Spreading depolarization (SD) is a feed‐forward wave that propagates slowly throughout brain tissue and recovery from SD involves substantial metabolic demand. Presynaptic Zn2+ release and ...intracellular accumulation occurs with SD, and elevated intracellular Zn2+ (Zn2+i) can impair cellular metabolism through multiple pathways. We tested here whether increased Zn2+i could exacerbate the metabolic challenge of SD, induced by KCl, and delay recovery in acute murine hippocampal slices. Zn2+i loading prior to SD, by transient ZnCl2 application with the Zn2+ ionophore pyrithione (Zn/Pyr), delayed recovery of field excitatory post‐synaptic potentials (fEPSPs) in a concentration‐dependent manner, prolonged DC shifts, and significantly increased extracellular adenosine accumulation. These effects could be due to metabolic inhibition, occurring downstream of pyruvate utilization. Prolonged Zn2+i accumulation prior to SD was required for effects on fEPSP recovery and consistent with this, endogenous synaptic Zn2+ release during SD propagation did not delay recovery from SD. The effects of exogenous Zn2+i loading were also lost in slices preconditioned with repetitive SDs, implying a rapid adaptation. Together, these results suggest that Zn2+i loading prior to SD can provide significant additional challenge to brain tissue, and could contribute to deleterious effects of Zn2+i accumulation in a range of brain injury models.
Synaptic Zn2+ release and accumulation occurs during spreading depolarization (SD). We show here that intracellular Zn2+ accumulation significantly impairs recovery from SD, as measured by suppression of field excitatory postsynaptic potentials and DC shift durations. These effects were mediated by enhanced adenosine accumulation and A1 receptor activation. The added challenge of Zn2+ release and loading during SD may contribute to deleterious effects of Zn2+ in brain injury.
Excessive type I interferon (IFNα/β) activity is implicated in a spectrum of human disease, yet its direct role remains to be conclusively proven. We investigated two siblings with severe early-onset ...autoinflammatory disease and an elevated IFN signature. Whole-exome sequencing revealed a shared homozygous missense Arg148Trp variant in
, a transcription factor that functions exclusively downstream of innate IFNs. Cells bearing STAT2
in homozygosity (but not heterozygosity) were hypersensitive to IFNα/β, which manifest as prolonged Janus kinase-signal transducers and activators of transcription (STAT) signaling and transcriptional activation. We show that this gain of IFN activity results from the failure of mutant STAT2
to interact with ubiquitin-specific protease 18, a key STAT2-dependent negative regulator of IFNα/β signaling. These observations reveal an essential in vivo function of STAT2 in the regulation of human IFNα/β signaling, providing concrete evidence of the serious pathological consequences of unrestrained IFNα/β activity and supporting efforts to target this pathway therapeutically in IFN-associated disease.
Graphitic systems have an electronic structure that can be readily manipulated through electrostatic or chemical doping, resulting in a rich variety of electronic ground states. Here we report the ...first observation and characterization of electronic stripes in the highly electron-doped graphitic superconductor, CaC6 , by scanning tunnelling microscopy and spectroscopy. The stripes correspond to a charge density wave with a period three times that of the Ca superlattice. Although the positions of the Ca intercalants are modulated, no displacements of the carbon lattice are detected, indicating that the graphene sheets host the ideal charge density wave. This provides an exceptionally simple material--graphene--as a starting point for understanding the relation between stripes and superconductivity. Furthermore, our experiments suggest a strategy to search for superconductivity in graphene, namely in the vicinity of striped 'Wigner crystal' phases, where some of the electrons crystallize to form a superlattice.
