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The structural flexibility of ZIF-7 is controlled via a mixed-linker approach resulting in modified adsorption properties tunable across 2 orders of magnitude of step pressure while maintaining the ZIF-7 structure throughout the compositional range.

The solid-state behaviour of five ionophore-encapsulated TCNQ complexes: (18-crown-6)K(TCNQ)2.5 (1), ([2.2.2]-cryptand)K(TCNQ)2.5 (2), (benzo-18-crown-6)K(TCNQ)2 (3), (dibenzo-18-crown-6)K(TCNQ)2 (4), and (dicyclohexano-18-crown-6)K(TCNQ)3 (5) has been explored. For both 1 and 2, the TCNQ components assemble as a pentameric repeat unit within infinite TCNQ columns with the cation complex sitting in a cavity between the columns; whereas for 3 and 4, neighbouring (crown ether)K+ complexes form dimers involving K+–π interactions which further assemble into one-dimensional columns sitting between infinite TCNQ stacks. In the solid-state complex 5, the crown ether adopts a chair conformation with the resulting (crown ether)K+ complex assembling into a one-dimensional ladder. Pairs of TCNQ dimers separated by an isolated TCNQ unit form infinite TCNQ columns. IR and Raman spectroscopy reveal the presence of partially charged TCNQ units within all five TCNQ complexes (1–5) and resistivity studies indicate that all five TCNQ complexes (1–5) are more conductive than the corresponding simple KTCNQ salts. Preliminary EPR studies of 1 and 2 indicate typical behaviour of complex TCNQ salts (containing both TCNQ0 and TCNQ˙−).

Background The Global Registry of Acute Coronary Events (GRACE) score was developed and validated in predominantly male patient populations. Growing evidence indicates distinct pathophysiologic and clinical characteristics of non-ST-segment elevation acute coronary syndromes (NSTE-ACS) in women and men. Purpose We aimed to assess sex differences in the performance of the GRACE score in NSTE-ACS in contemporary populations. Methods We calculated GRACE 2.0 risk estimates for patients with NSTE-ACS in contemporary nation-wide ACS cohorts from England, Wales, and Northern Ireland (MINAP, 2005–2017, n=400,054) and from Switzerland (AMIS Plus, 2005–2020, n=20,727; SPUM-ACS, 2009–2017, n=2,239). Sex disaggregated analyses were stratified according to the mortality endpoint of the score (in-hospital death, death at 6 months, death at 1 year), the clinical setting (calculated at admission and calculated for hospital survivors, respectively), the geographic region (United Kingdom and Switzerland, respectively) and the level of care (all hospitals and PCI-capable university hospitals, respectively). The area under the receiver operating characteristic curve (AUC), the average prediction error (APE), and the misclassification rate (MCR) were compared between women and men. Results The discriminatory performance of GRACE 2.0 for in-hospital death was lower and the APE and MCR were higher in women as compared to men in the United Kingdom (AUC female: 80.4%, 95% confidence interval [CI], 80.0 to 80.8, AUC male: 84.7%, 95% CI, 84.4 to 85.1, p Conclusion Thus far, this is the largest investigation on the GRACE risk score. We confirmed good overall score performance and found decreased performance in contemporary female patients with NSTE-ACS irrespective of the mortality endpoint, the clinical setting, the geographic region, and the level of care. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science FoundationSwiss Heart Foundation

This paper describes hollow fiber sorbents made of the parent polymer of intrinsic microporosity, PIM-1, using a spinning method designed to control the formation of dense barrier layers followed b...

