1,214 research outputs found

    Author Correction: The CaMKII/NMDA receptor complex controls hippocampal synaptic transmission by kinase-dependent and independent mechanisms.

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    The originally published version of this Article contained errors in Figure 5, for which we apologise. In panel c, the scatter graph was inadvertently replaced with a scatter graph comprising a subset of data points from panel d. Furthermore, the legends to Figures 5c and 5d were inverted. These errors have now been corrected in both the PDF and HTML versions of the Article, and the incorrect version of Fig. 5c is presented in the Author Correction associated with this Article

    The CaMKII/NMDA receptor complex controls hippocampal synaptic transmission by kinase-dependent and independent mechanisms.

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    CaMKII is one of the most studied synaptic proteins, but many critical issues regarding its role in synaptic function remain unresolved. Using a CRISPR-based system to delete CaMKII and replace it with mutated forms in single neurons, we have rigorously addressed its various synaptic roles. In brief, basal AMPAR and NMDAR synaptic transmission both require CaMKIIα, but not CaMKIIβ, indicating that, even in the adult, synaptic transmission is determined by the ongoing action of CaMKIIα. While AMPAR transmission requires kinase activity, NMDAR transmission does not, implying a scaffolding role for the CaMKII protein instead. LTP is abolished in the absence of CaMKIIα and/or CaMKIIβ and with an autophosphorylation impaired CaMKIIα (T286A). With the exception of NMDAR synaptic currents, all aspects of CaMKIIα signaling examined require binding to the NMDAR, emphasizing the essential role of this receptor as a master synaptic signaling hub

    Diagnostic Application of IS900 PCR Using Blood as a Source Sample for the Detection of Mycobacterium avium Subspecies Paratuberculosis in Early and Subclinical Cases of Caprine Paratuberculosis

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    Efficacy of IS900 blood PCR was evaluated for the presence of MAP infection. Serum, fecal, and blood samples of kids, young, and adult goats from farm and farmer's herds in Mathura district were also screened by ELISA, microscopy and culture. Of 111 goats (kids: 40, young: 14, adults: 57) screened, 77.5% were positive by blood PCR. Of 76 goats, 90.8% (kids: 87.5% and adults: 94.4%) were positive by PCR. From 21 kids and 14 young goats, 42.8 and 57.1% were positive. gDNA from goats was genotyped as MAP “Indian Bison type”. Of 21 fecal samples of kids examined by microscopy, 66.7% were positive. In ELISA, 9.5 and 57.1% kids were positives as “type I” and “type II” reactors, respectively. Screening 14 young goats by culture of blood clots, 28.6% were positive. Agreement was substantial between PCR and microscopy. It was fair and moderate when PCR and microscopy were compared with type I and type II reactors, respectively. Presence of MAP in non-clinical kids and young goats indicate early or subclinical infection. Blood PCR was rapid, sensitive, and specific assay for detection of MAP in any stage (early, subclinical, and clinical) and age (kids, young, and adult) of goats

    A mouse model of autism implicates endosome pH in the regulation of presynaptic calcium entry.

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    Psychoactive compounds such as chloroquine and amphetamine act by dissipating the pH gradient across intracellular membranes, but the physiological mechanisms that normally regulate organelle pH remain poorly understood. Interestingly, recent human genetic studies have implicated the endosomal Na+/H+ exchanger NHE9 in both autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD). Plasma membrane NHEs regulate cytosolic pH, but the role of intracellular isoforms has remained unclear. We now find that inactivation of NHE9 in mice reproduces behavioral features of ASD including impaired social interaction, repetitive behaviors, and altered sensory processing. Physiological characterization reveals hyperacidic endosomes, a cell-autonomous defect in glutamate receptor expression and impaired neurotransmitter release due to a defect in presynaptic Ca2+ entry. Acute inhibition of synaptic vesicle acidification rescues release but without affecting the primary defect due to loss of NHE9

    Therapeutic Effects of a New “Indigenous Vaccine” Developed Using Novel Native “Indian Bison Type” Genotype of Mycobacterium avium Subspecies paratuberculosis for the Control of Clinical Johne's Disease in Naturally Infected Goatherds in India

