Gßγ subunits colocalize with RNA polymerase II and regulate transcription in cardiac fibroblasts.

Gßγ subunits mediate many different signaling processes in various compartments of the cell, including the nucleus. To gain insight into the functions of nuclear Gßγ signaling, we investigated the functional role of Gßγ signaling in the regulation of GPCR-mediated gene expression in primary rat neonatal cardiac fibroblasts. We identified a novel, negative, regulatory role for the Gß1γ dimer in the fibrotic response. Depletion of Gß1 led to derepression of the fibrotic response at the mRNA and protein levels under basal conditions and an enhanced fibrotic response after sustained stimulation of the angiotensin II type I receptor. Our genome-wide chromatin immunoprecipitation experiments revealed that Gß1 colocalized and interacted with RNA polymerase II on fibrotic genes in an angiotensin II-dependent manner. Additionally, blocking transcription with inhibitors of Cdk9 prevented association of Gßγ with transcription complexes. Together, our findings suggest that Gß1γ is a novel transcriptional regulator of the fibrotic response that may act to restrict fibrosis to conditions of sustained fibrotic signaling. Our work expands the role for Gßγ signaling in cardiac fibrosis and may have broad implications for the role of nuclear Gßγ signaling in other cell types.

Characteristics of primary care practices by proportion of patients unvaccinated against SARS-CoV-2: a cross-sectional cohort study.

BACKGROUND: Variations in primary care practices may explain some differences in health outcomes during the COVID-19 pandemic. We sought to evaluate the characteristics of primary care practices by the proportion of patients unvaccinated against SARS-CoV-2. METHODS: We conducted a population-based, cross-sectional cohort study using linked administrative data sets in Ontario, Canada. We calculated the percentage of patients unvaccinated against SARS-CoV-2 enrolled with each comprehensive-care family physician, ranked physicians according to the proportion of patients unvaccinated, and identified physicians in the top 10% (v. the other 90%). We compared characteristics of family physicians and their patients in these 2 groups using standardized differences. RESULTS: We analyzed 9060 family physicians with 10 837 909 enrolled patients. Family physicians with the largest proportion (top 10%) of unvaccinated patients (n = 906) were more likely to be male, to have trained outside of Canada, to be older, and to work in an enhanced fee-for-service model than those in the remaining 90%. Vaccine coverage (≥ 2 doses of SARS-CoV-2 vaccine) was 74% among patients of physicians with the largest proportion of unvaccinated patients, compared with 87% in the remaining patient population. Patients in the top 10% group tended to be younger and live in areas with higher levels of ethnic diversity and immigration and lower incomes. INTERPRETATION: Primary care practices with the largest proportion of patients unvaccinated against SARS-CoV-2 served marginalized communities and were less likely to use team-based care models. These findings can guide resource planning and help tailor interventions to integrate public health priorities within primary care practices.

Transition metal oxide complexes as molecular catalysts for selective methane to methanol transformation: any prospects or time to retire?

Transition metal oxides have been extensively used in the literature for the conversion of methane to methanol. Despite the progress made over the past decades, no method with satisfactory performance or economic viability has been detected. The main bottleneck is that the produced methanol oxidizes further due to its weaker C-H bond than that of methane. Every improvement in the efficiency of a catalyst to activate methane leads to reduction of the selectivity towards methanol. Is it therefore prudent to keep studying (both theoretically and experimentally) metal oxides as catalysts for the quantitative conversion of methane to methanol? This perspective focuses on molecular metal oxide complexes and suggests strategies to bypass the current bottlenecks with higher weight on the computational chemistry side. We first discuss the electronic structure of metal oxides, followed by assessing the role of the ligands in the reactivity of the catalysts. For better selectivity, we propose that metal oxide anionic complexes should be explored further, while hydrophylic cavities in the vicinity of the metal oxide can perturb the transition-state structure for methanol increasing appreciably the activation barrier for methanol. We also emphasize that computational studies should target the activation reaction of methanol (and not only methane), the study of complete catalytic cycles (including the recombination and oxidation steps), and the use of molecular oxygen as an oxidant. The titled chemical conversion is an excellent challenge for theory and we believe that computational studies should lead the field in the future. It is finally shown that bottom-up approaches offer a systematic way for exploration of the chemical space and should still be applied in parallel with the recently popular machine learning techniques. To answer the question of the title, we believe that metal oxides should still be considered provided that we change our focus and perform more systematic investigations on the activation of methanol.