Research question Are endometrial stem/progenitor cells shed into uterine menstrual blood (UMB) and the peritoneal cavity in women with and without endometriosis during menstruation? Design Women with (n = 32) and without endometriosis (n = 29) at laparoscopy (total 61), carried out during the menstrual (n = 41) and non-menstrual phase (n = 20) were recruited. The UMB, peritoneal fluid and peripheral blood were analysed by clonogenicity assay and flow cytometry to quantify the concentrations of endometrial clonogenic cells, SUSD2+ mesenchymal stem cells (eMSC) and N-cadherin+ epithelial progenitor cells (eEPC). Results Clonogenic endometrial cells, eMSC and eEPC were found in most UMB samples at similar concentrations in women with and without endometriosis. In contrast, 62.5% of women with endometriosis and 75.0% without (controls) had clonogenic cells in peritoneal fluid samples during menses. The eMSC were present in the peritoneal fluid of 76.9% of women with endometriosis and 44.4% without, and eEPC were found in the peritoneal fluid of 60.0% of women with and 25.0% without endometriosis during menses. Median clonogenic, eMSC and eEPC concentrations in peritoneal fluid were not significantly different between groups. More clonogenic cells persisted beyond the menstrual phase in the peritoneal fluid of women with endometriosis (menstrual 119/ml [0–1360/ml] versus non-menstrual 8.5/ml [0–387/ml]; P = 0.277) compared with controls (menstrual 76.5/ml [1–1378/ml] versus non-menstrual 0/ml [0–14/ml]; P = 0.0362). No clonogenic endometrial cells were found in peripheral blood. Conclusions Clonogenic endometrial cells, SUSD2+ eMSC and N-cadherin+ eEPC are present in UMB and the peritoneal fluid of women with and without endometriosis. Further study of the function of these cells may shed light on the cellular origins of endometriosis.

Hyperactivation of PI3K/PTEN-mTOR signaling during neural development is associated with focal cortical dysplasia (FCD), autism, and epilepsy. mTOR can signal through two major hubs, mTORC1 and mTORC2, both of which are hyperactive following PTEN loss of function (LOF). Here, we tested the hypothesis that genetic inactivation of the mTORC2 complex via deletion ofRictoris sufficient to rescue morphologic and electrophysiological abnormalities in the dentate gyrus caused by PTEN loss, as well as generalized seizures. An established, early postnatal mouse model of PTEN loss in male and female mice showed spontaneous seizures that were not prevented by mTORC2 inactivation. This lack of rescue occurred despite the normalization or amelioration of many morphologic and electrophysiological phenotypes. However, increased excitatory connectivity proximal to dentate gyrus granule neuron somas was not normalized by mTORC2 inactivation. Further studies demonstrated that, although mTORC2 inactivation largely rescued the dendritic arbor overgrowth caused by PTEN LOF, it increased synaptic strength and caused additional impairments of presynaptic function. These results suggest that a constrained increase in excitatory connectivity and co-occurring synaptic dysfunction is sufficient to generate seizures downstream of PTEN LOF, even in the absence of characteristic changes in morphologic properties.SIGNIFICANCE STATEMENTHomozygous deletion of thePtengene in neuronal subpopulations in the mouse serves as a valuable model of epilepsy caused by mTOR hyperactivation. To better understand the physiological mechanisms downstream ofPtenloss that cause epilepsy, as well as the therapeutic potential of targeted gene therapies, we tested whether genetic inactivation of the mTORC2 complex could improve the cellular, synaptic, andin vivoeffects ofPtenloss in the dentate gyrus. We found that mTORC2 inhibition improved or rescued all morphologic effects ofPtenloss in the dentate gyrus, but synaptic changes and seizures persisted. These data suggest that synaptic dysfunction can drive epilepsy caused by hyperactivation of PI3K/PTEN-mTOR, and that future therapies should focus on this mechanistic link.

Mitigation of anthropogenic climate change is expected to require large-scale deployment of carbon dioxide removal strategies. Prominent among these strategies is direct air capture with sequestration (DACS), which encompasses the removal and long-term storage of atmospheric CO

