Exploring the Interaction of Drosophila TDP-43 and the Type II Voltage-Gated Calcium Channel, Cacophony, in Regulating Motor Function and Behavior

Amyotrophic lateral sclerosis (ALS) is the most common adult onset motor neurodegenerative disease. The cause of the disease remains obscure, and as such there is no effective treatment or cure. Amyotrophic lateral sclerosis and other neurodegenerative diseases are frequently characterized by dysfunction of the RNA-binding protein, TDP-43. Using model systems to understand the mechanisms underlying TDP-43 dysfunction should accelerate identification of therapeutic targets. A recent report has shown that motor defects caused by the deletion of the Drosophila TDP-43 ortholog, tbph, are not driven by changes in the physiology at the neuromuscular junction. Rather, defective motor burst rhythmicity and coordination, displayed by tbph mutants, are rescued by genetically restoring a voltage-gated calcium channel to either motor neurons or just a single pair of neurons in the brain. If these effects are mirrored in human TDP-43 proteinopathies, these observations could open new avenues to investigate alternative therapeutic targets for these neurodegenerative diseases

Rubidium in the Interstellar Medium

We present observations of interstellar rubidium toward o Per, zeta Per, AE Aur, HD 147889, chi Oph, zeta Oph, and 20 Aql. Theory suggests that stable 85Rb and long-lived 87Rb are produced predominantly by high-mass stars, through a combination of the weak s- and r-processes. The 85Rb/87Rb ratio was determined from measurements of the Rb I line at 7800 angstroms and was compared to the solar system meteoritic ratio of 2.59. Within 1-sigma uncertainties all directions except HD 147889 have Rb isotope ratios consistent with the solar system value. The ratio toward HD 147889 is much lower than the meteoritic value and similar to that toward rho Oph A (Federman et al. 2004); both lines of sight probe the Rho Ophiuchus Molecular Cloud. The earlier result was attributed to a deficit of r-processed 85Rb. Our larger sample suggests instead that 87Rb is enhanced in these two lines of sight. When the total elemental abundance of Rb is compared to the K elemental abundance, the interstellar Rb/K ratio is significantly lower than the meteoritic ratio for all the sight lines in this study. Available interstellar samples for other s- and r- process elements are used to help interpret these results.Comment: 24 pages, 3 figures. Accepted for publication in Ap

Observations of X-rays and Thermal Dust Emission from the Supernova Remnant Kes 75

We present Spitzer Space Telescope and Chandra X-ray Observatory observations of the composite Galactic supernova remnant Kes 75 (G29.7-0.3). We use the detected flux at 24 microns and hot gas parameters from fitting spectra from new, deep X-ray observations to constrain models of dust emission, obtaining a dust-to-gas mass ratio M_dust/M_gas ~0.001. We find that a two-component thermal model, nominally representing shocked swept-up interstellar or circumstellar material and reverse-shocked ejecta, adequately fits the X-ray spectrum, albeit with somewhat high implied densities for both components. We surmise that this model implies a Wolf-Rayet progenitor for the remnant. We also present infrared flux upper limits for the central pulsar wind nebula.Comment: 7 pages, 2 tables, 4 figures, uses emulateapj. Accepted for publication in Ap

Effect of ration level and dietary docosahexaenoic acid content on the requirements for long-chain polyunsaturated fatty acids by juvenile barramundi (Lates calcarifer)

Juvenile barramundi were fed one of six diets containing differing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels. Fish were restricted fed on a pair-fed feeding regime to eliminate variability in feed intake, with two diets fed to satiety to examine the effects of fixed or variable feed rations on EFA requirements. Weight gain, feed intake, feed utilisation, and physical clinical signs were monitored. No effect of dietary DHA and EPA concentration, DHA:EPA ratio or total LC-PUFA level was observed on weight gain, growth rate, feed conversion ratio (FCR), survival or physical clinical health signs (P>0.05). Satiety fed fish had higher feed intake, final weight, weight gain and growth rate compared to their respective restrictively fed treatments (P<0.05). No effect of ration level on the responses to DHA concentration was observed. Body fatty acid composition was affected by diet, increasing dietary DHA resulted in higher body tissue DHA concentration, and a similar relationship was observed for EPA. Plasma haemoglobin increased with increasing DHA+EPA levels (P<0.05) while glutamate dehydrogenase increased for fish fed DHA+EPA in a 1:1 ratio, regardless of total dietary LC-PUFA (P<0.05). Juvenile barramundi may be fed diets containing as low as 1gkg-1 DHA without compromising growth or health status.&nbsp

Effect of oil palm sustainability certification on deforestation and fire in Indonesia.

