Cardiac Myosin Inhibition for Treatment of LVOT Obstruction in a Patient With Severe AS.

Aortic stenosis and obstructive hypertrophic cardiomyopathy are common conditions. When both are present in the same patient, the management can be challenging. We report what we believe to be the first time a cardiac myosin inhibitor has been used before transcutaneous aortic valve replacement.

Paucicellular Fibroma of the Ascending Aorta.

Primary tumors of the aorta are extremely rare. To the best of our knowledge, herein, we present the first case in the literature of a paucicellular fibroma originating from the aortic wall.

William R. Brinkley: A giant in biomedical research and public policy.

Susan A. Gerbi, Robert E. Palazzo, William C.

Risk stratification for nonagenarians undergoing transcatheter aortic valve replacement.

Background: There are disparate data on the outcomes of nonagenarians undergoing transcatheter aortic valve replacement (TAVR) compared with younger patients. The purpose of this study is to determine whether the Society of Thoracic Surgeons (STS) score can be used to identify the subset of nonagenarians that are at a significantly higher risk for poor postoperative outcomes after TAVR.

Methods: A total of 425 patients above the age of 80 underwent elective TAVR between 12/2013 and 2/2018 and were included in this study.

Using centrosome fragments in the directed assembly of microtubules.

In animal cells, microtubules are organized by centrosomes, which are 1-2 microm diameter organelles. The generation of functional centrosome fragments in-vitro through ultrasonication is presented along with microtubule assembly directed by the patterned centrosome fragments. While centrosome fragments are smaller than the fully constituted centrosomes, their microtubule organization function is retained.

The small organic compound HMN-176 delays satisfaction of the spindle assembly checkpoint by inhibiting centrosome-dependent microtubule nucleation.

HMN-176 is a potential new cancer therapeutic known to retard the proliferation of tumor cell lines. Here, we show that this compound inhibits meiotic spindle assembly in surf clam oocytes and delays satisfaction of the spindle assembly checkpoint in human somatic cells by inducing the formation of short and/or multipolar spindles. HMN-176 does not affect centrosome assembly, nuclear envelope breakdown, or other aspects of meiotic or mitotic progression, nor does it affect the kinetics of Spisula or mammalian microtubule (MT) assembly in vitro.

BRCA1 regulates gamma-tubulin binding to centrosomes.

Centrosomes are the cellular organelles that nucleate microtubules (MTs) via the activity of gamma-tubulin ring complex(s) (gammaTuRC) bound to the pericentriolar material of the centrosomes. BRCA1, the breast and ovarian cancer specific tumor suppressor, inhibits centrosomal MT nucleation via its ubiquitin ligase activity, and one of the known BRCA1 substrates is the key gammaTuRC component, gamma-tubulin. We analyzed the mechanism by which BRCA1 regulates centrosome function using an in vitro reconstitution assay, which includes separately staged steps.

Aurora-A kinase regulates breast cancer associated gene 1 inhibition of centrosome-dependent microtubule nucleation.

Breast cancer-associated gene 1 (BRCA1) regulates the duplication and the function of centrosomes in breast cells. We have previously shown that BRCA1 ubiquitin ligase activity directly inhibits centrosome-dependent microtubule nucleation. However, there is a paradox because centrosome microtubule nucleation potential is highest during mitosis, a phase when BRCA1 is most abundant at the centrosome.

Laser intensity dependence of femtosecond near-infrared optoinjection.

We report an experimental study on transient membrane permeabilization of single living bovine aortic endothelial cells (BAEC) by tightly focused femtosecond near-infrared laser pulses. The membrane permeabilization of the BAEC cells was studied as a function of the incident laser intensity. The rate of dye uptake by the cells was analyzed using time-lapse imaging.

Cyclin E/Cdk2 is required for sperm maturation, but not DNA replication, in early sea urchin embryos.

The cell cycle is driven by the activity of cyclin/cdk complexes. In somatic cells, cyclin E/cdk2 oscillates throughout the cell cycle and has been shown to promote S-phase entry and initiation of DNA replication. In contrast, cyclin E/cdk2 activity remains constant throughout the early embryonic development of the sea urchin and localizes to the sperm nucleus following fertilization.

Centrosome-associated RNA in surf clam oocytes.

Centrosomes are the major microtubule-organizing center in animal cells. They are composed of a pair of [9(3) + 0] centrioles surrounded by a relatively ill-defined pericentriolar matrix, provide the ciliary centriole-kinetosome (basal body) progenitor, and organize the assembly of microtubules into the mitotic spindle during cell division. Despite >100 years of microscopic observation and their obvious significance, our understanding of centrosome composition, dynamic organization, and mechanism of action is limited when compared with that of other cellular organelles.

Direct patterning of centrosome arrays as templates for the assembly of microtubules.

We have achieved, for the first time, the selective patterning of centrosomes onto solid substrates. The use of such patterned centrosome arrays as templates for the directed polymerization of microtubules was also demonstrated. Centrosomes are small organelles in animal cells that serve as nucleation and organization centers of microtubules.

Warming up at the poles.

Workshop on Centrosomes and Spindle Pole Bodies

Spontaneous right ventricular disruption following treatment of sternal infection.

Background: Spontaneous right ventricular disruption is a rare and frequently catastrophic event that occurs during the treatment of mediastinitis complicating median sternotomy wound.

Objective: The purpose of this study is to understand the pathogenesis of the spontaneous right ventricular disruption and to suggest strategies for the prevention and treatment of this rare but potentially fatal complication of cardiac surgery.

Methods: We report three cases as an introduction to the review of 39 cases found in the English-language literature.

Rapid tau aggregation and delayed hippocampal neuronal death induced by persistent thrombin signaling.

Tau hyperphosphorylation, leading to self-aggregation, is widely held to underlie the neurofibrillary degeneration found in Alzheimer's disease (AD) and other tauopathies. However, it is unclear exactly what environmental factors may trigger this pathogenetic tau hyperphosphorylation. From several perspectives, the coagulation serine protease, thrombin, has been implicated in AD and activates several different protein kinase pathways but has not previously been shown how it may contribute to AD pathogenesis.

Effect of gamma-synuclein overexpression on matrix metalloproteinases in retinoblastoma Y79 cells.

gamma-Synuclein is a small cytoplasmic protein implicated in neurodegenerative diseases and cancer. However, the mechanism of its involvement in diseases is not clear. We studied the role of gamma-synuclein in the regulation of matrix metalloproteinases in retinoblastoma cell culture.

Characterization of Cep135, a novel coiled-coil centrosomal protein involved in microtubule organization in mammalian cells.

By using monoclonal antibodies raised against isolated clam centrosomes, we have identified a novel 135-kD centrosomal protein (Cep135), present in a wide range of organisms. Cep135 is located at the centrosome throughout the cell cycle, and localization is independent of the microtubule network. It distributes throughout the centrosomal area in association with the electron-dense material surrounding centrioles.