The metastatic potential of grade 1 breast carcinoma of no special type: A deep insight into putative molecular mechanisms

Mechanically activated (MA) ion channels convert physical forces into electrical signals, and are essential for eukaryotic physiology. Despite their importance, few bona-fide MA channels have been described in plants and animals. Here, we show that various members of the OSCA and TMEM63 family of proteins from plants, flies, and mammals confer mechanosensitivity to naïve cells. We conclusively demonstrate that OSCA1.2, one of the Arabidopsis thaliana OSCA proteins, is an inherently mechanosensitive, pore-forming ion channel. Our results suggest that OSCA/TMEM63 proteins are the largest family of MA ion channels identified, and are conserved across eukaryotes. Our findings will enable studies to gain deep insight into molecular mechanisms of MA channel gating, and will facilitate a better understanding of mechanosensory processes in vivo across plants and animals.

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Insect embryogenesis – what is ancestral and what is derived?

Development ◽

10.1242/dev.1994.supplement.193 ◽

1994 ◽

Vol 1994 (Supplement) ◽

pp. 193-199

Author(s):

Diethard Tautz ◽

Markus Friedrich ◽

Reinhard Schröder

Keyword(s):

Pattern Formation ◽

Genetic Analysis ◽

Early Development ◽

Molecular Mechanisms ◽

Early Embryogenesis ◽

Molecular Pathways ◽

Deep Insight ◽

Insect Embryogenesis ◽

Definitive Answer ◽

Insight Into

The systematic genetic analysis of Drosophila development has provided us with a deep insight into the molecular pathways of early embryogenesis. The question arises now whether these insights can serve as a more general paradigm of early development, or whether they apply only to advanced insect orders. Though it is too early to give a definitive answer to this question, we suggest that there is currently no firm reason to believe that the molecular mechanisms that were elucidated in Drosophila may not also apply to other forms of insect embryogenesis. Thus, many of the Drosophila genes involved in early pattern formation may have comparable functions in other insects and possibly throughout the arthropods.

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Patient-Specific iPSCs-Based Models of Neurodegenerative Diseases: Focus on Aberrant Calcium Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms23020624 ◽

2022 ◽

Vol 23 (2) ◽

pp. 624

Author(s):

Dmitriy A. Grekhnev ◽

Elena V. Kaznacheyeva ◽

Vladimir A. Vigont

Keyword(s):

Neurodegenerative Diseases ◽

Calcium Signaling ◽

Molecular Mechanisms ◽

Patient Specific ◽

Cell Reprogramming ◽

Deep Insight ◽

Regulatory Pathway ◽

Sporadic Cases ◽

Effective Drugs ◽

Insight Into

The development of cell reprogramming technologies became a breakthrough in the creation of new models of human diseases, including neurodegenerative pathologies. The iPSCs-based models allow for the studying of both hereditary and sporadic cases of pathologies and produce deep insight into the molecular mechanisms underlying neurodegeneration. The use of the cells most vulnerable to a particular pathology makes it possible to identify specific pathological mechanisms and greatly facilitates the task of selecting the most effective drugs. To date, a large number of studies on patient-specific models of neurodegenerative diseases has been accumulated. In this review, we focused on the alterations of such a ubiquitous and important intracellular regulatory pathway as calcium signaling. Here, we reviewed and analyzed the data obtained from iPSCs-based models of different neurodegenerative disorders that demonstrated aberrant calcium signaling.

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Thousands of human sequences provide deep insight into single genomes

Nature ◽

10.1038/d41586-020-01485-4 ◽

2020 ◽

Vol 581 (7809) ◽

pp. 385-386

Author(s):

Deanna M. Church

Keyword(s):

Deep Insight ◽

Insight Into

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Mobile-Friendly Dashboards to Display Associations Between Cited-by and Similar Journals on Mobile Health Research: A Bibliometric Study (Preprint)

10.2196/preprints.11771 ◽

2018 ◽

Author(s):

Tsair-Wei Chien ◽

Hsien-Yi Wang ◽

Yang Shao ◽

Willy Chou

Keyword(s):

Social Network ◽

Mobile Health ◽

Health Research ◽

Similarity Criteria ◽

Network Density ◽

Deep Insight ◽

Density Indices ◽

The Subject ◽

The Given ◽

Insight Into

BACKGROUND Researchers often spend a great deal of time and effort retrieving related journals for their studies and submissions. Authors often designate one article and then retrieve other articles that are related to the given one using PubMed’s service for finding cited-by or similar articles. However, to date, none present the association between cited-by and similar journals related to a given journal. Authors need one effective and efficient way to find related journals on the topic of mobile health research. OBJECTIVE This study aims (1) to show the related journals for a given journal by both cited-by and similarity criteria; (2) to present the association between cited-by and similarity journals related to a given journal; (3) to inspect the patterns of network density indices among clusters classified by social network analysis (SNA); (4) to investigate the feature of Kendall's coefficient(W) of concordance. METHODS We obtained 676 abstracts since 2013 from Medline based on the keywords of ("JMIR mHealth and uHealth"[Journal]) on June 30, 2018, and plotted the clusters of related journals on Google Maps by using MS Excel modules. The features of network density indices were examined. The Kendall coefficient (W) was used to assess the concordance of clusters across indices. RESULTS This study found that (1) the journals related to JMIR mHealth and uHealth are easily presented on dashboards; (2) a mild association(=0.14) exists between cited-by and similar journals related to JMIR mHealth and uHealth; (3) the median Impact Factor were 3.37 and 2.183 based on the representatives of top ten clusters grouped by the cited-by and similar journals, respectively; (4) all Kendall’s coefficients(i.e., 0.82, 0.89, 0.92, and 0.75) for the four sets of density centrality have a statistically significant concordance (p < 0.05). CONCLUSIONS SNA provides deep insight into the relationships of related journals to a given journal. The results of this research can provide readers with a knowledge and concept diagram to use with future submissions to a given journal in the subject category of Mobile Health Research. CLINICALTRIAL Not available