Many major corporations and countries have made commitments to purchase or produce only "sustainable" palm oil, a commodity responsible for substantial tropical forest loss. Sustainability certification is the tool most used to fulfill these procurement policies, and around 20% of global palm oil production was certified by the Roundtable on Sustainable Palm Oil (RSPO) in 2017. However, the effect of certification on deforestation in oil palm plantations remains unclear. Here, we use a comprehensive dataset of RSPO-certified and noncertified oil palm plantations (∼188,000 km2) in Indonesia, the leading producer of palm oil, as well as annual remotely sensed metrics of tree cover loss and fire occurrence, to evaluate the impact of certification on deforestation and fire from 2001 to 2015. While forest loss and fire continued after RSPO certification, certified palm oil was associated with reduced deforestation. Certification lowered deforestation by 33% from a counterfactual of 9.8 to 6.6% y-1 Nevertheless, most plantations contained little residual forest when they received certification. As a result, by 2015, certified areas held less than 1% of forests remaining within Indonesian oil palm plantations. Moreover, certification had no causal impact on forest loss in peatlands or active fire detection rates. Broader adoption of certification in forested regions, strict requirements to avoid all peat, and routine monitoring of clearly defined forest cover loss in certified and RSPO member-held plantations appear necessary if the RSPO is to yield conservation and climate benefits from reductions in tropical deforestation

Neonatal Subventricular Zone Neural Stem Cells Release Extracellular Vesicles that Act as a Microglial Morphogen

Subventricular zone (SVZ) neural stem cells (NSCs) are the cornerstone of the perinatal neurogenic niche. Microglia are immune cells of the nervous system that are enriched in the neonatal SVZ. Although microglia regulate NSCs, the extent to which this interaction is bi-directional is unclear. Extracellular vesicles (EVs) are cell-derived particles that encase miRNA and proteins. Here, we demonstrate that SVZ NSCs generate and release EVs. Neonatal electroporated fluorescent EV fusion proteins were released by NSCs and subsequently cleared from the SVZ. EVs were preferentially targeted to microglia. Small RNA sequencing identified miRNAs within the EVs that regulate microglia physiology and morphology. EVs induced a transition to a CD11b/Iba1 non-stellate microglial morphology. The transition accompanied a microglial transcriptional state characterized by Let-7-regulated cytokine release and a negative feedback loop that controlled NSC proliferation. These findings implicate an NSC-EV-microglia axis and provide insight to normal and pathophysiological brain development

Characterization of microtubule-associated protein tau isoforms and Alzheimer’s disease-like pathology in normal sheep (Ovis aries):Relevance to their potential as a model of Alzheimer’s disease

Alzheimer’s disease is a chronic neurodegenerative disease that accounts for up to 80% of all dementias. Characterised by deteriorations of memory and cognitive function, the key neuropathological features are accumulations of β-amyloid and hyperphosphorylated tau, as ‘plaques’ and ‘tangles’, respectively. Despite extensive study, however, the exact mechanism underlying aggregate formation in Alzheimer’s disease remains elusive, as does the contribution of these aggregates to disease progression. Importantly, a recent evaluation of current Alzheimer’s disease animal models suggested that rodent models are not able to fully recapitulate the pathological intricacies of the disease as it occurs in humans. Therefore, increasing attention is being paid to species that might make good alternatives to rodents for studying the molecular pathology of Alzheimer’s disease. The sheep (Ovis aries) is one such species, although to date, there have been few molecular studies relating to Alzheimer’s disease in sheep. Here, we investigated the Alzheimer’s disease relevant histopathological characteristics of 22 sheep, using anti-β-amyloid (Abcam 12267 and mOC64) and phosphorylation specific anti-tau (AT8 and S396) antibodies. We identified numerous intraneuronal aggregates of both β-amyloid and tau that are consistent with early Alzheimer’s disease-like pathology. We confirmed the expression of two 3-repeat (1N3R, 2N3R) and two 4-repeat (1N4R, 2N4R) tau isoforms in the ovine brain, which result from the alternative splicing of two tau exons. Finally, we investigated the phosphorylation status of the serine396 residue in 30 sheep, and report that the phosphorylation of this residue begins in sheep aged as young as 2 years. Together, these data show that sheep exhibit naturally occurring β-amyloid and tau pathologies, that reflect those that occur in the early stages of Alzheimer’s disease. This is an important step towards the validation of the sheep as a feasible large animal species in which to model Alzheimer’s disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-022-04572-z

Measuring the magnetic field of a trans-equatorial loop system using coronal seismology

Context. EIT waves are freely-propagating global pulses in the low corona which are strongly associated with the initial evolution of coronal mass ejections (CMEs). They are thought to be large-Amplitude, fast-mode magnetohydrodynamic waves initially driven by the rapid expansion of a CME in the low corona. Aims. An EIT wave was observed on 6 July 2012 to impact an adjacent trans-equatorial loop system which then exhibited a decaying oscillation as it returned to rest. Observations of the loop oscillations were used to estimate the magnetic field strength of the loop system by studying the decaying oscillation of the loop, measuring the propagation of ubiquitous transverse waves in the loop and extrapolating the magnetic field from observed magnetograms. Methods. Observations from the Atmospheric Imaging Assembly onboard the Solar Dynamics Observatory (SDO/AIA) and the Coronal Multi-channel Polarimeter (CoMP) were used to study the event. An Empirical Mode Decomposition analysis was used to characterise the oscillation of the loop system in CoMP Doppler velocity and line width and in AIA intensity. Results. The loop system was shown to oscillate in the 2nd harmonic mode rather than at the fundamental frequency, with the seismological analysis returning an estimated magnetic field strength of 5.5 ± 1.5 G. This compares to the magnetic field strength estimates of 1-9 G and 3-9 G found using the measurements of transverse wave propagation and magnetic field extrapolation respectively.Fil: Long, David M.. Colegio Universitario de Londres; Reino UnidoFil: Valori, G.. Colegio Universitario de Londres; Reino UnidoFil: Pérez-Suárez, D.. Colegio Universitario de Londres; Reino UnidoFil: Morton, R. J.. University Of Northumbria; Reino UnidoFil: Vasquez, Alberto Marcos. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; Argentin