363 research outputs found
Victor McKusick and his short course.
The Short Course in Human and Mammalian Genetics and Genomics (aka the Short Course or the Bar Harbor course ) is one of Victor McKusick\u27s landmark contributions to medical genetics. Conceived in 1959 as a way to increase the contribution of genetic advances to medicine, it has directly affected more than 7000 students and 600 participating faculty from around the world. Now, more than 10 years after his death, it continues to be a vibrant disseminator of genetics, and genomics knowledge for medicine, a catalytic agent for ongoing research and a source of collegiality in our field. What an extraordinary gift
Knockdown of Amyloid Precursor Protein: Biological Consequences and Clinical Opportunities
Amyloid precursor protein (APP) and its cleavage fragment Amyloid-β (Aβ) have fundamental roles in Alzheimer’s disease (AD). Genetic alterations that either increase the overall dosage of APP or alter its processing to favour the generation of longer, more aggregation prone Aβ species, are directly causative of the disease. People living with one copy of APP are asymptomatic and reducing APP has been shown to lower the relative production of aggregation-prone Aβ species in vitro. For these reasons, reducing APP expression is an attractive approach for AD treatment and prevention. In this review, we will describe the structure and the known functions of APP and go on to discuss the biological consequences of APP knockdown and knockout in model systems. We highlight progress in therapeutic strategies to reverse AD pathology via reducing APP expression. We conclude that new technologies that reduce the dosage of APP expression may allow disease modification and slow clinical progression, delaying or even preventing onset
Tau Protein Hyperphosphorylation and Aggregation in Alzheimer’s Disease and Other Tauopathies, and Possible Neuroprotective Strategies
Acknowledgments This work was supported by The Croatian Science Foundation grant No. IP-2014-09-9730 (“Tau protein hyperphosphorylation, aggregation, and trans-synaptic transfer in Alzheimer’s disease: cerebrospinal fluid analysis and assessment of potential neuroprotective compounds”) and European Cooperation in Science and Technology (COST) Action CM1103 (“Stucture-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain”). PRH is supported in part by NIH grant P50 AG005138. We also thank Mate Babić for help in preparation of schematics.Peer reviewedPublisher PD
Human myeloid progenitor glucocorticoid receptor activation causes genomic instability, type 1 IFN- response pathway activation and senescence in differentiated microglia; an early life stress model
One form of early life stress, prenatal exposure to glucocorticoids (GCs), confers a higher risk of psychiatric and neurodevelopmental disorders in later life. Increasingly, the importance of microglia in these disorders is recognized. Studies on GCs exposure during microglial development have been limited, and there are few, if any, human studies. We established an in vitro model of ELS by continuous pre-exposure of human iPS-microglia to GCs during primitive hematopoiesis (the critical stage of iPS-microglial differentiation) and then examined how this exposure affected the microglial phenotype as they differentiated and matured to microglia, using RNA-seq analyses and functional assays. The iPS-microglia predominantly expressed glucocorticoid receptors over mineralocorticoid receptors, and in particular, the GR-α splice variant. Chronic GCs exposure during primitive hematopoiesis was able to recapitulate in vivo ELS effects. Thus, pre-exposure to prolonged GCs resulted in increased type I interferon signaling, the presence of Cyclic GMP-AMP synthase-positive (cGAS) micronuclei, cellular senescence and reduced proliferation in the matured iPS-microglia. The findings from this in vitro ELS model have ramifications for the responses of microglia in the pathogenesis of GC- mediated ELS-associated disorders such as schizophrenia, attention-deficit hyperactivity disorder and autism spectrum disorder
Bi2Te1.6S1.4 - a Topological Insulator in the Tetradymite Family
We describe the crystal growth, crystal structure, and basic electrical
properties of Bi2Te1.6S1.4, which incorporates both S and Te in its Tetradymite
quintuple layers in the motif -[Te0.8S0.2]-Bi-S-Bi-[Te0.8S0.2]-. This material
differs from other Tetradymites studied as topological insulators due to the
increased ionic character that arises from its significant S content.
Bi2Te1.6S1.4 forms high quality crystals from the melt and is the S-rich limit
of the ternary Bi-Te-S {\gamma}-Tetradymite phase at the melting point. The
native material is n-type with a low resistivity; Sb substitution, with
adjustment of the Te to S ratio, results in a crossover to p-type and resistive
behavior at low temperatures. Angle resolved photoemission study shows that
topological surface states are present, with the Dirac point more exposed than
it is in Bi2Te3 and similar to that seen in Bi2Te2Se. Single crystal structure
determination indicates that the S in the outer chalcogen layers is closer to
the Bi than the Te, and therefore that the layers supporting the surface states
are corrugated on the atomic scale.Comment: To be published in Physical Review B Rapid Communications 16 douuble
spaced pages. 4 figures 1 tabl
Monoaminergic Neuropathology in Alzheimer's disease
Acknowledgments This work was supported by The Croatian Science Foundation grant. no. IP-2014-09-9730 (“Tau protein hyperphosphorylation, aggregation, and trans-synaptic transfer in Alzheimer’s disease: cerebrospinal fluid analysis and assessment of potential neuroprotective compounds”) and European Cooperation in Science and Technology (COST) Action CM1103 (“Stucture-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain”). PRH is supported in part by NIH grant P50 AG005138.Peer reviewedPostprin
Fostering bioinformatics education through skill development of professors: Big Genomic Data Skills Training for Professors.
Bioinformatics has become an indispensable part of life science over the past 2 decades. However, bioinformatics education is not well integrated at the undergraduate level, especially in liberal arts colleges and regional universities in the United States. One significant obstacle pointed out by the Network for Integrating Bioinformatics into Life Sciences Education is the lack of faculty in the bioinformatics area. Most current life science professors did not acquire bioinformatics analysis skills during their own training. Consequently, a great number of undergraduate and graduate students do not get the chance to learn bioinformatics or computational biology skills within a structured curriculum during their education. To address this gap, we developed a module-based, week-long short course to train small college and regional university professors with essential bioinformatics skills. The bioinformatics modules were built to be adapted by the professor-trainees afterward and used in their own classes. All the course materials can be accessed at https://github.com/TheJacksonLaboratory/JAXBD2K-ShortCourse
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