Publications by authors named "Natalia Volinsky"
Coronary artery disease (CAD) is the leading cause of mortality worldwide. In chronic and myocardial infarction (MI) states, aberrant levels of circulating microRNAs compromise gene expression and pathophysiology. We aimed to compare microRNA expression in chronic-CAD and acute-MI male patients in peripheral blood vasculature versus coronary arteries proximal to a culprit area.
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- The study focuses on the aortic valve (AV), which is the most commonly affected valve in heart diseases, aiming to identify specific microRNA (miRNA) molecules related to two types of valvular heart diseases: calcification and rheumatism.
- Researchers collected human aortic valves during surgery, extracted RNA, and conducted next-generation sequencing to discover different miRNA expressions, later validating the findings with a quantitative method.
- The results showed that certain miRNAs (miR-145-5p, miR-199a-5p, and miR-5701) had distinct expression levels between rheumatic and calcified AVs, providing significant evidence to better understand the mechanisms behind these heart conditions.
The serum or plasma microRNA (miRNA) molecules have been suggested as diagnostic and prognostic biomarkers, in various pathological conditions. However, these molecules are also found in different serum fractions, such as exosomes and Argonaute (Ago) protein complexes. Ago1 is the predominant Ago protein expressed in heart tissue.
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- - The study aims to investigate the levels of specific microRNAs (miRNAs) in the coronary sinus of heart failure (HF) patients during cardiac resynchronization therapy and compare them to miRNA levels in peripheral blood samples.
- - Researchers analyzed samples from 60 patients, identifying differences in levels of four specific miRNAs, finding that HF patients had higher levels of certain miRNAs in their peripheral blood compared to control subjects.
- - The findings suggest that changes in miRNA levels in the coronary sinus may provide more insight into heart failure mechanisms than traditional systemic blood analysis, highlighting the importance of localized cardiac assessments.
Congestive heart failure (CHF) often leads to progressive cardiac hypertrophy and salt/water retention as evident by peripheral and lung edema. Although the pathogenesis of CHF remains largely unclarified, it is widely accepted that neurohormonal changes and inflammatory processes are profoundly involved in structural and functional deterioration of vital organs including, heart, kidney and lungs. Corin, a cardiac serine protease, is responsible for converting pro-ANP and pro-BNP to biologically active natriuretic peptides (NPs).
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- Feedback control plays a crucial role in cellular responses, and this study reveals a new way that the PHLDA1 protein negatively affects ErbB receptor signaling by preventing receptor oligomerization.
- The research shows that the ligand heregulin increases PHLDA1 expression in MCF-7 cells, which binds to ErbB3 and reduces the interaction between ErbB3 and ErbB2 when PHLDA1 levels are decreased.
- A mathematical model was developed to show that PHLDA1 inhibits the formation of dimers and tetramers in ErbB receptors, and this model's predictions were confirmed through single-molecule imaging experiments.
Article Synopsis
- Dynamic interactions between RhoA and Rac1 are essential for cell migration control in cancer cells.
- Using advanced techniques, researchers found that variations in PAK inhibition lead to bistable responses from these proteins, affecting cell behavior.
- PAK plays a crucial role in mediating how RhoA and Rac1 interact, influencing cell shape and migration through switch-like behavior in response to changes in PAK levels.
In MCF-7 breast cancer cells epidermal growth factor (EGF) induces cell proliferation, whereas heregulin (HRG)/neuregulin (NRG) induces irreversible phenotypic changes accompanied by lipid accumulation. Although these changes in breast cancer cells resemble processes that take place in the tissue, there is no understanding of signalling mechanisms regulating it. To identify molecular mechanisms mediating this cell-fate decision process, we applied different perturbations to pathways activated by these growth factors.
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- ERK is crucial for signal transduction, influencing whether cells differentiate or proliferate based on how long it remains active.
- Sustained ERK activation is linked with longer-lasting mRNA expression of late response genes, while transient activation does not have this effect.
- The study suggests that sustained ERK activity not only stabilizes proteins of early-response genes but also enhances the longevity of mRNA for late response genes, playing a key role in cell fate decisions.
Article Synopsis
- Western blot data are crucial for quantitative analysis, but to ensure accuracy and comparability, normalization of replicates is needed, and different techniques can influence statistical results.
- The study evaluates three normalization strategies: fixed point, sum of all data points, and optimal alignment, focusing on their impact on the coefficient of variation (CV) and hypothesis testing outcomes.
- Findings indicate that using fixed normalization points can lead to higher false negatives, while sum and optimal alignment techniques can alter false positive and negative rates depending on the intensity of data, helping users select appropriate normalization methods for better analysis.
Complexity of receptor tyrosine kinase signal processing.
Cold Spring Harb Perspect Biol
August 2013
Article Synopsis
- Advances in our understanding of receptor tyrosine kinase (RTK) signaling are rapid, but how these signals affect cellular outcomes still needs more exploration.
- Systems-centered experimental and computational methods can clarify how RTK signal networks govern cell fate decisions.
- Mathematical modeling helps decode RTK network behaviors, revealing complex properties like bistability and oscillations in signaling activities.
Article Synopsis
- Protein phosphorylation is crucial for regulating essential biological processes, and while protein kinases are well-studied for their catalytic roles, their non-catalytic properties are equally important.
- These non-catalytic functions include forming protein complexes, affecting protein interactions, targeting subcellular locations, and binding DNA, which can all influence phosphorylation events beyond just catalytic activity.
- The text emphasizes kinase-independent functions of both protein and lipid kinases in regulating key cellular processes like cell growth, differentiation, programmed cell death, and movement.
The Paks (p21-activated kinases) Pak1, Pak2 and Pak3 are among the most studied effectors of the Rho-family GTPases, Rac, Cdc42 (cell division cycle 42) and Chp (Cdc42 homologous protein). Pak kinases influence a variety of cellular functions, but the process of Pak down-regulation, following activation, is poorly understood. In the present study, we describe for the first time a negative-inhibitory loop generated by the small Rho-GTPases Cdc42 and Chp, resulting in Pak1 inhibition.
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- Pak serine/threonine kinases play a role in how immune cells sense and move along chemokine gradients, particularly in navigating through restrictive environments like the extracellular matrix.
- A specific inhibitor, Pak(i), was developed and shown to block Pak activation during SDF-1alpha-induced chemotaxis in T cells without causing cell toxicity or affecting other cell functions.
- The study found that Pak and its partner PIX are crucial for migration through smaller barriers but not larger ones, highlighting a unique aspect of the SDF-1alpha signaling pathway where different mechanisms may operate based on barrier size.