scholarly journals Large Scale Molecular Studies of Pituitary Neuroendocrine Tumors: Novel Markers, Mechanisms and Translational Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1395
Author(s):  
Raitis Peculis ◽  
Helvijs Niedra ◽  
Vita Rovite
Keyword(s):  
Neuroendocrine Tumors ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Research Field ◽  
Driver Mutations ◽  
Cell Cycle Regulators ◽  
Circulating Nucleic Acids ◽  
Molecular Studies ◽  
Insight Into ◽  
Modern Technologies

Pituitary neuroendocrine tumors (PitNETs) are non-metastatic neoplasms of the pituitary, which overproduce hormones leading to systemic disorders, or tumor mass effects causing headaches, vertigo or visual impairment. Recently, PitNETs have been investigated in large scale (exome and genome) molecular analyses (transcriptome microarrays and sequencing), to uncover novel markers. We performed a literature analysis on these studies to summarize the research data and extrapolate overlapping gene candidates, biomarkers, and molecular mechanisms. We observed a tendency in samples with driver mutations (GNAS, USP8) to have a smaller overall mutational rate, suggesting driver-promoted tumorigenesis, potentially changing transcriptome profiles in tumors. However, direct links from drivers to signaling pathways altered in PitNETs (Notch, Wnt, TGF-β, and cell cycle regulators) require further investigation. Modern technologies have also identified circulating nucleic acids, and pinpointed these as novel PitNET markers, i.e., miR-143-3p, miR-16-5p, miR-145-5p, and let-7g-5p, therefore these molecules must be investigated in the future translational studies. Overall, large-scale molecular studies have provided key insight into the molecular mechanisms behind PitNET pathogenesis, highlighting previously reported molecular markers, bringing new candidates into the research field, and reapplying traditional perspectives to newly discovered molecular mechanisms.

An Insight into the Driver Mutations and Molecular Mechanisms Underlying Mucinous Adenocarcinoma of the Rectum

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Ian S. Reynolds ◽  
Emer O’Connell ◽  
Michael Fichtner ◽  
Anna Blümel ◽  
Sam E. Mason ◽  
...  
Keyword(s):  
Mucinous Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Driver Mutations ◽  
Insight Into

scholarly journals CloneSifter: enrichment of rare clones from heterogeneous cell populations

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
David Feldman ◽  
FuNien Tsai ◽  
Anthony J. Garrity ◽  
Ryan O’Rourke ◽  
Lisa Brenan ◽  
...  
Keyword(s):  
Large Scale ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Population Level ◽  
Fitness Assessment ◽  
Large Populations ◽  
Organismal Development ◽  
Insight Into

Abstract Background Many biological processes, such as cancer metastasis, organismal development, and acquisition of resistance to cytotoxic therapy, rely on the emergence of rare sub-clones from a larger population. Understanding how the genetic and epigenetic features of diverse clones affect clonal fitness provides insight into molecular mechanisms underlying selective processes. While large-scale barcoding with NGS readout has facilitated cellular fitness assessment at the population level, this approach does not support characterization of clones prior to selection. Single-cell genomics methods provide high biological resolution, but are challenging to scale across large populations to probe rare clones and are destructive, limiting further functional analysis of important clones. Results Here, we develop CloneSifter, a methodology for tracking and enriching rare clones throughout their response to selection. CloneSifter utilizes a CRISPR sgRNA-barcode library that facilitates the isolation of viable cells from specific clones within the barcoded population using a sequence-specific retrieval reporter. We demonstrate that CloneSifter can measure clonal fitness of cancer cell models in vitro and retrieve targeted clones at abundance as low as 1 in 1883 in a heterogeneous cell population. Conclusions CloneSifter provides a means to track and access specific and rare clones of interest across dynamic changes in population structure to comprehensively explore the basis of these changes.

scholarly journals CausalTab: PSI-MITAB 2.8 updated format for signaling data representation and dissemination

2018 ◽  
Author(s):  
L. Perfetto ◽  
M.L. Acencio ◽  
G. Bradley ◽  
G. Cesareni ◽  
N.Del Toro ◽  
...  
Keyword(s):  
Molecular Interaction ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Data Representation ◽  
Research Field ◽  
Controlled Vocabulary ◽  
Causal Interaction ◽  
Signalling Network ◽  
Cellular Phenotypes ◽  
Biological Entities

