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Astrocytes are considered an essential source of blood-borne glucose or its metabolites to neurons. Nonetheless, the necessity of the main astrocyte glucose transporter, i.e., GLUT1, for brain glucose metabolism has not been defined. Unexpectedly, we found that brain glucose metabolism was paradoxically augmented in mice with astrocytic GLUT1 reduction (GLUT1 ΔGFAP mice). These mice also exhibited improved peripheral glucose metabolism especially in obesity, rendering them metabolically healthier. Mechanistically, we observed that GLUT1-deficient astrocytes exhibited increased insulin receptor-dependent ATP release, and that both astrocyte insulin signaling and brain purinergic signaling are essential for improved brain function and systemic glucose metabolism. Collectively, we demonstrate that astrocytic GLUT1 is central to the regulation of brain energetics, yet its depletion triggers a reprogramming of brain metabolism sufficient to sustain energy requirements, peripheral glucose homeostasis, and cognitive function.

Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer's disease (AD), with recent proteomic studies highlighting disrupted glial metabolism in AD. We report that inhibition of indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN), rescues hippocampal memory function in mouse preclinical models of AD by restoring astrocyte metabolism. Activation of astrocytic IDO1 by amyloid β and tau oligomers increases KYN and suppresses glycolysis in an aryl hydrocarbon receptor-dependent manner. In amyloid and tau models, IDO1 inhibition improves hippocampal glucose metabolism and rescues hippocampal long-term potentiation in a monocarboxylate transporter-dependent manner. In astrocytic and neuronal cocultures from AD subjects, IDO1 inhibition improved astrocytic production of lactate and uptake by neurons. Thus, IDO1 inhibitors presently developed for cancer might be repurposed for treatment of AD.

Introduction: Tropomyosin related kinase B (TrkB) and C (TrkC) receptor signaling promotes synaptic plasticity and interacts with pathways affected by amyloid beta (Aβ) toxicity. Upregulating TrkB/C signaling could reduce Alzheimer's disease (AD)-related degenerative signaling, memory loss, and synaptic dysfunction., Methods: PTX-BD10-2 (BD10-2), a small molecule TrkB/C receptor partial agonist, was orally administered to aged London/Swedish-APP mutant mice (APP L/S ) and wild-type controls. Effects on memory and hippocampal long-term potentiation (LTP) were assessed using electrophysiology, behavioral studies, immunoblotting, immunofluorescence staining, and RNA sequencing., Results: In APP L/S mice, BD10-2 treatment improved memory and LTP deficits. This was accompanied by normalized phosphorylation of protein kinase B (Akt), calcium-calmodulin-dependent kinase II (CaMKII), and AMPA-type glutamate receptors containing the subunit GluA1; enhanced activity-dependent recruitment of synaptic proteins; and increased excitatory synapse number. BD10-2 also had potentially favorable effects on LTP-dependent complement pathway and synaptic gene transcription., Discussion: BD10-2 prevented APP L/S /Aβ-associated memory and LTP deficits, reduced abnormalities in synapse-related signaling and activity-dependent transcription of synaptic genes, and bolstered transcriptional changes associated with microglial immune response., Highlights: Small molecule modulation of tropomyosin related kinase B (TrkB) and C (TrkC) restores long-term potentiation (LTP) and behavior in an Alzheimer's disease (AD) model. Modulation of TrkB and TrkC regulates synaptic activity-dependent transcription. TrkB and TrkC receptors are candidate targets for translational therapeutics. Electrophysiology combined with transcriptomics elucidates synaptic restoration. LTP identifies neuron and microglia AD-relevant human-mouse co-expression modules., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

A brain abscess is a neurosurgical emergency and frequently requires drainage to relieve intracranial pressure and identify the offending organism. Surgical adjuncts including neuronavigation and intra-operative CT and MRI facilitate surgery, but have limitations, including cost and not offering real time intracranial views. Intra-operative ultrasound is a fast and relatively cheap tool which offers live, real time imaging and visualisation of an abscess being aspirated, but is less frequently used. We describe our technique of ultrasound guidance as an adjunct with neuronavigation for brain abscess aspiration, review the literature on surgical adjuncts and remind the neurosurgical community of its value in this and other cranial procedures. We summarise our recent experience in its use in six patients with a brain abscess. There is a learning curve to using intra-operative ultrasound, but we recommend its routine use in abscess drainage surgery.

