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Journal of Postdoctoral Research (JPR) - Vol. 2, No. 11, November 2014
Design and Synthesis of Small Molecule Inhibitors against the Protective Antigen of Bacillus anthracis
Melanie Lödige, PhD

Discovery of BRM Promoter Polymorphisms: Importance in Risk Stratification and Clinical Application
Stefanie B.Marquez, PhD

Aerobic Oxidation of Secondary Alcohols to Ketones Catalyzed by Ionic Liquid Functionalized TEMPO
Lingyao Wang, Kexian Chen, Lu Yin, and Haoran Li.

YAP/TAZ Join the Play with ß-catenin to Orchestrate Wnt Signaling
Noushin Nabavi, PhD 

Soluble Adenylyl Cyclase (sAC) Rescues Neurons from Inhibitory Myelin Cues
Ambika Chandrasekhar, PhD, and Anand Krishnan, PhD

Luminescence Properties and Application of Versatile Coordination Compounds Based on Modified Platinum(II) Terpyridyl Complexes
Lu Yin,Kexian Chen, Lingyao Wang, Jia yao, and Haoran Li

Role of Mammalian Sterile20-like Kinase 1 and 2 in Oxidative Stress
Sonali J. Rawat, Ph.D.

Risk Based Monitoring—Current Challenges with Implementation
Prajna Kumar, Jeroze Dalal, and Manoj P. Jadhav.

Opinion-Editorial : Assessing the Negativity Around Negative Results
Stephan C. Jahn, PhD.


Author(s)
Melanie Lödige, PhD
Address

Perelman School of Medicine, 415 Curie Blvd, Philadelphia,PA 19104, USA

Abstract:

Bacillus anthracis carries a special type of bacterial toxin and is considered to be a potential biological weapon. The highly lethal spores of B. anthracis cause severe diseases such as cutaneous, gastrointestinal, and inhalation anthrax. The multicomponent binarytoxin (AB-type) of B. anthracis consists of two separate components: component A with enzymatic activity (edema factor and lethal factor) and component B (protective antigen, PA - the binding portion). Component B is essential for the formation of transmembrane channels (PApores) that translocate component A from endosomes to the cytoplasm, thereby causing lethal effects in the target cells. We have designed and synthesized small molecule inhibitors belonging to a novel class of aminoquinolinium substances that block the entry of the enzymatic components through the PA pore. 


Author(s)
Stefanie B.Marquez, PhD
Address

Division of Hematology/Oncology, PO Box 100278 Gainesville, Florida32610, USA

Abstract:

Lung cancer is the most common cause of all cancer deaths in the United States and worldwide. Despite advances in surgical techniques and therapies, the cure rates for lung cancer have not changed in the last thirty years. Lung cancer typically presents in the advanced stages when the cancer has already spread beyond the chest wall. Therefore, a goal of clinicians is to treat these patients while their lung cancers are at an earlier stage. The screening of smokers and former smokers by computed tomography (CT) is usually the recommended approach in order to detect early-stage lung cancer. However, given that only a small percentage of smokers will get lung cancer, researchers have sought to determine the causes of lung cancer other than tobacco exposure. Throughout the past decade, investigators have attempted to find suitable biomarkers to determine cancer risk so that individuals can be risk-stratified prior to screening. This process would target a much more specific at-risk population and would minimize the risks of CT and other diagnostic modalities in those individuals who are not at the highest risk. The polymorphisms in the promoter of the Brahma (BRM) gene are two candidate biomarkers that have been associated with loss of the tumor susceptibility protein BRM, which in turn is correlated with an increase in cancer risk. Much progress has been made since the initial discovery of these polymorphisms in 2011, and the aim of this commentary is to review the discovery of the BRM polymorphisms and to discuss their pertinence to clinical practice.


Author(s)
Lingyao Wang, Kexian Chen, Lu Yin, and Haoran Li.
Address

Department of Chemistry, ZJU-NHU United R&D Center, AND State Key Laboratory of Chemical Engineering,Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, P.R. China

Abstract:

Protocols of aerobic oxidation of secondary alcohols to ketones by using TEMPO modified by bi-functionalized imidazolium-based ionic liquids have been developed. [Imim-TEMPO][X] (X= FeCl4, CuCl2)has been proved to be efficient and recyclable catalysts with modest or excellent yields and selectivity. Therefore, relevant literatures are summarized herein.


