To function in diverse cellular processes, the dynamic properties of microtubules must be tightly regulated. Cellular microtubules are influenced by a multitude of regulatory proteins, but how their activities are spatiotemporally coordinated within the cell, or on specific microtubules, remains mostly obscure. The conserved kinesin-8 motor proteins are important microtubule regulators, and family members from diverse species combine directed motility with the ability to modify microtubule dynamics. Yet how kinesin-8 activities are appropriately deployed in the cellular context is largely unknown. Here we reveal the importance of the nonmotor tail in differentially controlling the physiological functions of the budding yeast kinesin-8, Kip3. We demonstrate that the tailless Kip3 motor domain adequately governs microtubule dynamics at the bud tip to allow spindle positioning in early mitosis. Notably, discrete regions of the tail mediate specific functions of Kip3 on astral and spindle microtubules. The region proximal to the motor domain operates to spatially regulate astral microtubule stability, while the distal tail serves a previously unrecognized role to control the timing of mitotic spindle disassembly. These findings provide insights into how nonmotor tail domains differentially control kinesin functions in cells and the mechanisms that spatiotemporally control the stability of cellular microtubules.
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http://dx.doi.org/10.1091/mbc.E18-03-0199 | DOI Listing |
Khirurgiia (Mosk)
December 2024
Penza State University, Penza, Russia.
Objective: To analyze the results of surgical treatment of discrete subaortic stenosis and identify the main factors of left ventricular outflow tract (LVOT) restenosis in long-term postoperative period.
Material And Methods: There were 87 surgical interventions in 63 patients with congenital subaortic stenosis between 2008 and 2023. Mean preoperative peak systolic LVOT pressure gradient was 72 mmHg (50-110 mmHg).
BMC Psychiatry
December 2024
Department of Economics, University of Bergen, Postboks, Bergen, 7802, 5020, Norway.
Background: Opioid use disorders constitute a vast disease burden, need for comprehensive treatment, and substantial costs to individuals, families, and society. The multifaceted needs of people with opioid dependence call for integrated care. The study aims to assess the added value of an integrated medically assisted rehabilitation (MAR) program providing opioid agonist therapy for patients with opioid dependence as compared to the standard of care (SoC) in Norway.
View Article and Find Full Text PDFJ Biomol Struct Dyn
December 2024
Amity Institute of Biotechnology, Amity University, Kolkata, India.
The first FDA approved, MDR-TB inhibitory drug bedaquiline (BDQ), entraps the c-ring of the proton-translocating F region of enzyme ATP synthase of , thus obstructing successive ATP production. Present-day BDQ-resistance has been associated with cardiotoxicity and mutation(s) in the atpE gene encoding the c subunit of ATP synthase (ATPc) generating five distinct ATPc mutants: Ala63→Pro, Ile66→Met, Asp28→Gly, Asp28→Val and Glu61→Asp. We created three discrete libraries, first by repurposing bedaquiline via scaffold hopping approach, second one having natural plant compounds and the third being experimentally derived analogues of BDQ to identify one drug candidate that can inhibit ATPc activity more efficiently with less toxic properties.
View Article and Find Full Text PDFFront Oncol
December 2024
Department of Radiology, Huadong Hospital, Fudan University, Shanghai, China.
Background: This study aimed to develop and validate a multiregional radiomic-based composite model to predict symptomatic radiation pneumonitis (SRP) in non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT).
Materials And Methods: 189 patients from two institutions were allocated into training, internal validation and external testing cohorts. The associations between the SRP and clinic-dosimetric factors were analyzed using univariate and multivariate regression.
J Environ Radioact
December 2024
College of Nuclear Technology and Automation Engineering, Chengdu University of Technology, Chengdu, 610000, China; Applied Nuclear Technology in Geosciences Key Laboratory of Sichuan Province, Chengdu, 610000, China. Electronic address:
Airborne gamma ray spectrum detection technology is an effective means to measure the concentration and spatial distribution of natural radionuclides in environmental media such as surface rocks and soil during aviation flight. Therefore, it is vital to fully explore the radiation information related to mineralization in airborne gamma spectrometry data and explore the dose distribution law of gamma radiation field of radionuclides in the detection area. This paper is based on the theoretical calculation model of ground-air interface gamma radiation field.
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