We have studied the role of loop 9 in the function of neuronal nicotinic receptors. By systematically mutating the residues in the loop we have determined that the most important amino acids determining the coupling of binding to gating are the ones closer to the transmembrane region. Single mutations at location E173 in homomeric alpha7 receptors destroyed their function by completely abolishing the current while preserving the expression at the membrane. In contrast, heteromeric receptor alpha3beta4 with the same mutations retained some function. We conclude that loop 9 has a different role in the function of homomeric and heteromeric receptors.
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http://dx.doi.org/10.1016/j.bbamem.2009.12.013 | DOI Listing |
Drugs Aging
January 2025
Program for the Care and Study of the Aging Heart, Department of Medicine, Weill Cornell Medicine, 420 East 70th St, New York, NY, LH-36510063, USA.
There are several pharmacologic agents that have been touted as guideline-directed medical therapy for heart failure with preserved ejection fraction (HFpEF). However, it is important to recognize that older adults with HFpEF also contend with an increased risk for adverse effects from medications due to age-related changes in pharmacokinetics and pharmacodynamics of medications, as well as the concurrence of geriatric conditions such as polypharmacy and frailty. With this review, we discuss the underlying evidence for the benefits of various treatments in HFpEF and incorporate key considerations for older adults, a subpopulation that may be at higher risk for adverse drug events.
View Article and Find Full Text PDFCell Mol Life Sci
January 2025
Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hypoxia, or a state of low tissue oxygenation, has been characterized as an important feature of solid tumors that is related to aggressive phenotypes. The cellular response to hypoxia is controlled by Hypoxia-inducible factors (HIFs), a family of transcription factors. HIFs promote the transcription of gene products that play a role in tumor progression including proliferation, angiogenesis, metastasis, and drug resistance.
View Article and Find Full Text PDFComput Biol Chem
January 2025
Center of Excellence in Structural and Computational Biology, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand; Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address:
Janus kinases (JAKs) are a family of intracellular tyrosine kinases that play a crucial role in signal transduction pathways. JAK2 has been implicated in the pathogenesis of leukemia, making it a promising target for research aimed at reducing the risk of this disease. This study examined the potential of mimosamycin as a JAK2 inhibitor using both in vitro and in silico approaches.
View Article and Find Full Text PDFCancer Med
January 2025
Department of Gastrointestinal Surgery, Affiliated Hospital and Medical School of Nantong University, Nantong, China.
Background: Lymphatic metastasis in gastric cancer (GC) profoundly influences its prognosis, but the precise mechanism remains elusive. In this study, we identified the long noncoding RNA MIR181A2HG as being upregulated in GC and associated with LNs metastasis and prognosis.
Methods: The expression of MIR181A2HG in GC was identified through bioinformatics screening analysis and qRT-PCR validation.
Cureus
December 2024
Gastroenterolgy, Sindh Institute of Urology and Transplantation, Karachi, PAK.
Background Heart failure (HF) is commonly managed by addressing water and sodium (Na) balance, with arterial circulation playing a major role in influencing renal Na and water excretion. Recently, chloride (Cl) has been recognized as an important factor in HF, associated with volume regulation and its modulation of renin-angiotensin-aldosterone system (RAAS) activity through macula densa signaling, which impacts Na retention and neurohormonal activation. Acetazolamide, a carbonic anhydrase inhibitor, can enhance decongestion in HF by increasing urinary Na and Cl excretion when added to loop diuretics, a mechanism supported by prior studies demonstrating improved urine output and decongestion.
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