An investigation of the solid-state behaviour of five 12-crown-4 alkali metal TCNQ complexes, (12-crown-4)2LiTCNQ (1), (12-crown-4)2NaTCNQ (2), (12-crown-4)2Li(TCNQ)2 (3), (12-crown-4)2Na(TCNQ)2 (4), and (12-crown-4)2K(TCNQ)2 (5), reveals an unusual “cross-stitch” packing motif with the extended face-to-face π-stacked TCNQ˙− columns present in complexes 1 and 2. The effect of the presence of additional neutral TCNQ0 has also been explored.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of AKT/mTOR signaling pathway. Mutations in PTEN are found in patients with autism, epilepsy, or macrocephaly. In mouse models, Pten loss results in neuronal hypertrophy, hyperexcitability, seizures, and ASD-like behaviors. The underlying molecular mechanisms of these phenotypes are not well delineated. We determined which of the Pten loss-driven aberrations in neuronal form and function are orchestrated by downstream mTOR complex 1 (mTORC1). Rapamycin-mediated inhibition of mTORC1 prevented increase in soma size, migration, spine density, and dendritic overgrowth in Pten knockout dentate gyrus granule neurons. Genetic knockout of Raptor to disrupt mTORC1 complex formation blocked Pten loss-mediated neuronal hypertrophy. Electrophysiological recordings revealed that genetic disruption of mTORC1 rescued Pten loss-mediated increase in excitatory synaptic transmission. We have identified an essential role for mTORC1 in orchestrating Pten loss-driven neuronal hypertrophy and synapse formation.

Bede’s double inscription of Aethelthryth in both narrative and hymn interrupts the temporal linearity of his Historia Ecclesiastica just as her adamant refusal of dynastic reproduction disrupts and threatens the futurity of the Northumbrian royal line. Her militant choice of virginity over marriage and of eternity over worldly time provides a female model for the male community to whom and for whom Bede writes. Bede dismantles binary gender as timebound, but he does so by appropriating women’s lived experience and literary expression. As both historical subject and devotional object, Aethelthryth thus constitutes a pivotal but problematic figure in Bede’s theoretical engagement with the entanglement of temporality, sexuality, and gender that underwrites monastic identity, male and female, in early medieval England.

Genetic epilepsies are often caused by variants in widely expressed genes, potentially impacting numerous brain regions and functions. For instance, gain-of-function (GOF) variants in the widely expressed Na+-activated K+ channel gene KCNT1 alter basic neurophysiological and synaptic properties of cortical neurons, leading to developmental epileptic encephalopathy. Yet, aside from causing seizures, little is known about how such variants reshape interictal brain activity, and how this relates to epileptic activity and other disease symptoms.To address this knowledge gap, we monitored neural activity across the dorsal cortex in a mouse model of human KCNT1-related epilepsy using in vivo, awake widefield Ca2+ imaging. We observed 52 spontaneous seizures and 1700 interictal epileptiform discharges (IEDs) in homozygous mutant (Kcnt1m/m) mice, allowing us to map their appearance and spread at high spatial resolution. Outside of seizures and IEDs, we detected ~46,000 events, representing interictal cortical activity, in both Kcnt1m/m and wild-type (WT) mice, and we classified them according to their spatial profiles.Spontaneous seizures and IEDs emerged within a consistent set of susceptible cortical areas, and seizures propagated both contiguously and non-contiguously within these areas in a manner influenced, but not fully determined, by underlying synaptic connectivity. Seizure emergence was predicted by a progressive concentration of total cortical activity within the impending seizure emergence zone. Outside of seizures and IEDs, similar events were detected in WT and Kcnt1m/m mice, suggesting that the spatial structure of interictal activity was largely preserved. Several features of these events, however, were altered in Kcnt1m/m mice. Most event types were briefer, and their intensity more variable, across Kcnt1m/m mice; mice showing more intense activity spent more time in seizure. Furthermore, the rate of events whose spatial profile overlapped with where seizures and IEDs emerged was increased in Kcnt1m/m mice.Taken together, these results demonstrate that an epilepsy-causing K+ channel variant broadly alters physiology. Yet, outside of seizures and IEDs, it acts not to produce novel types of cortical activity, but rather to modulate its amount. The areas where seizures and IEDs emerge show excessively frequent and intense interictal activity and the mean intensity of an individual’s cortical activity predicts its seizure burden. These findings provide critical guidance for targeting future research and therapy development.

