Phosphorylation of ATXN1 at Ser776 in the cerebellum

Spinocerebellar ataxia type 1 (SCA1) is one of nine inherited neurodegenerative disorders caused by a mutant protein with an expanded polyglutamine tract. Phosphorylation of ataxin-1 (ATXN1) at serine 776 is implicated in SCA1 pathogenesis. Previous studies, utilizing transfected cell lines and a Drosophila photoreceptor model of SCA1, suggest that phosphorylating ATXN1 at S776 renders it less susceptible to degradation. This work also indicated that oncogene from AKR mouse thymoma (Akt) promotes the phosphorylation of ATXN1 at S776 and severity of neurodegeneration. Here, we examined the phosphorylation of ATXN1 at S776 in cerebellar Purkinje cells, a prominent site of pathology in SCA1. We found that while phosphorylation of S776 is associated with a stabilization of ATXN1 in Purkinje cells, inhibition of Akt either in vivo or in a cerebellar extract-based phosphorylation assay did not decrease the phosphorylation of ATXN1-S776. In contrast, immunodepletion and inhibition of cyclic AMP-dependent protein kinase decreased phosphorylation of ATXN1-S776. These results argue against Akt as the in vivo kinase that phosphorylates S776 of ATXN1 and suggest that cyclic AMP-dependent protein kinase is the active ATXN1-S776 kinase in the cerebellum.     

Neurogenetics: advancing the "next-generation" of brain research

There can be little doubt that genetics has transformed our understanding of mechanisms mediating brain disorders. The last two decades have brought tremendous progress in terms of accurate molecular diagnoses and knowledge of the genes and pathways that are involved in a large number of neurological and psychiatric disorders. Likewise, new methods and analytical approaches, including genome array studies and "next-generation" sequencing technologies, are bringing us deeper insights into the subtle complexities of the genetic architecture that determines our risks for these disorders. As we now seek to translate these discoveries back to clinical applications, a major challenge for the field will be in bridging the gap between genes and biology. In this Overview of Neuron's special review issue on neurogenetics, we reflect on progress made over the last two decades and highlight the challenges as well as the exciting opportunities for the future.     

Investigation of thermoluminescence glow curves in quartz extracted from the Central Eastern Desert,Egypt

The current study investigated the thermoluminescence (TL) properties of milky quartz samples collected from the Central Eastern Desert, Egypt. The crystallinity and the elemental concentrations of the milky quartz samples were examined using X‐ray diffraction and an atomic absorption spectrometer. Samples were irradiated using a gamma source at different doses from 250 mGy up to 2 kGy. For annealing, the samples were heated at 400°C for 1 h, followed by slow cooling. Kinetic analyses for the TL glow curves were performed using new designed TL deconvolution software. The glow curves were composed of six overlapped trapping sites at 428, 468, 498, 545, 586, and 639 K. The samples also displayed a linear dose–response from 0.25 Gy up to 20 Gy and a supralinear response from 20 Gy up to 200 Gy. The samples exhibited very low sensitivity for gamma radiation compared with LiF and the minimum detectable dose was 545 μGy. From its linear nature, it was observed that the sensitivity had changed. This study recommends starting measurements of these milky quartz samples after 4 days to give established measurements.     

Roles of oxidative stress,apoptosis, and inflammation in metal-induced dysfunction of beta pancreatic cells isolated from CD1 mice

The diabetogenic effects of metals including lead (Pb), mercury (Hg), cadmium (Cd), and molybdenum (Mo) have been reported with poorly identified underlying mechanisms. The current study assessed the effect of metals on the roles of oxidative stress, apoptosis, and inflammation in beta pancreatic cells isolated from CD-1 mice, via different biochemical assays. Data showed that the tested metals were cytotoxic to the isolated cells with impaired glucose stimulated insulin secretion (GSIS). This was associated with increased reactive oxygen species (ROS) production, lipid peroxidation, antioxidant enzymes activities, active proapoptotic caspase-3 (cas-3), inflammatory cytokines interleukin–6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels in the intoxicated cells. Furthermore, antioxidant-reduced glutathione (GSH-R), cas-3 inhibitor z-VAD-FMK, IL-6 inhibitor bazedoxifene (BZ), and TNF-α inhibitor etanercept (ET) were found to significantly decrease metal-induced cytotoxicity with improved GSIS in metals’ intoxicated cells. In conclusion, oxidative stress, apoptosis, and inflammation can play roles in metals–induced diabetogenic effect.     

Reproductive Organ and Vascular Specific Promoter of the Rice Plasma Membrane Ca2+ATPase Mediates Environmental Stress Responses in Plants

Background

Plasma membrane Ca²⁺ATPase is a transport protein in the plasma membrane of cells and helps in removal of calcium (Ca²⁺) from the cell, hence regulating Ca²⁺ level within cells. Though plant Ca²⁺ATPases have been shown to be involved in plant stress responses but their promoter regions have not been well studied.

Results

The 1478 bp promoter sequence of rice plasma membrane Ca²⁺ATPase contains cis-acting elements responsive to stresses and plant hormones. To identify the functional region, serial deletions of the promoter were fused with the GUS sequence and four constructs were obtained. These were differentially activated under NaCl, PEG cold, methyl viologen, abscisic acid and methyl jasmonate treatments. We demonstrated that the rice plasma membrane Ca²⁺ATPase promoter is responsible for vascular-specific and multiple stress-inducible gene expression. Only full-length promoter showed specific GUS expression under stress conditions in floral parts. High GUS activity was observed in roots with all the promoter constructs. The −1478 to −886 bp flanking region responded well upon treatment with salt and drought. Only the full-length promoter presented cold-induced GUS expression in leaves, while in shoots slight expression was observed for −1210 and −886 bp flanking region. The −1210 bp deletion significantly responded to exogenous methyl viologen and abscisic acid induction. The −1210 and −886 bp flanking region resulted in increased GUS activity in leaves under methyl jasmonate treatments, whereas in shoots the −886 bp and −519 bp deletion gave higher expression. Salicylic acid failed to induce GUS activities in leaves for all the constructs.