Human genetics implicate defective myeloid responses in the development of late-onset Alzheimer disease. A decline in peripheral and brain myeloid metabolism, triggering maladaptive immune responses, is a feature of aging. The role of TREM1, a pro-inflammatory factor, in neurodegenerative diseases is unclear. Here we show that Trem1 deficiency prevents age-dependent changes in myeloid metabolism, inflammation and hippocampal memory function in mice. Trem1 deficiency rescues age-associated declines in ribose 5-phosphate. In vitro, Trem1-deficient microglia are resistant to amyloid-β 42 oligomer-induced bioenergetic changes, suggesting that amyloid-β 42 oligomer stimulation disrupts homeostatic microglial metabolism and immune function via TREM1. In the 5XFAD mouse model, Trem1 haploinsufficiency prevents spatial memory loss, preserves homeostatic microglial morphology, and reduces neuritic dystrophy and changes in the disease-associated microglial transcriptomic signature. In aging APP Swe mice, Trem1 deficiency prevents hippocampal memory decline while restoring synaptic mitochondrial function and cerebral glucose uptake. In postmortem Alzheimer disease brain, TREM1 colocalizes with Iba1 + cells around amyloid plaques and its expression is associated with Alzheimer disease clinical and neuropathological severity. Our results suggest that TREM1 promotes cognitive decline in aging and in the context of amyloid pathology., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Agricultural crops especially fruit trees are constrained by edaphic stresses in shallow soils with low water retention and poor fertility. Therefore, interventions of shifting to trench planting for better root anchorage and replacing the filling soil were evaluated for 8 years in dragon fruit ( Hylocereus undatus ) cultivated in Deccan Plateau of peninsular India. When averaged for last 5-years, 44 % higher fruit yield (18.2 ± 1.0 Mg ha -1 ) was harvested from trees planted in trenches filled with 1:1 mixture ( T -mixed) of native soil (loamy sand with 26.7 % stones (>2mm), field capacity, FC 0.20 cm 3 cm -3 ; organic carbon, OC 0.17 %; Av-N 54.6 kg ha -1 ) and a black soil (clay 54.4 %; FC 0.42 cm 3 cm -3 ; OC 0.70 %; Av-N 157.1 kg ha -1 ) than the recommended pit planting (12.4 ± 1.2 Mg ha -1 ). Improvements in fruit yields with trenches filled with black ( T -black) and native ( T -native) soil were 32 and 13 %, respectively. Yield losses (total- marketable yield) were reduced by 40, 20 and 18 % over pit method with T- mixed, T -black and T -native soil, respectively. Marketable quality attributes like fruit weight, fruit size metrics and pulp/peel content were further improved under T -mixed soil. Accumulation of total soluble solids (TSS), sugar content, phenolic and flavonoid compounds were higher in fruits from T -native soil. During storage, fruits from T -native soil and pit planting exhibited minimum physiological weight loss and retained more firmness, TSS, sugars, titratable acidity, phenolic-flavonoids contents, FARP and DPPH activities. T -mixed soil provided better hydrozone and nutrients for resilience of fruit plants while protecting from aeration problems envisaged in poorly drained black soils. With B:C ratio (1.85) and lower payback period (4-years), T -mixed soil showed superior economic viability. Therefore, soil management module of planting in trenches filled-in with mixture of native and black soils can be recommended to boost productivity of fruits from shallow soils under water scarce degraded regions without penalising agro-ecosystem., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Wastewater generated from urban agglomerations in India is estimated to be 26.4 km 3 annually and 28% of it is treated. This has a potential to irrigate about 2.1 million-ha agricultural land, contribute 4 million Mg of plant nutrients, generate 2.8 million person-days of employment and reduce green house gas (GHG) emission by 73.7 million Mg CO 2 -e. Farmers in peri-urban areas depend largely on raw and partially treated wastewater for livelihood via raising high value crops such as vegetable, fodders and fruits. Both controlled and uncontrolled disposal of waste waters leads to progressive and irreversible contamination of soils, surface and ground waters with pathogens, heavy metals and organic micro-contaminants and consequently their bio-transfer through the chain: sewage-soil-vegetation-animal-humans. This has led to the development of a considerable assortment of regulatory measures and guidelines aimed at reducing or eliminating wastewater related health risks. Because conventional treatment technologies are cost prohibitive, alternate methods based on biological and land treatment systems are being advocated. Since soils are the most logical sinks for wastewater, efforts are to optimise rates and methods of water application, quantify the sink capacity of soils to immobilise contaminants and protect the quality of produce. Reuse of diluted or undiluted wastewaters improves crop productivity by 10-36% though production sustainability depends on soil type, climatic conditions, crop grown, irrigation techniques and socio-political factors. Disposal of wastewater in tree plantations and constructed wetlands with consequent removal of toxic metals/compounds using hyper-accumulators/accumulators plants provide for a possible alternative. Ignoring the associated risks, using pisciculture for sewage disposal is quite popular in high rainfall areas. With growing water scarcities, it is utmost important to recognise wastewaters as a valuable resource and formulate appropriate policy initiatives considering the health and livelihood issues of the per-urban farmers and consumers of food as well as risks to environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The present study is the first report of isolation and characterization of endophytic actinobacteria from cactus (Opuntia ficus-indica). A total of 179 morphologically distinct endophytic actinobacterial isolates were purified from the roots of two different genetic accessions of cactus. All these isolates were screened for their plant growth promotion traits, namely, growth on N-free medium, P-solubilization, siderophore production, ACC deaminase activity and auxin production. A majority of the endophytic actinobacterial isolates (85%) exhibited their potential for plant growth promotion under in vitro conditions. Ten among the isolates were selected based on their multi-PGP traits and were identified as Streptomyces sp. following the 16S rRNA gene sequencing and phylogenetic analysis. Plant growth promotion potential of these selected endophytic Streptomyces was studied in wheat seedlings. All these selected isolates significantly enhanced the growth parameters such as seedling length and rootlets number compared to the uninoculated control. The wheat seeds inoculated with Streptomyces tuirus VL-70-IX exhibited maximum number of rootlets (6.33) compared to uninoculated control (3.67). The inoculation of endophytic actinobacteria Streptomyces levis VL-70-XII caused maximum seedling length (20.53 cm) and root length (8.26 cm), while the inoculation of S. radiopugnans HV-VIII resulted in highest shoot length (12.33 cm). These endophytic actinobacteria isolated from the roots of cactus accessions showed potential PGP traits. This work lays foundation for characterization and selection of endophytic actinobacteria from the under-exploited, drought tolerant species such as cactus with potential cross-compatibility for the improvement of plant growth of field crops especially under abiotic stress conditions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Strokectomy means surgical excision of infarcted brain tissue post-stroke with preservation of skull integrity, distinguishing it from decompressive hemicraniectomy. Both can mitigate malignant middle cerebral artery (MCA) syndrome but evidence regarding strokectomy is sparse. Here, we report our data and meta-analysis of strokectomy compared to hemicraniectomy for malignant MCA infarction. All malignant MCA stroke cases requiring surgical intervention in a large tertiary centre (January 2012-December 2017, N = 24) were analysed for craniotomy diameter, complications, length of follow-up and outcome measured using the modified Rankin score (mRS). Good outcome was defined as mRS 0-3 at 12 months. In a meta-analysis, outcome from strokectomy (pooled from our cohort and published strokectomy studies) was compared with hemicraniectomy (our cohort pooled with published DECIMAL, DESTINY and HAMLET clinical trial data). In our series (N = 24, 12/12 F/M; mean age: 45.83 ± 8.91, range 29-63 years), 4 patients underwent strokectomy (SC) and 20 hemicraniectomy (HC). Among SC patients, craniotomy diameter was smaller, relative to HC patients (86 ± 13.10 mm, 120 ± 4.10 mm, respectively; p = 0.003), complications were less common (25%, 55%) and poor outcomes were less common (25%, 70%). In the pooled data (N = 41 SC, 71 HC), strokectomy tended towards good outcome more than hemicraniectomy (OR 2.2, 95% CI 0.99-4.7; p = 0.051). In conclusion, strokectomy may be non-inferior, lower risk and cost saving relative to hemicraniectomy sufficiently to be worthy of further investigation and maybe a randomised trial., (© 2020. The Author(s).)

