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| http://dx.doi.org/10.1016/j.brs.2024.03.008 | DOI Listing |
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Synapse-specific catecholaminergic modulation of neuronal glutamate release.
Proc Natl Acad Sci U S A
January 2025
Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720.
Norepinephrine in vertebrates and its invertebrate analog, octopamine, regulate the activity of neural circuits. We find that, when hungry, larvae switch activity in type II octopaminergic motor neurons (MNs) to high-frequency bursts, which coincide with locomotion-driving bursts in type I glutamatergic MNs that converge on the same muscles. Optical quantal analysis across hundreds of synapses simultaneously reveals that octopamine potentiates glutamate release by tonic type Ib MNs, but not phasic type Is MNs, and occurs via the G-coupled octopamine receptor (OAMB).
View Article and Find Full Text PDFComputational-aided rational mutation design of pertuzumab to overcome active HER2 mutation S310F through antibody-drug conjugates.
Proc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFOppositional and competitive instigation of hippocampal synaptic plasticity by the VTA and locus coeruleus.
Proc Natl Acad Sci U S A
January 2025
Department of Neurophysiology, Medical Faculty, Ruhr University Bochum, Bochum 44780, Germany.
The novelty, saliency, and valency of ongoing experiences potently influence the firing rate of the ventral tegmental area (VTA) and the locus coeruleus (LC). Associative experience, in turn, is recorded into memory by means of hippocampal synaptic plasticity that is regulated by noradrenaline sourced from the LC, and dopamine, sourced from both the VTA and LC. Two persistent forms of synaptic plasticity, long-term potentiation (LTP), and long-term depression (LTD) support the encoding of different kinds of spatial experience.
View Article and Find Full Text PDFUnveiling Sociocultural Barriers to Breast Cancer Awareness Among the South Asian Population: Case Study of Bangladesh and West Bengal, India.
JMIR Hum Factors
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New College of Florida, Sarasota, FL, United States.
Background: Bangladesh and West Bengal, India, are 2 densely populated South Asian neighboring regions with many socioeconomic and cultural similarities. In dealing with breast cancer (BC)-related issues, statistics show that people from these regions are having similar problems and fates. According to the Global Cancer Statistics 2020 and 2012 reports, for BC (particularly female BC), the age-standardized incidence rate is approximately 22 to 25 per 100,000 people, and the age-standardized mortality rate is approximately 11 to 13 per 100,000 for these areas.
View Article and Find Full Text PDFDevelopment and validation of a high-throughput qPCR platform for the detection of soil-transmitted helminth infections.
PLoS Negl Trop Dis
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DeWorm3 Project, Seattle, Washington, United States of America.
Background: Historically, soil-transmitted helminth (STH) control and prevention strategies have relied on mass drug administration efforts targeting preschool and school-aged children. While these efforts have succeeded in reducing morbidity associated with STH infection, recent modeling efforts have suggested that expanding intervention to treatment of the entire community could achieve transmission interruption in some settings. Testing the feasibility of such an approach requires large-scale clinical trials, such as the DeWorm3 cluster randomized trial.
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