[Fe4S4] cubane in sulfite reductases: new insights into bonding properties and reactivity.

The dissimilatory sulfite reductase enzyme has very characteristic active site where the substrate binds to an iron site, ligated by a siroheme macrocycle and a thiol directly connected to a [Fe4S4] cluster. This arrangement gives the enzyme remarkable efficiency in reducing sulfite and nitrite all the way to hydrogen sulfide and ammonia. For the first time we present a theoretical study where substrate binding modalities and activation are elucidated using active site models containing proton supply side chains and the [Fe4S4] cluster. Density functional theory (DFT) was deployed in conjunction with the energy decomposition scheme (as implemented in AMS), the quantum theory of atoms in molecules (QTAIM), and conceptual DFT (cDFT) descriptors. We quantified the role of the electrostatic interactions inside the active site created by the side chains as well as the influence of the [Fe4S4] cluster on the substrate binding. Furthermore, using conceptual DFT results we shed light of the activation process, thus, laying foundation for further mechanistic studies. We found that the bonding of the ligands to the iron complex is dominated by electrostatic interactions, but the presence of the [Fe4S4] cubane leads to substantial changes in electronic interaction. The spin state of the cubane, however, affects the binding energy only marginally. The conceptual DFT results show that the presence of the [Fe4S4] cubane affects the reactivity of the active site as it is involved in electron transfer. This is corroborated by an increase in the electrophilicity index, thus making the active site more prone to react with the ligands. The interaction energies between the ligand and the siroheme group are also increased upon the presence of the cubane group, thus, suggesting that the siroheme group is not an innocent spectator but plays an active role in the reactivity of the dSIR active site.

Electronic Structure of RhO2+, Its Ammoniated Complexes (NH3)1-5RhO2+, and Mechanistic Exploration of CH4 Activation by Them.

High-level electronic structure calculations are initially performed to investigate the electronic structure of RhO2+. The construction of potential energy curves for the ground and low-lying excited states allowed the calculation of spectroscopic constants, including harmonic and anharmonic vibrational frequencies, bond lengths, spin-orbit constants, and excitation energies. The equilibrium electronic configurations were used for the interpretation of the chemical bonding. We further monitored how the Rh-O bonding scheme changes with the gradual addition of ammonia ligands. The nature of this bond remains unaffected up to four ammonia ligands but adopts a different electronic configuration in the pseudo-octahedral geometry of (NH3)5RhO2+. This has consequences in the activation mechanism of the C-H bond of methane by these complexes, especially (NH3)4RhO2+. We show that the [2 + 2] mechanism in the (NH3)4RhO2+ case has a very low energy barrier comparable to that of a radical mechanism. We also demonstrate that methane can coordinate to the metal in a similar fashion to ammonia and that knowledge of the electronic structure of the pure ammonia complexes provides qualitative insights into the optimal reaction mechanism.

Impact of meteorological parameters and population density on variants of SARS-CoV-2 and outcome of COVID-19 pandemic in Japan.

Although vaccines have become available, emergence and rapid transmission of new variants have added new paradigm in the coronavirus disease-2019 (COVID-19) pandemic. Weather, population and host immunity have been detected as the regulatory elements of COVID-19. This study aims to investigate the effects of weather, population and host factors on the outcome of COVID-19 and mutation frequency in Japan. Data were collected during January 2020 to February 2021. About 92% isolates were form GR clades. Variants 501Y.V1 (53%) and 452R.V1 (24%) were most prevalent in Japan. The strongest correlation was detected between fatalities and population density (rs = 0.81) followed by total population (rs = 0.72). Relative humidity had the highest correlation (rs = -0.71) with the case fatality rate. Cluster mutations namely N501Y (45%), E484K (30%), N439K (16%), K417N (6%) and T478I (3%) at spike protein have increased during January to February 2021. Above 90% fatality was detected in patients aged >60 years. The ratio of male to female patients of COVID-19 was 1.35:1. This study will help to understand the seasonality of COVID-19 and impact of weather on the outcome which will add knowledge to reduce the health burden of COVID-19 by the international organisations and policy makers.

Monitoring, treatment and control of blood glucose and lipids in Ontario First Nations people with diabetes.