We used an LC-MS/MS metabolomics approach to investigate one-carbon metabolism in the plasma of flaxseed-fed White Leghorn laying hens (aged 3.5 years). In our study, dietary flaxseed (via the activity of a vitamin B6 antagonist known as “1-amino d-proline”) induced at least 15-fold elevated plasma cystathionine. Surprisingly, plasma homocysteine (Hcy) was stable in flaxseed-fed hens despite such highly elevated cystathionine. To explain stable Hcy, our data suggest accelerated Hcy remethylation via BHMT and MS-B12. Also supporting accelerated Hcy remethylation, we observed elevated S-adenosylmethionine (SAM), an elevated SAM:SAH ratio, and elevated methylthioadenosine (MTA), in flaxseed-fed hens. These results suggest that flaxseed increases SAM biosynthesis and possibly increases polyamine biosynthesis. The following endpoint phenotypes were observed in hens consuming flaxseed: decreased physiological aging, increased empirical lifespan, 9–14% reduced body mass, and improved liver function. Overall, we suggest that flaxseed can protect women from ovarian tumor metastasis by decreasing omental adiposity. We also propose that flaxseed protects cancer patients from cancer-associated cachexia by enhancing liver function.

The large-scale deployment of carbon capture technologies is expected to play a crucial role in efforts to meet stringent climate targets set forth by the Paris Agreement, but current models rely heavily upon carbon dioxide removal (CDR) strategies for which viability at the gigatonne scale is uncertain. While most 1.5 and 2 °C scenarios project rapid decarbonization of the energy sector facilitated by carbon capture and sequestration (CCS), they generally assume that CCS units can only capture ∼90% of the CO2 in coal and natural gas combustion flues because this was previously considered the optimal condition for aqueous amine scrubbers. In this Perspective, we discuss a small but growing body of literature that examines the prospect of moving significantly beyond 90% capture-a concept we term deep CCS-in light of recent developments in materials and process design. The low incremental costs associated with performing varying degrees of deep CCS suggest that this approach is not only feasible but may also alleviate burdens placed upon CDR techniques facing significant barriers to large-scale deployment. We estimate that rapid deployment of deep CCS in deep decarbonization pathways could avoid more than 1 gigatonne of CO2 globally each year. The principles of deep CCS could also be applied directly to the CDR strategy of employing bioenergy with CCS, which could lead to a significant alleviation of the land and freshwater burden associated with this technology.

Expression of the Neuronal tRNA n-Tr20 Regulates Synaptic Transmission and Seizure Susceptibility Kapur M, Ganguly A, Nagy G, Adamson SI, Chuang JH, Frankel WN, Ackerman SL. Neuron. 2020;108(1):193-208. e9. doi:10.1016/j.neuron.2020.07.023; PMID: 32853550; PMCID: PMC7572898The mammalian genome has hundreds of nuclear-encoded tRNAs, but the contribution of individual tRNA genes to cellular and organismal function remains unknown. Here, we demonstrate that mutations in a neuronally enriched arginine tRNA, n-Tr20, increased seizure threshold and altered synaptic transmission. n-Tr20 expression also modulated seizures caused by an epilepsy-linked mutation in Gabrg2, a gene encoding a GABAA receptor subunit. Loss of n-Tr20 altered translation initiation by activating the integrated stress response and suppressing mTOR signaling, the latter of which may contribute to altered neurotransmission in mutant mice. Deletion of a highly expressed isoleucine tRNA similarly altered these signaling pathways in the brain, suggesting that regulation of translation initiation is a conserved response to tRNA loss. Our data indicate that loss of a single member of a tRNA family results in multiple cellular phenotypes, highlighting the disease-causing potential of tRNA mutations.

