Alzheimer\u27s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially During Resting and Task States

β-amyloid (Aβ) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here, we explored potential relationships between functional connectivity (FC) patterns within the default-mode network (DMN), age, CSF biomarkers (Aβ42 and pTau181), and cognitive status in older adults. Multiple measures of FC were explored, including a novel time series-based measure [total interdependence (TI)]. In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aβ42 or pTau181 and cognitive scores or regional brain volumes. However, we observed several novel relationships between these biomarkers and measures of FC in DMN during both resting-state and a short-term memory task. First, increased connectivity between bilateral anterior middle temporal gyri was associated with higher levels of CSF Aβ42 and Aβ42/pTau181 ratio (reflecting lower AD risk) during both rest and task. Second, increased bilateral parietal connectivity during the short-term memory task, but not during rest, was associated with higher levels of CSF pTau181 (reflecting higher AD risk). Third, increased connectivity between left middle temporal and left parietal cortices during the active task was associated with decreased global cognitive status but not CSF biomarkers. Lastly, we found that our new TI method was more sensitive to the CSF Aβ42-connectivity relationship whereas the traditional cross-correlation method was more sensitive to levels of CSF pTau181 and cognitive status. With further refinement, resting-state connectivity and task-driven connectivity measures hold promise as non-invasive neuroimaging markers of Aβ and pTau burden in cognitively normal older adults

Olfactory Jump Reflex Habituation in Drosophila and Effects of Classical Conditioning Mutations

Habituation is a nonassociative learning mechanism, in which an initial response toward repeated stimuli gradually wanes. This is amongst the simplest and most widespread forms of behavioral plasticity. So far, neither the underlying molecular mechanisms nor the precise neural networks of habituation are well understood. We have developed a novel paradigm to quantify habituation of the olfactory jump reflex in Drosophila. We present data demonstrating several behavioral properties of this phenomenon, generally observed in other species. We also show that the dunce and rutabaga memory mutants behave abnormally in this assay, suggesting that this assay might be used in behavioral screens for new mutants with defects in this simpler form of behavioral plasticity

parMERASA – multicore execution of parallelised hard real-time applications supporting analysability

Abstract-Engineers who design hard real-time embedded systems express a need for several times the performance available today while keeping safety as major criterion. A breakthrough in performance is expected by parallelizing hard real-time applications and running them on an embedded multi-core processor, which enables combining the requirements for high-performance with timing-predictable execution. parMERASA will provide a timing analyzable system of parallel hard real-time applications running on a scalable multicore processor. parMERASA goes one step beyond mixed criticality demands: It targets future complex control algorithms by parallelizing hard real-time programs to run on predictable multi-/many-core processors. We aim to achieve a breakthrough in techniques for parallelization of industrial hard real-time programs, provide hard real-time support in system software, WCET analysis and verification tools for multi-cores, and techniques for predictable multi-core designs with up to 64 cores

Whole genome sequencing reveals that genetic conditions are frequent in intensively ill children

Purpose With growing evidence that rare single gene disorders present in the neonatal period, there is a need for rapid, systematic, and comprehensive genomic diagnoses in ICUs to assist acute and long-term clinical decisions. This study aimed to identify genetic conditions in neonatal (NICU) and paediatric (PICU) intensive care populations. Methods We performed trio whole genome sequence (WGS) analysis on a prospective cohort of families recruited in NICU and PICU at a single site in the UK. We developed a research pipeline in collaboration with the National Health Service to deliver validated pertinent pathogenic findings within 2andndash;3andnbsp;weeks of recruitment. Results A total of 195 families had whole genome analysis performed (567 samples) and 21% received a molecular diagnosis for the underlying genetic condition in the child. The phenotypic description of the child was a poor predictor of the gene identified in 90% of cases, arguing for gene agnostic testing in NICU/PICU. The diagnosis affected clinical management in more than 65% of cases (83% in neonates) including modification of treatments and care pathways and/or informing palliative care decisions. A 2andndash;3andnbsp;week turnaround was sufficient to impact most clinical decision-making. Conclusions The use of WGS in intensively ill children is acceptable and trio analysis facilitates diagnoses. A gene agnostic approach was effective in identifying an underlying genetic condition, with phenotypes and symptomatology being primarily used for data interpretation rather than gene selection. WGS analysis has the potential to be a first-line diagnostic tool for a subset of intensively ill children.</p

Lactobacillus casei Shirota modulation of ammonia metabolism in physical exercise

Ammonia is a continuously produced metabolic toxic waste product. Decompensated liver disease patients have elevated ammonia levels and are prone to infection. Increased ammonia levels have been recorded following physical exertion. Mechanisms to control ammonia overspill are limited. Urea cycle disorders receive therapeutic phenylacetate to lower ammonia, captured as glutamine. Bacteria of the genus Lactobacillus synthesise phenylacetate and this may provide a useful mechanism to control ammonia overspill in athletes. A pilot study with male football players investigated the possibility that L. casei Shirota probiotic supplement could naturally generate phenylacetate, and contributes to ammonia removal through glutamine sequestration as phenylacetylglutamine via the kidneys, volunteers were assigned to one of two groups: probiotic supplemented (x2/day) or controls. All subjects undertook an exhaustive exercise routine in a 9-station static exercise program. Urine samples were collected 4hr after fhe exercise program. The program was repeated after 1 month. Urinary phenyacetylglutamine and ammonia, corrected by creatinine levels, were measured. Expressed as the difference in urinary levels between the two sampling points. Phenylacetylglutamine was significantly increased in the probiotic group (P<0.01) ammonia levels were lower compared to the control group (P-0.064). Probiotic Lactobacillus supplementation may °e useful in controlling exercise-generated ammonia