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Prematurely born infants are deprived of maternal hormones and cared for in the stressful environment of Neonatal Intensive Care Units (NICUs). They suffer from long-lasting deficits in learning and memory. Here, we show that prematurity and associated neonatal stress disrupt dentate gyrus (DG) development and induce long-term cognitive deficits and that these effects are mediated by insulin growth factor-1 (IGF1). Nonmaternal care of premature rabbits increased the number of granule cells and interneurons and reduced neurogenesis, suggesting accelerated premature maturation of DG. However, the density of glutamatergic synapses, mature dendritic spines, and synaptic transmission were reduced in preterm kits compared with full-term controls, indicating that premature synaptic maturation was abnormal. These findings were consistent with cognitive deficits observed in premature rabbits and appeared to be driven by transcriptomic changes in the granule cells. Preterm kits displayed reduced weight, elevated serum cortisol and growth hormone, and higher IGF1 expression in the liver and DG relative to full-term controls. Importantly, blocking IGF-1 receptor in premature kits restored cognitive deficits, increased the density of glutamatergic puncta, and rescued NR2B and PSD95 levels in the DG. Hence, IGF1 inhibition alleviates prematurity-induced cognitive dysfunction and synaptic changes in the DG through modulation of NR2B and PSD95. The study identifies a novel strategy to potentially rescue DG maldevelopment and cognitive dysfunction in premature infants under stress in NICUs.

Hyperactivity of amygdala is observed in patients with major depressive disorder. Although the role of α1-adrenoceptor in amygdala on fear memory has been well studied, the role of α1-adrenoceptor in amygdala on depression-like behaviors remains unclear. Therefore, we investigated the effect of α1A-adrenoreceptor in amygdala on despair behavior, evaluated by the immobility time during tail suspension test (TST), pharmacological intervention, and immunohistological methods. C57BL6/J mice given a bilateral intra-amygdala injection of artificial cerebrospinal fluid exhibited an increased duration of immobility in the latter half of both trials of TST with a 24-h interval, a phenomenon known as learned despair. Intra-amygdala injection of WB4101 (1.7 nmol/0.1 µl), an α1 adrenoreceptor antagonist, but not propranolol (250 pmol/0.1 µl), a β-adrenoreceptor antagonist, blocked the induction of learned despair during TST. Immunostaining experiments revealed that ~61-75% of α1A-adrenoreceptor-positive neurons were colocalized with GAD65/67 in amygdala, implying that the α1-adrenoceptors in amygdala may enormously regulate the GABA release. Protein kinase C-beta (PKCβ) was predominantly expressed in the α1A-adrenoreceptor-positive neurons in the BLA, whereas protein kinase C-epsilon (PKCε) was highly expressed with the α1A-adrenoreceptor in the Central nucleus of amygdala. Intra-amygdala injection of ruboxistaurin (10 pmol/0.1 µl), a PKCβ inhibitor, blocked the induction of learned despair during TST, whereas neither TAT-εV1-2 (500 ng/0.1 μl), a cell-permeant PKCε inhibitory peptide, nor HBDDE (50 pmol/0.1 µl), an inhibitor of PKCα and -γ, affected the duration of immobility during TST. These data suggest that the α1-adrenoreceptor in amygdala regulates the induction of learned despair via PKCβ.

Arsenic (As) contamination in paddy soils and its further translocation to the rice is a serious global issue. Arsenic loading to the rice depends on soil physico-chemical parameters and agronomic practices. To minimize this natural threat, as a natural substance, rice straw was used to produce rice biochar (RBC) and doped with iron oxide (IO) nanoparticles, another eco-friendly composite. In this study, RBC was used at three different concentrations- 0.5%, 1%, and 1.5% alone as well as conjugated with fixed 20 ppm IO nanoparticles. These treatments were compared with the control soil and control plants that had only As in the setup, without any amendments. The application of these treatments was efficient in reducing soil As bioavailability by 43.9%, 60.5%, and 57.3% respectively. Experimental data proved a significant percentage of As was adsorbed onto the RBC + IO conjugate. Further, the 1% RBC + IO conjugate was found to be the best treatment in terms of making soil macro-nutrients bioavailable. Rice seedlings grown under this treatment was more stress tolerant and produced less antioxidant enzymes and stress markers compared to the control plants grown under As-stress only. Rice plants from these different growth setups were observed for internal anatomical integrity and found that the RBC alone and RBC + IO conjugate, both improved the internal vascular structure compared to the control plants. To minimize soil As stress in crops, IO-doped RBC was proven to be the best sustainable amendment for improving soil-crop quality and achieving the proposed motto of Sustainable Development Goals by the United Nations.

District Gorakhpur possess severe vulnerability to earthquake and climatologically induced hazards such as drought, heat wave, cold wave, flood, hailstorm, untimely and incessant rainfall. This article gives an in-depth perspective of the need for formation of Climate Cell in Gorakhpur followed by emphasizing the ongoing and futuristic targeted approaches of District Disaster Management Authority of Gorakhpur (DDMA) for enhancing Climate Change Adaptation & Disaster Risk Reduction. Apart from the above-mentioned measures, the workshop on ‘Formation and Activation of Climate Cell in Gorakhpur’ has been discussed comprehensively in this article that led to the adoption of ‘Gorakhpur Declaration’ which is a brief outcome of the workshop. The ongoing & targeted efforts of DDMA-Gorakhpur mentioned in this article are wide expansion of green infrastructure in the district focusing on adequate plantation at adequate places; adoption of pervious pavements for urban flood mitigation; outcome of the Installation of Automatic Weather Station in SADAR sub-division of Gorakhpur; all the above mentioned activities are identified & executed by Climate Cell under the aegis of DDMA-Gorakhpur and other activity that is being done in expeditious way is formation of School Disaster Management Plan (SDMP) in Gorakhpur. In light of the vulnerability of Gorakhpur, on November 16, 2018, various stakeholders concerned with Disaster Risk Reduction (DRR) & Climate Change Adaptation (CCA) met and identified a common goal to work out for the strengthening of climate cell in Gorakhpur at the occasion of workshop. All the sessions that led to exploration of precise outcome in the workshop for enhancing the framework of CCA & DRR have been discussed in this article. How to cite this article: Gupta G, Gupta A, Khan S. Enhancing Climate Change Adaptation & Disaster Risk Reduction in Gorakhpur. J Adv Res Alt Energ Env Eco 2019; 6(3&4): 7-21.

