Malaria remains a major public health issue, infecting nearly 220 million people every year. The spread of drug-resistant strains of Plasmodium falciparum around the world threatens the progress made ...against this disease. Therefore, identifying druggable and essential pathways in P. falciparum parasites remains a major area of research. One poorly understood area of parasite biology is the formation of disulfide bonds, which is an essential requirement for the folding of numerous proteins. Specialized chaperones with thioredoxin (Trx) domains catalyze the redox functions necessary for breaking incorrect and forming correct disulfide bonds in proteins. Defining the substrates of these redox chaperones is difficult and immunoprecipitation based assays cannot distinguish between substrates and interacting partners. Further, the substrate or client interactions with the redox chaperones are usually transient in nature. Activity based crosslinkers that rely on the nucleophilic cysteines on Trx domains and the disulfide bond forming cysteines on clients provide an easily scalable method to trap and identify the substrates of Trx-domain containing chaperones. The cell permeable crosslinker divinyl sulfone (DVSF) is active only in the presence of nucleophilic cysteines in proteins and, therefore, traps Trx domains with their substrates, as they form mixed disulfide bonds during the course of their catalytic activity. This allows the identification of substrates that rely on Trx activity for their folding, as well as discovering small molecules that interfere with Trx domain activity.Graphic abstract:Identification of thioredoxin domain substrates via divinylsulfone crosslinking and immunoprecipitation-mass spectrometry.
Malaria remains a major public health issue, infecting nearly 220 million people every year. The spread of drug-resistant strains of
around the world threatens the progress made against this disease. ...Therefore, identifying druggable and essential pathways in
parasites remains a major area of research. One poorly understood area of parasite biology is the formation of disulfide bonds, which is an essential requirement for the folding of numerous proteins. Specialized chaperones with thioredoxin (Trx) domains catalyze the redox functions necessary for breaking incorrect and forming correct disulfide bonds in proteins. Defining the substrates of these redox chaperones is difficult and immunoprecipitation based assays cannot distinguish between substrates and interacting partners. Further, the substrate or client interactions with the redox chaperones are usually transient in nature. Activity based crosslinkers that rely on the nucleophilic cysteines on Trx domains and the disulfide bond forming cysteines on clients provide an easily scalable method to trap and identify the substrates of Trx-domain containing chaperones. The cell permeable crosslinker divinyl sulfone (DVSF) is active only in the presence of nucleophilic cysteines in proteins and, therefore, traps Trx domains with their substrates, as they form mixed disulfide bonds during the course of their catalytic activity. This allows the identification of substrates that rely on Trx activity for their folding, as well as discovering small molecules that interfere with Trx domain activity. Graphic abstract: Identification of thioredoxin domain substrates via divinylsulfone crosslinking and immunoprecipitation-mass spectrometry.
Fundamental knowledge about the brain is primarily acquired through two distinct groups of methods. Techniques with low spatiotemporal resolution, such as functional magnetic resonance imaging (fMRI) ...and electroencephalography (EEG), have provided insights into meso- and macroscopic neural activity. Owing to their noninvasiveness and growing availability to the general population, these techniques enable longitudinal studies of changes in brain states in the same individuals. Conversely, high spatiotemporal resolution techniques, such as single-neuron electrophysiology and imaging, have facilitated a deep understanding of the basic building blocks of the brain, from individual ion channels to single-neuron activity, and to region-wide dynamics of neuronal circuitry. However, high spatiotemporal techniques have largely been precluded from translating to long-term studies because of their invasiveness and a mismatch of properties with neural tissue. This spatiotemporal span (cross-sectional vs. longitudinal) and resolution gap has led to a significant division in our exploration of the brain's dynamics.This dissertation aims to explore flexible electronics, a recently developed electrophysiology tool, as a platform for bridging this very gap to enable a new longitudinal understanding of the brain at the single-neuron resolution. In Chapter 1, I provide background on the electric basis of neuronal communication, a historical perspective on methods used to electrically interface with the nervous system, and present an argument for developing more compliant, brain-like neural probes. Chapter 2 introduces flexible electronics as a competitive class of neural probes for interfacing with the brain as compared with conventional neurotechnologies and reviews the properties and previous applications of bioinspired, brain-like mesh electronics. In Chapter 3, I present key hardware improvements made to the mesh electronics platform to enable chronic interfacing with the brain. Chapter 4 reviews work conducted to facilitate simultaneous electrophysiology and behavioral neuroscience through the integration of a virtual reality (VR) system. Chapter 5 is centered around work measuring the longitudinal neural correlates of aging and neurodegeneration in wildtype (WT) and 3xTg Alzheimer's Disease (AD) mouse models, respectively. In Chapter 6, I introduce a novel application of mesh electronics to studying spatial cognition in a nonstandard amphibian model, the cane toad (Rhinella marina). Finally, I present a broad outlook for the future of flexible electronics and its applications to neuroscience.