Interactions between glioma cells and their local environment are critical determinants of brain tumor growth, infiltration and neovascularisation. Communication with host cells and stroma via ...microvesicles represents one pathway by which tumors can modify their surroundings to achieve a tumor-permissive environment. Here we have taken an unbiased approach to identifying RNAs in glioma-derived microvesicles, and explored their potential to regulate gene expression in recipient cells. We find that glioma microvesicles are predominantly of exosomal origin and contain complex populations of coding and noncoding RNAs in proportions that are distinct from those in the cells from which they are derived. Microvesicles show a relative depletion in microRNA compared with their cells of origin, and are enriched in unusual or novel noncoding RNAs, most of which have no known function. Short-term exposure of brain microvascular endothelial cells to glioma microvesicles results in many gene expression changes in the endothelial cells, most of which cannot be explained by direct delivery of transcripts. Our data suggest that the scope of potential actions of tumor-derived microvesicles is much broader and more complex than previously supposed, and highlight a number of new classes of small RNA that remain to be characterized.
Background
Following the implementation of pandemic response measures, concerns arose regarding the impact for population health and wellbeing.
Methods
This study reports findings from a survey ...(N = 2510) conducted in Warwickshire (UK) during August and September 2020, and for the first time investigates behaviours which may worsen or mitigate the association between COVID-19-related stressors and wellbeing.
Results
Increased stressors were associated with lower mental wellbeing and higher loneliness. Participants with a mental health condition reported lower wellbeing, as did younger groups, women and participants not in employment. To cope with restrictions, more participants engaged in healthier behaviours over unhealthy behaviours, and relaxing reduced the association between stressors and poor wellbeing. Some participants reported increasing alcohol and unhealthy dietary behaviours to cope with restrictions, however, these behaviours did not mitigate the impact of COVID-19 stressors and were instead negatively associated with wellbeing. Around half of participants helped neighbours during the pandemic, a behaviour positively associated with wellbeing particularly among older adults.
Conclusion
These findings contribute understanding about how various positive and negative health behaviours may mitigate or worsen the impact of COVID-19 on wellbeing, and how public health interventions may effectively target behaviours and groups in similar populations.
We present here a simple and robust framework for quantifying the effective sensor depth of cosmic ray soil moisture neutron probes such that reliable water fluxes may be computed from a time series ...of cosmic ray soil moisture. In particular, we describe how the neutron signal depends on three near‐surface hydrogen sources: surface water, soil moisture, and lattice water (water in minerals present in soil solids) and also their vertical variations. Through a combined modeling study of one‐dimensional water flow in soil and neutron transport in the atmosphere and subsurface, we compare average water content between the simulated soil moisture profiles and the universal calibration equation which is used to estimate water content from neutron counts. By using a linear sensitivity weighting function, we find that during evaporation and drainage periods the RMSE of the two average water contents is 0.0070 m3 m−3 with a maximum deviation of 0.010 m3 m−3 for a range of soil types. During infiltration, the RMSE is 0.011 m3 m−3 with a maximum deviation of 0.020 m3 m−3, where piston like flow conditions exists for the homogeneous isotropic media. Because piston flow is unlikely during natural conditions at the horizontal scale of hundreds of meters that is measured by the cosmic ray probe, this modeled deviation of 0.020 m3 m−3 represents the worst case scenario for cosmic ray sensing of soil moisture. Comparison of cosmic ray soil moisture data and a distributed sensor soil moisture network in Southern Arizona indicates an RMSE of 0.011 m3 m−3 over a 6 month study period.
Key Points
Effective depth of cosmic‐ray soil moisture probe
Intermediate‐scale soil moisture measurements
Uncertainty of measurements and support volume
Abstract Tyrosine kinase inhibitors (TKI) such as imatinib, nilotinib and dasatinib are now established as highly effective frontline therapies for chronic myeloid leukaemia (CML). Disease control is ...achieved in the majority of patients and survival is excellent such that recent focus has been on toxicities of these agents. Cumulative data have reported an excess of serious vascular complications, including arterial thrombosis and peripheral arterial occlusive disease, in patients receiving nilotinib in comparison with other TKIs, with resultant interest in delineating the pathophysiology and implications for rationale cardiovascular risk modification. To address this issue, we studied the effects of imatinib, nilotinib and dasatinib on platelet function and thrombus formation in human and mouse models using in vitro, ex vivo and in vivo approaches. In vitro studies demonstrated that dasatinib and imatinib but not nilotinib inhibited ADP, CRP, and collagen-induced platelet aggregation and moreover, that nilotinib potentiated PAR-1-mediated alpha granule release. Pretreatment of wild-type C57BL/6 mice with nilotinib but not imatinib or dasatinib, significantly increased thrombus growth and stability, on type I collagen under ex vivo arterial flow conditions and increased thrombus growth and stability following FeCl3 -induced vascular injury of mesenteric arterioles and carotid artery injury in vivo . Whole blood from nilotinib-treated CML patients, demonstrated increased platelet adhesion ex vivo under flow, increased plasma soluble P- and E -selectin, sICAM-1, sVCAM-1, TNF-alpha, IL-6 levels and endogenous thrombin potential (ETP) levels in vivo, despite being on daily low-dose aspirin. These results demonstrate that nilotinib can potentiate platelet and endothelial activation and platelet thrombus formation ex vivo and in vivo.
