Neuronal influences are necessary to produce mitochondrial co-localization with glutamate transporters in astrocytes.

yesAbstract Recent evidence suggests that the predominant astrocyte glutamate transporter, GLT-1/ Excitatory Amino Acid Transporter 2 (EAAT2) is associated with mitochondria. We used primary cultures of mouse astrocytes to assess co-localization of GLT-1 with mitochondria, and tested whether the interaction was dependent on neurons, actin polymerization or the kinesin adaptor, TRAK2. Mouse primary astrocytes were transfected with constructs expressing V5-tagged GLT-1, pDsRed1-Mito with and without dominant negative TRAK2. Astrocytes were visualized using confocal microscopy and co-localization was quantified using Volocity software. Image analysis of confocal z-stacks revealed no co-localization between mitochondria and GLT-1 in pure astrocyte cultures. Co-culture of astrocytes with primary mouse cortical neurons revealed more mitochondria in processes and a positive correlation between mitochondria and GLT-1. This co-localization was not further enhanced after neuronal depolarization induced by 1 h treatment with 15 mM K+. In pure astrocytes, a rho kinase inhibitor, Y27632 caused the distribution of mitochondria to astrocyte processes without enhancing GLT-1/mitochondrial co-localization, however, in co-cultures, Y27632 abolished mitochondrial: GLT-1 co-localization. Disrupting potential mitochondrial: kinesin interactions using dominant negative TRAK2 did not alter GLT-1 distribution or GLT-1: mitochondrial co-localization. We conclude that the association between GLT-1 and mitochondria is modest, is driven by synaptic activity and dependent on polymerized actin filaments. Mitochondria have limited co-localization with the glutamate transporter GLT-1 in primary astrocytes in culture. Few mitochondria are in the fine processes where GLT-1 is abundant. It is necessary to culture astrocytes with neurones to drive a significant level of co-localization, but co-localization is not further altered by depolarization, manipulating sodium ion gradients or Na/K ATPase activity

Sonic hedgehog signalling mediates astrocyte crosstalk with neurons to confer neuroprotection

Sonic hedgehog (SHH) is a glycoprotein associated with development that is also expressed in the adult CNS and released after brain injury. Since the SHH receptors patched homolog-1 and Smoothened are highly expressed on astrocytes, we hypothesized that SHH regulates astrocyte function. Primary mouse cortical astrocytes derived from embryonic Swiss mouse cortices, were treated with two chemically distinct agonists of the SHH pathway, which caused astrocytes to elongate and proliferate. These changes are accompanied by decreases in the major astrocyte glutamate transporter-1 and the astrocyte intermediate filament protein glial fibrillary acidic protein. Multisite electrophysiological recordings revealed that the SHH agonist, smoothened agonist suppressed neuronal firing in astrocyte-neuron co-cultures and this was abolished by the astrocyte metabolic inhibitor ethylfluoroacetate, revealing that SHH stimulation of metabolically active astrocytes influences neuronal firing. Using three-dimensional co-culture, MAP2 western blotting and immunohistochemistry, we show that SHH-stimulated astrocytes protect neurons from kainate-induced cell death. Altogether the results show that SHH regulation of astrocyte function represents an endogenous neuroprotective mechanism

What is the relationship between elements of ICU treatment and memories after discharge in adult ICU survivors?

Objectives: Patients admitted to an intensive care unit (ICU) often experience distressing memories during recovery that have been associated with poor psychological and cognitive outcomes. The aim of this literature review was to synthesise the literature reporting on relationships between elements of ICU treatment and memories after discharge in adult ICU survivors. Review method used: Integrative review methods were used to systematically search, select, extract, appraise and summarise current knowledge from the available research and identify gaps in the literature. Data sources: The following electronic databases were systematically searched: PubMed, Ovid EMBASE, EBSCOhost CINAHL, PsycINFO and Cochrane Central Register of Controlled Trials. Additional studies were identified through searches of bibliographies. Original quantitative research articles written in English that were published in peer-review journals were included. Review methods: Data extracted from studies included authors, study aims, population, sample size and characteristics, methods, ICU treatments, ICU memory definitions, data collection strategies and findings. Study quality assessment was based on elements of the Critical Appraisal Skills Programme using the checklists developed for randomised controlled trials and cohort studies. Results: Fourteen articles containing data from 13 studies met the inclusion criteria and were included in the final analysis. The relatively limited evidence about the association between elements of ICU treatment and memories after ICU discharge suggest that deep sedation, corticoids and administration of glucose 50% due to hypoglycaemia contribute to the development of delusional memories and amnesia of ICU stay. Conclusions: The body of literature on the relationship between elements of ICU treatment and memories after ICU discharge is small and at its early stages. Larger studies using rigorous study design are needed in order to evaluate the effects of different elements of ICU treatment on the development of memories of the ICU during recovery