The present study analysed the levels of potentially toxic elements along with physico-chemical properties of agricultural soil samples (n = 59) collected from fields situated along the path of river Ganga in the middle Gangetic floodplain in two districts, Ballia and Ghazipur. Arsenic (As), chromium (Cr), copper (Cu), nickel (Ni), zinc (Zn), lead (Pb), iron (Fe) and manganese (Mn) levels were analysed by Wavelength Dispersive-X-Ray Fluorescence Spectroscopy (WD-XRF) and the associated health risks along with diverse indices were calculated. The mean concentrations of As, Cu, Cr, Pb, Zn and Ni were found to be 15, 42, 85, 18, 87 and 47 mg kg

Background While schizophrenia differs between males and females in the age of onset, symptomatology, and disease course, the molecular mechanisms underlying these differences remain uncharacterized. Methods To address questions about the sex-specific effects of schizophrenia, we performed a large-scale transcriptome analysis of RNA sequencing data from 437 controls and 341 cases from two distinct cohorts from the CommonMind Consortium. Results Analysis across the cohorts identified a reproducible gene expression signature of schizophrenia that was highly concordant with previous work. Differential expression across sex was reproducible across cohorts and identified X- and Y-linked genes, as well as those involved in dosage compensation. Intriguingly, the sex expression signature was also enriched for genes involved in neurexin family protein binding and synaptic organization. Differential expression analysis testing a sex-by-diagnosis interaction effect did not identify any genome-wide signature after multiple testing corrections. Gene coexpression network analysis was performed to reduce dimensionality from thousands of genes to dozens of modules and elucidate interactions among genes. We found enrichment of coexpression modules for sex-by-diagnosis differential expression signatures, which were highly reproducible across the two cohorts and involved a number of diverse pathways, including neural nucleus development, neuron projection morphogenesis, and regulation of neural precursor cell proliferation. Conclusions Overall, our results indicate that the effect size of sex differences in schizophrenia gene expression signatures is small and underscore the challenge of identifying robust sex-by-diagnosis signatures, which will require future analyses in larger cohorts.

While schizophrenia differs between males and females in age of onset, symptomatology and the course of the disease, the molecular mechanisms underlying these differences remain uncharacterized. In order to address questions about the sex-specific effects of schizophrenia, we performed a large-scale transcriptome analysis of RNA-seq data from 437 controls and 341 cases from two distinct cohorts from the CommonMind Consortium. Analysis across the cohorts identifies a reproducible gene expression signature of schizophrenia that is highly concordant with previous work. Differential expression across sex is reproducible across cohorts and identifies X- and Y-linked genes, as well as those involved in dosage compensation. Intriguingly, the sex expression signature is also enriched for genes involved in neurexin family protein binding and synaptic organization. Differential expression analysis testing a sex-by-diagnosis interaction effect did not identify any genome-wide signature after multiple testing corrections. Gene coexpression network analysis was performed to reduce dimensionality and elucidate interactions among genes. We found enrichment of co-expression modules for sex-by-diagnosis differential expression signatures, which were highly reproducible across the two cohorts and involve a number of diverse pathways, including neural nucleus development, neuron projection morphogenesis, and regulation of neural precursor cell proliferation. Overall, our results indicate that the effect size of sex differences in schizophrenia gene expression signatures is small and underscore the challenge of identifying robust sex-by-diagnosis signatures, which will require future analyses in larger cohorts.

The nanocomposite thin films of Tin oxide (SnO2) and Titanium dioxide(TiO2) were deposited on silicon and ITO substrate by RF magnetron sputtering technique using sintered pellet formed by mixing S...

Copper nanowires have been synthesized at different pH values through the template assisted electrodeposition technique using polycarbonate track-etch membranes as scaffolds. The effect of pH (0.8–2.8) of the electrolyte on structure, morphology, composition and deposition rate of copper into the pores of the template, while keeping other electrochemical conditions same, was investigated. X-ray diffraction analysis confirmed the face centered cubic phase of synthesized nanowires. With the change in pH, no shift in peaks was observed except the inclusion of an additional peak of copper oxide in nanowires synthesized at pH 2.8. The nanocrystallite size, strain, lattice stress and energy density were evaluated by X-ray analysis. Field emission scanning electron microscopy images revealed that nanowires obtained at pH 0.8, 1.1 and 1.4 showed incomplete deposition in the pores of the membrane whereas, the nanowires obtained at pH 1.7 were densely stacked, vertically aligned and uniform along the diameter and that obtained from pH 2.0–2.8 had overdeposition on their top. An increase in deposition rate was observed with the increase in pH value. The average diameter of Cu nanowires was found to be ~ 105 nm. The electrical conductivity of as-grown nanowires was observed to decrease 13-fold as the transition from bulk values to the nanosystem. Nanowires prepared at pH of 1.7 were characterized for their field-emission properties. A very large field-enhancement factor of ~ 10,855 was obtained indicating that Cu nanowires grown by reported technique shows outstanding potential as efficient field-emitters for flat panel displays.