Mitochondria are the main site for generating reactive oxygen species, which are key players in diverse biological processes. However, the molecular pathways of redox signal transduction from the matrix to the cytosol are poorly defined. Here we report an inside-out redox signal of mitochondria. Cysteine oxidation of MIC60, an inner mitochondrial membrane protein, triggers the formation of disulfide bonds and the physical association of MIC60 with Miro, an outer mitochondrial membrane protein. The oxidative structural change of this membrane-crossing complex ultimately elicits cellular responses that delay mitophagy, impair cellular respiration and cause oxidative stress. Blocking the MIC60-Miro interaction or reducing either protein, genetically or pharmacologically, extends lifespan and health-span of healthy fruit flies, and benefits multiple models of Parkinson's disease and Friedreich's ataxia. Our discovery provides a molecular basis for common treatment strategies against oxidative stress., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Ageing is characterized by the development of persistent pro-inflammatory responses that contribute to atherosclerosis, metabolic syndrome, cancer and frailty 1-3 . The ageing brain is also vulnerable to inflammation, as demonstrated by the high prevalence of age-associated cognitive decline and Alzheimer's disease 4-6 . Systemically, circulating pro-inflammatory factors can promote cognitive decline 7,8 , and in the brain, microglia lose the ability to clear misfolded proteins that are associated with neurodegeneration 9,10 . However, the underlying mechanisms that initiate and sustain maladaptive inflammation with ageing are not well defined. Here we show that in ageing mice myeloid cell bioenergetics are suppressed in response to increased signalling by the lipid messenger prostaglandin E 2 (PGE 2 ), a major modulator of inflammation 11 . In ageing macrophages and microglia, PGE 2 signalling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. This energy-deficient state, which drives maladaptive pro-inflammatory responses, is further augmented by a dependence of aged myeloid cells on glucose as a principal fuel source. In aged mice, inhibition of myeloid EP2 signalling rejuvenates cellular bioenergetics, systemic and brain inflammatory states, hippocampal synaptic plasticity and spatial memory. Moreover, blockade of peripheral myeloid EP2 signalling is sufficient to restore cognition in aged mice. Our study suggests that cognitive ageing is not a static or irrevocable condition but can be reversed by reprogramming myeloid glucose metabolism to restore youthful immune functions.

The molecular mechanisms that restore microglial quiescence after acute stimulation remain largely unexplored, unlike those that drive microglial activation. In this issue of Immunity, Shemer et al. discover that the microglial IL-10 receptor counteracts the pro-inflammatory effects of TNF to allow restoration of microglial quiescence after peripheral endotoxin challenge., (Copyright © 2020. Published by Elsevier Inc.)