BACKGROUND: Indigenous people worldwide are disproportionately affected by diabetes and its complications. We aimed to assess the monitoring, treatment and control of blood glucose and lipids in First Nations people in Ontario. METHODS: We conducted a longitudinal population-based study using administrative data for all people in Ontario with diabetes, stratified by First Nations status. We assessed age- and sex-specific rates of completion of recommended monitoring for low-density lipoprotein (LDL) and glycated hemoglobin (A1c) from 2001/02 to 2014/15. We used data from 2014/15 to conduct a cross-sectional analysis of rates of achievement of A1c and LDL targets and use of glucose-lowering medications. RESULTS: The study included 22 240 First Nations people and 1 319 503 other people in Ontario with diabetes. Rates of monitoring according to guidelines were 20%-50% for A1c and 30%-70% for lipids and were lowest for younger First Nations men. The mean age- and sex-adjusted A1c level was higher among First Nations people than other people (7.59 [95% confidence interval (CI) 7.57 to 7.61] v. 7.03 [95% CI 7.02 to 7.03]). An A1c level of 8.5% or higher was observed in 24.7% (95% CI 23.6 to 25.0) of First Nations people, compared to 12.8% (95% CI 12.1 to 13.5) of other people in Ontario. An LDL level of 2.0 mmol/L or less was observed in 60.3% (95% CI 59.7 to 61.6) of First Nations people, compared to 52.0% (95% CI 51.1 to 52.9) of other people in Ontario. Among those aged 65 or older, a higher proportion of First Nations people than other Ontarians were using insulin (28.1% v. 15.1%), and fewer were taking no medications (28.3% v. 40.1%). INTERPRETATION: As of 2014/15, monitoring and achievement of glycemic control in both First Nations people and other people in Ontario with diabetes remained suboptimal. Interventions to support First Nations patients to reach their treatment goals and reduce the risk of complications need further development and study.

Diabetes prevalence, incidence and mortality in First Nations and other people in Ontario, 1995-2014: a population-based study using linked administrative data.

BACKGROUND: Diabetes mellitus is an established health concern in First Nations communities and is associated with complex influences of colonization. This study, a partnership between First Nations and academic researchers, was undertaken to determine patterns of diabetes prevalence, incidence and mortality in Ontario. METHODS: Using health services and population data from Ontario for 1995 to 2014, linked with the federal Indian Register, we calculated age- and sex-adjusted annual estimates of diabetes prevalence, incidence and mortality for First Nations people (living within and outside First Nations communities) and other people in Ontario. We also examined age- and sex-specific crude diabetes prevalence. RESULTS: Between 1995 and 2014, the prevalence of diabetes increased and the incidence decreased somewhat in all populations. Both prevalence and incidence were substantially higher among First Nations people than among other people in Ontario. In particular, First Nations women had higher prevalence than other women (4.2% v. 1.6% for ages 20-34 yr and 17.6% v. 6.0% for ages 35-49 yr). The lifetime risk of diabetes was higher among First Nations people than among other people in Ontario (57.0%, 95% confidence interval [CI] 56.3%-57.6% v. 44.5%, 95% CI 44.4%-44.6%). Over time, all-cause mortality for those with diabetes declined but remained consistently higher for First Nations people than for other people in Ontario. INTERPRETATION: Diabetes is more common among First Nations people than among other people in Ontario, particularly at younger ages and in women. First Nations-led approaches to address the high prevalence of diabetes in younger First Nations women have the potential to improve metabolic health across generations.

Scandium in Neutral and Positively Charged Ammonia Complexes: Balancing between Sc2+ and Sc3.

High-level quantum chemical approaches are performed to study the stability and electronic structure of tri-, di-, monocationic, and neutral scandium ammonia complexes. The calculated binding energies of all Sc(NH3)1-83+,2+,+,0 complexes reveal the higher stability of hexa- and octacoordinated systems. The ground states of Sc(NH3)6,82+ and Sc(NH3)6,8 have a Sc2+(3d1) center, while there are two competitive electronic states for Sc(NH3)6,8+ with a Sc2+(3d1) or a Sc3+ center. The remaining electrons occupy an outer diffuse s-type orbital (1s). The lower lying states involve 3d-3d transitions for Sc(NH3)6,82+ but outer 1s-1p transitions for Sc(NH3)6,8+,0. The addition of one electron to Sc(NH3)6,83+,2+,+ reduces the binding energies but shortens the Sc-N bond lengths. The comparison with the vanadium and yttrium ammonia complexes (studied earlier) reveal the unique identity of scandium balancing between a d- and s-block element.

