scholarly journals Master Regulator Analysis of the SARS-CoV-2/Human Interactome

2020 ◽  
Vol 9 (4) ◽  
pp. 982 ◽  
Author(s):  
Pietro H. Guzzi ◽  
Daniele Mercatelli ◽  
Carmine Ceraolo ◽  
Federico M. Giorgi
Keyword(s):  
Current Knowledge ◽  
Master Regulator ◽  
Human Interactome ◽  
Evolutionary Origins ◽  
Molecular Features ◽  
Host Cell Proteins ◽  
Protein Receptor ◽  
Receptor Recognition ◽  
Tract Disease ◽  
Shed Light

The recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. In this paper, we set out to shed light on the SARS-CoV-2/host receptor recognition, a crucial factor for successful virus infection. Based on the current knowledge of the interactome between SARS-CoV-2 and host cell proteins, we performed Master Regulator Analysis to detect which parts of the human interactome are most affected by the infection. We detected, amongst others, affected apoptotic and mitochondrial mechanisms, and a downregulation of the ACE2 protein receptor, notions that can be used to develop specific therapies against this new virus.

scholarly journals Master Regulator Analysis of the SARS-CoV-2/Human interactome

2020 ◽  
Author(s):  
Pietro Hiram Guzzi ◽  
Daniele Mercatelli ◽  
Carmine Ceraolo ◽  
Federico M. Giorgi
Keyword(s):  
Current Knowledge ◽  
Master Regulator ◽  
Human Interactome ◽  
Evolutionary Origins ◽  
Molecular Features ◽  
Host Cell Proteins ◽  
Protein Receptor ◽  
Receptor Recognition ◽  
Tract Disease ◽  
Shed Light

Abstractthe recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 and causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. In this paper, we set out to shed light on the SARS-CoV-2/host receptor recognition, a crucial factor for successful virus infection. Based on the current knowledge of the interactome between SARS-CoV-2 and host cell proteins, we performed Master Regulator Analysis to detect which parts of the human interactome are most affected by the infection. We detected, amongst others, affected apoptotic and mitochondrial mechanisms, and a downregulation of the ACE2 protein receptor, notions that can be used to develop specific therapies against this new virus.

scholarly journals Cancer of Unknown Primary: Challenges and Progress in Clinical Management

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 451
Author(s):  
Noemi Laprovitera ◽  
Mattia Riefolo ◽  
Elisa Ambrosini ◽  
Christiane Klec ◽  
Martin Pichler ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Distant Metastases ◽  
Cancer Of Unknown Primary ◽  
Unknown Primary ◽  
Diagnostic Strategies ◽  
Molecular Features ◽  
Tissue Of Origin ◽  
Novel Therapeutic Strategies ◽  
Aggressive Clinical Behavior

Distant metastases are the main cause of cancer-related deaths in patients with advanced tumors. A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). Accounting for approximately 3–5% of all cancer diagnoses, CUPs are characterized by an aggressive clinical behavior and represent a real therapeutic challenge. The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based therapeutic options or access to clinical trial, which significantly impacts their life expectancy. In the era of precision medicine, it is essential to characterize CUP molecular features, including the expression profile of non-coding RNAs, to improve our understanding of CUP biology and identify novel therapeutic strategies. This review article sheds light on this enigmatic disease by summarizing the current knowledge on CUPs focusing on recent discoveries and emerging diagnostic strategies.

scholarly journals Degenerative Cervical Myelopathy: Insights into Its Pathobiology and Molecular Mechanisms

2021 ◽  
Vol 10 (6) ◽  
pp. 1214
Author(s):  
Ji Tu ◽  
Jose Vargas Castillo ◽  
Abhirup Das ◽  
Ashish D. Diwan
Keyword(s):  
Cervical Myelopathy ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Disease Process ◽  
Classification Systems ◽  
Molecular Features ◽  
Formidable Challenge ◽  
Long Term Treatment ◽  
Degenerative Cervical Myelopathy

Degenerative cervical myelopathy (DCM), earlier referred to as cervical spondylotic myelopathy (CSM), is the most common and serious neurological disorder in the elderly population caused by chronic progressive compression or irritation of the spinal cord in the neck. The clinical features of DCM include localised neck pain and functional impairment of motor function in the arms, fingers and hands. If left untreated, this can lead to significant and permanent nerve damage including paralysis and death. Despite recent advancements in understanding the DCM pathology, prognosis remains poor and little is known about the molecular mechanisms underlying its pathogenesis. Moreover, there is scant evidence for the best treatment suitable for DCM patients. Decompressive surgery remains the most effective long-term treatment for this pathology, although the decision of when to perform such a procedure remains challenging. Given the fact that the aged population in the world is continuously increasing, DCM is posing a formidable challenge that needs urgent attention. Here, in this comprehensive review, we discuss the current knowledge of DCM pathology, including epidemiology, diagnosis, natural history, pathophysiology, risk factors, molecular features and treatment options. In addition to describing different scoring and classification systems used by clinicians in diagnosing DCM, we also highlight how advanced imaging techniques are being used to study the disease process. Last but not the least, we discuss several molecular underpinnings of DCM aetiology, including the cells involved and the pathways and molecules that are hallmarks of this disease.