Deficit irrigation (DI) and plant growth regulators (PGRs) have strategic role for sustaining crop productivity and mitigating water stress in drought prone areas. However, their impacts are yet to be quantified for eggplant (Solanum melongena L.), a popular drought tolerant vegetable crop grown in water scarce Deccan Plateau of India. We conducted field experiments during 2016-17 and 2017-18 in a drought prone region of Deccan Plateau, India to evaluate the interactive effect of PGRs viz., 1.38 mg L -1 salicylic acid (SA), 1.5% potassium nitrate (PN), 500 ppm thio-urea (TU) and 100 ml L -1 bio-stimulant (BS) and varied levels of DI generated using line source sprinkler system. The marketable fruit yields were reduced to 86, 74, 50, 30, 12 and 8% with increased level of DI i.e. when the applied irrigation water (IW) equalled 0.00, 0.15, 0.30, 0.45, 0.60 and 0.75 times the cumulative open pan evaporation (CPE) against the recommended irrigation practice (IW:CPE 0.90). Application of PGRs improved fruit yields by 7.3-22.7% and their role to alleviate water stress was indicated by lower canopy temperatures, maintaining higher leaf relative water content, modulation of stomatal opening and higher consumptive use of water. Particularly SA and TU were superior under low to medium water stress (IW:CPE 0.45-0.75) whereas PN was effective in severe water stress (IW:CPE 0.0-0.44) while the effect of BS was almost similar with PGRs like TU under medium stress conditions. The maximum water productivity (WP) varied between 5.50 and 6.77 kg m -3 for different PGRs and it was 5.16 kg m -3 without PGRs indicating water savings to the order of 28.8-57.4% with the former. The fruit quality attributes such as mean diameter, sphericity, fruit weight and firmness traits declined with water stress while these were considerably rectified with PGRs. Higher accumulation of dry matter, sugar, protein, total phenolics, flavonoids and improved rehydration quality as well as potentially affecting enzymatic activity were monitored with PGRs. It is concluded that exogenous application of PGRs like SA and PN along with medium levels of DI can help in rational utilization of water resources and could effectively improve yield and post-harvest quality of eggplant fruits especially under water scarce environment of Deccan Plateau., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's disease and affects 1% of the population above 60 years old. Although Parkinson's disease commonly manifests with motor symptoms, a majority of patients with Parkinson's disease subsequently develop cognitive impairment, which often progresses to dementia, a major cause of morbidity and disability. Parkinson's disease is characterized by α-synuclein accumulation that frequently associates with amyloid-β and tau fibrils, the hallmarks of Alzheimer's disease neuropathological changes; this co-occurrence suggests that onset of cognitive decline in Parkinson's disease may be associated with appearance of pathological amyloid-β and/or tau. Recent studies have highlighted the appearance of the soluble form of the triggering receptor expressed on myeloid cells 2 (sTREM2) receptor in CSF during development of Alzheimer's disease. Given the known association of microglial activation with advancing Parkinson's disease, we investigated whether CSF and/or plasma sTREM2 differed between CSF biomarker-defined Parkinson's disease participant subgroups. In this cross-sectional study, we examined 165 participants consisting of 17 cognitively normal elderly subjects, 45 patients with Parkinson's disease with no cognitive impairment, 86 with mild cognitive impairment, and 17 with dementia. Stratification of subjects by CSF amyloid-β and tau levels revealed that CSF sTREM2 concentrations were elevated in Parkinson's disease subgroups with a positive tau CSF biomarker signature, but not in Parkinson's disease subgroups with a positive CSF amyloid-β biomarker signature. These findings indicate that CSF sTREM2 could serve as a surrogate immune biomarker of neuronal injury in Parkinson's disease., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Out of the myriad of complications associated with septic shock, septic-associated encephalopathy (SAE) carries a significant risk of morbidity and mortality. Blood-brain-barrier (BBB) impairment, which subsequently leads to increased vascular permeability, has been associated with neuronal injury in sepsis. Thus, preventing BBB damage is an attractive therapeutic target. Mitochondrial dysfunction is an important contributor of sepsis-induced multi-organ system failure. More recently, mitochondrial dysfunction in endothelial cells has been implicated in mediating BBB failure in stroke, multiple sclerosis and in other neuroinflammatory disorders. Here, we focused on Drp1-mediated mitochondrial dysfunction in endothelial cells as a potential target to prevent BBB failure in sepsis., Methods: We used lipopolysaccharide (LPS) to induce inflammation and BBB disruption in a cell culture as well as in murine model of sepsis. BBB disruption was assessed by measuring levels of key tight-junction proteins. Brain cytokines levels, oxidative stress markers, and activity of mitochondrial complexes were measured using biochemical assays. Astrocyte and microglial activation were measured using immunoblotting and qPCR. Transwell cultures of brain microvascular endothelial cells co-cultured with astrocytes were used to assess the effect of LPS on expression of tight-junction proteins, mitochondrial function, and permeability to fluorescein isothiocyanate (FITC) dextran. Finally, primary neuronal cultures exposed to LPS were assessed for mitochondrial dysfunction., Results: LPS induced a strong brain inflammatory response and oxidative stress in mice which was associated with increased Drp1 activation and mitochondrial localization. Particularly, Drp1-(Fission 1) Fis1-mediated oxidative stress also led to an increase in expression of vascular permeability regulators in the septic mice. Similarly, mitochondrial defects mediated via Drp1-Fis1 interaction in primary microvascular endothelial cells were associated with increased BBB permeability and loss of tight-junctions after acute LPS injury. P110, an inhibitor of Drp1-Fis1 interaction, abrogated these defects, thus indicating a critical role for this interaction in mediating sepsis-induced brain dysfunction. Finally, LPS mediated a direct toxic effect on primary cortical neurons, which was abolished by P110 treatment., Conclusions: LPS-induced impairment of BBB appears to be dependent on Drp1-Fis1-mediated mitochondrial dysfunction. Inhibition of mitochondrial dysfunction with P110 may have potential therapeutic significance in septic encephalopathy.

Root-tissue colonizing bacteria demonstrated with multiple PGP traits from sorghum plants were identified as Ochrobactrum sp. EB-165, Microbacterium sp. EB-65, Enterobacter sp. EB-14 and Enterobacter cloacae strain EB-48 on the basis of 16S rRNA gene sequencing. Here, the in vivo experiments using ½-MS media and ½-MS media + 15% PEG 8000 (for inducing drought stress) indicated stress tolerance imparting ability of these rhizobacterial endophytes in a non-stay green and senescent genotype (R-16) of sorghum. In the experiment with sterile soilrite mix base, seed bacterization with these isolates showed improved plant growth specifically the roots, in terms of root length (~ 44.2 to 50.8% over controls), root dry weight (~ 91.3 to 99.8% over controls) and root surface area (~ 1 to 1.5 fold over controls) under drought stress. Rhizobacterial endophytes were successful, not only in providing better cellular osmotic adjustment in leaves (≥ 1-fold increase in proline accumulation over controls), but favorable physiological responses like Relative Water Content (RWC) and cell Membrane Stability Index (MSI) in the inoculated plants during the drought stress induction. Up-regulation of drought responsive genes like sbP5CS2 and sbP5CS1 was observed in these endophytes-treated plants as compared to untreated control and Escherichia coli DH5α (negative control)-treated plants. Interestingly, the stress imparting traits of rhizobacterial endophytes, including up-regulation of specific genes, were observed during sorghum seedling growth only under drought stresses. The results of this study lead to the conclusion that the potential endophytic rhizobacterial interactions can contribute to plant growth promotion as well as induced stress tolerance in sorghum., Competing Interests: Conflict of interestThe authors declare that they do not have any conflict of interest., (© King Abdulaziz City for Science and Technology 2019.)

Aldehyde dehydrogenase 2 deficiency (ALDH2*2) causes facial flushing in response to alcohol consumption in approximately 560 million East Asians. Recent meta-analysis demonstrated the potential link between ALDH2*2 mutation and Alzheimer's Disease (AD). Other studies have linked chronic alcohol consumption as a risk factor for AD. In the present study, we show that fibroblasts of an AD patient that also has an ALDH2*2 mutation or overexpression of ALDH2*2 in fibroblasts derived from AD patients harboring ApoE ε4 allele exhibited increased aldehydic load, oxidative stress, and increased mitochondrial dysfunction relative to healthy subjects and exposure to ethanol exacerbated these dysfunctions. In an in vivo model, daily exposure of WT mice to ethanol for 11 weeks resulted in mitochondrial dysfunction, oxidative stress and increased aldehyde levels in their brains and these pathologies were greater in ALDH2*2/*2 (homozygous) mice. Following chronic ethanol exposure, the levels of the AD-associated protein, amyloid-β, and neuroinflammation were higher in the brains of the ALDH2*2/*2 mice relative to WT. Cultured primary cortical neurons of ALDH2*2/*2 mice showed increased sensitivity to ethanol and there was a greater activation of their primary astrocytes relative to the responses of neurons or astrocytes from the WT mice. Importantly, an activator of ALDH2 and ALDH2*2, Alda-1, blunted the ethanol-induced increases in Aβ, and the neuroinflammation in vitro and in vivo. These data indicate that impairment in the metabolism of aldehydes, and specifically ethanol-derived acetaldehyde, is a contributor to AD associated pathology and highlights the likely risk of alcohol consumption in the general population and especially in East Asians that carry ALDH2*2 mutation.

