Regulating the stability of microtubule (MT)-kinetochore attachments is fundamental to avoiding mitotic errors and ensuring proper chromosome segregation during cell division. Although biochemical factors involved in this process have been identified, their mechanics still need to be better understood. Here we introduce and simulate a mechanical model of MT-kinetochore interactions in which the stability of the attachment is ruled by the geometrical conformations of curling MT-protofilaments entangled in kinetochore fibrils. The model allows us to reproduce, with good accuracy, in vitro experimental measurements of the detachment times of yeast kinetochores from MTs under external pulling forces. Numerical simulations suggest that geometrical features of MT-protofilaments may play an important role in the switch between stable and unstable attachments.
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http://dx.doi.org/10.1016/j.bpj.2014.06.004 | DOI Listing |
Viruses
November 2024
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Kaposi's sarcoma-associated herpesvirus (KSHV), a γ-herpesvirus, is predominantly associated with Kaposi's sarcoma (KS) as well as two lymphoproliferative disorders: primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). Like other herpesviruses, KSHV employs two distinct life cycles: latency and lytic replication. To establish a lifelong persistent infection, KSHV has evolved various strategies to manipulate the epigenetic machinery of the host.
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December 2024
Innovation Platform of Micro/Nano Technology for Biosensing, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 311200, China.
As a crucial biomarker for the early warning and prognosis of liver cancer diseases, elevated levels of alpha-fetoprotein (AFP) are associated with hepatocellular carcinoma and germ cell tumors. Herein, we present a novel signal-on electrochemical aptamer sensor, utilizing AuNPs-MXene composite materials, for sensitive AFP quantitation. The AuNPs-MXene composite was synthesized through a simple one-step method and modified on portable microelectrodes.
View Article and Find Full Text PDFPharmaceutics
December 2024
Department of Chemistry, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.
Glucagon-like peptide-1 (GLP-1) receptor is currently one of the most explored targets exploited for the management of diabetes and obesity, with many aspects of its mechanisms behind cardiovascular protection yet to be fully elucidated. Research dedicated towards the development of oral GLP-1 therapy and non-peptide ligands with broader clinical applications is crucial towards unveiling the full therapeutic capacity of this potent class of medicines. This study describes the virtual screening of a natural product database consisting of 695,133 compounds for positive GLP-1 allosteric modulation.
View Article and Find Full Text PDFPharmaceuticals (Basel)
December 2024
Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait.
: The mammalian target of the rapamycin (mTOR) signaling pathway is a central regulator of cell growth, proliferation, metabolism, and survival. Dysregulation of mTOR signaling contributes to many human diseases, including cancer, diabetes, and obesity. Therefore, inhibitors against mTOR's catalytic kinase domain (KD) have been developed and have shown significant antitumor activities, making it a promising therapeutic target.
View Article and Find Full Text PDFPharmaceuticals (Basel)
December 2024
School of Life Sciences, Guangzhou University, Guangzhou 510006, China.
Background: Durazz. is one of the most popular herbs used for depression treatment, but the molecular basis for its mechanism of action has not been fully addressed. Previously, we isolated and identified two lignan glycoside derivatives that were shown to noncompetitively inhibit serotonin transporter (SERT) activity but with a relatively low inhibitory potency compared with those of conventional antidepressants.
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