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\"A thousand years from now, Vance Astro, Yondu, Martinex and Charlie-27 will rise to free the enslaved planet Earth -- as the Guardians of the Galaxy! Soon, Captain America, Doctor Strange, the Thing, the Hulk and more join the time-spanning heroes in the war to reclaim the future! Threats arise from other worlds -- as well as new allies Nikki and the uncanny Starhawk! But when Guardians and Avengers join forces in the present day, will even the combined might of two millennia be enough to stop the deranged demigod Michael Korvac? Plus: the Silver Surfer, Ms. Marvel, Spider-Man and Adam Warlock!\"-- Amazon.com description.

Current evidence suggests that delta oscillations (0.5–4 Hz) in the brain are generated by intrinsic network mechanisms involving cortical and thalamic circuits. Here we report that delta band oscillation in spike and local field potential (LFP) activity in the whisker barrel cortex of awake mice is phase locked to respiration. Furthermore, LFP oscillations in the gamma frequency band (30–80 Hz) are amplitude modulated in phase with the respiratory rhythm. Removal of the olfactory bulb eliminates respiration-locked delta oscillations and delta-gamma phase-amplitude coupling. Our findings thus suggest respiration-locked olfactory bulb activity as a main driving force behind delta oscillations and gamma power modulation in the whisker barrel cortex in the awake state. Oscillatory neuronal activity in the mammalian neocortex is implicated in cognitive processes but its generation is poorly understood. In this study, the authors show that delta band oscillatory activity in mice phase-locks with respiratory activity and that this is mediated by activity in the olfactory bulb.

Induction of neuroprotective heat-shock proteins via pharmacological Hsp90 inhibitors is currently being investigated as a potential treatment for neurodegenerative diseases. Two major hurdles for therapeutic use of Hsp90 inhibitors are systemic toxicity and limited central nervous system permeability. We demonstrate here that chronic treatment with a proprietary Hsp90 inhibitor compound (OS47720) not only elicits a heat-shock-like response but also offers synaptic protection in symptomatic Tg2576 mice, a model of Alzheimer’s disease, without noticeable systemic toxicity. Despite a short half-life of OS47720 in mouse brain, a single intraperitoneal injection induces rapid and long-lasting (>3 days) nuclear activation of the heat-shock factor, HSF1. Mechanistic study indicates that the remedial effects of OS47720 depend upon HSF1 activation and the subsequent HSF1-mediated transcriptional events on synaptic genes. Taken together, this work reveals a novel role of HSF1 in synaptic function and memory, which likely occurs through modulation of the synaptic transcriptome.

Red blotch disease, a threat to the grape industry, is caused by grapevine red blotch virus. This work is the first to study epidemiological patterns in a vineyard over the course of a decade, revealing an increase in disease incidence from 3.9% in 2014 to 36.4% in 2023 with rapid virus spread proximal to a transmission hotspot. Logistic and exponential models provided the best fit of spread in areas of high and low disease incidence and aggregation, respectively. An inverse spatial incidence of virus strains 1 and 2 suggested secondary spread mostly from diseased to neighboring vines and virus influx from background sources. Precipitation (3-4 years later) and air temperature (the same or 1 year later) significantly influenced epidemic parameters. Finally, asymptomatic infections contributed to spatial aggregations at increasing lags. These findings were salient for considering zonal roguing, the removal of diseased and surrounding vines, as a disease management option.

In trained reaching rats, we recorded simple spikes of pairs of Purkinje cells that, with respect to each other, were either aligned on a beam of shared parallel fibers or instead were located off beam. Rates of simple spike firing in both on-beam and off-beam Purkinje cell pairs commonly showed great variety in depth of modulation during reaching behavior. But with respect to timing, on-beam Purkinje cell pairs had simple spikes that were tightly time-locked to each other (either delayed or simultaneous) and to movement, despite the variability in rate. By contrast, off-beam Purkinje cell pairs had simple spikes that were not time-locked to each other, neither delayed nor simultaneous. We discuss the implications of these observations for the cerebellar role in timing and coordinating movement.