A2059G mutation in the 23S rRNA gene is the only reported mechanism conferring high-level azithromycin resistance (HL-AZMR) in
Through U.S. gonococcal antimicrobial resistance surveillance projects, ...we identified four HL-AZMR gonococcal isolates lacking this mutational genotype. Genetic analysis revealed an A2058G mutation of 23S rRNA alleles in all four isolates.
selected gonococcal strains with homozygous A2058G recapitulated the HL-AZMR phenotype. Taken together, we postulate that the A2058G mutation confers HL-AZMR in
.
Hunger for legitimacy based on glories of an idyllic (and fast-receding) past is nothing new. In the final third of the nineteenth century, the works of American artists Edwin Austin Abbey, Frank ...Millet, and George Henry Boughton reflected an engagement with the historical past that moved beyond memory to fantasy. In so doing, these images reveal the palimpsestic nature of American identity in the transatlantic gilded age. In order to target the constructs of memory and identity, this article includes relevant contextual information for the American artists and genre images in question. The bulk of the article focuses on genre and narrative scenes by Abbey and Boughton set in seventeenth and eighteenth-century England and the American Colonies, respectively. While an anachronistic scene might be out of reach of personal memory, setting the scene in a recent past could place it within access of collective memory. By deformalizing the past, the artist renders that past moment more accessible to his intended audience. From subject matter and style to reception, these images demonstrate an important facet of contemporary American identity, even as it has become increasingly self-reflexive: nostalgia for an imagined, possibly fantastical, history that legitimates our present.
El hambre de legitimidad basada en las glorias de un pasado idílico (y en retroceso rápido) no es nada nuevo. En el último tercio del siglo XIX, las obras de los artistas estadounidenses Edwin Austin ...Abbey, Frank Millet y George Henry Boughton reflejaron un compromiso con el pasado histórico que se trasladó más allá de la memoria a la fantasía. Al hacerlo, estas imágenes revelan la naturaleza palimpsésica de la identidad estadounidense en la era dorada transatlántica. Para aportar a las construcciones de la memoria y la identidad, este artículo incluye información contextual relevante sobre los artistas estadounidenses y las imágenes de género en cuestión. La mayor parte del artículo se centra en el género y las escenas narrativas de Abbey y Boughton ambientadas en la Inglaterra y las colonias americanas de los siglos XVII y XVIII, respectivamente. Si bien una escena anacrónica puede estar fuera del alcance de la memoria personal, establecer la escena en un pasado reciente podría colocarla dentro del acceso de la memoria colectiva. Al desformalizar el pasado, el artista hace que ese momento pasado sea más accesible para su público objetivo. Desde el tema y el estilo hasta la recepción, estas imágenes demuestran una faceta importante de la identidad estadounidense contemporánea, incluso a pesar de habers evuelto cada vez más auto-reflexiva: la nostalgia de una historia imaginada, posiblemente fantástica, que legitima nuestro presente.
Hunger for legitimacy based on glories of an idyllic (and fast-receding) past is
nothing new. In the final third of the nineteenth century, the works of American artists
Edwin Austin Abbey, Frank ...Millet, and George Henry Boughton reflected an engagement
with the historical past that moved beyond memory to fantasy. In so doing, these images
reveal the palimpsestic nature of American identity in the transatlantic gilded age.