RF Sputtering deposition technique was used to deposit the thin films of nanocomposite oxides as SnO2–TiO2 on Si and ITO coated glass substrate. As a target, SnO2–TiO2 was taken according to their molecular weight percent ratio of 3:1. Material modification has been induced by low energy ion beam with varying ion fluence from 5E13 to 5E16 ions/cm2. Glancing Angle X-ray Diffraction technique was used to study crystallite size, phase transformation and stability of different planes of pristine and irradiated thin films. The important peaks observed in XRD pattern were at angles 26.95°, 34.27°, 37.60°, 50.88° and 52.46°. The grain size distribution and surface morphology were studied by Atomic Force Microscopy technique in tapping mode. The results show that the grain size varies with ion fluence. Raman analysis revealed that the sharp peak at the frequency of 520 cm−1 ascribed to the T2g mode was observed for the pristine and lowest fluence irradiated film deposited on Si substrate. With increasing ion fluence, an opposite trend in SnO2 B2g peak was observed at nearly 775 cm−1 and the also peak bump was observed as a function of ion beam fluence. The optical band gap decreases from 3.90 to 3.63 eV due to the generation of ions and free radicals in valance band by varying ion fluence which was observed by UV/Visible Spectroscopy. The film thickness was determined to be 220 nm using Rutherford Backscattering Spectrometry. It also confirmed the absence of any impurities in the pristine and irradiated thin films. The material properties were mainly modified by the point defects and grain size growth arising due to nuclear energy loss.

Low-dose dexmedetomidine may be a suitable alternative to opioids for pediatric ambulatory procedures under general anesthesia (GA). However, the recovery profile remains unclear. Herein, we aimed to evaluate the effects of low-dose dexmedetomidine on the recovery profile of children.Seventy-two children undergoing ambulatory oral rehabilitation under GA were randomly and equally distributed into two groups (D and F). Group D received an infusion of dexmedetomidine 0.25 µg/kg for 4 min for induction, followed by maintenance of 0.4 µg/kg/h. Group F received an infusion of fentanyl 1 µg/kg over 4 min for induction, followed by maintenance at 1 µg/kg/h. The primary outcome was the extubation time. The secondary outcomes were awakening time, end-tidal sevoflurane (ET-Sevo) requirement, change in hemodynamic parameters, Richmond Agitation-Sedation Scale (RASS), Children's Hospital of Eastern Ontario pain scale (CHEOPS) score, length of PACU stay, and incidence of adverse events.Statistically significant differences were observed in the recovery profile between the groups: the median time for extubation was 3.65 (3.44-6.2) vs. 6.25 (4.21-7) minutes in groups D vs. F (P = 0.001), respectively, while the corresponding awakening times were 19 (18.75-21) and 22.5 (22-24) minutes, respectively (P0.001). The mean ET-Sevo was low in group D (1.1 vs. 1.2; P0.001). The heart rate was significantly low across all time points in group D, without resulting in bradycardia. The median RASS and CHEOPS scores were also significantly lower in group D. No significant differences were observed in the mean arterial pressure, incidence of adverse events, or length of PACU stay.Low-dose dexmedetomidine was more effective than fentanyl as an opioid substitute at providing a better recovery profile in pediatric ambulatory oral rehabilitation under GA. Dexmedetomidine also significantly reduced sevoflurane consumption without causing adverse events or prolonging hospital stay.

Using indium (III) triflate as a mild Lewis acid catalyst, the Friedel Crafts alkylation of o-hydroxy bisbenzylic alcohols with aromatic/heteroaromatic arenes under solvent free conditions was achieved to give the corresponding unsymmetrical triarylmethanes in high yields (up to 80% yield). Calculation of the different green metrics for the above reaction revealed it to have high atom economy (94–96%), high reaction mass efficiency (66–77%) and high carbon efficiency (70–80%). The Lewis acid was found to be air and moisture tolerant. The protocol was found to be operationally simple and can be carried out in an “open-flask” leaving behind water as the sole by product. Gratifyingly the Lewis acid catalyst could be recycled and reused up to 5 catalytic cycles without compromising much on the yield thus further highlighting the importance of the protocol.

Radiation exposure modifies the nano scale free volume of the polymers which has direct correlation to certain properties of polymeric materials. CR-39 (DOP) polycarbonate polymeric films were exposed to gamma radiation at different doses for the study of nano scale free volume as well as structural and optical properties. An overall increase in the number of free volume holes at all doses was observed. UV–visible studies showed an improvement in the optical properties due to decrease in direct band gap energy. X-ray diffraction spectra of the polymer samples showed the increased amorphous nature of the polymer.

The optical, structural and chemical properties of polyimide Kapton-H polymer thin film samples were modified by irradiation with 100 MeV O 7+ ions (in the fluence range of 1 × 10 11 to 5 × 10 12 ions/cm 2 ) and the modifications of these properties were observed by UV–visible (UV–Vis) spectroscopy, X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy respectively. The band gap energy of the polymer decreased considerably with discrete increment of the ion fluence (different fluence for each sample) and effective change for the sample irradiated at a fluence of 5 × 10 12 ions/cm 2 was observed from that of pristine sample. The amorphous nature of the polymer was observed to be decreased with increase of ion fluence. The vibrations of C C appeared at mid fluences but the stretching vibrations of O H bond disappeared at these fluences due to the high LET of the oxygen ions.