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Clinical Candidates Targeting the ATR–CHK1–WEE1 Axis in Cancer

Cancers ◽

10.3390/cancers13040795 ◽

2021 ◽

Vol 13 (4) ◽

pp. 795

Author(s):

Lukas Gorecki ◽

Martin Andrs ◽

Jan Korabecny

Keyword(s):

Cell Cycle ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Patient Survival ◽

Current Status ◽

Future Perspectives ◽

Phase Ii Trials ◽

Anticancer Treatment ◽

Positive Outlook ◽

Insight Into

Selective killing of cancer cells while sparing healthy ones is the principle of the perfect cancer treatment and the primary aim of many oncologists, molecular biologists, and medicinal chemists. To achieve this goal, it is crucial to understand the molecular mechanisms that distinguish cancer cells from healthy ones. Accordingly, several clinical candidates that use particular mutations in cell-cycle progressions have been developed to kill cancer cells. As the majority of cancer cells have defects in G1 control, targeting the subsequent intra‑S or G2/M checkpoints has also been extensively pursued. This review focuses on clinical candidates that target the kinases involved in intra‑S and G2/M checkpoints, namely, ATR, CHK1, and WEE1 inhibitors. It provides insight into their current status and future perspectives for anticancer treatment. Overall, even though CHK1 inhibitors are still far from clinical establishment, promising accomplishments with ATR and WEE1 inhibitors in phase II trials present a positive outlook for patient survival.

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Molecular Pathways Involved in the Development of Congenital Erythrocytosis

Genes ◽

10.3390/genes12081150 ◽

2021 ◽

Vol 12 (8) ◽

pp. 1150

Author(s):

Jana Tomc ◽

Nataša Debeljak

Keyword(s):

Signal Transduction ◽

Iron Homeostasis ◽

Molecular Mechanisms ◽

Oxygen Affinity ◽

Molecular Pathways ◽

Disease Development ◽

Post Translational Modifications ◽

Hemoglobin Oxygen Affinity ◽

Insight Into ◽

Idiopathic Erythrocytosis

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

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Deep insight into the charge transfer interactions in 1,2,4,5-tetracyanobenzene-phenazine cocrystal

Chinese Chemical Letters ◽

10.1016/j.cclet.2021.03.045 ◽

2021 ◽

Author(s):

Hongnan Wu ◽

Yajing Sun ◽

Lingjie Sun ◽

Liwei Wang ◽

Xiaotao Zhang ◽

...

Keyword(s):

Charge Transfer ◽

Deep Insight ◽

Insight Into

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Pathomechanisms in the Kidneys in Selected Protozoan Parasitic Infections

International Journal of Molecular Sciences ◽

10.3390/ijms22084209 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4209

Author(s):

Karolina Kot ◽

Natalia Łanocha-Arendarczyk ◽

Michał Ptak ◽

Aleksandra Łanocha ◽

Elżbieta Kalisińska ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Molecular Mechanisms ◽

Kidney Injury ◽

Therapeutic Interventions ◽

Parasitic Infections ◽

Injury Mechanisms ◽

Kidney Involvement ◽

Leishmania Spp ◽

Apoptosis Process ◽

Insight Into

Leishmaniasis, malaria, toxoplasmosis, and acanthamoebiasis are protozoan parasitic infections. They remain important contributors to the development of kidney disease, which is associated with increased patients’ morbidity and mortality. Kidney injury mechanisms are not fully understood in protozoan parasitic diseases, bringing major difficulties to specific therapeutic interventions. The aim of this review is to present the biochemical and molecular mechanisms in kidneys infected with Leishmania spp., Plasmodium spp., Toxoplasma gondii, and Acanthamoeba spp. We present available mechanisms of an immune response, oxidative stress, apoptosis process, hypoxia, biomarkers of renal injury in the serum or urine, and the histopathological changes of kidneys infected with the selected parasites. Pathomechanisms of Leishmania spp. and Plasmodium spp. infections have been deeply investigated, while Toxoplasma gondii and Acanthamoeba spp. infections in the kidneys are not well known yet. Deeper knowledge of kidney involvement in leishmaniasis and malaria by presenting their mechanisms provides insight into how to create novel and effective treatments. Additionally, the presented work shows gaps in the pathophysiology of renal toxoplasmosis and acanthamoebiasis, which need further research.

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