Intraperitoneal Delivery of Acetate-Encapsulated Liposomal Nanoparticles for Neuroprotection of the Penumbra in a Rat Model of Ischemic Stroke

Background: Ischemic stroke is a devastating condition, with metabolic derangement and persistent inflammation enhancing the initial insult of ischaemia. Recombinant tissue plasminogen remains the only effective treatment but limited as therapy must commence soon after the onset of symptoms. Purpose: We investigated whether acetate, which modulates many pathways including inflammation, may attenuate brain injury in stroke. As acetate has a short blood half-life and high amounts irritate the gastrointestinal tract, acetate was administered encapsulated in a liposomal nanoparticle (liposomal-encapsulated acetate, LITA). Methods: Transient ischemia was induced by 90 mins middle-cerebral artery occlusion (MCAO) in Sprague-Dawley rats, and LITA or control liposomes given intraperitoneally at occlusion and daily for up to two weeks post-MCAO. Magnetic resonance imaging (MRI) was used to estimate lesion volume at 24 h, 1 and 2 weeks post-MCAO and anterior lateral ventricular volume (ALVv) at 2 weeks post-MCAO. Locomotive behaviour was tested prior to the final MRI scan. After the final scan, brains were collected, and immunohistochemistry was performed. Results: Lesion volumes were decreased by ~80% from 24 h to one-week post-MCAO, in both control and LITA groups (P<0.05). However, the lesion was increased by ~50% over the subsequent 1 to 2 weeks after MCAO in the control group (from 24.1±10.0 to 58.7±28.6 mm3; P<0.05) but remained unchanged in the LITA group. ALVv were also attenuated by LITA treatment at 2 weeks post-MCAO (177.2±11.9% and 135.3±10.9% of contralateral ALVv for control and LITA groups, respectively; P<0.05). LITA-treated animals also appeared to have improved motor activity, moving with greater average velocity than control animals. Microglial immunoreactivity was ~40% lower in the LITA group compared to the control group (P<0.05), but LITA did not modulate neurogenesis, apoptosis, histone acetylation and lipid peroxidation. Conclusion: LITA appears to attenuate the harmful chronic neuroinflammation observed during brain remodeling after a focal ischemic insult

Annealing schedule from population dynamics

We introduce a dynamical annealing schedule for population-based optimization algorithms with mutation. On the basis of a statistical mechanics formulation of the population dynamics, the mutation rate adapts to a value maximizing expected rewards at each time step. Thereby, the mutation rate is eliminated as a free parameter from the algorithm.Comment: 6 pages RevTeX, 4 figures PostScript; to be published in Phys. Rev.

Development of an acute and chronic ecotoxicity assay using lux -marked Rhizobium leguminosarum biovar trifolii

A soil isolate of Rhizobium leguminosarum bv. trifolii was marked with a lux CDABE gene cassette to enable the expression of bioluminescence. The suitability of the bacterium as a soil pollution biosensor was assessed using acute and chronic assays. Bacterial bioluminescence responded sensitively to the metals studied, The order of sensitivity was found to be Cd > Ni = Zn > Cu for the acute test and Cd > Ni = Zn = Cu for the chronic test. The sensitive response of the biosensor highlighted its potential for use as an indicator of soil pollution

Sedimentary mechanisms of a modern banded iron formation on Milos Island, Greece

An Early Quaternary shallow submarine hydrothermal iron formation (IF) in the Cape Vani sedimentary basin (CVSB) on Milos Island, Greece, displays banded rhythmicity similar to Precambrian banded iron formation (BIF). Sedimentary, stratigraphic reconstruction, biogeochemical analysis and micro-nanoscale mineralogical characterization confirms the Milos rocks as modern Precambrian BIF analogues. Spatial coverage of the BIF-type rocks in relation to the economic grade Mn ore that brought prominence to the CVSB implicates tectonic activity and changing redox in the deposition of the BIF-type rocks. Field-wide stratigraphic and biogeochemical reconstruction demonstrates two temporal and spatially isolated iron deposits in the CVSB with distinct sedimentological character. Petrographic screening suggest the previously described photoferrotrophic-like microfossil-rich IF (MFIF), accumulated on basement andesite in a ~ 150 m wide basin, in the SW margin of the basin. A strongly banded non-fossiliferous IF (NFIF) caps the Mn-rich sandstones at the transition to the renowned Mn-rich formation. Geochemical evidence relates the origin of the NFIF to periodic submarine volcanism and water column oxidation of released Fe(II) in conditions apparently predominated by anoxia, similar to the MFIF. This is manifested in the lack of shale-normalized Ce anomalies. Raman spectroscopy pairs hematite-rich grains in the NFIF with relics of a carbonaceous material carrying an average δ13Corg signature of ~ −25 ‰. However, a similar δ13Corg signature in the MFIF is not directly coupled to hematite by mineralogy. The NFIF, which post dates large-scale Mn deposition in the CVSB, is composed primarily of amorphous Si (opal-SiO2 · nH2O) while crystalline quartz (SiO2) predominates the MFIF. An intricate interaction between tectonic processes, changing redox, biological activity and abiotic Si precipitation, formed the unmetamorphosed BIF-type deposits

