Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Sensitivity and specificity of current diagnostic tests for gill-associated virus in Penaeus mondon

This study reports the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy between a reverse transcriptase-nested polymerase chain reaction (RT-nPCR) and an enzyme-linked immunosorbent assay (ELISA) for the detection of gill-associated virus (GAV) from a sample of 120 Penaeus monodon. Subsequently, the same comparisons were applied to the ELISA and haemagglutination (HA) assays for detection of GAV from a second 120 prawns. The optical density (OD) or dilution cut-off point had a direct influence on the tested parameters. The cut-off OD of 0.5–0.6 with the ELISA produced a sensitivity of 98% compared with RT-nPCR. However, these OD produced the lowest accuracy (85.8% and 86.7%, respectively). The OD cut off of 0.75 resulted in the highest accuracy (91.7%) and NPV (81.3%) while it had the second highest sensitivity (97%) and PPV (93.3%). However, the OD cut off of 0.9 had the highest specificity (80%). With regards to HA, the titre cut off at 8 resulted in the highest sensitivity, specificity and NPV (94%, 100% and 100%, respectively) compared with the ELISA, while the HA titre of 16 gave the highest accuracy (73%) and the second highest specificity (75%). A HA titre of 64 gave the highest PPV (81%). Using the RT-nPCR as the gold standard, the ELISA had an accuracy of 91.7% when using a cut off >0.75 as a positive result. When compared with the ELISA, the HA had an accuracy of 73% when using an HA titre cut off greater than 16 as a positive result. These results indicate that alternative tests for GAV (ELISA and HA) can be used to explore multiple questions about the disease status of P. monodon stocks in a cost-effective manner

Viral diseases of penaeid shrimp with particular reference to four viruses recently found in shrimp from Queensland

The culture of penaeid shrimp world-wide is primarily dependent on wild-caught broodstock which has an enormous potential to introduce new pathogens, particularly viruses, into culture systems. Of the 13 viruses described for cultured penaeid shrimp, seven have been described within the past 5 years; the most devastating viral epidemics on record for cultured penaeid shrimp have also occurred within the past 5 years. During examination of local wild and cultured shrimp, four new viruses were found. Bennettae baculovirus was discovered in the digestive gland of wild Metapenaeus bennettae. It closely resembles monodon baculovirus (MBV) but has a more slender virion, does not cross-react with a DNA probe for MBV and is not infectious to Penaeus monodon. Two morphologically indistinguishable viruses, one pathogenic (gill-associated virus, GAV) and the other benign (lymphoid organ virus, LOV), were found in cultured P. monodon. LOV and GAV closely resemble yellow head virus (YHV) of Thailand. A parvo-like virus was found recently in dying post-larvae of P. japonicus. As the intensity of shrimp culture world-wide increases, researchers can expect to discover more penaeid viruses. The need to close the life cycle of P. monodon and other cultured species and develop rapid diagnostic methods for viral infections has become imperative

Baculovirus of Metapenaeus bennettae from the Moreton Bay region of Australia

Adult Metapenaeus bennettae shrimp, trawled from Moreton Bay, Australia, were found infected with a baculovirus which resembled Monodon Baculovirus (MBV) in its ultrastructure and histological appearance. It differed in that infected material gave negative results with an in situ hybridization test using a DNA probe for MBV, and Penaeus monodon postlarvae, experimentally exposed to the virus, failed to become infected. This new baculovirus, designate MbSNPV or Bennettae Baculovirus (BBV), is the first virus reported from a Metapenaeus spp. taken from the wild

Haemagglutination as a low-cost detection method for gill-associated virus and by inference, yellowhead virus in Penaeus monodon Fabricius, 1798

A quantitative, low-cost test based on haemagglutination (HA) using chicken erythrocytes was developed to indicate the viral load of Australian yellowhead-like virus, gill-associated virus (GAV), in Penaeus monodon. The study tested the haemolymph, gill, lymphoid organ, heart, sub-cutaneous tissue, eye stalk, pleopods, uropods and the central nerve cord for agglutination activity in 100 prawns, with the haemolymph and gill tissue giving the highest end-point titres of 1:1370 and 1:361 respectively. The sensitivity of the test was demonstrated by testing two different populations of P. monodon, which showed a highly significant difference (P<0.001) in HA activity, indicating a difference in viral load. By testing three other penaeid prawn species (n=20), Penaeus esculentus, Penaeus merguiensis and Penaeus longistylis, and the crayfish Cherax quadricarinatus, it was demonstrated that natural agglutinins were not causing the high agglutination in the population of P. monodon being tested. It was also demonstrated that there was no effect of freezing and thawing of samples on HA activity. The speed and low cost of this test makes it a very useful tool, particularly in the developing world, for on-farm testing of penaeid prawns to indicate yellowhead virus and GAV loads which can contribute to management practices with respect to harvesting of ponds.James Munro and Leigh Owen

Hepatopancreatic parvo-like virus (HPV) of Penaeus japonicus cultured in Australia

A hepatopancreatic parvo-like virus (HPV) infection was identified in the hepatopancreata of moribund Penaeus japonicus postlarvae from a hatchery in Queensland.virus formed basophilic, fine granular intranuclear inclusion bodies within the hepatopancreocytes. These caused nuclear hypertrophy and displacement of the nucleolus. Subsphencal viral particles, 17-20 nm in diameter, were observed embedded within the inclusions. We wlll refer to this virus as HPV to avoid confusion within the literature. However, molecular data is required to definitively identif

The Mechanical Design of a Compensated Pulsed Alternator Prototype

A prototype of a compensated pulsed alternator (compulsator) is presently under construction at the Center for Electromechanics (CEM) of The University of Texas at Austin. The unique machine configuration and peak output current (150 kA) generate large forces not typically seen by conventional rotating machines. The rotor is made of 2913 laminations shrink fitted on a vertical shaft. Since the rotor has an L/D of 3.2 and a maximum speed of 5400 rpm, these insulated laminations are clamped on the ends with large Belleville washers to increase the effective stiffness. The stator is mounted on a torque frame which allows it to rotate during discharge to reduce the forces transmitted to ground. The mechanical considerations and design of this machine are presented.Center for Electromechanic