Quantitative analyses of single mitochondrial components reveal an early role of small-mitochondrial-networks in priming neoplasticity.

Unlabelled: Quantitative understanding of mitochondrial heterogeneity is necessary for elucidating the precise role of these multifaceted organelles in tumor cell development. We demonstrate an early mechanistic role of mitochondria in initiating neoplasticity by performing quantitative analyses of structure-function of single mitochondrial components coupled with single cell transcriptomics. We demonstrate that the large Hyperfused-Mitochondrial-Networks (HMNs) of keratinocytes promptly get converted to the heterogenous Small-Mitochondrial-Networks (SMNs) as the stem cell enriching dose of the model carcinogen, TCDD, depolarizes mitochondria.

Direct cardiac reprogramming via combined CRISPRa-mediated endogenous Gata4 activation and exogenous Mef2c and Tbx5 expression.

Direct cardiac reprogramming of fibroblasts into induced cardiomyocytes (iCMs) can be achieved by ectopic expression of cardiac transcription factors (TFs) via viral vectors. However, risks like genomic mutations, viral toxicity, and immune response limited its clinical application. Transactivation of endogenous TFs emerges as an alternative approach that may partially mitigate some of the risks.

Cardiac Aging in the Multi-Omics Era: High-Throughput Sequencing Insights.

Cardiovascular diseases are a leading cause of mortality worldwide, and the risks of both developing a disease and receiving a poor prognosis increase with age. With increasing life expectancy, understanding the mechanisms underlying heart aging has become critical. Traditional techniques have supported research into finding the physiological changes and hallmarks of cardiovascular aging, including oxidative stress, disabled macroautophagy, loss of proteostasis, and epigenetic alterations, among others.

Single-cell chromatin profiling reveals genetic programs activating proregenerative states in nonmyocyte cells.

Cardiac regeneration requires coordinated participation of multiple cell types whereby their communications result in transient activation of proregenerative cell states. Although the molecular characteristics and lineage origins of these activated cell states and their contribution to cardiac regeneration have been studied, the extracellular signaling and the intrinsic genetic program underlying the activation of the transient functional cell states remain largely unexplored. In this study, we delineated the chromatin landscapes of the noncardiomyocytes (nonCMs) of the regenerating heart at the single-cell level and inferred the cis-regulatory architectures and trans-acting factors that control cell type-specific gene expression programs.

Fibroblast Reprogramming in Cardiac Repair.

Cardiovascular disease is one of the major causes of death worldwide. Limited proliferative capacity of adult mammalian cardiomyocytes has prompted researchers to exploit regenerative therapy after myocardial injury, such as myocardial infarction, to attenuate heart dysfunction caused by such injury. Direct cardiac reprogramming is a recently emerged promising approach to repair damaged myocardium by directly converting resident cardiac fibroblasts into cardiomyocyte-like cells.

Can we stop one heart from breaking: triumphs and challenges in cardiac reprogramming.

Ischemic cardiac injury causes irreversible muscle loss and scarring, but recent years have seen dramatic advances in cardiac reprogramming, the field focused on regenerating cardiac muscle. With SARS-CoV2 increasing the age-adjusted cardiovascular disease mortality rate, it is worth evaluating the state of this field. Here, we summarize novel innovations in reprogramming strategies, insights into their mechanisms, and technologies for factor delivery.

Tracing the history of a heart.

Newly developed tools will help researchers understand how the human heart develops and build better models to study and treat congenital heart disease.

Fine-tuned repression of Drp1-driven mitochondrial fission primes a 'stem/progenitor-like state' to support neoplastic transformation.

Gene knockout of the master regulator of mitochondrial fission, Drp1, prevents neoplastic transformation. Also, mitochondrial fission and its opposing process of mitochondrial fusion are emerging as crucial regulators of stemness. Intriguingly, stem/progenitor cells maintaining repressed mitochondrial fission are primed for self-renewal and proliferation.

Mito-SinCe Approach to Analyze Mitochondrial Structure-Function Relationship in Single Cells.

The cross talk between mitochondrial dynamic structure, determined primarily by mitochondrial fission and fusion events, and mitochondrial function of energetics, primarily ATP and ROS production, is widely appreciated. Understanding the mechanistic details of such cross talk between mitochondrial structure and function needs integrated quantitative analyses between mitochondrial dynamics and energetics. Here we describe our recently designed approach of mito-SinCe that involves high resolution confocal microscopy of genetically expressed ratiometric fluorescent probes targeted to mitochondria, and its quantitative analyses.

Strategy of Isolating 'Primed' Tumor Initiating Cells Based on Mitochondrial Transmembrane Potential.

Various stem cells have been found to be dependent on mitochondrial energetics. The role of mitochondria in regulating the self-renewal of normal stem cells and stem-like tumor initiating cells (TICs) is increasingly being appreciated. We proposed that TIC populations have a sub population of cells that are "primed" by mitochondria for self-renewal.

Nurse Staffing and Coronavirus Infections in California Nursing Homes.

In the United States, 1.4 million nursing home residents have been severely impacted by the COVID-19 pandemic with at least 25,923 resident and 449 staff deaths reported from the virus by June 1, 2020. The majority of residents have chronic illnesses and conditions and are vulnerable to infections and many share rooms and have congregate meals.

Interplay of mitochondrial fission-fusion with cell cycle regulation: Possible impacts on stem cell and organismal aging.

Declining mitochondrial function and homeostasis is a hallmark of aging. It is appreciated that the role of mitochondria is much more complex than generating reactive oxygen species to cause aging-related tissue damage. More recent literature describes that the ability of mitochondria to undergo fission or fusion events with each other impacts aging processes.

