The role of sleep disturbance in the relationship between post-traumatic stress disorder and suicidal ideation

•PTSD symptoms indirectly predicted suicidal ideation via comorbid sleep disturbances, but had no direct effect.•Polyvictimization predicted sleep disturbances and suicidal ideation independently of PTSD or major depression.•No relationships were substantively altered after adjusting for comorbid major depression. We tested if the risk of suicidal ideation in individuals with PTSD symptoms was dependent on comorbid sleep disturbance. Our cross-sectional sample included 2465 participants with complete data from the 21 year follow-up of the Mater University Study of Pregnancy (MUSP), a birth cohort study of young Australians. Using structural equation modelling with indirect pathways we found that 12 month PTSD symptoms did not directly predict suicidal ideation at 21 when adjusting for major depression symptoms, polyvictimization and gender. However, PTSD symptoms had an indirect effect on suicidal ideation via past-month sleep disturbance. Our results suggest that increased suicidal ideation in those with PTSD may result from the fact that PTSD sufferers often exhibit other comorbid psychiatric conditions which are themselves known to predict suicidal behaviours. Sleep disturbance may be targeted in those who experience PTSD to help prevent suicidal ideation

Pharmacological Effects of Asiatic acid in Glioblastoma Cells under Hypoxia

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Despite current treatment options including surgery followed by radiation and chemotherapy with temozolomide (TMZ) and cisplatin, the median survival rate remains low (<16 months). Combined with increasing drug resistance and the inability of some compounds to cross the blood brain barrier (BBB), novel compounds are being sought for the treatment of this disease. Here, we aimed to examine the pharmacological effect of Asiatic acid (AA) in glioblastoma under hypoxia. To investigate the effects of AA on cell viability, proliferation, apoptosis and wound healing, SVG p12 fetal glia and U87-MG grade IV glioblastoma cells were cultured under normoxic (21% O2) and hypoxic (1% O2) conditions. In normoxia, AA reduced cell viability in U87-MG cells in a time and concentration-dependent manner. A significant decrease in viability, compared to cisplatin, was observed following 2hrs of AA treatment with no significant changes in cell proliferation or cell cycle progression observed. Under hypoxia, a significantly greater number of cells underwent apoptosis in comparison to cisplatin. While cisplatin showed a reduction in wound healing in normoxia, a significantly greater reduction was observed following AA treatment. An overall reduction in wound healing was observed under hypoxia. The results of this study show that AA has cytotoxic effects on glioma cell lines and has the potential to become an alternative treatment for glioblastoma

Cell-autonomous and environmental contributions to the interstitial migration of T cells

A key to understanding the functioning of the immune system is to define the mechanisms that facilitate directed lymphocyte migration to and within tissues. The recent development of improved imaging technologies, most prominently multi-photon microscopy, has enabled the dynamic visualization of immune cells in real-time directly within intact tissues. Intravital imaging approaches have revealed high spontaneous migratory activity of T cells in secondary lymphoid organs and inflamed tissues. Experimental evidence points towards both environmental and cell-intrinsic cues involved in the regulation of lymphocyte motility in the interstitial space. Based on these data, several conceptually distinct models have been proposed in order to explain the coordination of lymphocyte migration both at the single cell and population level. These range from “stochastic” models, where chance is the major driving force, to “deterministic” models, where the architecture of the microenvironment dictates the migratory trajectory of cells. In this review, we focus on recent advances in understanding naïve and effector T cell migration in vivo. In addition, we discuss some of the contradictory experimental findings in the context of theoretical models of migrating leukocytes

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe

A New Direction for ESF

The team partnered with the Emergency Services Foundation (ESF) to provide recommendations for holistic retirement programming for Victorian operational emergency service workers retiring of age. With the large number of workers over the age of fifty-five and the rise of mental health issues in retirement, there is a clear need for retirement programming. We gathered data from eight emergency service agencies, current and retired workers from across the sector and experts in the retirement process. Through interviews and surveys, we were able to assess the current landscape of retirement programs within the sector and learn about the needs of Emergency Service Workers. From here, we provided recommendations for best practices and developed ideas for how ESF could add value to the sector