In this work, a method for the rapid synthesis of metallic microtracks on polyetherimide is presented. The method relies on the photosynthesis of silver nanoparticles on the surface of the polymer ...substrates from photosensitive silver chloride (AgCl), which is synthesized directly on the polyetherimide surface. The study reveals that the use of AgCl as a photosensitive intermediate accelerates the reactions leading to the formation of silver nanoparticles by up to two orders of magnitude faster than other photodecomposition schemes. The patterning can be conducted under blue light, with notable advantages over UV exposure. Polymers of significant interest to the microelectronics and 3D printing industries can be directly patterned by light using this photography‐inspired technique at throughputs high enough to be commercially advantageous. Light exposures as short as a few seconds are sufficient to allow the direct metallization of the illuminated polyetherimide surface. The results show that the silver required for the seed layer is minimal, and the later copper electroless plating results in the selective growth of conductive tracks for circuitry on the light‐patterned areas, both on flexible films and 3D printed surfaces.
A rapid photopatterning method for the selective plating on polyetherimide is presented. The use of AgCl as photosensitive intermediate allows manufacturing with very short exposures. Conductive copper tracks are produced on both flexible substrates for microelectronics and 3D printed pieces.
The cosmic-ray method for measuring soil moisture, used in the Cosmic-Ray Soil Moisture Observing System (COSMOS), relies on the exceptional ability of hydrogen to moderate fast neutrons. Sources of ...hydrogen near the ground, other than soil moisture, affect the neutron measurement and therefore must be quantified. This study investigates the effect of atmospheric water vapor on the cosmic-ray probe signal and evaluates the fast neutron response in realistic atmospheric conditions using the neutron transport code Monte Carlo N-Particle eXtended (MCNPX). The vertical height of influence of the sensor in the atmosphere varies between 412 and 265m in dry and wet atmospheres, respectively. Model results show that atmospheric water vapor near the surface affects the neutron intensity signal by up to 12%, corresponding to soil moisture differences on the order of 0.10 m³ m−3. A simple correction is defined to identify the true signal associated with integrated soil moisture that rescales the measured neutron intensity to that which would have been observed in the atmospheric conditions prevailing on the day of sensor calibration. Use of this approach is investigated with in situ observations at two sites characterized by strong seasonality in water vapor where standard meteorological measurements are readily available.
The Botryosphaeriales, and in particular the Botryosphaeriaceae, are a well-studied group of fungi best known for the canker diseases they cause on woody hosts especially in stressed or damaged ...trees. Australian Plant Pathology herbaria contain many records for this group, but due to considerable taxonomic changes over the past decade, many of the species names have since been reclassified. In this article we used all published records with available sequence data of the Botryosphaeriaceae in Australia to examine the distribution and host range of these taxa. There are 24 genera encompassing 222 species in the Botryosphaeriaceae; 9 genera and 62 species have been recorded in Australia. Some genera such as
Neoscytalidium
are only found in warm, humid climates while
Dothiorella
species are more common in temperate climates. There were species, such as
Lasiodiplodia theobromae
,
Neofusicoccum parvum
and
Botryosphaeria dothidea
, which had a wide host range with many records. However, there were also several species found only in one location on a single host. While systematic data collection is still required, the information presented here provides a baseline of species present in Australia and will underpin future studies into this group of important pathogens.
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