The Herschel Planetary Nebula Survey (HerPlaNS) I. Data Overview and Analysis Demonstration with NGC 6781

This is the first of a series of investigations into far-IR characteristics of 11 planetary nebulae (PNs) under the Herschel Space Observatory Open Time 1 program, Herschel Planetary Nebula Survey (HerPlaNS). Using the HerPlaNS data set, we look into the PN energetics and variations of the physical conditions within the target nebulae. In the present work, we provide an overview of the survey, data acquisition and processing, and resulting data products. We perform (1) PACS/SPIRE broadband imaging to determine the spatial distribution of the cold dust component in the target PNs and (2) PACS/SPIRE spectral-energy-distribution (SED) and line spectroscopy to determine the spatial distribution of the gas component in the target PNs. For the case of NGC 6781, the broadband maps confirm the nearly pole-on barrel structure of the amorphous carbon-richdust shell and the surrounding halo having temperatures of 26-40 K. The PACS/SPIRE multi-position spectra show spatial variations of far-IR lines that reflect the physical stratification of the nebula. We demonstrate that spatially-resolved far-IR line diagnostics yield the (T_e, n_e) profiles, from which distributions of ionized, atomic, and molecular gases can be determined. Direct comparison of the dust and gas column mass maps constrained by the HerPlaNS data allows to construct an empirical gas-to-dust mass ratio map, which shows a range of ratios with the median of 195+-110. The present analysis yields estimates of the total mass of the shell to be 0.86 M_sun, consisting of 0.54 M_sun of ionized gas, 0.12 M_sun of atomic gas, 0.2 M_sun of molecular gas, and 4 x 10^-3 M_sun of dust grains. These estimates also suggest that the central star of about 1.5 M_sun initial mass is terminating its PN evolution onto the white dwarf cooling track.Comment: 27 pages, 16 figures, accepted for publication in A&

Predicting risk of unplanned hospital readmission in survivors of critical illness: a population-level cohort study

BackgroundIntensive care unit survivors experience high levels of morbidity after hospital discharge and are at high risk of unplanned hospital readmission. Identifying those at highest-risk before hospital discharge may allow targeting of novel risk reduction strategies. We aimed to identify risk factors for unplanned 90-day readmission, develop a risk prediction model and assess its performance to screen for ICU survivors at highest readmission risk.MethodsPopulation cohort study linking registry data for patients discharged from general ICUs in Scotland (2005-2013). Independent risk factors for 90-day readmission and discriminant ability (c-index) of groups of variables were identified using multivariable logistic regression. Derivation and validation risk prediction models were constructed using a time-based split.ResultsOf 55,975 ICU survivors, 24.1% (95%CI 23.7%,24.4%) had unplanned 90-day readmission. Pre-existing health factors were fair discriminators of readmission (c-index 0.63,95%CI 0.63,0.64), but better than acute illness factors (0.60) or demographics (0.54). In a subgroup of those with no comorbidity, acute illness factors (0.62) were better discriminators than pre-existing health factors (0.56). Overall model performance and calibration in the validation cohort was fair (0.65,95%CI 0.64,0.66) but did not perform sufficiently well as a screening tool, demonstrating high false positive/false negative rates at clinically relevant thresholds.ConclusionsUnplanned 90-day hospital readmission is common. Pre-existing illness indices are better predictors of readmission than acute illness factors. Identifying additional patient-centred drivers of readmission may improve risk prediction models. Improved understanding of risk factors that are amenable to intervention could improve the clinical and cost-effectiveness of post-ICU care and rehabilitation

Aneuploidy Drives Genomic Instability in Yeast

Aneuploidy decreases cellular fitness, yet it is also associated with cancer, a disease of enhanced proliferative capacity. To investigate one mechanism by which aneuploidy could contribute to tumorigenesis, we examined the effects of aneuploidy on genomic stability. We analyzed 13 budding yeast strains that carry extra copies of single chromosomes and found that all aneuploid strains exhibited one or more forms of genomic instability. Most strains displayed increased chromosome loss and mitotic recombination, as well as defective DNA damage repair. Aneuploid fission yeast strains also exhibited defects in mitotic recombination. Aneuploidy-induced genomic instability could facilitate the development of genetic alterations that drive malignant growth in cancer