an exciting area of cell death research. The status of current knowledge about the mechanisms and functions of MDPs is reviewed here, and some areas for future research are outlined. Therapeutic opportunities emerging from a growing understanding of MDPs with respect to their three-dimensional structures, biochemical actions, and roles in disease raise hopes that the foundation of basic research laid by Korsmeyer and others will eventually be translated into clinical benefits, leaving a legacy that benefits the world for many decades.
Alfred Werner, who pioneered the field of coordination chemistry, envisioned coordination complexes as a single, transition metal atom at the epicenter of a vast ligand space. The idea that the locus ...of a coordination complex could be shared by multiple metals held together with covalent bonds would eventually lead to the discovery of the quadruple and quintuple bond, which have no analogues outside of the transition metal block. Metal–metal bonding can be classified into homometallic and heterometallic groups. Although the former is dominant, the latter is arguably more intriguing because of the inherently larger chemical space in which metal–metal bonding can be explored. In 2013, Lu and Thomas independently reported the isolation of heterometallic multiple bonds with exclusively first-row transition metals. Structural and theoretical data supported triply bonded Fe–Cr and Fe–V cores. This Account describes our continued efforts to configure bonds between first-row transition metals from titanium to copper. Double-decker ligands, or binucleating platforms that brace two transition metals in proximity, have enabled the modular synthesis of diverse metal–metal complexes. The resulting complexes are also ideal for investigating the effects of an “ancillary” metal on the properties and reactivities of an “active” metal center. A total of 38 bimetallic complexes have been compiled comprising 18 unique metal–metal pairings. Twenty-one of these bimetallics are strictly isostructural, allowing for a systematic comparison of metal–metal bonding. The nature of the chemical bond between first-row metals is remarkably variable and depends on two primary factors: the total d-electron count, and the metals’ relative d-orbital energies. Showcasing the range of covalent bonding are a quintuply bonded (d-d)10 Mn–Cr heterobimetallic and the singly bonded late–late pairings, e.g., Fe–Co, which adopt unusually high spin states. A long-term goal is to rationally tailor the properties and reactivities of the bimetallic complexes. In some cases, synergistic redox and magnetic properties were found that are different from the expected sum of the individual metals. Intermetal charge transfer was shown in a Co–M series, for M = Mn to Cu, where the transition energy decreases as M is varied across the first-row period. The potential of using metal–metal complexes for multielectron reduction of small-molecules is addressed by N2 binding studies and a mechanistic study of a dicobalt catalyst in reductive silylation of N2 to N(SiMe3)3. Finally, metal-ion exchange reactions with metal–metal complexes can be selective under appropriate reaction conditions, providing an alternative synthetic route to metal–metal species.
Abstract
The process of crystallization is often understood in terms of the fundamental microstructural elements of the crystallite being formed, such as surface orientation or the presence of ...defects. Considerably less is known about the role of the liquid structure on the kinetics of crystal growth. Here atomistic simulations and machine learning methods are employed together to demonstrate that the liquid adjacent to solid-liquid interfaces presents significant structural ordering, which effectively reduces the mobility of atoms and slows down the crystallization kinetics. Through detailed studies of silicon and copper we discover that the extent to which liquid mobility is affected by interface-induced ordering (IIO) varies greatly with the degree of ordering and nature of the adjacent interface. Physical mechanisms behind the IIO anisotropy are explained and it is demonstrated that incorporation of this effect on a physically-motivated crystal growth model enables the quantitative prediction of the growth rate temperature dependence.
Understanding the level and characteristics of protection from past SARS-CoV-2 infection against subsequent re-infection, symptomatic COVID-19 disease, and severe disease is essential for predicting ...future potential disease burden, for designing policies that restrict travel or access to venues where there is a high risk of transmission, and for informing choices about when to receive vaccine doses. We aimed to systematically synthesise studies to estimate protection from past infection by variant, and where data allow, by time since infection.
In this systematic review and meta-analysis, we identified, reviewed, and extracted from the scientific literature retrospective and prospective cohort studies and test-negative case-control studies published from inception up to Sept 31, 2022, that estimated the reduction in risk of COVID-19 among individuals with a past SARS-CoV-2 infection in comparison to those without a previous infection. We meta-analysed the effectiveness of past infection by outcome (infection, symptomatic disease, and severe disease), variant, and time since infection. We ran a Bayesian meta-regression to estimate the pooled estimates of protection. Risk-of-bias assessment was evaluated using the National Institutes of Health quality-assessment tools. The systematic review was PRISMA compliant and was registered with PROSPERO (number CRD42022303850).
