scholarly journals Embracing Transparency Through Data Sharing

2018 ◽  
Vol 37 (6) ◽  
pp. 466-471 ◽  
Author(s):  
Stéphanie Boué ◽  
Michael Byrne ◽  
A. Wallace Hayes ◽  
Julia Hoeng ◽  
Manuel C. Peitsch
Keyword(s):  
Life Cycle ◽  
Best Practices ◽  
Industry Funding ◽  
Animal Models Of Disease ◽  
Funding Agencies ◽  
Standard Operating ◽  
Standards And Guidelines ◽  
Areas Of Concern ◽  
Models Of Disease ◽  
Testing Protocols

Low rates of reproducibility and translatability of data from nonclinical research have been reported. Major causes of irreproducibility include oversights in study design, failure to characterize reagents and protocols, a lack of access to detailed methods and data, and an absence of universally accepted and applied standards and guidelines. Specific areas of concern include uncharacterized antibodies and cell lines, the use of inappropriate sampling and testing protocols, a lack of transparency and access to raw data, and deficiencies in the translatability of findings to the clinic from studies using animal models of disease. All stakeholders—academia, industry, funding agencies, regulators, nonprofit entities, and publishers—are encouraged to play active roles in addressing these challenges by formulating and promoting access to best practices and standard operating procedures and validating data collaboratively at each step of the biomedical research life cycle.

Targeting AMPK in Diabetes and Diabetic Complications: Energy Homeostasis, Autophagy and Mitochondrial Health

2019 ◽  
Vol 26 (27) ◽  
pp. 5207-5229 ◽  
Author(s):  
Y.V. Madhavi ◽  
Nikhil Gaikwad ◽  
Veera Ganesh Yerra ◽  
Anil Kumar Kalvala ◽  
Srinivas Nanduri ◽  
...  
Keyword(s):  
Diabetic Complications ◽  
Energy Homeostasis ◽  
Cardiovascular Complications ◽  
Living System ◽  
Animal Models Of Disease ◽  
Beneficial Effects ◽  
Inflammatory Processes ◽  
Energy Sensing ◽  
Healthy Functioning ◽  
Models Of Disease

Adenosine 5′-monophosphate activated protein kinase (AMPK) is a key enzymatic protein involved in linking the energy sensing to the metabolic manipulation. It is a serine/threonine kinase activated by several upstream kinases. AMPK is a heterotrimeric protein complex regulated by AMP, ADP, and ATP allosterically. AMPK is ubiquitously expressed in various tissues of the living system such as heart, kidney, liver, brain and skeletal muscles. Thus malfunctioning of AMPK is expected to harbor several human pathologies especially diseases associated with metabolic and mitochondrial dysfunction. AMPK activators including synthetic derivatives and several natural products that have been found to show therapeutic relief in several animal models of disease. AMP, 5-Aminoimidazole-4-carboxamide riboside (AICA riboside) and A769662 are important activators of AMPK which have potential therapeutic importance in diabetes and diabetic complications. AMPK modulation has shown beneficial effects against diabetes, cardiovascular complications and diabetic neuropathy. The major impact of AMPK modulation ensures healthy functioning of mitochondria and energy homeostasis in addition to maintaining a strict check on inflammatory processes, autophagy and apoptosis. Structural studies on AMP and AICAR suggest that the free amino group is imperative for AMPK stimulation. A769662, a non-nucleoside thienopyridone compound which resulted from the lead optimization studies on A-592107 and several other related compound is reported to exhibit a promising effect on diabetes and its complications through activation of AMPK. Subsequent to the discovery of A769662, several thienopyridones, hydroxybiphenyls pyrrolopyridones have been reported as AMPK modulators. The review will explore the structure-function relationships of these analogues and the prospect of targeting AMPK in diabetes and diabetic complications.

Potential for Treatment of Neurodegenerative Diseases with Natural Products or Synthetic Compounds that Stabilize Microtubules

2020 ◽  
Vol 26 (35) ◽  
pp. 4362-4372
Author(s):  
John H. Miller ◽  
Viswanath Das
Keyword(s):  
Natural Products ◽  
Neurodegenerative Diseases ◽  
In Vivo Models ◽  
Synthetic Compounds ◽  
Stabilizing Agents ◽  
Animal Models Of Disease ◽  
Model Studies ◽  
Models Of Disease

No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, or Pick’s disease. A number of in vitro and in vivo models exist for studying neurodegenerative diseases, including cell models employing induced-pluripotent stem cells, cerebral organoids, and animal models of disease. Recent research has focused on microtubulestabilizing agents, either natural products or synthetic compounds that can prevent the axonal destruction caused by tau protein pathologies. Although promising results have come from animal model studies using brainpenetrant natural product microtubule-stabilizing agents, such as paclitaxel analogs that can access the brain, epothilones B and D, and other synthetic compounds such as davunetide or the triazolopyrimidines, early clinical trials in humans have been disappointing. This review aims to summarize the research that has been carried out in this area and discuss the potential for the future development of an effective microtubule stabilizing drug to treat neurodegenerative disease.

scholarly journals The Art of Writing and Implementing Standard Operating Procedures (SOPs) for Laboratories in Low-Resource Settings: Review of Guidelines and Best Practices