The Ra&scaron, a Bay (North Adriatic, Croatia) has been receiving various pollutants by inflowing streams laden with untreated municipal and coalmine effluents for decades. The locality was a regional center of coalmining (Ra&scaron, a coal), coal combustion, and metal processing industries for more than two centuries. As local soil and stream water were found to be contaminated with sulfur and potentially toxic trace elements (PTEs) as a consequence of weathering of Ra&scaron, a coal and its waste, some clean-up measures are highly required. Therefore, the aim of this study was to test the remediating potential of selected microorganisms and synthetic zeolites in the case of soil and coal-mine water, respectively, for the first time. By employing bacterial cultures of Ralstonia sp., we examined removal of sulfur and selected PTEs (As, Ba, Co, Cr, Cu, Ni, Pb, Rb, Se, Sr, U, V, and Zn) from soil. The removal of sulfur was up to 60%, arsenic up to 80%, while Se, Ba, and V up to 60%, and U up to 20%. By applying synthetic zeolites on water from the Ra&scaron, a coalmine and a local stream, the significant removal values were found for Sr (up to 99.9%) and Ba (up to 99.2%) only. Removal values were quite irregular (insignificant) in the cases of Fe, Ni, Zn, and Se, which were up to 80%, 50%, 30%, and 20%, respectively. Although promising, the results call for further research on this topic.

Over the past decades, a multitude of experimental drugs have been shown to delay disease progression in preclinical animal models of amyotrophic lateral sclerosis (ALS) but failed to show efficacy in human clinical trials or are still waiting for approval under Phase I-III trials. Riluzole, a glutamatergic neurotransmission inhibitor, is the only drug approved by the USA Food and Drug Administration for ALS treatment with modest benefits on survival. Recently, an antioxidant drug, edaravone, developed by Mitsubishi Tanabe Pharma was found to be effective in halting ALS progression during early stages. The newly approved drug edaravone is a force multiplier for ALS treatment. This short report provides an overview of the two drugs that have been approved for ALS treatment and highlights an update on the timeline of drug development, how clinical trials were done, the outcome of these trials, primary endpoint, mechanism of actions, dosing information, administration, side effects, and storage procedures. Moreover, we also discussed the pressing issues and challenges of ALS clinical trials and drug developments as well as future outlook.

Capturing the full potential of human pluripotent stem cell (PSC)-derived neurons in disease modeling and regenerative medicine requires analysis in complex functional systems. Here we establish optogenetic control in human PSC-derived spinal motorneurons and show that co-culture of these cells with human myoblast-derived skeletal muscle builds a functional all-human neuromuscular junction that can be triggered to twitch upon light stimulation. To model neuromuscular disease we incubated these co-cultures with IgG from myasthenia gravis patients and active complement. Myasthenia gravis is an autoimmune disorder that selectively targets neuromuscular junctions. We saw a reversible reduction in the amplitude of muscle contractions, representing a surrogate marker for the characteristic loss of muscle strength seen in this disease. The ability to recapitulate key aspects of disease pathology and its symptomatic treatment suggests that this neuromuscular junction assay has significant potential for modeling of neuromuscular disease and regeneration.

Crystalline thin films of cobalt doped SnO2 undergoes modification by dense electronic excitation induced by Swift Heavy Ion (SHI) irradiation using 100 MeV Au8+ ion beam. Atomic Force Microscopy (AFM) and Power Spectral Density (PSD) analysis shows that the surface modification is dominated by diffusion of surface adatoms. Modification in surface features viz. grain size, rms roughness and roughness exponent can be controlled with homogeneity in surface features due to dense electronic excitation as observed from AFM-PSD and MFM analysis. X-ray diffraction results shows formation of new crystalline phase due to dense electronic excitation. The variation in strain along (101) and (110) crystal plane are nearly equal at irradiation fluence of 5 × 1012 ions/cm2 as calculated using X-ray diffraction results. UV–Visible studies shows formation of local energy states within the optical band gap region due to modification in electronic state of the system. The significant variation in Urbach's energy at irradiation fluence of 5 × 1012 ions/cm2 was observed. Transition in magnetic property after critical irradiation fluence of 5 × 1012 ions/cm2 with high coercivity and lowest saturated magnetization is observed. Resonance RBS studies shows Impurity free phase formation and amorphization causes reduction in density of the target due to amorphization. Very small modification in room temperature electrical conductivity was observed. Overall results shows that the modification in impurity free phase occurred by 100 MeV Au8+ ion irradiation in cobalt doped SnO2 thin films is tough to achieve by other techniques.

The derivation of somatic motoneurons (MNs) from ES cells (ESCs) after exposure to sonic hedgehog (SHH) and retinoic acid (RA) is one of the best defined, directed differentiation strategies to specify fate in pluripotent lineages. In mouse ESCs, MN yield is particularly high after RA + SHH treatment, whereas human ESC (hESC) protocols have been generally less efficient. In an effort to optimize yield, we observe that functional MNs can be derived from hESCs at high efficiencies if treated with patterning molecules at very early differentiation steps before neural induction. Remarkably, under these conditions, equal numbers of human MNs were obtained in the presence or absence of SHH exposure. Using pharmacological and genetic strategies, we demonstrate that early RA treatment directs MN differentiation independently of extrinsic SHH activation by suppressing the induction of GLI3. We further demonstrate that neural induction triggers a switch from a poised to an active chromatin state at GLI3. Early RA treatment prevents this switch by direct binding of the RA receptor at the GLI3 promoter. Furthermore, GLI3 knock-out hESCs can bypass the requirement for early RA patterning to yield MNs efficiently. Our data demonstrate that RA-mediated suppression of GLI3 is sufficient to generate MNs in an SHH-independent manner and that temporal changes in exposure to patterning factors such as RA affect chromatin state and competency of hESC-derived lineages to adopt specific neuronal fates. Finally, our work presents a streamlined platform for the highly efficient derivation of human MNs from ESCs and induced pluripotent stem cells. SIGNIFICANCE STATEMENT Our study presents a rapid and efficient protocol to generate human motoneurons from embryonic and induced pluripotent stem cells. Surprisingly, and in contrast to previous work, motoneurons are generated in the presence of retinoic acid but in the absence of factors that activate sonic hedgehog signaling. We show that early exposure to retinoic acid modulates the chromatin state of cells to be permissive for motoneuron generation and directly suppresses the induction of GLI3, a negative regulator of SHH signaling. Therefore, our data point to a novel mechanism by which retinoic acid exposure can bypass the requirement for extrinsic SHH treatment during motoneuron induction.