Molecular determinants of therapy response of venetoclax-based combinations in acute myeloid leukemia

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Philipp Makowka ◽  
Verena Stolp ◽  
Karoline Stoschek ◽  
Hubert Serve
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Current Knowledge ◽  
Therapy Response ◽  
Secondary Resistance ◽  
Molecular Alterations ◽  
Molecular Features ◽  
Slow Progress ◽  
Molecular Aberrations ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a heterogeneous, highly malignant disease of the bone marrow. After decades of slow progress, recent years saw a surge of novel agents for its treatment. The most recent advancement is the registration of the Bcl-2 inhibitor ventoclax in combination with a hypomethylating agent (HMA) in the US and Europe for AML patients not eligible for intensive chemotherapy. Treatment of newly diagnosed AML patients with this combination results in remission rates that so far could only be achieved with intensive treatment. However, not all AML patients respond equally well, and some patients relapse early, while other patients experience longer periods of complete remission. A hallmark of AML is its remarkable genetic, molecular and clinical heterogeneity. Here, we review the current knowledge about molecular features of AML that help estimate the probability of response to venetoclax-containing therapies. In contrast to other newly developed AML therapies that target specific recurrent molecular alterations, it seems so far that responses are not specific for a certain subgroup. One exception is spliceosome mutations, where good response has been observed in clinical trials with venetoclax/azacitidine. These mutations are rather associated with a more unfavorable outcome with chemotherapy. In summary, venetoclax in combination with hypomethylating agents represents a significant novel option for AML patients with various molecular aberrations. Mechanisms of primary and secondary resistance seem to overlap with those towards chemotherapy.

scholarly journals ACE2 polymorphisms as potential players in COVID-19 outcome

2020 ◽  
Author(s):  
André Salim Khayat ◽  
Paulo Pimentel de Assumpção ◽  
Bruna Claudia Meireles Khayat ◽  
Taíssa Maíra Thomaz Araújo ◽  
Jéssica Almeida Batista-Gomes ◽  
...  
Keyword(s):  
South American ◽  
Angiotensin I ◽  
Biological Aspect ◽  
Death Rates ◽  
Angiotensin I Converting Enzyme ◽  
Protein Receptor ◽  
Biological Explanation ◽  
The Many ◽  
Shed Light ◽  
Regulatory Sites

AbstractThe clinical condition COVID-19, caused by SARS-CoV-2, was declared a pandemic by the WHO in March 2020. Currently, there are more than 5 million cases worldwide, and the pandemic has increased exponentially in many countries, with different incidences and death rates among regions/ethnicities and, intriguingly, between sexes. In addition to the many factors that can influence these discrepancies, we suggest a biological aspect, the genetic variation at the viral S protein receptor in human cells, ACE2 (angiotensin I-converting enzyme 2), which may contribute to the worse clinical outcome in males and in some regions worldwide. We performed exomics analysis in native and admixed South American populations, and we also conducted in silico genomics databank investigations in populations from other continents. Interestingly, at least ten polymorphisms in coding, noncoding and regulatory sites were found that can shed light on this issue and offer a plausible biological explanation for these epidemiological differences. In conclusion, ACE2 polymorphisms should influence epidemiological discrepancies observed among ancestry and, moreover, between sexes.

scholarly journals Aerosol Detection and Transmission of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): What Is the Evidence, and What Are the Knowledge Gaps?

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 712 ◽  
Author(s):  
Andréia Gonçalves Arruda ◽  
Steve Tousignant ◽  
Juan Sanhueza ◽  
Carles Vilalta ◽  
Zvonimir Poljak ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Field Conditions ◽  
Respiratory Syndrome Virus ◽  
Transmission Route ◽  
Knowledge Gaps ◽  
Airborne Transmission ◽  
Infectious Individual ◽  
Transmission Data ◽  
Outbreak Investigations ◽  
Shed Light

In human and veterinary medicine, there have been multiple reports of pathogens being airborne under experimental and field conditions, highlighting the importance of this transmission route. These studies shed light on different aspects related to airborne transmission such as the capability of pathogens becoming airborne, the ability of pathogens to remain infectious while airborne, the role played by environmental conditions in pathogen dissemination, and pathogen strain as an interfering factor in airborne transmission. Data showing that airborne pathogens originating from an infectious individual or population can infect susceptible hosts are scarce, especially under field conditions. Furthermore, even though disease outbreak investigations have generated important information identifying potential ports of entry of pathogens into populations, these investigations do not necessarily yield clear answers on mechanisms by which pathogens have been introduced into populations. In swine, the aerosol transmission route gained popularity during the late 1990’s as suspicions of airborne transmission of porcine reproductive and respiratory syndrome virus (PRRSV) were growing. Several studies were conducted within the last 15 years contributing to the understanding of this transmission route; however, questions still remain. This paper reviews the current knowledge and identifies knowledge gaps related to PRRSV airborne transmission.