Validation Assessment Model for Atmospheric Retrievals

A linear mathematical error model for the assessment of validation activity of atmospheric retrievals is presented. The purpose of the validation activity is to assess the actual performance of the remote sensing validated system while in orbit by comparing its measurements to some relevant—validating—data sets. The validating system samples volumes of the atmosphere at times and locations that are different from the ones when and where the validated system makes its own observations. The location of the validating system can be either stationary, e.g. a ground ARM site, or movable, e.g. an aircraft or some other satellites. The true states may be correlated or not. The sampled volumes differ from each other by their location, timing, and size. The validated and validating systems have different vertical resolution and grid, absolute accuracy, and noise level. All the above factors cause apparent differences between the data to be compared. The validation assessment model makes the comparison accurate by allowing for the differences. The model can be used for assessment and interpretation of the validation results when the above mentioned sources of discrepancies are significant, as well as for evaluation of a particular validating data source

Inflammasome-derived cytokine IL18 suppresses amyloid-induced seizures in Alzheimer-prone mice

Alzheimer\u27s disease (AD) is characterized by the progressive destruction and dysfunction of central neurons. AD patients commonly have unprovoked seizures compared with age-matched controls. Amyloid peptide-related inflammation is thought to be an important aspect of AD pathogenesis. We previously reported that NLRP3 inflammasome KO mice, when bred into APPswe/PS1DeltaE9 (APP/PS1) mice, are completely protected from amyloid-induced AD-like disease, presumably because they cannot produce mature IL1beta or IL18. To test the role of IL18, we bred IL18KO mice with APP/PS1 mice. Surprisingly, IL18KO/APP/PS1 mice developed a lethal seizure disorder that was completely reversed by the anticonvulsant levetiracetam. IL18-deficient AD mice showed a lower threshold in chemically induced seizures and a selective increase in gene expression related to increased neuronal activity. IL18-deficient AD mice exhibited increased excitatory synaptic proteins, spine density, and basal excitatory synaptic transmission that contributed to seizure activity. This study identifies a role for IL18 in suppressing aberrant neuronal transmission in AD

Control of the innate immune response by the mevalonate pathway

Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-translational modification that is catalyzed by protein geranylgeranyl transferase I (GGTase I). Pyrin is an innate immune sensor that forms an active inflammasome in response to bacterial toxins. Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. We found that protein geranylgeranylation enabled Toll-like receptor (TLR)-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110delta. Macrophages that were deficient in GGTase I or p110delta exhibited constitutive release of interleukin 1beta that was dependent on MEFV but independent of the NLRP3, AIM2 and NLRC4 inflammasomes. In the absence of protein geranylgeranylation, compromised PI(3)K activity allows an unchecked TLR-induced inflammatory responses and constitutive activation of the Pyrin inflammasome

Life in the spray zone - overlooked diversity in West African torrent-frogs (Anura, Odontobatrachidae, Odontobatrachus)

West African torrent-frogs of the genus Odontobatrachus currently belong to a single species: Odontobatrachus natator (Boulenger, 1905). Recently, molecular results and biogeographic separation led to the recognition of five Operational Taxonomic Units (OTUs) thus identifying a species-complex. Based on these insights, morphological analyses on more than 150 adult specimens, covering the entire distribution of the family and all OTUs, were carried out. Despite strong morphological congruence, combinations of morphological characters made the differentiation of OTUs successful and allowed the recognition of five distinct species: Odontobatrachus natator, and four species new to science: Odontobatrachus arndti sp. n., O. fouta sp. n., O. smithi sp. n. and O. ziama sp. n. All species occur in parapatry: Odontobatrachus natator is known from western Guinea to eastern Liberia, O. ziama sp. n. from eastern Guinea, O. smithi sp. n. and O. fouta sp. n. from western Guinea, O. arndti sp. n. from the border triangle Guinea-Liberia-Cote d'Ivoire. In addition, for the first time the advertisement call of a West African torrent-frog (O. arndti sp. n.) is described