Nanocomposite thin films of TiO2 doped SnO2 were grown on silicon and quartz matrices by electron beam evaporation deposition technique using sintered nanocomposite pellet of SnO2/TiO2 taken in the mass percentage ratio of 90:10. The deposition was done in high vacuum (~10−6 mbar) condition. 100 MeV Au8+ Swift Heavy Ion (SHI) beam were used at Inter University Accelerator Center, New Delhi, India for dense electronic excitation in these nanocomposite thin films. The SHI irradiation fluencies were varied from 1 × 1011 ions/cm2 to 5 × 1013 ions/cm2. Surface morphology studies and grain growth due to swift heavy ion irradiation induced dense electronic excitation at different ion fluencies characterized by Atomic Force Microscopy–Magnetic Force Microscopy (AFM–MFM) technique using Nanoscope – IIIA shows magnetic nature of grains. Sectional analysis of AFM images shows dependence of grain size on irradiation fluence. Grain size varies between 15 nm and 100 nm at different irradiation ion fluencies. The variation in roughness exponent as calculated from power spectral density data and RMS roughness with respect to irradiation fluence are similar in nature. Amorphous to crystalline phase transformation occurs due to SHI irradiation. The SnO2 dominated crystalline planes observed at irradiation fluence of 1 × 1013 ions/cm2 and 5 × 1013 ions/cm2 were (0 2 0), (0 2 1), (1 2 4) and (2 0 4). Literature survey suggests these planes were not achieved by thermal annealing as observed from GAXRD data. At low irradiation fluencies up to 5 × 1012 ions/cm2 the variation in optical band gap (∼3.7 eV) was negligible as studied by UV–Visible Spectroscopy. Rutherford Backscattering (RBS) results supports transformation from lower crystalline to higher crystalline state due to absence of any impurities in the samples by 100 MeV Au8+ SHI irradiation and reduction in RBS yield for Sn and O at highest fluence of 5 × 1013 ions/cm2.

Thin films of tin(IV) oxide (SnO 2 ) of 100 nm thickness were grown on silicon (1 0 0) matrices by electron beam evaporation deposition technique under high vacuum. The thicknesses of these films were monitored by piezo-sensor attached to the deposition chamber. Nanocrystallinity is achieved in these thin films by 100 MeV Au 8+ using 1 pnA current at normal incidence with ion fluences varying from 1 × 10 11 ions/cm 2 to 5 × 10 13 ions/cm 2 . Swift Heavy Ion beam irradiation was carried out by using 15 UD Pelletron Accelerator at IUAC, New Delhi, India. Optical studies of pristine and ion irradiated thin films were characterized by UV–Visible spectroscopy and Fourier Transform Infrared (FTIR) spectroscopy. Prominent peak at 610 cm −1 in FTIR spectrum confirmed the O–Sn–O bonding of tin(IV) oxide. For Surface topographical studies and grain size calculations, these films were characterized by Atomic Force Microscope (AFM) using Nanoscope III-A. Crystallinity and phase transformation due to irradiation of pristine and irradiated films were characterized by Glancing Angle X-ray Diffraction (GAXRD) using Brucker-D8 advance model. GAXRD results show improvement in crystallinity and phase transformation due to swift heavy ion irradiation. Grain size distribution was verified by AFM and GAXRD results. Swift heavy ion induced modifications in thin films of SnO 2 were confirmed by the presence of prominent peaks at 2 θ values of 30.65°, 32.045°, 43.94°, 44.96° and 52.36° in GAXRD spectrum.

Nanocomposite thin films of tin oxide (SnO 2 )/titanium oxide (TiO 2 ) were grown on silicon (1 0 0) substrates by electron beam evaporation deposition technique using sintered nanocomposite pellet of SnO 2 /TiO 2 in the percentage ratio of 95:5. Sintering of the nanocomposite pellet was done at 1300 °C for 24 h. The thicknesses of these films were measured to be 100 nm during deposition using piezo-sensor attached to the deposition chamber. TiO 2 doped SnO 2 nanocomposite films were irradiated by 100 MeV Au 8+ ion beam at fluence range varying from 1 × 10 11 ions/cm 2 to 5 × 10 13 ions/cm 2 at Inter University Accelerator Center (IUAC), New Delhi, India. Chemical properties of pristine and ion irradiation modified thin films were characterized by Fourier Transform Infrared (FTIR) spectroscopy. FTIR peak at 610 cm −1 confirms the presence of O–Sn–O bridge of tin (IV) oxide signifying the composite nature of pristine and irradiated thin films. Atomic Force Microscope (AFM) in tapping mode was used to study the surface morphology and grain growth due to swift heavy ion irradiation at different fluencies. Grain size calculations obtained from sectional analysis of AFM images were compared with results obtained from Glancing Angle X-ray Diffraction (GAXRD) measurements using Scherrer’s formulae. Phase transformation due to irradiation was observed from Glancing Angle X-ray Diffraction (GAXRD) results. The prominent 2 θ peaks observed in GAXRD spectrum are at 30.67°, 32.08°, 43.91°, 44.91° and 52.35° in the irradiated films.