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    Therapeutic efficacy of an “Indigenous vaccine” has been evaluated with respect to a commercial vaccine (Gudair, Spain), for the control of clinical Johne's disease (JD) in naturally infected goatherds. Seventy-one goats (JD positive) were randomly divided into 3 groups (“Bison”, “Gudair” and “Sham-immunized”). After vaccination, goats were monitored for physical condition, morbidity, mortality, body weights, shedding of M. paratuberculosis (MAP) in feces, internal condition and lesions, as well as humoral and cell-mediated immune responses for 210 days. Study showed marked overall improvement in physical condition of vaccinated goats and average body weight gain was significantly higher (P < .05) in “Bison” group as compared to “Sham-immunized” goats. Mortality due to JD was significantly (P < .05) lower in vaccinated groups than in “sham-immunized”. Morbidity rates (due to diarrhea and weakness) were lower in “Bison” group as compared to other groups. Died goats from vaccinated groups showed regression of gross JD lesions and regeneration of fat layer around visceral organs while “Sham-immunized” goats exhibited frank lesions. Vaccinated goats had higher protective CMI response and also higher antibody titer for the trial period as compared to “Sham immunized”. Both vaccines also reduced shedding of MAP in feces significantly (P < .05). Though the two vaccines effectively restricted the severity of clinical symptoms of JD, however “Indigenous vaccine” was superior in many respects

    Degradation Issues in Solid Oxide Cells During High Temperature Electrolysis

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    Idaho National Laboratory (INL) is performing high-temperature electrolysis (HTE) research to generate hydrogen using solid oxide electrolysis cells (SOECs). The project goals are to address the technical and degradation issues associated with the SOECs. This paper provides a summary of ongoing INL and INL-sponsored activities aimed at addressing SOEC degradation. These activities include stack testing, post-test examination, degradation modeling, and issues that need to be addressed in the future. Major degradation issues relating to solid oxide fuel cells (SOFC) are relatively better understood than those for SOECs. Some of the degradation mechanisms in SOFCs include contact problems between adjacent cell components, microstructural deterioration (coarsening) of the porous electrodes, and blocking of the reaction sites within the electrodes. Contact problems include delamination of an electrode from the electrolyte, growth of a poorly (electronically) conducting oxide layer between the metallic interconnect plates and the electrodes, and lack of contact between the interconnect and the electrode. INL's test results on HTE using solid oxide cells do not provide clear evidence as to whether different events lead to similar or drastically different electrochemical degradation mechanisms. Post-test examination of the SOECs showed that the hydrogen electrode and interconnect get partially oxidized and become nonconductive. This is most likely caused by the hydrogen stream composition and flow rate during cooldown. The oxygen electrode side of the stacks seemed to be responsible for the observed degradation because of large areas of electrode delamination. Based on the oxygen electrode appearance, the degradation of these stacks was largely controlled by the oxygen electrode delamination rate. Virkar et al. [19-22] have developed a SOEC model based on concepts in local thermodynamic equilibrium in systems otherwise in global thermodynamic nonequilibrium. This model is under continued development. It shows that electronic conduction through the electrolyte, however small, must be taken into account for determining local oxygen chemical potential within the electrolyte. The chemical potential within the electrolyte may lie out of bounds in relation to values at the electrodes in the electrolyzer mode. Under certain conditions, high pressures can develop in the electrolyte just under the oxygen electrode (anode)/electrolyte interface, leading to electrode delamination. This theory is being further refined and tested by introducing some electronic conduction in the electrolyte.United States. Department of Energy. Office of Energy Efficiency and Renewable EnergyUnited States. Office of the Assistant Secretary for Nuclear Energ

    Impact of Maternal Air Pollution exposure on children's lung health: An Indian perspective

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    © 2018 by the authors. Air pollution has become an emerging invisible killer in recent years and is a major cause of morbidity and mortality globally. More than 90% of the world's children breathe toxic air every day. India is among the top ten most highly polluted countries with an average PM 10 level of 134 μg/m 3 per year. It is reported that 99% of India's population encounters air pollution levels that exceed the World Health Organization Air Quality Guideline, advising a PM 2.5 permissible level of 10 μg/m 3 . Maternal exposure to air pollution has serious health outcomes in offspring because it can affect embryonic phases of development during the gestation period. A fetus is more prone to effects from air pollution during embryonic developmental phases due to resulting oxidative stress as antioxidant mechanisms are lacking at that stage. Any injury during this vulnerable period (embryonic phase) will have a long-term impact on offspring health, both early and later in life. Epidemiological studies have revealed that maternal exposure to air pollution increases the risk of development of airway disease in the offspring due to impaired lung development in utero. In this review, we discuss cellular mechanisms involved in maternal exposure to air pollution and how it can impact airway disease development in offspring. A better understanding of these mechanisms in the context of maternal exposure to air pollution can offer a new avenue to prevent the development of airway disease in offspring
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