Two Different Hydrogen Bond Donor Ligands Together: A Selectivity Improvement in Organometallic {Re(CO)3} Anion Hosts

Rhenium(I) compounds [Re(CO)3(Hdmpz)2(ampy)]BAr′4 and [Re(CO)3(N-MeIm)2(ampy)]BAr′4 (Hdmpz = 3,5-dimethylpyrazole, N-MeIm = N-methylimidazole, ampy = 2-aminopyridine or 3-aminopyridine) have been prepared stepwise as the sole reaction products in good yields. The cationic complexes feature two different types of hydrogen bond donor ligands, and their anion binding behavior has been studied both in solution and in the solid state. Compounds with 2-ampy ligands are labile in the presence of nearly all of the anions tested. The X-ray structure of the complex [Re(CO)3(Hdmpz)2(ampy)]+ (2) shows that the 2-ampy ligand is metal-coordinated through the amino group, a fact that can be responsible for its labile character. The 3-ampy derivatives (coordinated through the pyridinic nitrogen atom) are stable toward the addition of several anions and are more selective anion hosts than their tris(pyrazole) or tris(imidazole) counterparts. This selectivity is higher for compound [Re(CO)3(N-MeIm)2(MeNA)]BAr′4 (5·BAr′4, MeNA = N-methylnicotinamide) that features an amido moiety, which is a better hydrogen bond donor than the amino group. Some of the receptor-anion adducts have been characterized in the solid state by X-ray diffraction, showing that both types of hydrogen bond donor ligands of the cationic receptor participate in the interaction with the anion hosts. DFT calculations suggest that coordination of the ampy ligands is more favorable through the amino group only for the cationic complex 2, as a consequence of the existence of a strong intramolecular hydrogen bond. In all other cases, the pyridinic coordination is clearly favored

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Excavations on the Route of the Dalkeith Northern Bypass, 1994-95 and 2006

An evaluation and subsequent targeted excavations were carried out along the route of the proposed A68 Dalkeith Northern Bypass by the Centre for Field Archaeology (CFA) between September 1994 and March 1995, with additional watching briefs taking place in 1997. The work was commissioned by Historic Scotland on behalf of the Roads Directorate of the Scottish Office Industry Department. The bypass was not constructed at the time, and further pre-construction mitigation work was recommended in 2005, with fieldwork being carried out in 2006-08 by CFA Archaeology Ltd, for Historic Scotland on behalf of Transport Scotland.This report describes the results of the evaluations and each excavation individually. The route traverses a narrow strip of the Lothian plain which contained several prehistoric sites (two ring-groove structures, a stone-paved area and two pit alignments), a Roman temporary camp, a post-medieval building, an 18th-century designed landscape, and two industrial sites (a brick and tile works and a coal pit engine house). Several sites also produced ephemeral remains of earlier or later date. Overall, the results indicated a settlement pattern and land use which concentrated on the sands and gravels of the river terraces, with far less settlement on the unforgiving compacted clays which otherwise characterise large parts of the road corridor

Fam49/CYRI interacts with Rac1 and locally suppresses protrusions

Actin-based protrusions are reinforced through positive feedback, but it is unclear what restricts their size, or limits positive signals when they retract or split. We identify an evolutionarily conserved regulator of actin-based protrusion: CYRI (CYFIP-related Rac interactor) also known as Fam49 (family of unknown function 49). CYRI binds activated Rac1 via a domain of unknown function (DUF1394) shared with CYFIP, defining DUF1394 as a Rac1-binding module. CYRI-depleted cells have broad lamellipodia enriched in Scar/WAVE, but reduced protrusion–retraction dynamics. Pseudopods induced by optogenetic Rac1 activation in CYRI-depleted cells are larger and longer lived. Conversely, CYRI overexpression suppresses recruitment of active Scar/WAVE to the cell edge, resulting in short-lived, unproductive protrusions. CYRI thus focuses protrusion signals and regulates pseudopod complexity by inhibiting Scar/WAVE-induced actin polymerization. It thus behaves like a ‘local inhibitor’ as predicted in widely accepted mathematical models, but not previously identified in cells. CYRI therefore regulates chemotaxis, cell migration and epithelial polarization by controlling the polarity and plasticity of protrusions

