Notes

Acclimation of photosynthetic equipment from the mesophilic crimson alga Dixoniella giordanoi.
Spin ice systems display a variety of very nontrivial properties, the most striking being the existence in them of magnetic monopoles. Such monopole states can also have nontrivial electric properties there exist electric dipoles attached to each monopole. A novel situation is encountered in the moment fragmentation (MF) state, in which monopoles and antimonopoles are perfectly ordered, whereas spins themselves remain disordered. We show that such partial ordering strongly modifies the electric activity of such systems the electric dipoles, which are usually random and dynamic, become paired in the MF state in (d, -d) pairs, thus strongly reducing their electric activity. The electric currents existing in systems with noncoplanar spins are also strongly influenced by MF. We also consider modifications in dipole and current patterns in magnetic textures (domain walls, local defects) and at excitations with nontrivial dynamics in a MF state, which show very rich behaviour and which could in principle allow to control them by electric field.All herpesviruses encode a conserved DNA polymerase that is required for viral genome replication and serves as an important therapeutic target. Currently available herpesvirus therapies include nucleoside and non-nucleoside inhibitors (NNI) that target the DNA-bound state of herpesvirus polymerase and block replication. Here we report the ternary complex crystal structure of Herpes Simplex Virus 1 DNA polymerase bound to DNA and a 4-oxo-dihydroquinoline NNI, PNU-183792 (PNU), at 3.5 Å resolution. PNU bound at the polymerase active site, displacing the template strand and inducing a conformational shift of the fingers domain into an open state. These results demonstrate that PNU inhibits replication by blocking association of dNTP and stalling the enzyme in a catalytically incompetent conformation, ultimately acting as a nucleotide competing inhibitor (NCI). Sequence conservation of the NCI binding pocket further explains broad-spectrum activity while a direct interaction between PNU and residue V823 rationalizes why mutations at this position result in loss of inhibition.Non-uniform illumination limits quantitative analyses of fluorescence imaging techniques. In particular, single molecule localization microscopy (SMLM) relies on high irradiances, but conventional Gaussian-shaped laser illumination restricts the usable field of view to around 40 µm × 40 µm. Pterostilbene We present Adaptable Scanning for Tunable Excitation Regions (ASTER), a versatile illumination technique that generates uniform and adaptable illumination. ASTER is also highly compatible with optical sectioning techniques such as total internal reflection fluorescence (TIRF). For SMLM, ASTER delivers homogeneous blinking kinetics at reasonable laser power over fields-of-view up to 200 µm × 200 µm. We demonstrate that ASTER improves clustering analysis and nanoscopic size measurements by imaging nanorulers, microtubules and clathrin-coated pits in COS-7 cells, and β2-spectrin in neurons. ASTER's sharp and quantitative illumination paves the way for high-throughput quantification of biological structures and processes in classical and super-resolution fluorescence microscopies.Approximately half of the freshwater discharged from the Greenland and Antarctic Ice Sheets enters the ocean subsurface as a result of basal ice melt, or runoff draining via the grounding line of a deep ice shelf or marine-terminating glacier. Around Antarctica and parts of northern Greenland, this freshwater then experiences prolonged residence times in large cavities beneath floating ice tongues. Due to the inaccessibility of these cavities, it is unclear how they moderate the freshwater associated supply of nutrients such as iron (Fe) to the ocean. Here, we show that subglacial dissolved Fe export from Nioghalvfjerdsbrae (the '79°N Glacier') is decoupled from particulate inputs including freshwater Fe supply, likely due to the prolonged ~162-day residence time of Atlantic water beneath Greenland's largest floating ice-tongue. Our findings indicate that the overturning rate and particle-dissolved phase exchanges in ice cavities exert a dominant control on subglacial nutrient supply to shelf regions.Images of DaTscan (ioflupane [123I] SPECT) have been used as an adjunct to clinical diagnosis to facilitate the differential diagnosis of neurodegenerative (ND) Parkinsonian Syndrome (PS) vs. non-dopamine deficiency aetiologies of Parkinsonism. Despite several systematic reviews having summarised the evidence on diagnostic accuracy, the impact of imaging results on clinical utility has not been systematically assessed. Our objective was to examine the available evidence on the clinical utility of DaTscan imaging in changing diagnosis and subsequent management of patients with suspected PS. We performed a systematic review of published studies of clinical utility from 2000 to 2019 without language restrictions. A meta-analysis of change in diagnosis and management rates reported from each study was performed using a random-effects model and logit transformation. Sub-group analysis, meta-regression and sensitivity analysis was performed to explore heterogeneity. Twenty studies met the inclusion criteria. Thirteen of these contributed to the meta-analyses including 950 and 779 patients with a reported change in management and change in diagnosis, respectively. The use of DaTscan imaging resulted in a change in management in 54% (95% CI 47-61%) of patients. Change in diagnosis occurred in 31% (95% CI 22-42%) of patients. The two pooled analyses were characterised by high levels of heterogeneity. Our systematic review and meta-analysis show that imaging with DaTscan was associated with a change in management in approximately half the patients tested and the diagnosis was modified in one third. Regardless of time from symptom onset to scan results, these changes were consistent. Further research focusing on specific patient subgroups could provide additional evidence on the impact on clinical outcomes.The SARS-CoV-2 pandemic has triggered global efforts to develop therapeutics. The main protease of SARS-CoV-2 (Mpro), critical for viral replication, is a key target for therapeutic development. An organoselenium drug called ebselen has been demonstrated to have potent Mpro inhibition and antiviral activity. We have examined the binding modes of ebselen and its derivative in Mpro via high resolution co-crystallography and investigated their chemical reactivity via mass spectrometry. Stronger Mpro inhibition than ebselen and potent ability to rescue infected cells were observed for a number of derivatives. A free selenium atom bound with cysteine of catalytic dyad has been revealed in crystallographic structures of Mpro with ebselen and MR6-31-2 suggesting hydrolysis of the enzyme bound organoselenium covalent adduct and formation of a phenolic by-product, confirmed by mass spectrometry. The target engagement with selenation mechanism of inhibition suggests wider therapeutic applications of these compounds against SARS-CoV-2 and other zoonotic beta-corona viruses.
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