AbstractCombining multiple layers of information underlying biological complexity into a structured framework, and in particular deciphering the molecular mechanisms behind cellular phenotypes, represent two challenges in systems biology. A key task is the formalisation of such information in models describing how biological entities interact to mediate the response to external and internal signals. Several databases with signaling information, such as SIGNOR, SignaLink and IntAct, focus on capturing, organising and displaying signaling interactions by representing them as binary, causal relationships between biological entities. The curation efforts that build these individual databases demand a concerted effort to ensure interoperability among resources, through the development of a standardized exchange format, ontologies and controlled vocabularies supporting the domain of causal interactions. Aware of the enormous benefits of standardization efforts in the molecular interaction research field, representatives of the signalling network community agreed to extend the PSI-MI controlled vocabulary to include additional terms representing aspects of causal interactions. Here, we present a common standard for the representation and dissemination of signaling information: the PSI Causal Interaction tabular format (CausalTAB) which is an extension of the existing PSI-MI tab-delimited format, now designated MITAB2.8. We define the new term “causal interaction”, and related child terms, which are children of the PSI-MI “molecular interaction” term. The new vocabulary terms in this extended PSI-MI format will enable systems biologists to model large-scale signaling networks more precisely and with higher coverage than before.

CONCEPT OF THE IMPROVEMENT OF A KEY PUBLIC SPACE (USING THE EXAMPLE OF «ALLEY OF ARCHITECTS», VORONEZH)

2020 ◽  
pp. 97-109
Author(s):  
С. Л. Подвальный ◽  
О. А. Сотникова ◽  
Я. А. Золотухина
Keyword(s):  
Urban Environment ◽  
Public Space ◽  
Large Scale ◽  
Economic Value ◽  
Ecological Condition ◽  
Territory Design ◽  
Definition Of ◽  
The City ◽  
Modern Technologies ◽  
Intensive Growth

Постановка задачи. В настоящее время формирование современной комфортной городской среды приобретает особое социально-экономическое значение и выдвигается в число приоритетных государственных масштабных программ. В связи с этим необходимо разработать концепцию благоустройства ключевого общественного пространства, а именно: определить основные и сопутствующие функции данной территории, создать эскизное предложение проекта благоустройства с учетом всех необходимых норм и стандартов, внедрить современные технологии. Результаты. Выполнен эскизный дизайн-проект «Аллеи архитекторов» по ул. Орджоникидзе г. Воронеж, включающий в себя основные элементы по зонированию территории, проектированию акцентных объектов и внедрению инновационных технологий «умного города», позволяющих повысить уровень комфорта горожан. Выводы. Благоустройство населенных мест приобретает особое значение в условиях дискомфорта среды. С выполнением комплекса мероприятий, направленных на благоустройство, и с внедрением современных технологий значительно улучшается экологическое состояние, внешний облик города. Оздоровление и модернизация среды, которая окружает человека в городе, благотворно влияет на психофизическое состояние, что особенно важно в период интенсивного роста городов. Statement of the problem. Currently the formation of the modern comfortable urban environment is gaining a special social and economic value and moving forward in the priorities of state large-scale programs. The purpose of development of the concept of improvement of public space is definition of the main and accompanying functions of this territory, design of the outline offer of the project of improvement considering all necessary norms and standards and implementation of modern technologies. Results. The conceptual project of “Alley of Architects” includes the basic elements of territory zoning, design of accent objects and implementation of technologies of a “smart-city”. These elements allow one to increase the level of comfort of inhabitants. Conclusions. Improvement of the inhabited places is of particular importance in the conditions of discomfort of the environment. Carrying out a complex of the actions directed to gardening and improvement, introducing modern technologies, the ecological condition, the physical appearance of the city considerably improves. Improvement and modernization of the environment which surrounds the person in the city influences a psychophysical state well that especially important during intensive growth of the cities.