Trends in cardiovascular care and event rates among First Nations and other people with diabetes in Ontario, Canada, 1996-2015.

BACKGROUND: Rates of cardiovascular disease among people with diabetes have declined over the last 20-30 years. To determine whether First Nations people have experienced similar declines, we compared time trends in rates of cardiac event and disease management among First Nations people with diabetes and other people with diabetes in Ontario, Canada. METHODS: We conducted a retrospective cohort study of patients aged 20 to 105 years with diabetes between 1996 and 2015, using linked health administrative databases. Outcomes compared were the annual incidence of each admission to hospital for myocardial infarction and heart failure, and death owing to ischemic heart disease. Management indicators were coronary revascularization and prescription rates for cardioprotective medications. Overall rates and annual percent changes were compared using Poisson regression. RESULTS: Incidence rates for all cardiac outcomes decreased over the study period. The greatest relative annual decline among First Nations men and women were observed in ischemic heart disease death (4.4%, 95% confidence interval [CI] 3.0 to 5.9) and heart failure (5.4%, 95% CI 4.5 to 6.4), respectively. Among other men and women, the greatest annual declines were seen in ischemic heart disease death (6.3%, 95% CI 6.1 to 6.5 and 7.3%, 95% CI 7.1 to 7.6, respectively). However, all absolute cardiac event rates were higher among First Nations people (p < 0.001). Coronary artery revascularization procedures and prescriptions for cardioprotective medications increased among First Nations people, while only prescriptions increased among other people. INTERPRETATION: Over the last 20 years, the incidence of cardiac events has declined among First Nations people with diabetes, but remains higher than other people with diabetes in Ontario. For continued reductions in incidence, future efforts need to recognize First Nations people's unique social and cultural determinants of health.

Methane to Methanol Conversion Facilitated by Transition-Metal Methyl and Methoxy Units: The Cases of FeCH3+ and FeOCH3.

The conversion of methane to methanol (MTM) catalyzed by FeOCH3+ and FeCH3+ is investigated by means of multireference configuration interaction (MRCI), single-reference coupled clusters (CC), and density functional theory (DFT) approaches. Our dual purpose is the assessment of the applied methodologies and the performance of the proposed catalytic cycle, which involves both of the titled units. The investigated cycle aims to bypass the limitations of metal-oxide catalysts and offers an alternative promising method for efficient MTM transformation. From the technical viewpoint, we found that generally accurate electron correlation treatment is more important than accurately calculated geometries. The combination of optimal DFT geometries with MRCI and CC energetics provides a good compromise between accuracy and efficiency, although there are cases where multireference calculations must be used to obtain correct structures.

Ligand field effects on the ground and excited states of reactive FeO2+ species.

High-valent Fe(iv)-oxo species have been found to be key oxidizing intermediates in the mechanisms of mononuclear iron heme and non-heme enzymes that can functionalize strong C-H bonds. Biomimetic Fe(iv)-oxo molecular complexes have been successfully synthesized and characterized, but their catalytic reactivity is typically lower than that of the enzymatic analogues. The C-H activation step proceeds through two competitive mechanisms, named σ- and π-channels. We have performed high-level wave function theory calculations on bare FeO2+ and a series of non-heme Fe(iv)-oxo model complexes in order to elucidate the electronic properties and the ligand field effects on those channels. Our results suggest that a coordination environment formed by a weak field gives access to both competitive channels, yielding more reactive Fe(iv)-oxo sites. In contrast, a strong ligand environment stabilizes only the σ-channel. Our concluding remarks will aid the derivation of new structure-reactivity descriptors that can contribute to the development of the next generation of functional catalysts.

The role of O(1D) in the oxidation mechanism of ethylene by iodosobenzene and other hypervalent molecules.

The role of the first excited state of oxygen (1D) is proven essential for the description of terminal iodine-oxygen chemical bonds. The description of the I-O bond as a dative one from iodine to O(1D) provides a simple and accurate picture which explains the oxidation properties of iodosobenzene and similar in nature molecules.

Gßγ subunits-Different spaces, different faces.