We identified a total of 65 studies from 19 different countries. Our meta-analyses showed that protection from past infection and any symptomatic disease was high for ancestral, alpha, beta, and delta variants, but was substantially lower for the omicron BA.1 variant. Pooled effectiveness against re-infection by the omicron BA.1 variant was 45·3% (95% uncertainty interval UI 17·3–76·1) and 44·0% (26·5–65·0) against omicron BA.1 symptomatic disease. Mean pooled effectiveness was greater than 78% against severe disease (hospitalisation and death) for all variants, including omicron BA.1. Protection from re-infection from ancestral, alpha, and delta variants declined over time but remained at 78·6% (49·8–93·6) at 40 weeks. Protection against re-infection by the omicron BA.1 variant declined more rapidly and was estimated at 36·1% (24·4–51·3) at 40 weeks. On the other hand, protection against severe disease remained high for all variants, with 90·2% (69·7–97·5) for ancestral, alpha, and delta variants, and 88·9% (84·7–90·9) for omicron BA.1 at 40 weeks.
Protection from past infection against re-infection from pre-omicron variants was very high and remained high even after 40 weeks. Protection was substantially lower for the omicron BA.1 variant and declined more rapidly over time than protection against previous variants. Protection from severe disease was high for all variants. The immunity conferred by past infection should be weighed alongside protection from vaccination when assessing future disease burden from COVID-19, providing guidance on when individuals should be vaccinated, and designing policies that mandate vaccination for workers or restrict access, on the basis of immune status, to settings where the risk of transmission is high, such as travel and high-occupancy indoor settings.
Bill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom.
Mo- and W-dichalcogenide compounds have a two-dimensional monolayer form that differs from graphene in an important respect: it can potentially have more than one crystal structure. Some of these ...monolayers exhibit tantalizing hints of a poorly understood structural metal-to-insulator transition with the possibility of long metastable lifetimes. If controllable, such a transition could bring an exciting new application space to monolayer materials beyond graphene. Here we discover that mechanical deformations provide a route to switching thermodynamic stability between a semiconducting and a metallic crystal structure in these monolayer materials. Based on state-of-the-art density functional and hybrid Hartree-Fock/density functional calculations including vibrational energy corrections, we discover that MoTe2 is an excellent candidate phase change material. We identify a range from 0.3 to 3% for the tensile strains required to transform MoTe2 under uniaxial conditions at room temperature. The potential for mechanical phase transitions is predicted for all six studied compounds.
Gender is emerging as a significant factor in the social, economic, and health effects of COVID-19. However, most existing studies have focused on its direct impact on health. Here, we aimed to ...explore the indirect effects of COVID-19 on gender disparities globally.
We reviewed publicly available datasets with information on indicators related to vaccine hesitancy and uptake, health care services, economic and work-related concerns, education, and safety at home and in the community. We used mixed effects regression, Gaussian process regression, and bootstrapping to synthesise all data sources. We accounted for uncertainty in the underlying data and modelling process. We then used mixed effects logistic regression to explore gender gaps globally and by region.
Between March, 2020, and September, 2021, women were more likely to report employment loss (26·0% 95% uncertainty interval 23·8–28·8, by September, 2021) than men (20·4% 18·2–22·9, by September, 2021), as well as forgoing work to care for others (ratio of women to men: 1·8 by March, 2020, and 2·4 by September, 2021). Women and girls were 1·21 times (1·20–1·21) more likely than men and boys to report dropping out of school for reasons other than school closures. Women were also 1·23 (1·22–1·23) times more likely than men to report that gender-based violence had increased during the pandemic. By September 2021, women and men did not differ significantly in vaccine hesitancy or uptake.
The most significant gender gaps identified in our study show intensified levels of pre-existing widespread inequalities between women and men during the COVID-19 pandemic. Political and social leaders should prioritise policies that enable and encourage women to participate in the labour force and continue their education, thereby equipping and enabling them with greater ability to overcome the barriers they face.
The Bill & Melinda Gates Foundation.
Monolayers of transition-metal dichalcogenides (TMDs) exhibit numerous crystal phases with distinct structures, symmetries and physical properties1-3. Exploring the physics of transitions between ...these different structural phases in two dimensions4 may provide a means of switching material properties, with implications for potential applications. Structural phase transitions in TMDs have so far been induced by thermal or chemical means5,6; purely electrostatic control over crystal phases through electrostatic doping was recently proposed as a theoretical possibility, but has not yet been realized7,8. Here we report the experimental demonstration of an electrostatic-doping-driven phase transition between the hexagonal and monoclinic phases of monolayer molybdenum ditelluride (MoTe2). We find that the phase transition shows a hysteretic loop in Raman spectra, and can be reversed by increasing or decreasing the gate voltage. We also combine second-harmonic generation spectroscopy with polarization-resolved Raman spectroscopy to show that the induced monoclinic phase preserves the crystal orientation of the original hexagonal phase. Moreover, this structural phase transition occurs simultaneously across the whole sample. This electrostatic-doping control of structural phase transition opens up new possibilities for developing phase-change devices based on atomically thin membranes.
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