2016 ◽  
Vol 10 (11) ◽  
pp. e0005053 ◽  
Author(s):  
Barbara Barbé ◽  
Kristien Verdonck ◽  
Deby Mukendi ◽  
Veerle Lejon ◽  
Jean-Roger Lilo Kalo ◽  
...  
Keyword(s):  
Best Practices ◽  
Standard Operating Procedures ◽  
Low Resource Settings ◽  
Low Resource ◽  
Standard Operating

scholarly journals Investigating collaborative and mobility networks: reflections on the core missions of universities

2021 ◽  
Author(s):  
Zsolt Tibor Kosztyán ◽  
Beáta Fehérvölgyi ◽  
Tibor Csizmadia ◽  
Kinga Kerekes
Keyword(s):  
Social Progress ◽  
Industry Funding ◽  
Multilayer Network ◽  
The Core ◽  
Funding Agencies ◽  
Valid Assessment ◽  
Increasing Demand ◽  
Public Money ◽  
University Performance

AbstractGiven the significant role of universities in economic growth and social progress as well as the increasing demand for greater transparency regarding the use of public money, a valid assessment of university performance has become crucial for various stakeholders, including government, industry, funding agencies, and society at large. Contemporary assessments still focus solely on universities’ properties, thereby failing to capture their network relations. To overcome this limitation, this paper proposes a multilayer network-based method to measure the embeddedness of universities in collaboration and mobility networks. This method has several advantages: first, it is relevant for HEIs’ core missions, introducing a new dimension complementary to the existing rankings; second, it is size invariant; and last but not least, it is fully transparent. The proposed multilayer network approach enables the integration of further networks, which creates opportunities for a more comprehensive assessment of universities’ performance in achieving their core missions.

Super-Enhancer-Associated Transcription Factors Maintain Transcriptional Regulation in Mature Podocytes

2021 ◽  
pp. ASN.2020081177
Author(s):  
Jingping Yang ◽  
Difei Zhang ◽  
Masaru Motojima ◽  
Tsutomu Kume ◽  
Qing Hou ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Animal Models ◽  
Cell Fate ◽  
Control Cell ◽  
Transgenic Animal ◽  
Animal Models Of Disease ◽  
Super Enhancer ◽  
Models Of Disease ◽  
Human Glomerulus

BackgroundTranscriptional programs control cell fate, and identifying their components is critical for understanding diseases caused by cell lesion, such as podocytopathy. Although many transcription factors (TFs) are necessary for cell-state maintenance in glomeruli, their roles in transcriptional regulation are not well understood.MethodsThe distribution of H3K27ac histones in human glomerulus cells was analyzed to identify superenhancer-associated TFs, and ChIP-seq and transcriptomics were performed to elucidate the regulatory roles of the TFs. Transgenic animal models of disease were further investigated to confirm the roles of specific TFs in podocyte maintenance.ResultsSuperenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B. Integration of transcriptome and cistrome data of FOXC1/2 in mice resolved transcriptional regulation in podocyte maintenance. FOXC1/2 regulated differentiation-associated transcription in mature podocytes. In both humans and animal models, mature podocyte injury was accompanied by deregulation of FOXC1/2 expression, and FOXC1/2 overexpression could protect podocytes in zebrafish.ConclusionsFOXC1/2 maintain podocyte differentiation through transcriptional stabilization. The genome-wide chromatin resources support further investigation of TFs’ regulatory roles in glomeruli transcription programs.

Review of the biological activity of maslinic acid1

2021 ◽  
Vol 22 ◽  
Author(s):  
Zhang Jing ◽  
Wang Rui ◽  
Li Ruihua ◽  
Yu Hao ◽  
Fang Hengtong
Keyword(s):  
Biological Activity ◽  
Cardiovascular Diseases ◽  
Animal Models ◽  
Mechanism Of Action ◽  
Maslinic Acid ◽  
Animal Models Of Disease ◽  
Positive Effects ◽  
Cancer Inflammation ◽  
Models Of Disease

: Since the discovery of (2α,3β)-2,3-dihydroxyolean-12-en-28-oic acid, also known as maslinic acid, many studies have examined its biological activity, which has been shown to promote health and resist various diseases. This article focuses on previous research on maslinic acid and mainly reviews its reported effects on cardiovascular diseases, neuroprotection, diabetes, cancer, inflammation, and pathogens. Maslinic acid exerts positive effects on both cell and animal models of disease. Although its mechanism of action has not yet been completely elucidated, maslinic acid is feasible as a nutritional additive and has the potential to be developed as a drug.

scholarly journals PROJECT RISK MANAGEMENT BASED ON A SET OF BEST PRACTICES

2021 ◽  
Vol 26 (3) ◽  
pp. 79-86
Author(s):  
Agnieszka JĘDRUSIK
Keyword(s):  
Risk Management ◽  
Life Cycle ◽  
Project Management ◽  
Best Practices ◽  
Project Manager ◽  
Project Risk Management ◽  
Project Risk ◽  
Golden Triangle ◽  
Project Life Cycle ◽  
Project Life

The purpose of this article is to present the process of risk management in project management. The analysis was based on a comparison of two best practices of IPMA and PRINCE. Risk management differs significantly between the two approaches, but it is up to the organization to choose its own management, monitoring and methodology tailored to the specific industry or sector. Risk management is an important aspect of the entire project life cycle and must be monitored throughout the project life cycle to protect not only the budget but all areas of the so-called "golden triangle". A very important aspect is the organization's awareness that risk management is everyone's responsibility, not just the project manager. This paper presents two different approaches to project risk management in two different methodologies.

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