Incidence and phenotypes of childhood-onset genetic epilepsies:a prospective population-based national cohort

Epilepsy is common in early childhood. In this age group it is associated with high rates of therapy-resistance, and with cognitive, motor, and behavioural comorbidity. A large number of genes, with wide ranging functions, are implicated in its aetiology, especially in those with therapy-resistant seizures. Identifying the more common single-gene epilepsies will aid in targeting resources, the prioritization of diagnostic testing and development of precision therapy. Previous studies of genetic testing in epilepsy have not been prospective and population-based. Therefore, the population-incidence of common genetic epilepsies remains unknown. The objective of this study was to describe the incidence and phenotypic spectrum of the most common single-gene epilepsies in young children, and to calculate what proportion are amenable to precision therapy. This was a prospective national epidemiological cohort study. All children presenting with epilepsy before 36 months of age were eligible. Children presenting with recurrent prolonged (>10 min) febrile seizures; febrile or afebrile status epilepticus (>30 min); or with clusters of two or more febrile or afebrile seizures within a 24-h period were also eligible. Participants were recruited from all 20 regional paediatric departments and four tertiary children’s hospitals in Scotland over a 3-year period. DNA samples were tested on a custom-designed 104-gene epilepsy panel. Detailed clinical information was systematically gathered at initial presentation and during follow-up. Clinical and genetic data were reviewed by a multidisciplinary team of clinicians and genetic scientists. The pathogenic significance of the genetic variants was assessed in accordance with the guidelines of UK Association of Clinical Genetic Science (ACGS). Of the 343 patients who met inclusion criteria, 333 completed genetic testing, and 80/333 (24%) had a diagnostic genetic finding. The overall estimated annual incidence of single-gene epilepsies in this well-defined population was 1 per 2120 live births (47.2/100 000; 95% confidence interval 36.9–57.5). PRRT2 was the most common single-gene epilepsy with an incidence of 1 per 9970 live births (10.0/100 000; 95% confidence interval 5.26–14.8) followed by SCN1A: 1 per 12 200 (8.26/100 000; 95% confidence interval 3.93–12.6); KCNQ2: 1 per 17 000 (5.89/100 000; 95% confidence interval 2.24–9.56) and SLC2A1: 1 per 24 300 (4.13/100 000; 95% confidence interval 1.07–7.19). Presentation before the age of 6 months, and presentation with afebrile focal seizures were significantly associated with genetic diagnosis. Single-gene disorders accounted for a quarter of the seizure disorders in this cohort. Genetic testing is recommended to identify children who may benefit from precision treatment and should be mainstream practice in early childhood onset epilepsy

Strong Carbon Features and a Red Early Color in the Underluminous Type Ia SN 2022xkq

We present optical, infrared, ultraviolet, and radio observations of SN 2022xkq, an underluminous fast-declining type Ia supernova (SN Ia) in NGC 1784 ($\mathrm{D}\approx31$ Mpc), from $<1$ to 180 days after explosion. The high-cadence observations of SN 2022xkq, a photometrically transitional and spectroscopically 91bg-like SN Ia, cover the first days and weeks following explosion which are critical to distinguishing between explosion scenarios. The early light curve of SN 2022xkq has a red early color and exhibits a flux excess which is more prominent in redder bands; this is the first time such a feature has been seen in a transitional/91bg-like SN Ia. We also present 92 optical and 19 near-infrared (NIR) spectra, beginning 0.4 days after explosion in the optical and 2.6 days after explosion in the NIR. SN 2022xkq exhibits a long-lived C I 1.0693 $\mu$m feature which persists until 5 days post-maximum. We also detect C II $\lambda$6580 in the pre-maximum optical spectra. These lines are evidence for unburnt carbon that is difficult to reconcile with the double detonation of a sub-Chandrasekhar mass white dwarf. No existing explosion model can fully explain the photometric and spectroscopic dataset of SN 2022xkq, but the considerable breadth of the observations is ideal for furthering our understanding of the processes which produce faint SNe Ia.Comment: 38 pages, 16 figures, accepted for publication in ApJ, the figure 15 input models and synthetic spectra are now available at https://zenodo.org/record/837925