Acute Knockdown of Depdc5 Leads to Synaptic Defects in mTOR-Related Epileptogenesis De Fusco A, Cerullo MS, Marte A, Michetti C, Romei A, Castroflorio E. Neurobiol Dis. 2020;139:104822. doi:10.1016/j.nbd.2020.104822DEP-domain containing 5 (DEPDC5) is part of the GATOR1 complex that functions as key inhibitor of the mechanistic target of rapamycin complex 1 (mTORC1). Loss-of-function mutations in DEPDC5 leading to mTOR hyperactivation have been identified as the most common cause of either lesional or non-lesional focal epilepsy. However, the precise mechanisms by which DEPDC5 loss-of-function triggers neuronal and network hyperexcitability are still unclear. In this study, we investigated the cellular mechanisms of hyperexcitability by comparing the constitutive heterozygous Depdc5 knockout mouse versus different levels of acute Depdc5 deletion (≈40% and ≈80% neuronal knockdown of Depdc5 protein) by RNA interference in primary cortical cultures. While heterozygous Depdc5+/− neurons have only a subtle phenotype, acutely knocked-down neurons exhibit a strong dose-dependent phenotype characterized by mTOR hyperactivation, increased soma size, dendritic arborization, excitatory synaptic transmission, and intrinsic excitability. The robust synaptic phenotype resulting from the acute knockdown Depdc5 deficiency highlights the importance of the temporal dynamics of Depdc5 knockdown in triggering the phenotypic changes, reminiscent of the somatic second-hit mechanism in patients with focal cortical dysplasia. These findings uncover a novel synaptic phenotype that is causally linked to Depdc5 knockdown, highlighting the developmental role of Depdc5. Interestingly, the synaptic defect appears to affect only excitatory synapses, while inhibitory synapses develop normally. The increased frequency and amplitude of miniature excitatory postsynaptic currents, paralleled by increased density of excitatory synapses and expression of glutamate receptors, may generate an excitation/inhibition imbalance that triggers epileptogenesis.

A new aluminosilicate zeolite, denoted EMM-37, with a 3D small pore channel system, has been synthesized using a diquaternary ammonium molecule as the structure directing agent (SDA) and metakaolin as the aluminum source. The structures of both as-made and calcined forms of EMM-37 were solved and refined using continuous rotation electron diffraction (cRED) data. cRED is a powerful method for the collection of 3D electron diffraction data from submicron- and nanosized crystals, which allows for successful solution and refinement of complex structures in symmetry as low as P1.

A new catalytically active zeolite, designated EMM-17 (ExxonMobil Material-17), with a three-dimensional (3D) 11 × 10 × 10-ring topology has been discovered from high throughput experiments while evaluating a family of new organic structure directing agents (OSDAs), 1-alkyl-4-(pyrrolidin-1-yl)pyridin-1-ium hydroxide. The framework structure was determined by model building techniques and confirmed by diffraction calculations. The EMM-17 structure is a random intergrowth of two polymorphs which have a 3D arrangement of intersecting 11 × 10 × 10-ring pores. EMM-17 is stable to calcination to remove the OSDA and can be reproducibly synthesized in the presence of fluoride using common, inexpensive reagents over a wide Si/Al range from 15 to infinity, enabling the catalyst acidity to be tailored to almost any petrochemical application. Unlike OSDAs for many new zeolite structures, the OSDAs for EMM-17 are prepared in one simple alkylation step, making EMM-17 an easy to prepare, highly accessible, catalytically active zeolite. Zeolites containing odd numbered channel sizes are rare, and this is the first confirmed example of a 3D 11-ring aluminosilicate zeolite with a pore size in between those of the commercially important 10- and 12-ring zeolites such as ZSM-5 and Zeolite-Y, respectively. Catalysts prepared from EMM-17 exhibit significantly higher activity for catalytic isomerization with no loss in selectivity than current state of the art catalysts. Catalytic isomerization of linear to branched alkanes is a critical component of commercial dewaxing, allowing for the improvement of cold flow properties of hydrocarbon fuels and lubricants through selective hydroisomerization of normal paraffins.