scholarly journals Immunological Aspects of Malignant Gliomas

2016 ◽  
Vol 43 (4) ◽  
pp. 494-502 ◽  
Author(s):  
Or Cohen-Inbar ◽  
Menashe Zaaroor
Keyword(s):  
Current Knowledge ◽  
Malignant Gliomas ◽  
Short Review ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Malignant Cells ◽  
Significant Progress ◽  
Complex Interplay ◽  
Mean Survival Time ◽  
Molecular Features

AbstractGlioblastoma Multiforme (GBM) is the most common malignant primary brain neoplasm having a mean survival time of <24 months. This figure remains constant, despite significant progress in medical research and treatment. The lack of an efficient anti-tumor immune response and the micro-invasive nature of the glioma malignant cells have been explained by a multitude of immune-suppressive mechanisms, proven in different models. These immune-resistant capabilities of the tumor result in a complex interplay this tumor shares with the immune system. We present a short review on the immunology of GBM, discussing the different unique pathological and molecular features of GBM, current treatment modalities, the principles of cancer immunotherapy and the link between GBM and melanoma. Current knowledge on immunological features of GBM, as well as immunotherapy past and current clinical trials, is discussed in an attempt to broadly present the complex and formidable challenges posed by GBM.

scholarly journals A Knowledge Management IT Tool: An Investigation within a Marketing Introductory Course

10.28945/3697 ◽  
2017 ◽  
Author(s):  
Samie Li Shang Ly ◽  
Raafat G Saade
Keyword(s):  
Knowledge Management ◽  
Knowledge Creation ◽  
Current Knowledge ◽  
Community Level ◽  
Future Research ◽  
Introductory Course ◽  
Repeated Practice ◽  
Common Goals ◽  
Shed Light ◽  
Over Time

Aim/Purpose: The purpose of this study is to shed light on how students learn within an environment tailored to knowledge creation. Background: We build on Nonaka, Toyama, and Konno’s three key elements: SECI model, Ba, Leadership as well as current knowledge management researchers critiques and improvements. Methodology: Based on an introductory marketing course, we used an in-house web based learning tool (peer-to peer) to capture score performances and perception surveys. The analysis was conducted through an exploratory factor analysis (EFA). Contribution: This study shed light on current knowledge management critiques by providing measures at the micro-level and community level. Findings: Perceptions of adaptability and usefulness change positively over time, while students’ repeated practice prepares them for different styles of questions as their performances increases over time. Recommendations for Practitioners: Organizations can understand how employees create knowledge through exchange of ideas, feedback, and common goals. Supervisor can understand their employees better and employees can gain a sense of control on their work. Recommendation for Researchers: The ability to capture information over time on the human and community level within a system allows further research to shed light on different variables of knowledge creation in the field. Impact on Society : An appreciation of the mechanism of knowledge creation can encourage organization to become more innovative and focus on people rather than material. Future Research: Measures such as the engagement level, the personality level, and compatibility level within a community to create knowledge are to be explored.

scholarly journals Total Recall: Intestinal TRM Cells in Health and Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Eva-Maria Paap ◽  
Tanja M. Müller ◽  
Katrin Sommer ◽  
Markus F. Neurath ◽  
Sebastian Zundler
Keyword(s):  
Immune Responses ◽  
Current Knowledge ◽  
Immune Surveillance ◽  
Adaptive Immune ◽  
Inflammatory Conditions ◽  
Mucosal Tissues ◽  
Health And Disease ◽  
Set Up ◽  
Resident Memory T Cells ◽  
Shed Light

Tissue-resident memory T cells (TRM cells) have crucial functions in host defense in mucosal tissues. They provide local adaptive immune surveillance and allow the fast initiation of targeted adaptive immune responses in case of antigen re-exposure. Recently, an aberrant activation in the case of immunologically mediated diseases has been increasingly acknowledged. As the organ with the largest interface to the environment, the gastrointestinal tract faces billions of antigens every day. Tightly balanced processes are necessary to ensure tolerance towards non-hazardous antigens, but to set up a powerful immune response against potentially dangerous ones. In this complex nexus of immune cells and their mediators, TRM cells play a central role and have been shown to promote both physiological and pathological events. In this review, we will summarize the current knowledge on the homeostatic functions of TRM cells and delineate their implication in infection control in the gut. Moreover, we will outline their commitment in immune dysregulation in gastrointestinal chronic inflammatory conditions and shed light on TRM cells as current and potential future therapeutic targets.

Sign in / Sign up

Export Citation Format

Share Document