In neurodegenerative diseases, debris of dead neurons are thought to trigger glia-mediated neuroinflammation, thus increasing neuronal death. Here we show that the expression of neurotoxic proteins associated with these diseases in microglia alone is sufficient to directly trigger death of naive neurons and to propagate neuronal death through activation of naive astrocytes to the A1 state. Injury propagation is mediated, in great part, by the release of fragmented and dysfunctional microglial mitochondria into the neuronal milieu. The amount of damaged mitochondria released from microglia relative to functional mitochondria and the consequent neuronal injury are determined by Fis1-mediated mitochondrial fragmentation within the glial cells. The propagation of the inflammatory response and neuronal cell death by extracellular dysfunctional mitochondria suggests a potential new intervention for neurodegeneration-one that inhibits mitochondrial fragmentation in microglia, thus inhibiting the release of dysfunctional mitochondria into the extracellular milieu of the brain, without affecting the release of healthy neuroprotective mitochondria.

Stroke is a multiphasic process in which initial cerebral ischemia is followed by secondary injury from immune responses to ischemic brain components. Here we demonstrate that peripheral CD11b + CD45 + myeloid cells magnify stroke injury via activation of triggering receptor expressed on myeloid cells 1 (TREM1), an amplifier of proinflammatory innate immune responses. TREM1 was induced within hours after stroke peripherally in CD11b + CD45 + cells trafficking to ischemic brain. TREM1 inhibition genetically or pharmacologically improved outcome via protective antioxidant and anti-inflammatory mechanisms. Positron electron tomography imaging using radiolabeled antibody recognizing TREM1 revealed elevated TREM1 expression in spleen and, unexpectedly, in intestine. In the lamina propria, noradrenergic-dependent increases in gut permeability induced TREM1 on inflammatory Ly6C + MHCII + macrophages, further increasing epithelial permeability and facilitating bacterial translocation across the gut barrier. Thus, following stroke, peripheral TREM1 induction amplifies proinflammatory responses to both brain-derived and intestinal-derived immunogenic components. Critically, targeting this specific innate immune pathway reduces cerebral injury.

Major nutrient management systems for rice-wheat cropping were compared for their potential to credit organic carbon (C) to the soil, its fractionation into active (very labile, VLc; labile, Lc) and passive (less labile, LLc; non-labile, NLc) pools, and crop yield responses. A ten-year long experiment was used to study effects of: (i) no inputs (Control, O), (ii) 100% inorganic fertilizers (F) compared to reduced fertilizers inputs (55%) supplemented with biomass incorporation from (iii) opportunity legume crop (Vigna radiata) (LE), (iv) green manure (Sesbania aculeata) (GM), (v) farmyard manure (FYM), (vi) wheat stubble (WS), and (vii) rice stubble (RS). Maximum C input to soil (as the percentage of C assimilated in the system) was in GM (36%) followed by RS (34%), WS (33%), LE (24%), and FYM (21%) compared to O (15%) and F (15%). Total C input to soil had a direct effect on soil C stock, soil C fractions (maximum in VLc and LLc), yet the responses in terms of biological yield were controlled by the quality of the biomass (C:N ratio, decomposition, etc.) incorporated. Legume-based biomass inputs accrued most benefits for soil C sequestration and biological productivity.

Recent advances highlight a pivotal role for cellular metabolism in programming immune responses. Here, we demonstrate that cell-autonomous generation of nicotinamide adenine dinucleotide (NAD + ) via the kynurenine pathway (KP) regulates macrophage immune function in aging and inflammation. Isotope tracer studies revealed that macrophage NAD + derives substantially from KP metabolism of tryptophan. Genetic or pharmacological blockade of de novo NAD + synthesis depleted NAD + , suppressed mitochondrial NAD + -dependent signaling and respiration, and impaired phagocytosis and resolution of inflammation. Innate immune challenge triggered upstream KP activation but paradoxically suppressed cell-autonomous NAD + synthesis by limiting the conversion of downstream quinolinate to NAD + , a profile recapitulated in aging macrophages. Increasing de novo NAD + generation in immune-challenged or aged macrophages restored oxidative phosphorylation and homeostatic immune responses. Thus, KP-derived NAD + operates as a metabolic switch to specify macrophage effector responses. Breakdown of de novo NAD + synthesis may underlie declining NAD + levels and rising innate immune dysfunction in aging and age-associated diseases.

