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"Frederick, Michael"
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The lost white tribe : explorers, scientists, and the theory that changed a continent
\"In 1876, in a mountainous region to the west of Lake Victoria, Africa--what is today Ruwenzori Mountains National Park in Uganda--the famed explorer Henry Morton Stanley encountered Africans with what he was convinced were light complexions and European features. Stanley's discovery of this African 'white tribe' haunted him and seemed to substantiate the so-called Hamitic Hypothesis: the theory that the descendants of Ham--the son of Noah--had populated Africa and other remote places, proving that the source and spread of human races around the world could be traced to and explained by a Biblical story. In [this book], Michael Robinson traces the rise and fall of the Hamitic Hypothesis\"--Amazon.com.
Book
TRPM2: a candidate therapeutic target for treating neurological diseases
Transient receptor potential melastatin 2 (TRPM2) is a calcium (Ca
2+
)-permeable non-selective cation channel belonging to the TRP ion channel family. Oxidative stress-induced TRPM2 activation provokes aberrant intracellular Ca
2+
accumulation and cell death in a variety of cell types, including neurons. Aberrant TRPM2 function has been implicated in several neurological disorders including ischemia/stroke, Alzheimer's disease, neuropathic pain, Parkinson's disease and bipolar disorder. In addition to research identifying a role for TRPM2 in disease, progress has been made in the identification of physiological functions of TRPM2 in the brain, including recent evidence that TRPM2 is necessary for the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term depression, an important form of synaptic plasticity at glutamate synapses. Here, we summarize recent evidence on the role of TRPM2 in the central nervous system (CNS) in health and disease and discuss the potential therapeutic implications of targeting TRPM2. Collectively, these studies suggest that TRPM2 represents a prospective novel therapeutic target for neurological disorders.
Journal Article
A tunable anthranilate-inducible gene expression system for Pseudomonas species
Pseudomonads are among the most common bacteria in soils, limnic ecosystems, and human, animal, or plant host environments, including intensively studied species such as Pseudomonas aeruginosa, P. putida, or P. fluorescens. Various gene expression systems are established for some species, but there is still a need for a simple system that is suitable for a wide range of pseudomonads and that can be used for physiological applications, i.e., with a tuning capacity at lower expression levels. Here, we report the establishment of the anthranilate-dependent PantA promoter for tunable gene expression in pseudomonads. During studies on P. fluorescens, we constructed an anthranilate-inducible AntR/PantA-based expression system, named pUCP20-ANT, and used GFP as reporter to analyze gene expression. This system was compared with the rhamnose-inducible RhaSR/PrhaB-based expression system in an otherwise identical vector background. While the rhamnose-inducible system did not respond to lower inducer concentrations and always reached high levels over time when induced, expression levels of the pUCP20-ANT system could be adjusted to a range of distinct lower or higher levels by variation of anthranilate concentrations in the medium. Importantly, the anthranilate-inducible expression system worked also in strains of P. aeruginosa and P. putida and therefore will be most likely useful for physiological and biotechnological purposes in a wide range of pseudomonads.Key points• We established an anthranilate-inducible gene expression system for pseudomonads.• This system permits tuning of gene expression in a wide range of pseudomonads.• It will be very useful for physiological and biotechnological applications.
Journal Article
Educational entrepreneurship today
Frederick M. Hess and Michael Q. McShane have assembled a diverse lineup of high-profile contributors to examine the forces that drive innovation within and outside the traditional education sector. Educational Entrepreneurship Today offers critical perspectives on the impact of entrepreneurship and also includes case studies by leading entrepreneurs that illustrate the realities of leading disruptive change in education and pose guiding questions for the next generation of innovators.
Book
Dual electrocatalysis enables enantioselective hydrocyanation of conjugated alkenes
Chiral nitriles and their derivatives are prevalent in pharmaceuticals and bioactive compounds. Enantioselective alkene hydrocyanation represents a convenient and efficient approach for synthesizing these molecules. However, a generally applicable method featuring a broad substrate scope and high functional group tolerance remains elusive. Here, we address this long-standing synthetic problem using dual electrocatalysis. Using this strategy, we leverage electrochemistry to seamlessly combine two canonical radical reactions—cobalt-mediated hydrogen-atom transfer and copper-promoted radical cyanation—to accomplish highly enantioselective hydrocyanation without the need for stoichiometric oxidants. We also harness electrochemistry’s unique feature of precise potential control to optimize the chemoselectivity of challenging substrates. Computational analysis uncovers the origin of enantio-induction, for which the chiral catalyst imparts a combination of attractive and repulsive non-covalent interactions to direct the enantio-determining C–CN bond formation. This work demonstrates the power of electrochemistry in accessing new chemical space and providing solutions to pertinent challenges in synthetic chemistry.A general method for the enantioselective hydrocyanation of alkenes has been a long-standing synthetic challenge. Now, using a dual electrocatalytic approach that combines two synergistic redox catalytic cycles, a wide variety of chiral nitriles can be synthesized from conjugated alkenes in high enantioselectivity.
Journal Article