Gßγ subunits play key roles in modulation of canonical effectors in G protein-coupled receptor (GPCR)-dependent signalling at the cell surface. However, a number of recent studies of Gßγ function have revealed that they regulate a large number of molecules at distinct subcellular sites. These novel, non-canonical Gßγ roles have reshaped our understanding of how important Gßγ signalling is compared to our original notion of Gßγ subunits as simple negative regulators of Gα subunits. Gßγ dimers have now been identified as regulators of transcription, anterograde and retrograde trafficking and modulators of second messenger molecule generation in intracellular organelles. Here, we review some recent advances in our understanding of these novel non-canonical roles of Gßγ.

Cost-Savings Analysis of the Better Beginnings, Better Futures Community-Based Project for Young Children and Their Families: A 10-Year Follow-up.

This study examined the long-term cost-savings of the Better Beginnings, Better Futures (BBBF) initiative, a community-based early intervention project for young children living in socioeconomically disadvantaged neighborhoods during their transition to primary school. A quasi-experimental, longitudinal two-group design was used to compare costs and outcomes for children and families in three BBBF project neighborhoods (n = 401) and two comparison neighborhoods (n = 225). A cost-savings analysis was conducted using all project costs for providing up to 4 years of BBBF programs when children were in junior kindergarten (JK) (4 years old) to grade 2 (8 years old). Data on 19 government service cost measures were collected from the longitudinal research sample from the time the youth were in JK through to grade 12 (18 years old), 10 years after ending project participation. The average family incremental net savings to government of providing the BBBF project was $6331 in 2014 Canadian dollars. When the BBBF monetary return to government as a ratio of savings to costs was calculated, for every dollar invested by the government, a return of $2.50 per family was saved. Findings from this study have important implications for government investments in early interventions focused on a successful transition to primary school as well as parenting programs and community development initiatives in support of children's development.

The expanding roles of Gßγ subunits in G protein-coupled receptor signaling and drug action.

Gßγ subunits from heterotrimeric G proteins perform a vast array of functions in cells with respect to signaling, often independently as well as in concert with Gα subunits. However, the eponymous term "Gßγ" does not do justice to the fact that 5 Gß and 12 Gγ isoforms have evolved in mammals to serve much broader roles beyond their canonical roles in cellular signaling. We explore the phylogenetic diversity of Gßγ subunits with a view toward understanding these expanded roles in different cellular organelles. We suggest that the particular content of distinct Gßγ subunits regulates cellular activity, and that the granularity of individual Gß and Gγ action is only beginning to be understood. Given the therapeutic potential of targeting Gßγ action, this larger view serves as a prelude to more specific development of drugs aimed at individual isoforms.

Validating the 8 CPCSSN case definitions for chronic disease surveillance in a primary care database of electronic health records.

PURPOSE: The Canadian Primary Care Sentinel Surveillance Network (CPCSSN) is Canada's first national chronic disease surveillance system based on electronic health record (EHR) data. The purpose of this study was to develop and validate case definitions and case-finding algorithms used to identify 8 common chronic conditions in primary care: chronic obstructive pulmonary disease (COPD), dementia, depression, diabetes, hypertension, osteoarthritis, parkinsonism, and epilepsy. METHODS: Using a cross-sectional data validation study design, regional and local CPCSSN networks from British Columbia, Alberta (2), Ontario, Nova Scotia, and Newfoundland participated in validating EHR case-finding algorithms. A random sample of EHR charts were reviewed, oversampling for patients older than 60 years and for those with epilepsy or parkinsonism. Charts were reviewed by trained research assistants and residents who were blinded to the algorithmic diagnosis. Sensitivity, specificity, and positive and negative predictive values (PPVs, NPVs) were calculated. RESULTS: We obtained data from 1,920 charts from 4 different EHR systems (Wolf, Med Access, Nightingale, and PS Suite). For the total sample, sensitivity ranged from 78% (osteoarthritis) to more than 95% (diabetes, epilepsy, and parkinsonism); specificity was greater than 94% for all diseases; PPV ranged from 72% (dementia) to 93% (hypertension); NPV ranged from 86% (hypertension) to greater than 99% (diabetes, dementia, epilepsy, and parkinsonism). CONCLUSIONS: The CPCSSN diagnostic algorithms showed excellent sensitivity and specificity for hypertension, diabetes, epilepsy, and parkinsonism and acceptable values for the other conditions. CPCSSN data are appropriate for use in public health surveillance, primary care, and health services research, as well as to inform policy for these diseases.

Factors affecting severity and prognosis of traumatic brain injury among Bangladeshi patients: An institution based cross-sectional study.