Food insecurity and declining availability of freshwater and new productive land in water-scarce areas and countries necessitate effective use of marginal-quality waters and underperforming soils. High‑magnesium waters and soils are emerging examples of water quality deterioration and land degradation leading to environmental and food security constraints in several irrigation schemes. A ratio of magnesium-to-calcium > 1 in irrigation waters and an exchangeable magnesium percentage > 25% in soils are considered high enough to result in soil degradation and impact crop yields negatively. These soil and water resources occur in the Aral Sea Basin in Central Asian countries, the Cauca River Valley in Colombia, the Central Plateau Basin in Iran, the Indus Basin in Pakistan, the Indo-Gangetic Plains in India, the Murray-Darling Basin in Australia, and the Coastal Mountain Range in California, among others. With limited and scattered information, their occurrence remains hidden or unnoticed in many cases due to the lack of criteria in water quality assessment and soil classification systems. Managing high‑magnesium waters and soils requires a source of calcium to mitigate magnesium effects, in addition to an effective drainage system for safe disposal of excess magnesium salts. There is a need to put high‑magnesium waters and soils on the public policy agenda. Pertinent policies can catalyze stakeholders' involvement in supporting water and land quality monitoring systems and introducing innovative financial mechanisms to facilitate provision of calcium-supplying amendments in affected areas. Equally important would be strengthening institutional and professionals' capacity, enhancing institutional collaboration, encouraging private sector involvement in at-risk areas, and engaging local communities and farmers. These efforts will support the 2030 Sustainable Development Agenda. Eradicating extreme poverty and meeting the Sustainable Development Goals in water-scarce areas without adequately addressing underperforming land and water resources is highly unlikely., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Although the proportion of ethnicities representing under-represented minorities in medicine (URM) in the general population has significantly increased, URM enrolment in medical schools within the USA has remained stagnant in recent years., Methods: This study sought to examine the effect of an immersion in community medicine (ICM) programme on secondary school students' desire to enter the field of medicine and serve their communities. The authors asked all 69 ICM alumni to complete a 14-question survey consisting of six demographic, four programme and four career questions, rated on a Likert scale of 1 (completely disagree) to 5 (completely agree), coupled with optional free-text questions. Data were analysed using GraphPad prism and nvivo software., Results: A total of 61 students responded, representing a response rate of 88.4 per cent, with a majority of respondents (73.7%) from URM backgrounds. An overwhelming majority of students agreed (with a Likert rating of 4 or 5) that the ICM programme increased their interest in becoming a physician (n = 56, 91.8%). Students reported shadowing patient-student-physician interactions to be the most useful (n = 60, 98.4%), and indicated that they felt that they would be more likely to lead to serving the local community as part of their future careers (n = 52, 85.3%). Of the students that were eligible to apply to medical school (n = 13), a majority (n = 11, 84.6%) have applied to medical school. URM enrolment in medical schools within the USA has remained stagnant in recent years DISCUSSION: Use of a community medicine immersion programme may help encourage secondary students from URM backgrounds to gain the confidence to pursue a career in medicine and serve their communities. Further examination of these programmes may yield novel insights into recruiting URM students to medicine., (© 2017 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Grain yield of wheat is primarily determined by both grain number and grain weight, which often influence each other in response to environmental stimuli. Some of the genotypes are capable of maintaining high single grain weight (SGW) across the environments. Understanding mechanisms and factors associated with the superiority of such genotypes over others is necessary to enhance productivity of wheat., Results: Experiments were conducted to elucidate the physiological basis of high SGW of LOK-1, a wheat cultivar grown in dry and hot environments in the central and peninsular zones of India. SGW of LOK-1 was least affected by removal of spikelets indicating little competition between the grains within the spike for assimilates. Reduction in SGW due to defoliation was less and the contribution of stem reserves to the grain development was high in LOK-1 relative to other cultivars. It seems that high level of expression of genes such as expansin (TaExpA6) contributes to the high SGW of LOK-1., Conclusions: Source was not a limiting factor for grain growth of LOK-1 in contrast to other cultivars, whereas sink appeared to be a limiting factor in recently released/identified cultivars. Differences in the amounts of water soluble stem carbohydrate reserves translocated to grain could be one of the factors contributing to higher grain weight in LOK-1. High level expression of TaExpA6, one of the genes contributing to the elongation of endosperm, seems to be crucial for grain growth in wheat.

We present a very rare case of a metastasising pleomorphic adenoma with spinal cord compression and review the small handful of cases with central nervous system (CNS) involvement in the literature. This case is unusual as most other reported cases are preceded by local recurrences; also, there is only one previous case of an MPA presenting with spinal cord compression. Metastasising pleomorphic adenoma is a rare malignant salivary gland tumour which, despite "benign" histological appearances produces secondary deposits in distant sites.

Symbiotic effectiveness of rhizobitoxine (Rtx)-producing strains of Bradyrhizobium spp. in soybean (cultivar NRC-37/Ahilya-4) under limited soil moisture conditions was evaluated using phenomics tools such as infrared(IR) thermal and visible imaging. Red, green and blue (RGB) colour pixels were standardized to analyse a total of 1017 IR thermal and 692 visible images. Plants inoculated with the Rtx-producing strains B. elkanii USDA-61 and USDA-94 and successive inoculation by B. diazoefficiens USDA-110 resulted in cooler canopy temperatures and increased canopy greenness. The results of the image analysis of plants inoculated with Rtx-producing strains were correlated with effective nodulation, improved photosynthesis, plant nitrogen status and yield parameters. Principal component analysis (PCA) revealed the reliability of the phenomics approach over conventional destructive approaches in assessing the symbiotic effectiveness of Bradyrhizobium strains in soybean plants under watered (87.41-89.96%) and water-stressed (90.54-94.21%) conditions. Multivariate cluster analysis (MCA) revealed two distinct clusters denoting effective (Rtx) and ineffective (non-Rtx) Bradyrhizobium inoculation treatments in soybean. Furthermore, correlation analysis showed that this phenotyping approach is a dependable alternative for screening drought tolerant genotypes or drought resilience symbiosis. This is the first report on the application of non-invasive phenomics techniques, particularly RGB-based image analysis, in assessing plant-microbe symbiotic interactions to impart abiotic stress tolerance.

A diverse group of bacteria colonize the exo- and endo-rhizospheres of sorghum and play a critical role in its tolerance to drought and other abiotic stresses. Two hundred and eighty endophytic bacteria were isolated from the surface-sterilized roots of four sorghum cultivars that were grown on three soil types at three different phenological stages of growth. The isolates were subjected to in vitro screening for their plant growth promoting traits. Out of 280 isolates, 70 could produce Indole 3-Acetic Acid (IAA), 28 showed N-fixation, 28 could solubilize phosphate, 24 had ACC deaminase activity and 13 isolates were able to produce siderophores. Functional diversity grouping of the isolates indicated one isolate having five PGP traits and two isolates having four PGP traits; two and 29 isolates having three and two PGP traits, respectively. Among the thirty-four isolates that possessed multiple PGP traits, 19 and 17 isolates were able to produce significant quantities of IAA in the presence and absence of L-tryptophan, an inducer. Eight isolates possessed high levels of ACC deaminase activity. PCR-RFLP of the 16Sr RNA gene revealed a distinct clustering and considerable genetic diversity among these functionally characterized isolates. The 16S rRNA gene based identification of the isolates of single and multiple PGP traits revealed phylogenetic dominance of Firmicutes; Acinetobacter, Bacillus, Enterobacter, Geobacillus, Lysinibacillus, Microbacterium, Ochrobactrum, Paenibacillus and Pseudomonas were the major genera present in the endo-rhizosphere of sorghum. Results of this study are constructive in selection of effective rhizobacterial endophytes or consortia for drought stress alleviation in sorghum.