Sexual stages of Plasmodium such as zygote, ookinete, and young oocysts express 25 kDa surface protein P25, which along with P28 proteins protect the parasite from harmful environment inside mosquito midgut. Vaccines against these proteins induce antibodies in vertebrate host capable to inhibit parasite development in mosquito midgut and thus preventing the transmission of parasite from mosquito to other human host. Transmission-blocking vaccines help reduce malaria burden. The purpose of this study was in silico structural characterization of P25 family proteins and to predict their phylogenetic relationships with other proteins. Results indicate that members of P25 family have four EGF domains arranged in triangular fashion with major variations lying in the loop regions. All 22 cysteines are conserved forming 11 disulphide bonds. The C-loop of EGF domain IV in P25 proteins is smaller in comparison to P28 proteins. B loop of EGF domain II showed maximum RMSD variations followed by loops of EGF domain III. P25 proteins are tile-like triangular flat proteins that protect the parasite inside mosquito midgut. Obtained structures will help in understanding the biology of the parasite inside the mosquito midgut. These structures may also help in designing transmission-blocking vaccine against malaria in absence of experimentally determined structures.

Selective motoneurons (MNs) degeneration in the brain stem, hypoglossal motoneurons (HMNs), and the spinal cord resulting in patients paralysis and eventual death are prominent features of amyotrophic lateral sclerosis (ALS). Previous studies have suggested that mitochondrial respiratory impairment, low Ca2+ buffering and homeostasis and excitotoxicity are the pathological phenotypes found in mice, and cell culture models of familial ALS (fALS) linked with Cu/Zn-superoxide dismutase 1 (SOD1) mutation. In our study, we aimed to understand the impact of riluzole and melatonin on excitotoxicity, neuronal protection and Ca2+ signaling in individual HMNs ex vivo in symptomatic adult ALS mouse brain stem slice preparations and in WT and SOD1-G93A transfected SH-SY5Y neuroblastoma cell line using fluorescence microscopy, calcium imaging with high speed charged coupled device camera, together with immunohistochemistry, cell survival assay and histology. In our experiments, riluzole but not melatonin ameliorates MNs degeneration and moderately inhibit excitotoxicity and cell death in SH-SY5YWT or SH-SY5YG93A cell lines induced by complex IV blocker sodium azide. In brain stem slice preparations, riluzole significantly inhibit HMNs cell death induced by inhibiting the mitochondrial electron transport chain by Na-azide. In the HMNs of brainstem slice prepared from adult (14-15 weeks) WT, and corresponding symptomatic SOD1G93A mice, we measured the effect of riluzole and melatonin on [Ca2+]i using fura-2 AM ratiometric calcium imaging in individual MNs. Riluzole caused a significant decrease in [Ca2+]i transients and reversibly inhibited [Ca2+]i transients in Fura-2 AM loaded HMNs exposed to Na-azide in adult symptomatic SOD1G93A mice. On the contrary, melatonin failed to show similar effects in the HMNs of WT and SOD1G93A mice. Intrinsic nicotinamide adenine dinucleotide (NADH) fluorescence, an indicator of mitochondrial metabolism and health in MNs, showed enhanced intrinsic NADH fluorescence in HMNs in presence of riluzole when respiratory chain activity was inhibited by Na-azide. Riluzole's inhibition of excitability and Ca2+ signaling may be due to its multiple effects on cellular function of mitochondria. Therefore formulating a drug therapy to stabilize mitochondria-related signaling pathways using riluzole might be a valuable approach for cell death protection in ALS. Taken together, the pharmacological profiles of the riluzole and melatonin strengthen the case that riluzole indeed can be used as a therapeutic agent in ALS whereas claims of the efficacy of melatonin alone need further investigation as it fail to show significant neuroprotection efficacy. peerReviewed

Background Vascular depression is regarded as a subtype of late-life depression characterized by a distinct clinical presentation and an association with cerebrovascular damage. Although the term is commonly used in research settings, widely accepted diagnostic criteria are lacking and vascular depression is absent from formal psychiatric manuals such as the Diagnostic and Statistical Manual of Mental Disorders, 5th edition – a fact that limits its use in clinical settings. Magnetic resonance imaging (MRI) techniques, showing a variety of cerebrovascular lesions, including extensive white matter hyperintensities, subcortical microvascular lesions, lacunes, and microinfarcts, in patients with late life depression, led to the introduction of the term “MRI-defined vascular depression”. Discussion This diagnosis, based on clinical and MRI findings, suggests that vascular lesions lead to depression by disruption of frontal–subcortical–limbic networks involved in mood regulation. However, despite multiple MRI approaches to shed light on the spatiotemporal structural changes associated with late life depression, the causal relationship between brain changes, related lesions, and late life depression remains controversial. While postmortem studies of elderly persons who died from suicide revealed lacunes, small vessel, and Alzheimer-related pathologies, recent autopsy data challenged the role of these lesions in the pathogenesis of vascular depression. Current data propose that the vascular depression connotation should be reserved for depressed older patients with vascular pathology and evident cerebral involvement. Based on current knowledge, the correlations between intra vitam neuroimaging findings and their postmortem validity as well as the role of peripheral markers of vascular disease in late life depression are discussed. Conclusion The multifold pathogenesis of vascular depression as a possible subtype of late life depression needs further elucidation. There is a need for correlative clinical, intra vitam structural and functional MRI as well as postmortem MRI and neuropathological studies in order to confirm the relationship between clinical symptomatology and changes in specific brain regions related to depression. To elucidate the causal relationship between regional vascular brain changes and vascular depression, animal models could be helpful. Current treatment options include a combination of vasoactive drugs and antidepressants, but the outcomes are still unsatisfying.

