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Regulation of Dopamine Release by Tonic Activity Patterns in the Striatal Brain Slice.
ACS Chem Neurosci
January 2025
Departments of Psychiatry and Neurology, Division of Molecular Therapeutics, New York State Psychiatric Institute, Columbia University Medical Center, New York, New York 10032, United States.
Voluntary movement, motivation, and reinforcement learning depend on the activity of ventral midbrain neurons, which extend axons to release dopamine (DA) in the striatum. These neurons exhibit two patterns of action potential activity: low-frequency tonic activity that is intrinsically generated and superimposed high-frequency phasic bursts that are driven by synaptic inputs. acute striatal brain preparations are widely employed to study the regulation of evoked DA release but exhibit very different DA release kinetics than recordings.
View Article and Find Full Text PDFSynthetic rational design of live-attenuated Zika viruses based on a computational model.
Nucleic Acids Res
January 2025
SynVaccine Ltd, Ramat Hachayal, 3 Golda Meir Street, Science Park, Nes Ziona 7403648, Israel.
Many viruses of the Flaviviridae family, including the Zika virus (ZIKV), are human pathogens of significant public health concerns. Despite extensive research, there are currently no approved vaccines available for ZIKV and specifically no live-attenuated Zika vaccine. In this current study, we suggest a novel computational algorithm for generating live-attenuated vaccines via the introduction of silent mutation into regions that undergo selection for strong or weak local RNA folding or into regions that exhibit medium levels of sequence conservation.
View Article and Find Full Text PDFRoadmap to discovery and early development of an mRNA loaded LNP formulation for liver therapeutic genome editing.
Expert Opin Drug Deliv
January 2025
Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Macclesfield, UK.
Introduction: mRNA therapeutics were a niche area in drug development before COVIDvaccines. Now they are used in vaccine development, for non-viral therapeuticgenome editing, chimericantigen receptor T (CAR T) celltherapies and protein replacement. mRNAis large, charged, and easily degraded by nucleases.
View Article and Find Full Text PDFMissense variants weakening a SOX9 phosphodegron linked to odontogenesis defects, scoliosis and other skeletal features.
HGG Adv
January 2025
Department of Surgery, Division of Orthopaedics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Electronic address:
SOX9 encodes an SRY-related transcription factor critical for chondrogenesis and sex determination among other processes. Loss-of-function variants cause campomelic dysplasia and Pierre Robin Sequence, while both gain- and loss-of-function variants cause disorders of sex development. SOX9 has also been linked to scoliosis and cancers, but variants are undetermined.
View Article and Find Full Text PDFDoxycycline Restores Gemcitabine Sensitivity in Preclinical Models of Multidrug-Resistant Intrahepatic Cholangiocarcinoma.
Cancers (Basel)
January 2025
Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
Background/objectives: Intrahepatic cholangiocarcinoma (iCCA) is a malignant liver tumor with a rising global incidence and poor prognosis, largely due to late-stage diagnosis and limited effective treatment options. Standard chemotherapy regimens, including cisplatin and gemcitabine, often fail because of the development of multidrug resistance (MDR), leaving patients with few alternative therapies. Doxycycline, a tetracycline antibiotic, has demonstrated antitumor effects across various cancers, influencing cancer cell viability, apoptosis, and stemness.
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