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Nat Struct Mol Biol 2022 May 16;29(5):483-492. Epub 2022 May 16.

Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.

A pair of extensively modified microtubules form the central apparatus (CA) of the axoneme of most motile cilia, where they regulate ciliary motility. The external surfaces of both CA microtubules are patterned asymmetrically with large protein complexes that repeat every 16 or 32 nm. The composition of these projections and the mechanisms that establish asymmetry and longitudinal periodicity are unknown. Read More

Molecules 2022 Apr 30;27(9). Epub 2022 Apr 30.

Department of Pharmacology, Perm State Academy of Pharmacy, 614990 Perm, Russia.

Despite the tubulin-binding agents (TBAs) that are widely used in the clinic for cancer therapy, tumor resistance to TBAs (both inherited and acquired) significantly impairs their effectiveness, thereby decreasing overall survival (OS) and progression-free survival (PFS) rates, especially for the patients with metastatic, recurrent, and unresectable forms of the disease. Therefore, the development of novel effective drugs interfering with the microtubules' dynamic state remains a big challenge in current oncology. We report here about the novel ethyl 2-amino-1-(furan-2-carboxamido)-5-(2-aryl/tert-butyl-2-oxoethylidene)-4-oxo-4,5-dihydro-1H-pyrrole-3-carboxylates (EAPCs) exhibiting potent anti-cancer activities against the breast and lung cancer cell lines in vitro. Read More

Int J Mol Sci 2022 Apr 23;23(9). Epub 2022 Apr 23.

Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA.

Reactive oxygen species (ROS) cause oxidative stress by generating reactive aldehydes known as 4-hydroxynonenal (4-HNE). 4-HNE modifies protein via covalent adduction; however, little is known about the degradation mechanism of 4-HNE-adducted proteins. Autophagy is a dynamic process that maintains cellular homeostasis by removing damaged organelles and proteins. Read More

Eur J Med Chem 2022 May 1;238:114409. Epub 2022 May 1.

Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, 79104, Freiburg, Germany.

The search of new therapeutic tools for the treatment of cancer is being a challenge for medicinal chemists. Due to their role in different pathological conditions, histone deacetylase (HDAC) enzymes are considered valuable therapeutic targets. HDAC6 is a well-investigated HDAC-class IIb enzyme mainly characterized by a cytoplasmic localization; HDAC8 is an epigenetic eraser, unique HDAC-class I member that displays some aminoacidic similarity to HDAC6. Read More

ACS Macro Lett 2021 09 3;10(9):1151-1158. Epub 2021 Sep 3.

Department of Physics and Biophysics, University of San Diego, 5998 Alcala Park, San Diego, California 92110, United States.

The composite cytoskeleton, comprising interacting networks of semiflexible actin and rigid microtubules, generates forces and restructures by using motor proteins such as myosins to enable key processes including cell motility and mitosis. Yet, how motor-driven activity alters the mechanics of cytoskeleton composites remains an open challenge. Here, we perform optical tweezers microrheology and confocal imaging of composites with varying actin-tubulin molar percentages (25-75, 50-50, and 75-25), driven by light-activated myosin II motors, to show that motor activity increases the elastic plateau modulus by over 2 orders of magnitude by active restructuring of both actin and microtubules that persists for hours after motor activation has ceased. Read More