Biology subjects

Rosenthal, H.

Publications and source records attributed to Rosenthal, H..

4 recordsLinked to original sources

bioRxiv2023

Rational development of a small-molecule activator of CK1γ2 that decreases C99 and beta-amyloid levels

Alzheimers disease (AD) is a debilitating neurodegenerative disorder characterized by the accumulation of beta-amyloid (A{beta}), C99, and Tau in vulnerable areas of the brain. Despite extensive research, current strategies to lower A{beta} levels have shown limited efficacy in slowing the cognitive decline associated with AD. Recent findings suggest that C99 may also play a crucial role in the pathogenesis of AD. Our laboratory has discovered that CK1{gamma}2 phosphorylates Presenilin 1 at the {gamma}-secretase complex, leading to decreased C99 and A{beta} levels. Thus, CK1{gamma}2 activation appears as a promising therapeutic target to lower both C99 and A{beta} levels. In this study, we demonstrate that CK1{gamma}2 is inhibited by intramolecular autophosphorylation and describe a high-throughput screen designed to identify inhibitors of CK1{gamma}2 autophosphorylation. We hypothesize that these inhibitors could lead to CK1{gamma}2 activation and increased PS1-Ser367 phosphorylation, ultimately reducing C99 and A{beta} levels. Using cultured cells, we investigated the impact of these compounds on C99 and A{beta} concentrations and confirmed that CK1{gamma}2 activation effectively reduces their levels. Our results provide proof of concept that CK1{gamma}2 is an attractive therapeutic target for AD. Future studies should focus on the identification of specific compounds that can inhibit CK1{gamma}2 autophosphorylation and evaluate their efficacy in preclinical models of AD. These studies will pave the way for the development of novel therapeutics for the treatment of AD.

pharmacology and toxicology↗

bioRxiv2022

Reinstatement of Pavlovian responses to alcohol cues by stress

RationaleStress may contribute to relapse to alcohol use in part by enhancing reactivity to cues previously paired with alcohol. Yet, standard models of stress-induced reinstatement generally use contingent presentations of alcohol-paired cues to reinforce instrumental behaviors, making it difficult to isolate the ability of cues to invigorate alcohol-seeking. ObjectiveHere we sought to test the impact of stress on behavioral responses to alcohol-paired cues, using a model of stress-induced reinstatement of Pavlovian conditioned approach, inspired by Nadia Chaudhris work on context-induced reinstatement. MethodsLong Evans rats were trained to associate one auditory cue with delivery of alcohol or sucrose and an alternative auditory cue with no reward. Following extinction training, rats were exposed to a stressor prior to being re-exposed to the cues under extinction conditions. We assessed the effects of yohimbine, intermittent footshock and olfactory cues paired with social defeat on responses to alcohol-paired cues, and the effects of yohimbine on responses to sucrose-paired cues. ResultsThe pharmacological stressor, yohimbine, enhanced Pavlovian responses to both alcohol and sucrose cues, but intermittent footshock and social defeat cues did not. ConclusionsWhile yohimbine elicited reinstatement of Pavlovian conditioned responses, these effects may be unrelated to activation of stress systems.

neuroscience↗

bioRxiv2021

The effects of host availability and fitness on Aedes albopictus blood feeding patterns in New York

Aedes albopictus is a competent vector of numerous pathogens, representing a range of transmission cycles involving unique hosts. Despite the important status of this vector, variation in its feeding patterns is poorly understood. We examined the feeding patterns of Ae. albopictus utilizing resting collections in Long Island, New York, and contextualized blood meal sources with host availability measured by household interviews and camera traps. We identified 90 blood meals, including 29 human, 22 cat, 16 horse, 12 opossum, 5 dog, 2 goat, and 1 rabbit, rat, squirrel and raccoon. Our study is the first to quantitatively assess Ae. albopictus feeding patterns in the context of host availability of wild animals in addition to humans and domestic animals. Host feeding indices showed that cats and dogs were fed upon disproportionately often compared to humans. Forage ratios suggested a tendency to feed on cats and opossums and to avoid raccoons, squirrels, and birds. This feeding pattern was different from another published study from Baltimore, where Ae. albopictus fed more often on rats than humans. To understand if these differences were due to host availability or mosquito population variation, we compared the fitness of Long Island and Baltimore Ae. albopictus after feeding on rat and human blood. In addition, we examined fitness within the Long Island population after feeding on human, rat, cat, horse, and opossum blood. Together, our results do not show major mosquito fitness differences by blood hosts, suggesting that fitness benefits do not drive Northeastern Ae. albopictus feeding patterns.

ecology↗

bioRxiv2020

Sugar feeding patterns of New York Aedes albopictus mosquitoes are affected by environmental dryness, flowers, and host seeking

BackgroundSugar feeding is an important behavior which may determine vector potential of mosquitoes. Sugar meals can reduce blood feeding frequency, enhance survival, and decrease fecundity, as well as provide energetic reserves to fuel energy intensive behaviors such as mating and host seeking. Sugar feeding behavior also can be harnessed for vector control (e.g. attractive toxic sugar baits). Few studies have addressed sugar feeding of Aedes albopictus, a vector of arboviruses of public health importance, including dengue and Zika viruses. To address this knowledge gap, we assessed sugar feeding patterns of Ae. albopictus for the first time in its invasive northeastern USA range. Methodology/ Principal FindingsUsing the cold anthrone fructose assay with robust sample sizes, we demonstrated that a large percentage of both male (49.6%) and female (41.8%) Ae. albopictus fed on plant or homopteran derived sugar sources within 24 hrs of capture. Our results suggest that sugar feeding behavior increases when environmental conditions are dry and may vary by behavioral status (host seeking vs. resting). Furthermore, mosquitoes collected on properties with flowers (>3 blooms) had higher fructose concentrations compared to those collected from properties with few to no flowers (0-3). Conclusions/SignificanceOur results provide the first evidence of Ae. albopictus sugar feeding behavior in the Northeastern US and reveal relatively high rates of sugar feeding. These results suggest the potential success for regional deployment of toxic sugar baits. In addition, we demonstrate the impact of several environmental and mosquito parameters (environmental dryness, presence of flowers, host seeking status, and sex) on sugar feeding. Placing sugar feeding behavior in the context of these environmental and mosquito parameters provides further insight into spatiotemporal dynamics of feeding behavior for Ae. albopictus, and in turn, provides information for evidence-based control decisions.

ecology↗