Abiotic stresses are the foremost limiting factors for agricultural productivity. Crop plants need to cope up adverse external pressure created by environmental and edaphic conditions with their intrinsic biological mechanisms, failing which their growth, development, and productivity suffer. Microorganisms, the most natural inhabitants of diverse environments exhibit enormous metabolic capabilities to mitigate abiotic stresses. Since microbial interactions with plants are an integral part of the living ecosystem, they are believed to be the natural partners that modulate local and systemic mechanisms in plants to offer defense under adverse external conditions. Plant-microbe interactions comprise complex mechanisms within the plant cellular system. Biochemical, molecular and physiological studies are paving the way in understanding the complex but integrated cellular processes. Under the continuous pressure of increasing climatic alterations, it now becomes more imperative to define and interpret plant-microbe relationships in terms of protection against abiotic stresses. At the same time, it also becomes essential to generate deeper insights into the stress-mitigating mechanisms in crop plants for their translation in higher productivity. Multi-omics approaches comprising genomics, transcriptomics, proteomics, metabolomics and phenomics integrate studies on the interaction of plants with microbes and their external environment and generate multi-layered information that can answer what is happening in real-time within the cells. Integration, analysis and decipherization of the big-data can lead to a massive outcome that has significant chance for implementation in the fields. This review summarizes abiotic stresses responses in plants in-terms of biochemical and molecular mechanisms followed by the microbe-mediated stress mitigation phenomenon. We describe the role of multi-omics approaches in generating multi-pronged information to provide a better understanding of plant-microbe interactions that modulate cellular mechanisms in plants under extreme external conditions and help to optimize abiotic stresses. Vigilant amalgamation of these high-throughput approaches supports a higher level of knowledge generation about root-level mechanisms involved in the alleviation of abiotic stresses in organisms.

Objectives: External ventricular drain (EVD)-related infection is a significant source of morbidity in neurosurgical patients. Recently, there has been a drive to adopt new catheters with bactericidal properties to reduce infection rates. We propose that the use of standard catheters combined with pre-emptive intrathecal vancomycin (ITV) 10 mg daily provides an effective alternative., Design: Retrospective study of all patients with EVDs between 2010 and 2012, comparing infection rates in those who did and did not receive pre-emptive ITV. All EVDs were of the standard silicon catheter type. CSF infection was defined, as per Centre for Disease Control (CDC) guidelines, as clinical suspicion ± positive CSF gram stain/culture or leucocytosis. Infection rates were compared using Pearson's chi-squared test., Results: 262 EVDs were included in the study, of which 111 were managed with pre-emptive ITV. The infection rate was 2.7% in the vancomycin group and 11.9% in the control group (p<.01). There were no cases of vancomycin-resistant infection in either group., Conclusion: The use of pre-emptive ITV is associated with a significantly lower EVD infection rate. This compares favourably with those reported in the literature for bactericidal catheters.

Halotolerant bacteria associated with Psoralea corylifolia L., a luxuriantly growing annual weed in salinity-affected semi-arid regions of western Maharashtra, India were evaluated for their plant growth-promoting activity in wheat. A total of 79 bacteria associated with different parts viz., root, shoot and nodule endophytes, rhizosphere, rhizoplane, and leaf epiphytes, were isolated and grouped based on their habitat. Twelve bacteria isolated for their potential in plant growth promotion were further selected for in vitro studies. Molecular identification showed the presence of the genera Bacillus, Pantoea, Marinobacterium, Acinetobacter, Enterobacter, Pseudomonas, Rhizobium, and Sinorhizobium (LC027447-53; LC027455; LC027457, LC027459, and LC128410). The phylogenetic studies along with carbon source utilization profiles using the Biolog® indicated the presence of novel species and the in planta studies revealed promising results under salinity stress. Whereas the nodule endophytes had minute plant growth-promoting (PGP) activity, the cell free culture filtrates of these strains enhanced seed germination of wheat (Triticum aestivum L). The maximum vigor index was monitored in isolate Y7 (Enterobacter sp strain NIASMVII). Indole acetic acid (IAA) production by the isolates ranged between 0.22 and 25.58 μg mL -1 . This signifies the need of exploration of their individual metabolites for developing next-generation bio-inoculants through co-inoculation with other compatible microbes. This study has potential in utilization of the weed-associated microbiome in terms of alleviation of salinity stress in crop plants.

The amelioration effect of water-soluble vitamin pyridoxine against stress was evaluated in milkfish, Chanos chanos exposed to endosulfan. Two hundred and twenty-five fish were distributed randomly into five treatments, each with three replicates. Four isocaloric and isonitrogenous diets with graded levels of pyridoxine feed were as follows: normal water and fed with control diet (En0/PY0); endosulfan-treated water and fed with control diet (En/PY0); and endosulfan-treated water and fed with 50 (En/PY 50 mg/kg), 75 (En/PY 75 mg/kg) and 100 mg/kg (En/PY 100 mg/kg) pyridoxine-supplemented feed. The endosulfan in treated water was maintained at a level of 1/40th of LC50 (0.52 ppb). The effect of dietary pyridoxine supplementation was studied in terms of antioxidative enzymes (catalase, superoxide dismutase, glutathione-S-transferase), stress markers [heat-shock protein 70, caspase-3, cortisol, acetylcholine esterase (AChE), blood glucose], immunohaematological parameters (total protein, albumin, globulin and A/G ratio, nitroblue tetrazolium, RBC, WBC, Hb), gill histopathology and a subsequent challenge study with Vibrio parahaemolyticus. The antioxidative enzymes, stress markers, albumin and A/G ratio were significantly (p < 0.01) elevated, brain AChE and immunohaematological parameters were significantly (p < 0.01) decreased, and chromosome aberration and gill histopathology were also altered due to endosulfan exposure. The relative survival % was reduced due to the combined effect of endosulfan stress and bacterial challenge. Fish fed the diet supplemented with pyridoxine at 75 and 100 mg/kg was found to restore the studied parameter towards normal compared with control and indicated protection against endosulfan-induced stress significantly (p < 0.01). Results obtained in the present study indicate that the supplementation of 75 and 100 mg/kg of pyridoxine in the diet has a definitive role in the mitigation of the endosulfan-induced stress in milkfish, C. chanos fingerlings., (© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