Supported by increasingly available reserves, natural gas is achieving greater adoption as a cleaner-burning alternative to coal in the power sector. As a result, carbon capture and sequestration from natural gas-fired power plants is an attractive strategy to mitigate global anthropogenic CO2 emissions. However, the separation of CO2 from other components in the flue streams of gas-fired power plants is particularly challenging due to the low CO2 partial pressure (∼40 mbar), which necessitates that candidate separation materials bind CO2 strongly at low partial pressures (≤4 mbar) to capture ≥90% of the emitted CO2. High partial pressures of O2 (120 mbar) and water (80 mbar) in these flue streams have also presented significant barriers to the deployment of new technologies for CO2 capture from gas-fired power plants. Here, we demonstrate that functionalization of the metal-organic framework Mg2(dobpdc) (dobpdc4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) with the cyclic diamine 2-(aminomethyl)piperidine (2-ampd) produces an adsorbent that is capable of ≥90% CO2 capture from a humid natural gas flue emission stream, as confirmed by breakthrough measurements. This material captures CO2 by a cooperative mechanism that enables access to a large CO2 cycling capacity with a small temperature swing (2.4 mmol CO2/g with ΔT = 100 °C). Significantly, multicomponent adsorption experiments, infrared spectroscopy, magic angle spinning solid-state NMR spectroscopy, and van der Waals-corrected density functional theory studies suggest that water enhances CO2 capture in 2-ampd-Mg2(dobpdc) through hydrogen-bonding interactions with the carbamate groups of the ammonium carbamate chains formed upon CO2 adsorption, thereby increasing the thermodynamic driving force for CO2 binding. In light of the exceptional thermal and oxidative stability of 2-ampd-Mg2(dobpdc), its high CO2 adsorption capacity, and its high CO2 capture rate from a simulated natural gas flue emission stream, this material is one of the most promising adsorbents to date for this important separation.

The solid-state behaviour of four alkali metal TCNQ complexes: (15-crown-5)LiTCNQ (1), (15-crown-5)NaTCNQ (2), (15-crown-5)Li(TCNQ)2.H2O (3.H2O) and (15-crown-5)Na(TCNQ)2.H2O (4.H2O) has been explored by single crystal X-ray diffraction, Infrared (IR), Raman and Electron Paramagnetic Resonance (EPR) measurements. The presence of a small cation and ionophore leads to subtle changes in behaviour compared with their larger alkali metal analogues and in the hydrated salts water bridges form links between the crown-encapsulated cations and neighbouring TCNQ stacks.

In recent years, the power sector has shown a growing reliance on natural gas, a cleaner-burning fuel than coal that emits approximately half as much CO2 per kWh of energy produced. This rapid growth in the consumption of natural gas has led to increased CO2 emissions from gas-fired power plants. To limit the contribution of fossil fuel combustion to atmospheric CO2 levels, carbon capture and sequestration has been proposed as a potential emission mitigation strategy. However, despite extensive exploration of solid adsorbents for CO2 capture, few studies have examined the performance of adsorbents in post-combustion capture processes specific to natural gas flue emissions. In this perspective, we emphasize the importance of considering gas-fired power plants alongside coal-fired plants in future analyses of carbon capture materials. We address specific challenges and opportunities related to adsorptive carbon capture from the emissions of gas-fired plants and discuss several promising candidate materials. Finally, we suggest experiments to determine the viability of new CO2 capture materials for this separation. This broadening in the scope of current carbon capture research is urgently needed to accelerate the deployment of transformational carbon capture technologies.

Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery.This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy.Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51-19.97) than planned admissions (OR: 2.32, 95% CI: 1.43-3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8-51.9%, P0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI.After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.

Significant advances have been made in the synthesis of chemically selective environments within metal-organic frameworks, yet materials development and industrial implementation have been hindered by the inability to predictively control crystallite size and shape. One common strategy to control crystal growth is the inclusion of coordination modulators, which are molecular species designed to compete with the linker for metal coordination during synthesis. However, these modulators can simultaneously alter the pH of the reaction solution, an effect that can also significantly influence crystal morphology. Herein, noncoordinating buffers are used to independently control reaction pH during metal-organic framework synthesis, enabling direct interrogation of the role of the coordinating species on crystal growth. We demonstrate the efficacy of this strategy in the synthesis of low-dispersity single-crystals of the framework Co

To investigate how initial fitness, maturity status, and training time explain changes in physical performance across one season. Eighty-eight adolescent male footballers, representing four age categories (Under 15 [n = 12], Under 14 [n = 21], Under 13 [n = 25], Under 12 [n = 30]), were tested using physical performance tests (20 m sprint, change of direction, squat jump and yo-yo intermittent recovery test level 1 [YYIRTL1]) and maturity offset at the season start (Test 1) and end (Test 2). Multiple regression determined the proportion of variance in test score changes, explained by three predictor variables: initial fitness (i.e., Test 1), maturity offset change, and training time. With combined categories, predictor variables explained 0.051 to 0.297 of the variance in physical performance score changes. Analysing age categories separately, predictor variables explained 0.047 to 0.407 (20 m sprint), 0.202 to 0.626 (change of direction), 0.336 to 0.502 (squat jump), and 0.196 to 0.777 (YYIRTL1) of variance in test score changes. Of the limited differences in relative predictor contribution, Test 1 was the strongest predictor of test score change. Initial fitness, maturity status change, and training time explain small and inconsistent proportions of variance in adolescent footballers’ physical development across one season.

