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Amini, A.

Publications and source records attributed to Amini, A..

3 recordsLinked to original sources

The reliability and heritability of cortical folds and their genetic correlations across hemispheres.

The structure of the brains cortical folds varies considerably in human populations. Specific patterns of cortical variation arise with development and aging, and cortical traits are partially influenced by genetic factors. The degree to which genetic factors affect cortical folding patterning remains unknown, yet may be estimated with large-scale in-vivo brain MRI. Using multiple MRI datasets from around the world, we estimated the reliability and heritability of sulcal morphometric characteristics including length, depth, width, and surface area, for 61 sulci per hemisphere of the human brain. Reliability was assessed across four distinct test-retest datasets. We meta-analyzed the heritability across three independent family-based cohorts (N > 3,000), and one cohort of largely unrelated individuals (N~9,000) to examine the robustness of our findings. Reliability was high (interquartile range for ICC: 0.65-0.85) for sulcal metrics. Most sulcal measures were moderately to highly heritable (heritability estimates = 0.3-0.7). These genetic influences vary regionally, with the earlier forming sulci having higher heritability estimates. The central sulcus, the subcallosal and the collateral fissure were the most highly heritable regions. For some frontal and temporal sulci, left and right genetic influences did not completely overlap, suggesting some lateralization of genetic effects on the cortex.

genetics

Activation of MAIT cells plays a critical role in viral vector vaccine immunogenicity

Mucosal-associated invariant T (MAIT) cells can be activated by viruses through a cytokine-dependent mechanism, and thereby protect from lethal infection. Given this, we reasoned MAIT cells may have a critical role in the immunogenicity of replication-incompetent adenovirus vectors, which are novel and highly potent vaccine platforms. In vitro, ChAdOx1 (Chimpanzee Adenovirus Ox1) induced potent activation of MAIT cells. Activation required transduction of monocytes and plasmacytoid dendritic cells to produce IL-18 and IFN-, respectively. IFN--induced monocyte-derived TNF- was identified as a novel intermediate in this activation pathway, and activation required combinatorial signaling of all three cytokines. Furthermore, ChAdOx1-induced in vivo MAIT cell activation in both mice and human volunteers. Strikingly, MAIT cell activation was necessary in vivo for development of ChAdOx1-induced HCV-specific CD8 T cell responses. These findings define a novel role for MAIT cells in the immunogenicity of viral vector vaccines, with potential implications for future design.\n\nOne sentence summaryRobust immunogenicity of candidate adenovirus vaccine vectors requires the activation of unconventional T cells.

immunology

Transcranial Pulse Stimulation with Ultrasound in Alzheimer’s disease – A new navigated focal brain therapy

Ultrasound-based brain stimulation techniques offer an exciting potential to modulate the human brain in a highly focal and precisely targeted manner. However, for clinical applications the current techniques have to be further developed. We introduce a new ultrasound stimulation technique, based on single ultrashort ultrasound pulses (transcranial pulse stimulation, TPS) and describe a first navigable clinical TPS system. Feasibility, safety and preliminary (uncontrolled) efficacy data in Alzheimers disease (AD) are provided. Simulation data, in vitro measurements with rat and human skulls/brains and clinical data in 35 AD patients were acquired in a multicentric setting (including CERAD scores and functional MRI). Preclinical results show large safety margins and patient results show high treatment tolerability. Neuropsychological scores improved significantly when tested immediately as well as 1 and 3 months after stimulation and fMRI data displayed significant connectivity increases within the memory network. The results encourage broad neuroscientific application and translation of the new method to clinical therapy and randomized sham-controlled studies.

neuroscience