This study investigated 96h median lethal concentration of endosulfan (99%, pure α: β ratio of 7:3) by conducting static non-renewable acute toxicity bio-assay in Chanos chanos juvenile with average weight (110±5.65g). Further, the effect of different definitive doses (18.5, 19.5, 20.5, 21.5 and 22.5µg/L) of endosulfan on metabolic, heamato-immunoligcal and histopathological response were probed. Anti-oxidative enzymes CAT, SOD and GST showed significant (p<0.01) increase of activity in the liver, gill and brain during exposure to endosulfan in a dose and time dependent manner. The brain AChE activity showed significant (p<0.01) inhibition from 18.5 to 22.5µg/L exposure of endosulfan than the control group. LDH and MDH activity gradually increased with consequent increasing dose of endosulfan exposure in the liver, gill and brain. Similarly, ALT, AST and G6PDH activities in both liver and gill increased with consequent increases in the dose of endosulfan exposure. Immunological profile such as blood glucose and serum cortisol level significantly enhanced while respiratory burst activity declined with consequent increasing doses of endosulfan exposure. Histopathological alteration in the gill demonstrated curling of secondary lamellae, thickening of primary epithelium, shorting of secondary lamellae, epithelial hyperplasia, fusion of secondary lamellae, aneurism, and collapsed secondary lamellae due to dose dependent exposure of endosulfan. Liver histology illustrated cloudy swelling and necrosis with pyknotic nuclei to the moderate dose of endosulfan, whereas higher dose of endosulfan (21.5µg/L) displayed severe necrosis of hepatic cells. Overall results clearly indicate that acute exposure of endosulfan led to pronounced deleterious alterations on biochemical, heamato-immunological, and histopathological responses of C. chanos juvenile., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We herein report the protective role of pyridoxine in enhancing thermal tolerance of Milkfish Chanos chanos reared under endosulfan-induced stress. Four isocaloric and isonitrogenous diets were prepared with graded levels of pyridoxine (0, 50, 75 and 100 mg/kg). Two hundred and twenty five fishes were randomly distributed into four treatment groups in triplicate, reared under endosulfan-treated water, which were fed with pyridoxine supplemented diet, while the negative control group was reared without endosulfan-treatment and control fed. The concentration of endosulfan in treated water was maintained at a level of 1/40th of LC50 i.e. 0.52 μg/L. Dietary pyridoxine supplementation had significant (p < 0.01) effect on temperature tolerance viz. CTmax (Critical temperature maxima), LTmax (Lethal temperature maxima), CTmin (Critical temperature minima) and LTmin (Lethal temperature minima) of milkfish. The positive correlation was observed between CT max and LTmax (Y = -1.54 + 15.6x, R(2), 0.943) as well as CTmin and LTmin (Y = -1.44 + 1.021x, R(2), 0.941). At the end of the thermal tolerance study, antioxidative status and HSP 70 were significantly reduced in pyridoxine supplemented groups, whereas brain AChE was significantly (p < 0.01) elevated compared to positive and negative control. It is concluded that CTmax, LTmax, CTmin and LTmin, antioxidative status, neurotransmitter enzyme and HSP 70 strengthened the enhancement of thermal tolerance of Milkfish., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The fisheries and livestock sectors capture the highest share of protein-rich animal food and demonstrate accelerated growth as an agriculture subsidiary. Environmental pollution, climate change, as well as pathogenic invasions exert increasing stress impacts that lead the productivity momentum at a crossroads. Oxidative stress is the most common form of stress phenomenon responsible for the retardation of productivity in fisheries and livestock. Essential micronutrients play a determinant role in combating oxidative stress. Selenium, one of the essential micronutrients, appears as a potent antioxidant with reduced toxicity in its nanoscale form. In the present review, different methods of synthesis and characterization of nanoscale selenium have been discussed. The functional characterization of nano-selenium in terms of its effect on growth patterns, feed digestibility, and reproductive system has been discussed to elucidate the mechanism of action. Moreover, its anti-carcinogenic and antioxidant potentiality, antimicrobial and immunomodulatory efficacy, and fatty acid reduction in liver have been deciphered as the new phenomena of nano-selenium application. Biologically synthesized nano-selenium raises hope for pharmacologically enriched, naturally stable nanoscale selenium with high ecological viability. Hence, nano-selenium can be administered with commercial feeds for improvising stress resilience and productivity of fish and livestock.

Farmers in developing countries irrigate crops using raw urban and industrial effluents with consequent risks from metal contamination. Therefore, soils, crops and groundwater from an effluent irrigation use site were assessed for Cd, Cr, Ni and Pb. Total and available contents of metals in soil followed the order Pb>Ni>Cr>Cd. Crops accumulated more Pb, followed by Cd, Ni and Cr. Pb exceeded the permissible limit with wastewater irrigation only, but Cd exceeded the limit even with combined irrigations of wastewater and groundwater. Among crops, sugar beet assimilated highest Cd (3.14 μg g(-1)) and Pb (6.42 μg g(-1)) concentrations. Legumes accumulated more metals than cereals. Long-term use of wastewater and its conjunctive use with groundwater led to toxic accumulations of Cd, Pb, Ni and Cr. Cd with higher availability and mobility indices and lower toxicity limit, posed the maximum risk of food-chain contamination.