Bronchoscopy is an aerosol-generating procedure (AGP) and the COVID-19 pandemic has necessitated changes in provision of our service This retrospective analysis reviews our institutional response to maintaining safe and efficient bronchoscopy services throughout the COVID-19 pandemic Aim To analyse changes in numbers of and indications for flexible bronchoscopy (FB) and endobronchial ultrasound (EBUS) between December 2019-August 2020, and the mitigating measures introduced by our centre to keep the service operating Method Data was pulled from our procedure database for the three months pre-COVID-19 (December 2019-February 2020), the COVID peak (March to May 2020) and the 'recovery' phase (June-mid August 2020) Patient records were analysed for the indication for procedure and diagnosis Cancelled procedures and research bronchoscopies were excluded Results 433 procedures were undertaken during the study period Figure 1 shows the number of endoscopic procedures by indication and procedure type There was an overall decrease in procedures during the pandemic, with predominantly EBUS cancer procedures being undertaken The number of cancer cases performed across all three periods was comparable Pre-procedure COVID swabs became mandatory in our institution from 29th April 2020 Of 167 cases, two were postponed (1 positive test and 1 febrile patient on procedure day) No patients were cancelled during pre-procedural telephone COVID-19 screening Discussion Bronchoscopy procedures declined during the COVID-19 pandemic However, our service maintained 4 lists per week during the peak with reinstatement of six lists during the COVID-endemic period Bronchoscopy training was maintained with all lists having an assigned trainee AGPrelated air exchange protocols limited the number of procedures per list and elective procedures were postponed early in the pandemic Our centre had a proactive approach to running the service, introducing mandatory pre-procedure COVID swabbing early together with telephone screening pre-BTS guidance Staff safety was prioritised via universal use of powered airpurifying respiratory (PAPR) use which eliminated the need for mask-fit testing and seeking FFP3 mask availability It is feasible to maintain a safe and efficient bronchoscopy service in the midst of a pandemic with the implementation of appropriate pathways and provision of adequate personal protective equipment

The nature and properties of the soil, along with other site factors such as climate, slope position, elevation, and aspect, determine the availability of water and nutrients to plants and therefore influence the success of forest restoration programs. Characteristics of the soil therefore warrant careful consideration when estimating the potential of a site for afforestation or reforestation. Many sites being considered for forest landscape restoration have soils that have been degraded through various human activities, which will need to be rehabilitated as part of the restoration process. Characteristics of degraded soils include loss of structure and organic matter, susceptibility to erosion by wind or water, diminished aeration and water-holding capacity, insufficient or excess nutrient supply, excess acidity or salinity, and diminished soil biota. In this chapter, we discuss each of these impairments and the restoration practices that can be applied to rehabilitate degraded soils.

In recent years, the power sector has shown a growing reliance on natural gas, a cleaner-burning fuel than coal that emits approximately half as much CO(2) per kWh of energy produced. This rapid growth in the consumption of natural gas has led to increased CO(2) emissions from gas-fired power plants. To limit the contribution of fossil fuel combustion to atmospheric CO(2) levels, carbon capture and sequestration has been proposed as a potential emission mitigation strategy. However, despite extensive exploration of solid adsorbents for CO(2) capture, few studies have examined the performance of adsorbents in post-combustion capture processes specific to natural gas flue emissions. In this perspective, we emphasize the importance of considering gas-fired power plants alongside coal-fired plants in future analyses of carbon capture materials. We address specific challenges and opportunities related to adsorptive carbon capture from the emissions of gas-fired plants and discuss several promising candidate materials. Finally, we suggest experiments to determine the viability of new CO(2) capture materials for this separation. This broadening in the scope of current carbon capture research is urgently needed to accelerate the deployment of transformational carbon capture technologies.