Citation: Paine A and Jaiswal MK (2016) Promise and Pitfalls of Mitochondrial Replacement for Prevention and Cure of Heritable Neurodegenerative Diseases Caused by Deleterious Mutations in Mitochondrial DNA. Front. Cell. Neurosci. 10:219. doi: 10.3389/fncel.2016.00219 Promise and Pitfalls of Mitochondrial Replacement for Prevention and Cure of Heritable Neurodegenerative Diseases Caused by Deleterious Mutations in Mitochondrial DNA

Monodisperse tin oxide nanocrystalline thin films are grown on silicon substrates by electron beam evaporation method followed by 100 MeV silver ion bombardment with varying ion fluence from 5 × 10 11 ions cm −2 to 1 × 10 13 ions cm −2 at constant ion flux. Enhancement of crystallinity of thin films with fluence is observed from glancing angle X-ray diffraction studies. Morphological studies by atomic force microscopy reveal the changes in grain size from 25 nm to 44 nm with variation in ion fluence. The effect of initial surface roughness and adatom mobility on topography is reported. In this work correlation between ion beam induced defect concentration with topography and grain size distribution is emphasized.

In this paper, we used Recurrence Quantification Analysis (RQA) in order to study pre-epileptic characteristics in rat's EEG recordings. Four adult rats were used to collect epileptic EEG data in an experiment of animal model of epilepsy. Three RQA measures, recurrence rate, determinism, and entropy were calculated from EEG recordings from rats. A moving average filter was used to identify the decreasing trend in pre-epileptic dynamics which will be useful early detection of seizures.

Tungsten-alloy has carcinogenic potential as demonstrated by cancer development in rats with intramuscular implanted tungsten-alloy pellets. This suggests a potential involvement of epigenetic events previously implicated as environmental triggers of cancer. Here, we tested metal induced cytotoxicity and epigenetic modifications including H3 acetylation, H3-Ser10 phosphorylation and H3-K4 trimethylation. We exposed human embryonic kidney (HEK293), human neuroepithelioma (SKNMC), and mouse myoblast (C2C12) cultures for 1-day and hippocampal primary neuronal cultures for 1-week to 50–200 μg/ml of tungsten-alloy (91% tungsten/6% nickel/3% cobalt), tungsten, nickel, and cobalt. We also examined the potential role of intracellular calcium in metal mediated histone modifications by addition of calcium channel blockers/chelators to the metal solutions. Tungsten and its alloy showed cytotoxicity at concentrations > 50 μg/ml, while we found significant toxicity with cobalt and nickel for most tested concentrations. Diverse cell-specific toxic effects were observed, with C2C12 being relatively resistant to tungsten-alloy mediated toxic impact. Tungsten-alloy, but not tungsten, caused almost complete dephosphorylation of H3-Ser10 in C2C12 and hippocampal primary neuronal cultures with H3-hypoacetylation in C2C12. Dramatic H3-Ser10 dephosphorylation was found in all cobalt treated cultures with a decrease in H3 pan-acetylation in C2C12, SKNMC and HEK293. Trimethylation of H3-K4 was not affected. Both tungsten-alloy and cobalt mediated H3-Ser10 dephosphorylation were reversed with BAPTA-AM, highlighting the role of intracellular calcium, confirmed with 2-photon calcium imaging. In summary, our results for the first time reveal epigenetic modifications triggered by tungsten-alloy exposure in C2C12 and hippocampal primary neuronal cultures suggesting the underlying synergistic effects of tungsten, nickel and cobalt mediated by changes in intracellular calcium homeostasis and buffering.

Although the detailed mechanism of spontaneous generation and regulation of rapid eye movement sleep (REMS) is yet unknown, it has been reported that noradrenergic REM-OFF neurons in the locus coeruleus (LC) cease firing during REMS and, if they are kept active, REMS is significantly reduced. On the other hand, the activity as well as expression of Na-K ATPase has been shown to increase in the LC following REMS deprivation. Ouabain is a specific inhibitor of Na-K ATPase, and endogenous ouabain-like compounds are present in the brain. These findings led us to propose that a decrease in the level of ouabain-like compounds spontaneously available in and around the LC would stimulate and increase the REM-OFF neuronal activities in this region and thus would reduce REMS. To test this hypothesis, we generated anti-ouabain antibodies and then microinjected it bilaterally into the LC in freely moving chronically prepared rats and recorded electrophysiological signals for evaluation of sleep-wakefulness states; suitable control experiments were also conducted. Injection of anti-ouabain antibodies into the LC, but not into adjacent brain areas, significantly reduced percent REMS (mean +/- SEM) from 7.12 (+/-0.74) to 3.63 (+/-0.65). The decrease in REMS was due to reduction in the mean frequency of REMS episode, which is likely due to increased excitation of the LC REM-OFF neurons. Control microinjections of normal IgG did not elicit this effect. These results support our hypothesis that interactions of naturally available endogenous ouabain-like compounds with the Na-K ATPase in the LC modulate spontaneous REMS.

Prolonged rapid eye movement sleep deprivation (REMSD) causes hypothermia and death; however, the effect of deprivation within 24 h and its mechanism(s) of action were unknown. Based on existing reports we argued that REMSD should, at least initially, induce hyperthermia and the death upon prolonged deprivation could be due to persistent hypothermia. We proposed that noradrenaline (NA), which modulates body temperature and is increased upon REMSD, may be involved in REMSD- associated body temperature changes. Adult male Wistar rats were REM sleep deprived for 6-9 days by the classical flower pot method; suitable free moving, large platform and recovery controls were carried out. The rectal temperature (Trec) was recorded every minute for 1 h, or once daily, or before and after i.p. injection of prazosin, an alpha-1 adrenergic antagonist. The Trec was indeed elevated within 24 h of REMSD which decreased steadily, despite continuation of deprivation. Prazosin injection into the deprived rats reduced the Trec within 30 min, and the duration of effect was comparable to its pharmacological half life. The findings have been explained on the basis of REMSD-induced elevated NA level, which has opposite actions on the peripheral and the central nervous systems. We propose that REMSD-associated immediate increase in Trec is due to increased Na-K ATPase as well as metabolic activities and peripheral vasoconstriction. However, upon prolonged deprivation, probably the persistent effect of NA on the central thermoregulatory sites induced sustained hypothermia, which if remained uncontrolled, results in death. Thus, our findings suggest that peripheral prazosin injection in REMSD would not bring the body temperature to normal, rather might become counterproductive.

Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons (MN) in the brain stem and spinal cord. Intracellular disruptions of cytosolic and mitochondrial calcium have been associated with selective MN degeneration, but the underlying mechanisms are not well understood. The present evidence supports a hypothesis that mitochondria are a target of mutant SOD1-mediated toxicity in familial amyotrophic lateral sclerosis (fALS) and intracellular alterations of cytosolic and mitochondrial calcium might aggravate the course of this neurodegenerative disease. In this study, we used a fluorescence charged cool device (CCD) imaging system to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells in an established cellular model of ALS. Results To gain insights into the molecular mechanisms of SOD1G93A associated motor neuron disease, we simultaneously monitored cytosolic and mitochondrial calcium concentrations in individual cells. Voltage – dependent cytosolic Ca2+ elevations and mitochondria – controlled calcium release mechanisms were monitored after loading cells with fluorescent dyes fura-2 and rhod-2. Interestingly, comparable voltage-dependent cytosolic Ca2+ elevations in WT (SH-SY5YWT) and G93A (SH-SY5YG93A) expressing cells were observed. In contrast, mitochondrial intracellular Ca2+ release responses evoked by bath application of the mitochondrial toxin FCCP were significantly smaller in G93A expressing cells, suggesting impaired calcium stores. Pharmacological experiments further supported the concept that the presence of G93A severely disrupts mitochondrial Ca2+ regulation. Conclusion In this study, by fluorescence measurement of cytosolic calcium and using simultaneous [Ca2+]i and [Ca2+]mito measurements, we are able to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells an established cellular model of ALS. The primary goals of this paper are (1) method development, and (2) screening for deficits in mutant cells on the single cell level. On the technological level, our method promises to serve as a valuable tool to identify mitochondrial and Ca2+-related defects during G93A-mediated MN degeneration. In addition, our experiments support a model where a specialized interplay between cytosolic calcium profiles and mitochondrial mechanisms contribute to the selective degeneration of neurons in ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of defined motoneuron populations in the brainstem and spinal cord. Although low cytosolic calcium ([Ca(2+)](i)) buffering and a strong interaction between metabolic mechanisms and [Ca(2+)](i) have been associated with selective motoneuron vulnerability, the underlying cellular mechanisms are barely understood. To elucidate the underlying molecular events, we used rapid charge-cooled device imaging to evaluate Ca(2+) signaling and metabolic signatures in the brainstem slices of SOD1(G93A) mice, the mouse model of human ALS, at 8 to 9 and 14 to 15 weeks of age, corresponding to the presymptomatic and symptomatic stages of motor dysfunction, respectively, and compared the results with corresponding age-matched wild-type littermates. We also monitored the mitochondrial membrane potential (Delta(Psim)) of brainstem motoneurons, a valuable tool for characterizing the metabolic signature of intrinsic energy profiles and considered to be a good experimental measure for monitoring energy metabolism in cells. We found that different pharmacological interventions substantially disrupt Delta(Psim) in SOD1(G93A) motoneurons during the symptomatic stage. Furthermore, we investigated the impact of impaired mitochondrial mechanisms on [Ca(2+)](i) regulation by using the membrane-permeable indicator fura-acetoxy methyl ester. Taken together, the results indicate that mitochondrial disruptions are critical elements of SOD1(G93A)-mediated motoneuron degeneration in which selective motoneuron vulnerability results from a synergistic accumulation of risk factors, including the disruption of electrochemical potential, low Ca(2+) buffering, and strong mitochondrial control of [Ca(2+)](i). The stabilization of mitochondria-related signal cascades may represent a useful strategy for clinical neuroprotection in ALS.

BackgroundInfections can aggravate the course of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Mutations in the anti-oxidant enzyme Cu,Zn superoxide dismutase (EC 1.15.1.1, SOD1) are associated with familial ALS. Streptococcus pneumoniae, the most frequent respiratory pathogen, causes damage by the action of the cholesterol-binding virulence factor pneumolysin and by stimulation of the innate immune system, particularly via Toll-like-receptor 2.MethodsSH-SY5Y neuroblastoma cells transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) and SH-SY5Y neuroblastoma cells transfected with wildtype SOD1 were both exposed to pneumolysin and in co-cultures with cultured human macrophages treated with the Toll like receptor 2 agonist N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-cysteinyl-[S]-seryl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysine × 3 HCl (Pam3CSK4). Cell viability and apoptotic cell death were compared morphologically and by in-situ tailing. With the help of the WST-1 test, cell viability was quantified, and by measurement of neuron-specific enolase in the culture supernatant neuronal damage in co-cultures was investigated. Intracellular calcium levels were measured by fluorescence analysis using fura-2 AM.ResultsSH-SY5Y neuroblastoma cells transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) were more vulnerable to the neurotoxic action of pneumolysin and to the attack of monocytes stimulated by Pam3CSK4than SH-SY5Y cells transfected with wild-type human SOD1. The enhanced pneumolysin toxicity in G93A-SOD1 neuronal cells depended on the inability of these cells to cope with an increased calcium influx caused by pores formed by pneumolysin. This inability was caused by an impaired capacity of the mitochondria to remove cytoplasmic calcium. Treatment of G93A-SOD1 SH-SY5Y neuroblastoma cells with the antioxidant N-acetylcysteine reduced the toxicity of pneumolysin.ConclusionThe particular vulnerability of G93A-SOD1 neuronal cells to hemolysins and inflammation may be partly responsible for the clinical deterioration of ALS patients during infections. These findings link infection and motor neuron disease and suggest early treatment of respiratory infections in ALS patients.