OBJECTIVE: Traumatic brain injury (TBI) proves to be an obstacle for Bangladeshi patients due to the lack of facilities and specialist doctors in regional sections of the country. This study aimed to record different attributes of Bangladeshi TBI patients over a year i.e., their injury characteristics, treatments received and understand their impacts on the severity of TBI. METHOD: This cross-sectional study was carried out among 280 TBI patients treated in a tertiary care hospital in Dhaka. The physicians determined TBI's severity and prognosis as per the Glasgow Coma Scale (GCS) and Glasgow Outcome Score (GOS) respectively. RESULTS: Most TBI patients were male (76.1%) and aged between 18 and 50 years (52.2%), as in previous studies in South Asian countries. However, the prevalence of TBI due to road traffic accidents (RTAs) was much higher (67.9%) than in the earlier studies in South Asia. Additionally, more patients suffered from severe TBI (29.3%) and moderate TBI (35.7%), and a higher percentage of patients went through surgery (56.8%) compared to previous studies. A significant association of demographic (residence) and clinical characteristics (consciousness after injury, CT scan findings and treatment type) with the severity of TBI was found in bivariate analysis. It also revealed the significant dependence of clinical characteristics (TBI etiology, post-injury consciousness, treatment type and TBI severity) on TBI prognosis. Multivariate analysis showed that patients who were unconscious after TBI and with evident brain injury observed in CT scans have a substantially higher risk of having moderate or severe TBI than mild TBI. Moreover, patients with TBI due to RTAs or falls, evident brain injury in CT scans, post-surgical seizure, and moderate or severe TBI have a significantly higher risk of getting a more unfavorable TBI prognosis than moderate disability. CONCLUSIONS: In this study, RTAs were found to be the major cause of TBI. Additionally, some variables were identified as possible determinants of TBI severity and prognosis among Bangladeshi patients. The correlation of these variables with TBI should be further studied with the hopes that steps will be taken to reduce TBI incidents and improve its management to reduce the overall burden.

Developing a method to estimate practice denominators for a national Canadian electronic medical record database.

BACKGROUND: Calculating disease prevalence requires both a numerator (number of persons with a disease) and a matching denominator (the 'population at risk' being studied). Determining primary care practice denominators is challenging. OBJECTIVE: To develop and test a method to calculate primary care practice denominators. METHODS: We compared a 'corrected yearly contact group', or practice population, with the number of patients enrolled with practices. The yearly contact group was the set of patients with a visit noted in the electronic medical records during the past year. The correction factor was the proportion of patients that reported contacting their physician in the past year. Eighty-one physicians from Toronto and Kingston, Ontario, provided data. The main outcome measure was the ratio of practice population to the number of enrolled patients. Other measures included the change in ratio over 2 years, differences between locations, and differences by provider, practice and patient characteristics. RESULTS: The ratio of practice population to enrolled patients was 1.03 in 2010 (95% confidence interval 1.00 to 1.05) and 1.03 in 2011 (95% confidence interval 1.00 to 1.05). There was no change in the ratio over time. Ratios by location, provider or practice characteristics differed by less than 10%. There was a slight under-estimation of practice population for younger male patients and over-estimation for female patients. CONCLUSION: This method provided a denominator that was reasonably similar to the enrolled population and was stable over time and by location, provider and practice characteristics. In regions without patient enrollment, this may provide an estimate of practice denominators.

A fresh perspective on metal ammonia molecular complexes and expanded metals: opportunities in catalysis and quantum information.

Recent advances in our comprehension of the electronic structure of metal ammonia complexes have opened avenues for novel materials with diffuse electrons. These complexes in their ground state can host peripheral "Rydberg" electrons which populate a hydrogenic-type shell model imitating atoms. Aggregates of such complexes form the so-called expanded or liquid metals. Expanded metals composed of d- and f-block metal ammonia complexes offer properties, such as magnetic moments and larger numbers of diffuse electrons, not present for alkali and alkaline earth (s-block) metals. In addition, tethering metal ammonia complexes via hydrocarbon chains (replacement of ammonia ligands with diamines) yields materials that can be used for redox catalysis and quantum computing, sensing, and optics. This perspective summarizes the recent findings for gas-phase isolated metal ammonia complexes and projects the obtained knowledge to the condensed phase regime. Possible applications for the newly introduced expanded metals and linked solvated electrons precursors are discussed and future directions are proposed.