Conclusions

The rice plasma membrane Ca²⁺ATPase promoter is a reproductive organ-specific as well as vascular-specific. This promoter contains drought, salt, cold, methyl viologen, abscisic acid and methyl jasmonate related cis-elements, which regulated gene expression. Overall, the tissue-specificity and inducible nature of this promoter could grant wide applicability in plant biotechnology.     

Mice Do Not Habituate to Metabolism Cage Housing–A Three Week Study of Male BALB/c Mice

The metabolism cage is a barren, non-enriched, environment, combining a number of recognized environmental stressors. We investigated the ability of male BALB/c mice to acclimatize to this form of housing. For three weeks markers of acute and oxidative stress, as well as clinical signs of abnormality were monitored. Forced swim tests were conducted to determine whether the animals experienced behavioral despair and the serotonergic integrity was tested using an 8-OH-DPAT challenge. The metabolism cage housed mice excreted approximately tenfold higher amounts of corticosterone metabolites in feces throughout the study when compared to controls. Urinary biomarkers confirmed that these mice suffered from elevated levels of oxidative stress, and increased creatinine excretions indicated increased muscle catabolism. Changes in the core body temperature (stress-induced hyperthermia) and the fur state of the mice also indicated impaired well-being in the metabolism cage housed mice. However, monitoring body weight and feed intake was found misleading in assessing the wellbeing of mice over a longer time course, and the forced swim test was found poorly suited for studying chronic stress in mice in the present setup. In conclusion, the mice were found not to acclimatize to the metabolism cages whereby concern for animal welfare would dictate that mice should be housed in this way for as short periods as possible. The elevated degree of HPA axis activity, oxidative stress, and increased overall metabolism warrant caution when interpreting data obtained from metabolism cage housed mice, as their condition cannot be considered representative of a normal physiology.     

Microbial-Activated Sediment Traps Associated with Oncolite Formation Along a Peritidal Beach,Northern Arabian (Persian) Gulf,Kuwait

Identification of microbial communities within shoreline sediments and sediment precipitates from the Tigris-Euphrates delta (northern Kuwait) were determined by microscopic/nanoscopic studies, and by molecular analysis. Oncolites are syn-diagenetic carbonate precipitates that are surviving in a shallow subtidal to intertidal siliciclastic environment with periodically excessive hydraulic energy, extreme salinity (up to 47 per mil), and high concentrations of organic matter. X-ray diffraction techniques reveal that oncolite cortices are predominantly composed of calcite, quartz, halite and dolomite, associated with minor fractions of clay minerals. Quantitative analysis of the Corey Shape Factor reveals distinct morphological populations but with local overlap. A plot of the Equivalent Diameter vs. Corey Shape Factor provided the best indicator of the morphological relationships within the total oncolite population, indicating a hydrodynamically controlled morphological distribution defining intertidal and subtidal oncolite classes. Direct microscopic examination of the samples indicates that diatoms are the most abundant eukaryotic algae in subtidal sediments and within actively precipitating carbonate cements, especially the genus Navicula. In contrast, filamentous cyanobacteria from the genus Anabaena are most abundant in the intertidal zone sediments. The PCR-DGGE of the 16SrRNA gene of the cyanobacteria shows a higher diversity for this genus of bacteria in all sediment samples and that the cyanobacterial population in the diagenetically precipitating oncolites are closely related to the population found in the subtidal sediments. Dunaliella viridis dominates the culturable algae obtained from the four tidal zones. Our results indicate that a range of microbial populations are actively contributing to the formation of microbially-induced sedimentary structures in the extreme conditions of the southern Tigris-Euphrates delta.     

Solving the autism puzzle a few pieces at a time

In this issue, a pair of studies (Levy et al. and Sanders et al.) identify several de novo copy-number variants that together account for 5%-8% of cases of simplex autism spectrum disorders. These studies suggest that several hundreds of loci are likely to contribute to the complex genetic heterogeneity of this group of disorders. An accompanying study in this issue (Gilman et al.), presents network analysis implicating these CNVs in neural processes related to synapse development, axon targeting, and neuron motility.     

Synthesis of a Nano-Silver Metal Ink for Use in Thick Conductive Film Fabrication Applied on a Semiconductor Package

The success of printing technology in the electronics industry primarily depends on the availability of metal printing ink. Various types of commercially available metal ink are widely used in different industries such as the solar cell, radio frequency identification (RFID) and light emitting diode (LED) industries, with limited usage in semiconductor packaging. The use of printed ink in semiconductor IC packaging is limited by several factors such as poor electrical performance and mechanical strength. Poor adhesion of the printed metal track to the epoxy molding compound is another critical factor that has caused a decline in interest in the application of printing technology to the semiconductor industry. In this study, two different groups of adhesion promoters, based on metal and polymer groups, were used to promote adhesion between the printed ink and the epoxy molding substrate. The experimental data show that silver ink with a metal oxide adhesion promoter adheres better than silver ink with a polymer adhesion promoter. This result can be explained by the hydroxyl bonding between the metal oxide promoter and the silane grouping agent on the epoxy substrate, which contributes a greater adhesion strength compared to the polymer adhesion promoter. Hypotheses of the physical and chemical functions of both adhesion promoters are described in detail.