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"McCarty, Peter"
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Jeremy draws a monster
A young boy who spends most of his time alone in his bedroom makes new friends after the monster in his drawing becomes a monstrous nuisance.
Book
Modelling of spatially extended open chemical systems
The development of open well-mixed chemical reactors led to tremendous advances in the understanding of the temporal behavior of nonlinear chemical systems. For instance, many transitions between different asymptotic states of the system are now well understood in terms of bifurcation theory. However, for spatially extended (unmixed) reactions, only closed systems were experimentally available, and theoretical investigation of such systems naturally focused on matters other than bifurcations between the asymptotic states of the system. The recent introduction of open, unmixed chemical systems has now thrown open the door to theoretical investigation of these systems in terms of the different asymptotic states available to the system, as well as how and when the system can undergo transitions from one state to another. We have formulated models for several such open chemical systems, and have used both analytic and numerical methods to study various aspects of their dynamical behavior. We examine the bifurcations that occur between the different kinds of spatio-temporal structures that can appear in these systems. We will consider the effects that spatial inhomogeneities, both intended and not, can have on the dynamical behavior of these structures. We will also examine in several contexts the connection between the complex spatio-temporal structures in the extended system and the underlying local behavior of the chemistry. This will lead to a qualitative understanding of why the system is doing what it is. We will also examine the process of convection-enhanced diffusion, which is used in some open spatially-extended chemical systems to increase the size of the spatial patterns occurring in the system.
Dissertation
The monster returns
When the monster that Jeremy created threatens to return, Jeremy enlists his neighbors to help him with a creative solution to the problem.
Book
Sequential action of a tRNA base editor in conversion of cytidine to pseudouridine
Post-transcriptional RNA editing modulates gene expression in a condition-dependent fashion. We recently discovered C-to-Ψ editing in
Vibrio cholerae
tRNA. Here, we characterize the biogenesis, regulation, and functions of this previously undescribed RNA editing process. We show that an enzyme, TrcP, mediates the editing of C-to-U followed by the conversion of U to Ψ, consecutively. AlphaFold-2 predicts that TrcP consists of two globular domains (cytidine deaminase and pseudouridylase) and a long helical domain. The latter domain tethers tRNA substrates during both the C-to-U editing and pseudouridylation, likely enabling a substrate channeling mechanism for efficient catalysis all the way to the terminal product. C-to-Ψ editing both requires and suppresses other modifications, creating an interdependent network of modifications in the tRNA anticodon loop that facilitates coupling of tRNA modification states to iron availability. Our findings provide mechanistic insights into an RNA editing process that likely promotes environmental adaptation.
C-to-Ψ conversion is a previously uncharacterized form of base editing. Here, the authors describe how the TrcP enzyme catalyzes this process in a stepwise fashion and how this editing process is controlled by a network of modifications and nutrient availability to optimize translation efficiency.
Journal Article
Henry in love
On the first day of school, Henry the cat vies for the attention of the most amazing girl in class, Chloe Rabbit.
Book
LETTERS
I enjoyed reading James Klurfeld's moving tribute to his high school English teacher, Ronald Barry, mostly because Klurfeld was one of my most memorable teachers [\"One great teacher can make a lasting difference,\" Opinion, June 30]. In a ratty, overcrowded building in South Jamaica, Klurfeld inspired and encouraged his classes in a way few ever could. We were all very sad when he left his short career as a teacher for journalism. According to a recent column, Ann Coulter is misunderstood and is really a funny, ironic wit in the tradition of Jonathan Swift [\"Ann Coulter: extreme satire,\" Opinion, June 29]. I think I understand hate when I see it, and this is exactly what Coulter peddles, hate. She hates all things she considers liberal, whether they be politicians, people or ideas. To say that this administration has stopped hiring nonpolitical ADAs is inaccurate and ironic coming from a former employee of a DA who took thousands of dollars in contributions from his ADAs. This DA won't accept a dime from an ADA in her office and is the author of the strictest nonpolitical policy of any DA in New York State.
Newspaper Article
Bunny dreams
\"In bunny dreams, anything can happen. A bunny might know the ABCs, or count by 1-2-3s. A bunny might find the perfect carrot. A bunny might hop, hop, hop. or even fly! But every bunny needs a cozy place to rest\"-- Provided by publisher.
Book
Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs
Dean Sheppard and his colleagues show that genetic or pharmacological inhibition of α
v
integrin signaling ameliorates fibrosis in several solid organs.
Myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis, and hepatic stellate cells (HSCs) are believed to be the major source of myofibroblasts in the liver. To date, robust systems to genetically manipulate these cells have not been developed. We report that Cre under control of the promoter of
Pdgfrb
(
Pdgfrb-
Cre) inactivates
loxP
-flanked genes in mouse HSCs with high efficiency. We used this system to delete the gene encoding α
v
integrin subunit because various α
v
-containing integrins have been suggested as central mediators of fibrosis in multiple organs. Such depletion protected mice from carbon tetrachloride–induced hepatic fibrosis, whereas global loss of β
3
, β
5
or β
6
integrins or conditional loss of β
8
integrins in HSCs did not. We also found that
Pdgfrb-
Cre effectively targeted myofibroblasts in multiple organs, and depletion of the α
v
integrin subunit using this system was protective in other models of organ fibrosis, including pulmonary and renal fibrosis. Pharmacological blockade of α
v
-containing integrins by a small molecule (CWHM 12) attenuated both liver and lung fibrosis, including in a therapeutic manner. These data identify a core pathway that regulates fibrosis and suggest that pharmacological targeting of all α
v
integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases.
Journal Article
Frozen girl
Discussses the discovery, history, and significance of an Incan mummy found frozen in the mountains of Peru.
Book
Antifungal Pipeline
In many ways, fungal diseases are forgotten or neglected. Given the significantly lower frequency compared to similar bacterial etiologies across the spectrum of infectious syndromes, it makes sense that anti-bacterial agents have seen the bulk of development in recent decades. The vast majority of new antifungal medications approved for use in the past 10 years have been new versions in the same class as existing agents. Clinical mycology is crying out for new mechanisms of action in the setting of rising resistance and emergence of new organisms. Fortunately, this trend appears to be reversing. There are numerous agents in advanced stages of development offering novel dosing regimens and mechanisms of action to combat these threats. Herein we review seven antifungal agents that we hope to see come to market in the coming years to aid physicians in the treatment of mucocutaneous and invasive fungal infections.
Journal Article