In order to target the constructs of memory and identity, this article includes relevant
contextual information for the American artists and genre images in question. The bulk
of the article focuses on genre and narrative scenes by Abbey and Boughton set in seventeenth and eighteenth-century England and the American Colonies, respectively. While
an anachronistic scene might be out of reach of personal memory, setting the scene in a
recent past could place it within access of collective memory. By de-formalizing the past,
the artist renders that past moment more accessible to his intended audience.
From subject matter and style to reception, these images demonstrate an important facet
of contemporary American identity, even as it has become increasingly self-reflexive: nostalgia for an imagined, possibly fantastical, history that legitimates our present.
A fome por legitimidade baseada em glórias de um passado idílico (e que re-trocede rapidamente) não é novidade. No terço final do século XIX, as obras dos artistas norte-americanos Edwin Austin Abbey, Frank Millet e George Henry Boughton refletiam um compromisso com o passado histórico que ultrapassava a memória e a fantasia. Ao fazê-lo, essas imagens revelam a natureza palimpséstica da identidade americana na era dourada transatlântica.A fim de direcionar os construtos de memória e identidade, este artigo inclui informações contextuais relevantes para os artistas americanos e imagens de gênero em questão. A maior parte do artigo enfoca cenas de gênero e narrativas de Abbey e Boughton, ambien-tadas na Inglaterra dos séculos XVII e XVIII e nas Colônias Americanas, respectivamente. Enquanto uma cena anacrônica pode estar fora do alcance da memória pessoal, definir a cena em um passado recente pode colocá-la no acesso à memória coletiva. Ao des-forma-lizar o passado, o artista torna esse momento passado mais acessível ao seu público-alvo.Do tema e estilo à recepção, essas imagens demonstram uma importante faceta da identi-dade americana contemporânea, ao mesmo tempo em que se tornou cada vez mais auto--reflexiva: nostalgia por uma história imaginária, possivelmente fantástica, que legitima nosso presente.
El hambre de legitimidad basada en las glorias de un pasado idílico (y en retroceso rápido) no es nada nuevo. En el último tercio del siglo XIX, las obras de los artistas
estadounidenses Edwin Austin Abbey, Frank Millet y George Henry Boughton reflejaron un compromiso con el pasado histórico que se trasladó más allá de la memoria a
la fantasía. Al hacerlo, estas imágenes revelan la naturaleza palimpsésica de la identidad
estadounidense en la era dorada transatlántica. Para aportar a las construcciones de la
memoria y la identidad, este artículo incluye información contextual relevante sobre los
artistas estadounidenses y las imágenes de género en cuestión. La mayor parte del artículo
se centra en el género y las escenas narrativas de Abbey y Boughton ambientadas en la
Inglaterra y las colonias americanas de los siglos XVII y XVIII, respectivamente. Si bien
una escena anacrónica puede estar fuera del alcance de la memoria personal, establecer la
escena en un pasado reciente podría colocarla dentro del acceso de la memoria colectiva.
Al desformalizar el pasado, el artista hace que ese momento pasado sea más accesible para
su público objetivo. Desde el tema y el estilo hasta la recepción, estas imágenes demuestran
una faceta importante de la identidad estadounidense contemporánea, incluso a pesar de
habers evuelto cada vez más auto-reflexiva: la nostalgia de una historia imaginada, posiblemente fantástica, que legitima nuestro presente.
This study explored the relationships among alcohol use, knowledge related to alcohol, and major (grouped by college). Participants consisted of 134 students recruited from a psychology research ...pool. The participants completed a measure about alcohol use (AUDIT-C) and a measure about knowledge related to alcohol (SAQ). This study found that gender was not significantly related to alcohol use; however, there was a significant difference between genders for alcohol-related knowledge in the overall sample. Men were found to have more knowledge related to alcohol than women. Additionally, this study found a statistically significant difference for alcohol use by college. The students in the College of Basic and Applied Sciences endorsed consuming more alcohol than the students in the College of Behavioral and Health Sciences. There was no difference found on knowledge related to alcohol by college. Lastly, there were positive correlations found between alcohol use and knowledge related to alcohol.
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