Green Synthesized Nanomaterials as Theranostic Platforms for Cancer Treatment: Principles, Challenges and the Road Ahead

2019 ◽  
Vol 26 (8) ◽  
pp. 1311-1327 ◽  
Author(s):  
Pala Rajasekharreddy ◽  
Chao Huang ◽  
Siddhardha Busi ◽  
Jobina Rajkumari ◽  
Ming-Hong Tai ◽  
...  
Keyword(s):  
Nanoparticle Synthesis ◽  
Research Field ◽  
Synthesis Methods ◽  
Synthetic Approach ◽  
Future Directions ◽  
The Road ◽  
New Methods ◽  
Recent Developments ◽  
Theranostic Applications ◽  
Insight Into

With the emergence of nanotechnology, new methods have been developed for engineering various nanoparticles for biomedical applications. Nanotheranostics is a burgeoning research field with tremendous prospects for the improvement of diagnosis and treatment of various cancers. However, the development of biocompatible and efficient drug/gene delivery theranostic systems still remains a challenge. Green synthetic approach of nanoparticles with low capital and operating expenses, reduced environmental pollution and better biocompatibility and stability is a latest and novel field, which is advantageous over chemical or physical nanoparticle synthesis methods. In this article, we summarize the recent research progresses related to green synthesized nanoparticles for cancer theranostic applications, and we also conclude with a look at the current challenges and insight into the future directions based on recent developments in these areas.

Empathy as moderator of gender differences in Chinese insurance agents' business ethical sensitivity

2017 ◽  
Vol 45 (6) ◽  
pp. 1029-1042 ◽  
Author(s):  
Na Zhang ◽  
Jian Zhang ◽  
Jing Wang
Keyword(s):  
Gender Differences ◽  
Business Ethics ◽  
Research Field ◽  
Ethical Sensitivity ◽  
Men And Women ◽  
Insurance Agents ◽  
Factors Associated ◽  
Ethics Research ◽  
The Relationship ◽  
Insight Into

To expand the business ethics research field, and to increase society's understanding of Chinese insurance agents' business ethics, we investigated how gender differences are related to agents' business ethical sensitivity and whether or not these relationships are moderated by empathy. Through a regression analysis of the factors associated with the business ethical sensitivity of 417 Chinese insurance agents, we found that gender played an important role in affecting business ethical sensitivity, and empathy significantly affected business ethical sensitivity. Furthermore, empathy had a moderating effect on the relationship between gender and business ethical sensitivity. Both men and women with strong empathy scored high on business ethical sensitivity; however, men with strong empathy had higher levels of business ethical sensitivity than did women with little empathy. The findings add to the literature by providing insight into the mechanisms responsible for the benefits of empathy in increasing business ethical sensitivity.

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

Cancers ◽  
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.

scholarly journals EGCG binds intrinsically disordered N-terminal domain of p53 and disrupts p53-MDM2 interaction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Zhao ◽  
Alan Blayney ◽  
Xiaorong Liu ◽  
Lauren Gandy ◽  
Weihua Jin ◽  
...  
Keyword(s):  
Large Scale ◽  
Molecular Mechanisms ◽  
Epigallocatechin Gallate ◽  
Cancer Drug ◽  
Dynamic Interactions ◽  
Cancer Drug Discovery ◽  
Intrinsically Disordered ◽  
Terminal Domain ◽  
Cancerous Cells

AbstractEpigallocatechin gallate (EGCG) from green tea can induce apoptosis in cancerous cells, but the underlying molecular mechanisms remain poorly understood. Using SPR and NMR, here we report a direct, μM interaction between EGCG and the tumor suppressor p53 (KD = 1.6 ± 1.4 μM), with the disordered N-terminal domain (NTD) identified as the major binding site (KD = 4 ± 2 μM). Large scale atomistic simulations (>100 μs), SAXS and AUC demonstrate that EGCG-NTD interaction is dynamic and EGCG causes the emergence of a subpopulation of compact bound conformations. The EGCG-p53 interaction disrupts p53 interaction with its regulatory E3 ligase MDM2 and inhibits ubiquitination of p53 by MDM2 in an in vitro ubiquitination assay, likely stabilizing p53 for anti-tumor activity. Our work provides insights into the mechanisms for EGCG’s anticancer activity and identifies p53 NTD as a target for cancer drug discovery through dynamic interactions with small molecules.

scholarly journals Molecular Pathways Involved in the Development of Congenital Erythrocytosis

Genes ◽  
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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