New quantitative approach reveals heterogeneity in mitochondrial structure-function relations in tumor-initiating cells.

Steady-state mitochondrial structure or morphology is primarily maintained by a balance of opposing fission and fusion events between individual mitochondria, which is collectively referred to as mitochondrial dynamics. The details of the bidirectional relationship between the status of mitochondrial dynamics (structure) and energetics (function) require methods to integrate these mitochondrial aspects. To study the quantitative relationship between the status of mitochondrial dynamics (fission, fusion, matrix continuity and diameter) and energetics (ATP and redox), we have developed an analytical approach called mito-SinCe After validating and providing proof of principle, we applied mito-SinCe on ovarian tumor-initiating cells (ovTICs).

Public Reporting of Hospital-Level Cancer Surgical Volumes in California: An Opportunity to Inform Decision Making and Improve Quality.

Purpose: Most patients, providers, and payers make decisions about cancer hospitals without any objective data regarding quality or outcomes. We developed two online resources allowing users to search and compare timely data regarding hospital cancer surgery volumes.

Methods: Hospital cancer surgery volumes for all California hospitals were calculated using ICD-9 coded hospital discharge summary data.

Crosstalk between the mitochondrial fission protein, Drp1, and the cell cycle is identified across various cancer types and can impact survival of epithelial ovarian cancer patients.

Mitochondrial metabolic reprogramming is a hallmark of tumorigenesis. Although mitochondrial function can impact cell cycle regulation it has been an understudied area in cancer research. Our study highlights a specific involvement of mitochondria in cell cycle regulation across cancer types.

Jet energy measurement and its systematic uncertainty in proton-proton collisions at [Formula: see text] TeV with the ATLAS detector.

The jet energy scale (JES) and its systematic uncertainty are determined for jets measured with the ATLAS detector using proton-proton collision data with a centre-of-mass energy of [Formula: see text] TeV corresponding to an integrated luminosity of [Formula: see text][Formula: see text]. Jets are reconstructed from energy deposits forming topological clusters of calorimeter cells using the anti-[Formula: see text] algorithm with distance parameters [Formula: see text] or [Formula: see text], and are calibrated using MC simulations. A residual JES correction is applied to account for differences between data and MC simulations.

Two-particle Bose-Einstein correlations in collisions at [Formula: see text] 0.9 and 7 TeV measured with the ATLAS detector.

The paper presents studies of Bose-Einstein Correlations (BEC) for pairs of like-sign charged particles measured in the kinematic range [Formula: see text] 100 MeV and [Formula: see text] 2.5 in proton collisions at centre-of-mass energies of 0.9 and 7 TeV with the ATLAS detector at the CERN Large Hadron Collider.

Measurement of three-jet production cross-sections in [Formula: see text] collisions at 7 [Formula: see text] centre-of-mass energy using the ATLAS detector.

Double-differential three-jet production cross-sections are measured in proton-proton collisions at a centre-of-mass energy of [Formula: see text] using the ATLAS detector at the large hadron collider. The measurements are presented as a function of the three-jet mass [Formula: see text], in bins of the sum of the absolute rapidity separations between the three leading jets [Formula: see text]. Invariant masses extending up to 5  TeV are reached for [Formula: see text].

Measurement of the top-quark mass in the fully hadronic decay channel from ATLAS data at [Formula: see text].

The mass of the top quark is measured in a data set corresponding to 4.6 [Formula: see text] of proton-proton collisions with centre-of-mass energy [Formula: see text] TeV collected by the ATLAS detector at the LHC. Events consistent with hadronic decays of top-antitop quark pairs with at least six jets in the final state are selected.

Measurement of the production and lepton charge asymmetry of [Formula: see text] bosons in Pb+Pb collisions at [Formula: see text] with the ATLAS detector.

A measurement of [Formula: see text] boson production in lead-lead collisions at [Formula: see text] is presented. It is based on the analysis of data collected with the ATLAS detector at the LHC in 2011 corresponding to an integrated luminosity of 0.14 [Formula: see text] and 0.

Search for [Formula: see text] decays in [Formula: see text] collisions at [Formula: see text] = 8 TeV with the ATLAS detector.

A search for a massive [Formula: see text] gauge boson decaying to a top quark and a bottom quark is performed with the ATLAS detector in [Formula: see text] collisions at the LHC. The dataset was taken at a centre-of-mass energy of [Formula: see text] and corresponds to [Formula: see text] of integrated luminosity. This analysis is done in the hadronic decay mode of the top quark, where novel jet substructure techniques are used to identify jets from high-momentum top quarks.

Performance of the ATLAS muon trigger in pp collisions at [Formula: see text] TeV.

The performance of the ATLAS muon trigger system is evaluated with proton-proton collision data collected in 2012 at the Large Hadron Collider at a centre-of-mass energy of 8 TeV. It is primarily evaluated using events containing a pair of muons from the decay of [Formula: see text] bosons. The efficiency of the single-muon trigger is measured for muons with transverse momentum [Formula: see text] GeV, with a statistical uncertainty of less than 0.

Measurements of the [Formula: see text] production cross sections in association with jets with the ATLAS detector.

This paper presents cross sections for the production of a [Formula: see text] boson in association with jets, measured in proton-proton collisions at [Formula: see text] with the ATLAS experiment at the large hadron collider. With an integrated luminosity of [Formula: see text], this data set allows for an exploration of a large kinematic range, including jet production up to a transverse momentum of [Formula: see text] and multiplicities up to seven associated jets. The production cross sections for [Formula: see text] bosons are measured in both the electron and muon decay channels.