The prevalence of obesity is high in the United States, especially among children and adults in most U.S. racial/ethnic minority and low-income populations, compared to whites or those with higher incomes. This observation continues to beg for explanations that can point the way toward effective and durable solutions. Several potential explanations relate to the social, economic, and physical environments that influence eating and physical activity.
Bacterial pathogenesis typically involves multiple factors that influence the infection process. Type VI Secretion Systems (T6SS) are nanomachines that deliver proteins called effectors into target cells. The machines are evolutionarily related to the contractile tails of bacteriophages but are located within the cell cytosol. Through dynamic conformational changes in the tail sheath-like structure, these machines deliver payloads of toxic effector proteins into target cells in less than five milliseconds.
Titia de Lange’s group is now working to determine the mechanism by which each shelterin protein inhibits its designated pathway, and how loss of telomere protection contributes to genome instability in human cancer. A major mechanistic insight arose from the identification of the t-loop structure of telomeres in which the single-stranded overhang is inserted in the double-stranded repeat array of the telomere, thereby hiding the telomere end from the DNA damage response. Recent data showed that the TRF2 component of shelterin is required to establish and/or maintain this structure.
During ontogeny the expression of genes encoding the beta-like globins in humans switches from embryonic, to fetal, to adult globins. The switch from fetal hemoglobin (HbF, alpha2 gamma2) to adult hemoglobin (HbA, alpha2 beta2) is critical to the beta-hemoglobin disorders, namely sickle-cell disease (SCD) and thalassemia. Family and natural-history studies have revealed the beneficial effects of increased HbF on the severity of these disorders. Thus, reactivation of HbF in adults has been a long-sought goal as a means to treat both SCD and beta-thalassemia.
The majority of human pathogenic fungi are soil-dwelling microbes that have no obvious need for animal hosts. This raises a fundamental question in microbial pathogenesis: Why do some of these organisms cause disease in mammals? In this lecture we will dissect the biology of the human pathogenic fungus Cryptococcus neoformans in an effort to glean an explanation for the origin of virulence. C.
A search for the origin of our adaptive immune system has revealed that the jawed vertebrates and jawless vertebrates (lampreys and hagfish) use different strategies for generating large repertoires of lymphocyte receptors for antigens.
Dr. Nedergaard and her colleagues recently described a macroscopic pathway in the central nervous system: the glymphatic system, which facilitates the clearance of interstitial waste products from neuronal metabolism. The glymphatic clearance of macromolecules is driven by cerebrospinal fluid (CSF) that flows along para-arterial spaces and through the brain parenchyma via support from astroglial aquaporin-4 water channels.
Dr. Eichler will summarize his recent findings regarding the discovery of new genes and genetic mutations that contribute to autism spectrum disorder (ASD) and developmental delays. The lecture will highlight the identification of rare disruptive mutations using copy-number variation from exome- and genome-sequencing approaches on thousands of individuals.
The promise of treating cancer with the host’s own immune system has long held allure for scientists and physicians, but successes have been modest and inconsistent until recently. For the past two decades, Dr. Mackall’s research has focused on developing immune-based therapies for childhood cancer. She began by describing the impact of standard cancer therapies on T-cell homeostasis and identifying factors that limit T-cell restoration in children and adults.
The advent of facile genome engineering using the bacterial RNA-guided CRISPR-Cas9 system in animals and plants is transforming biology. Dr. Doudna will present a brief history of CRISPR biology from its initial discovery through the elucidation of the CRISPR-Cas9 enzyme mechanism, providing the foundation for remarkable developments using this technology to modify, regulate or mark genomic loci in a wide variety of cells and organisms.
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