Natural gas has become the dominant source of electricity in the United States, and technologies capable of efficiently removing carbon dioxide (CO2) from the flue emissions of natural gas-fired power plants could reduce their carbon intensity. However, given the low partial pressure of CO2 in the flue stream, separation of CO2 is particularly challenging. Taking inspiration from the crystal structures of diamine-appended metal-organic frameworks exhibiting two-step cooperative CO2 adsorption, we report a family of robust tetraamine-functionalized frameworks that retain cooperativity, leading to the potential for exceptional efficiency in capturing CO2 under the extreme conditions relevant to natural gas flue emissions. The ordered, multimetal coordination of the tetraamines imparts the materials with extraordinary stability to adsorption-desorption cycling with simulated humid flue gas and enables regeneration using low-temperature steam in lieu of costly pressure or temperature swings.

Developmental epileptic encephalopathies (DEEs) are severe seizure disorders that occur in infants and young children, characterized by developmental delay, cognitive decline, and early mortality. Recent efforts have identified a wide variety of genetic variants that cause DEEs. Among these, variants in the DNM1 gene have emerged as definitive causes of DEEs, including infantile spasms and Lennox-Gastaut syndrome. A mouse model of Dnm1-associated DEE, known as “Fitful” (Dnm1Ftfl), recapitulates key features of the disease, including spontaneous seizures, early lethality, and neuronal degeneration. Previous work showed that DNM1 is a key regulator of synaptic vesicle (SV) endocytosis and synaptic transmission, and suggested that inhibitory neurotransmission may be more reliant on DNM1 function than excitatory transmission. The Dnm1Ftfl variant is thought to encode a dominant negative DNM1 protein, however, the effects of the Dnm1Ftfl variant on synaptic transmission are largely unknown. To understand these synaptic effects, we recorded from pairs of cultured mouse cortical neurons and characterized all four major connection types (E-E, E-I, I-E, I-I). Miniature and spontaneous EPSCs and IPSCs were larger, but less frequent, at all Dnm1Ftfl synaptic types, and Dnm1Ftfl neurons had reduced expression of excitatory and inhibitory SV markers. Baseline evoked transmission, however, was reduced only at inhibitory synapses onto excitatory neurons, due to a smaller pool of releasable SVs. In addition to these synaptic alterations, Dnm1Ftfl neurons degenerated later in development, even though their activity levels were reduced, suggesting that Dnm1Ftfl may impair synaptic transmission and neuronal health through distinct mechanisms. Significance Statement Recent work has identified genetic variants in DNM1 as among the more common causes of developmental epileptic encephalopathies (DEEs), but the physiological consequences of its mutation are unclear. Here, we make use of an in vitro model of Dnm1-associated DEE to determine the effects of a Dnm1 variant on the four main cortical synapse types. The variant caused both synapse-specific and synapse-wide alterations, and decreased neuronal activity. Despite this, neurons still degenerated after two weeks in vitro, suggesting that neuronal degeneration in these mice may be independent of seizures, and that stopping seizures may do little to mitigate key features of DEEs.

Gain-of-function (GOF) variants in K+ channels cause severe childhood epilepsies, but there are no mechanisms to explain how increased K+ currents lead to network hyperexcitability. Here, we introduced a human Na+-activated K+ (KNa) channel variant (KCNT1-Y796H) into mice and, using a multiplatform approach, found motor cortex hyperexcitability and early-onset seizures, phenotypes strikingly similar to those of human patients. Although the variant increased KNa currents in cortical excitatory and inhibitory neurons, there was a selective increase in the KNa current across subthreshold voltages in inhibitory neurons, particularly in those with non-fast spiking properties, resulting in impaired excitability and AP generation. We further observed evidence of synaptic rewiring associated with hyperexcitable networks, including increases in homotypic synaptic connectivity and the ratio of excitatory-to-inhibitory synaptic input. These findings support inhibitory neuron-specific mechanisms in mediating the epileptogenic effects of K+ channel GOF, offering cell-type-specific currents and effects as promising targets for therapeutic intervention.