Analysis of the Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) at 48 months' follow-up showed that addition of zoledronic acid to adjuvant endocrine therapy significantly improved disease-free survival. We have now assessed long-term clinical efficacy including disease-free survival and disease outcomes in patients receiving anastrozole or tamoxifen with or without zoledronic acid. ABSCG-12 is a randomised, controlled, open-label, two-by-two factorial, multicentre trial in 1803 premenopausal women with endocrine-receptor-positive early-stage (stage I–II) breast cancer receiving goserelin (3·6 mg every 28 days), comparing the efficacy and safety of anastrozole (1 mg per day) or tamoxifen (20 mg per day) with or without zoledronic acid (4 mg every 6 months) for 3 years. Randomisation (1:1:1:1 ratio) was computerised and based on the Pocock and Simon minimisation method to balance the four treatment arms across eight prognostic variables (age, neoadjuvant chemotherapy, pathological tumour stage; lymph-node involvement, type of surgery or locoregional therapy, complete axillary dissection, intraoperative radiation therapy, and geographical region). Treatment allocation was not masked. The primary endpoint was disease-free survival (defined as disease recurrence or death) and analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00295646; follow-up is ongoing. At a median follow-up of 62 months (range 0–114·4 months), more than 2 years after treatment completion, 186 disease-free survival events had been reported (53 events in 450 patients on tamoxifen alone, 57 in 453 patients on anastrozole alone, 36 in 450 patients on tamoxifen plus zoledronic acid, and 40 in 450 patients on anastrozole plus zoledronic acid). Zoledronic acid reduced risk of disease-free survival events overall (HR 0·68, 95% CI 0·51–0·91; p=0·009), although the difference was not significant in the tamoxifen (HR 0·67, 95% CI 0·44–1·03; p=0·067) and anastrozole arms (HR 0·68, 95% CI 0·45–1·02; p=0·061) assessed separately. Zoledronic acid did not significantly affect risk of death (30 deaths with zoledronic acid vs 43 deaths without; HR 0·67, 95% CI 0·41–1·07; p=0·09). There was no difference in disease-free survival between patients on tamoxifen alone versus anastrozole alone (HR 1·08, 95% CI 0·81–1·44; p=0·591), but overall survival was worse with anastrozole than with tamoxifen (46 vs 27 deaths; HR 1·75, 95% CI 1·08–2·83; p=0·02). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. Bone pain was reported in 601 patients (33%; 349 patients on zoledronic acid vs 252 not on the drug), fatigue in 361 (20%; 192 vs 169), headache in 280 (16%; 147 vs 133), and arthralgia in 266 (15%; 145 vs 121). Addition of zoledronic acid improved disease-free survival in the patients taking anastrozole or tamoxifen. There was no difference in disease-free survival between patients receiving anastrozole and tamoxifen overall, but those on anastrozole alone had inferior overall survival. These data show persistent benefits with zoledronic acid and support its addition to adjuvant endocrine therapy in premenopausal patients with early-stage breast cancer. AstraZeneca; Novartis.

To understand spatiotemporally coordinated activity in neural networks and interaction between different areas or layers in brain tissue, simultaneous multisite recording is a prerequisite. For in vitro studies pursuing these goals, substrate integrated, planar microelectrode arrays (MEAs) have been developed to monitor spikes and local field potentials. Here we report for the first time recordings of single-unit spike activity with MEAs in acute slice preparations of the rat cerebellum. We compare these recordings to results of conventional techniques, and discuss the recording conditions in view of the equivalent circuits commonly used. Simultaneous recordings with tungsten microelectrodes and MEAs verified that recording characteristics and signal-to-noise ratios of MEA electrodes were comparable to those of conventional extracellular electrodes. Spike shapes were identical on both electrodes. We found no detectable overlap between spike signals recorded at neighboring MEA electrodes (200 microm spacing). Neuronal spike activity was detected with MEA electrodes at distances of up to 100 microm from the site of spike generation. We conclude that extracellular recording of independent single-unit spike activity with MEAs is indeed suitable to monitor network activity in acute slices, making MEAs an exceptionally useful tool for the assessment of fast network dynamics in acute slices.

Banana production is seriously threatened by Fusarium wilt (FW), a disease caused by the soil-borne fungus Fusarium oxysporum f. sp. cubense (Foc). In the mid-twentieth century FW, also known as ?Panama disease?, wiped out the Gros Michel banana industry in Central America. The devastation caused by Foc race 1 was mitigated by a shift to resistant Cavendish cultivars, which are currently the source of 99% of banana exports. However, a new strain of Foc, the tropical race 4 (TR4), attacks Cavendish clones and a diverse range of other banana varieties. Foc TR4 has been restricted to East and parts of Southeast Asia for more than 20 years, but since 2010 the disease has spread westward into five additional countries in Southeast and South Asia (Vietnam, Laos, Myanmar, India, and Pakistan) and at the transcontinental level into the Middle East (Oman, Jordan, Lebanon, and Israel) and Africa (Mozambique). The spread of Foc TR4 is of great concern due to the limited knowledge about key aspects of disease epidemiology and the lack of effective management models, including resistant varieties and soilmanagement approaches. In this reviewwe summarize the current knowledge on the epidemiology of FWof banana, highlighting knowledge gaps in pathogen survival and dispersal, factors driving disease intensity, soil and plant microbiome and the dynamics of the disease. Comparisons with FW in other crops were also made to indicate possible differences and commonalities. Our current understanding of the role of main biotic and abiotic factors on disease intensity is reviewed, highlighting research needs and futures directions. Finally, a set of practices and their impact on disease intensity are discussed and proposed as an integrative management approach that could eventually be used by a range of users, including plant protection organizations, researchers, extension workers and growers.

Background and purposeAs evidence accumulates that carotid artery stenting (CAS) is a durable and effective procedure for stroke prevention, the utility of the procedure hinges on the perioperative risk. The perioperative risk of CAS procedures has historically been higher than carotid endarterectomy in most clinical trials. The perioperative risk of the series presented here is lower than any previously reported in the context of a clinical trial.MethodsData were collected prospectively from 227 consecutive elective CAS procedures by a single neurointerventionalist performed as part of carotid stenting clinical trials as per the trial protocols, which included randomized trials of “average risk” patients and non-randomized trials of “high risk” patients. The primary outcome measures were 30 day stroke and death, and in most cases 30 day myocardial infarction (MI) also.ResultsFollow-up was 100%. There were no deaths. There was one technical failure. The overall 30 day stroke/death/MI rate was 5/226 (2.2%). There was one MI. The 30 day stroke and death rate for symptomatic patients was 2.5% and for asymptomatic patients 1.4%. Two of the four strokes occurred in vascular territories separate from the target carotid artery.ConclusionsThe perioperative CAS complications in this series were well below the 6% for symptomatic patients and 3% for asymptomatic patients currently recommended based on historic carotid endarterectomy data. Carotid stenting can be performed safely in the community, provided there are experienced interventionalists and proper patient selection.