Author(s)
Noushin Nabavi, PhD 
Address

Department of Cellular and Molecular Pharmacology, UCSF, 600 16th Street, MC 2140, CA 94158-2140, USA 

Abstract:

For the purpose of studying Wnt signaling, the intestinal epithelium has been the most relevant biological tissue for its differential topology expression of Wnt signaling: active in all crypt cells (helping in proliferation, stemness, regeneration, and tissue homeostasis) and inactive in the villi cells. Interestingly though, YAP/TAZ regulation through Wnt signaling has been more controversial and the subject of this review.  Recent work shows that Wnt signaling inactivates the cytoplasmic pool of destruction complex through dissociating β-TrCP E3 ligase from the complex.  Further, in addition toβ-catenin, YAP and TAZ, two related proteins known for their roles in the Hippo signaling cascade, are two other pivotal regulators of cell proliferation and stemness during organ growth, regeneration, and tumorigenesis. The biological function of YAP/TAZ andβ-catenin overlap to suggest that these factors are not completely independent of one another and may influence each other’s activities.


Author(s)
Ambika Chandrasekhar, PhD, and Anand Krishnan, PhD
Address

Alberta Diabetes Institute and Division of Neurology, Faculty of Medicine,UA, 116 St and 85Ave, Edmonton, AB T6G 2R3, Canada

Abstract:

Myelin associated proteins are known to pose hurdles to central nervous system (CNS) axon regeneration. The myelin mediated inhibition on axon regeneration can be reversed by brain derived neurotrophic factor (BDNF). BDNF enhances cyclic AMP (cAMP) levels for eliciting its beneficial effects on axon regeneration. A recent article by Martinez et al., revealed that soluble adenylyl cyclase (sAC) is a potential catalytic source for cAMP in BDNF stimulated neurons. Interestingly BDNF stimulated or exogenously administered sAC was able to reverse the inhibitory effects of myelin on axon regeneration suggesting that sAC is a potential therapeutic opportunity in CNS injury.


Author(s)
Lu Yin,Kexian Chen, Lingyao Wang, Jia yao, and Haoran Li
Address
Department of Chemistry, ZJU-NHU United R&D Center, AND State Key Laboratory of Chemical Engineering,Department of Chemical and Biological Engineering
Abstract:

A series of square-planar Platinum(II) terpyridyl modified by alkynyl, crown ether pendants, or supramolecular triblock copolymers have versatile luminescence behaviors. In this field, the utilization of the Platinum(II) terpyridyl coordination compounds have received great attention in the past few decades. This paper will summarize several relevant literatures about luminescence properties and application in responsing pH, conformational change, microenviromental change and detection of heparin quantification. 


Author(s)
Sonali J. Rawat, Ph.D.
Address
FCCC, Cottman Avenue, Philadelphia, PA, 19111 USA
Abstract:

Mammalian sterile 20 like kinase (Mst) 1 and Mst2 are stress-activated kinases, activated by various stress stimuli including oxidative stress. Mst1/2 act as tumor suppressor proteins and their deregulation is associated with the development of cancers, such as liver cancer and prostate cancer. Cellular oxidative stress is known to upregulate Mst1/2activity; activation of Mst1/2 induces apoptosis in oxidative stress conditions.Until recently, the exact mechanism/s of Mst1/2 activation and Mst1/2-induced apoptosis under oxidative stress conditions was not clear. But some recent reports have begun to elucidate the mechanisms of Mst1/2 activation by oxidative stress. Not only Mst1/2 activity is regulated by oxidative stress, but Mst1/2 are also involved in the regulation of redox levels in cells. In this short report we will discuss various mechanisms of Mst1/2 activation and Mst1/2-dependent apoptosis in response to oxidative stress. 


Author(s)
Prajna Kumar, Jeroze Dalal, and Manoj P. Jadhav.
Address
TexilaAmerican University, Guyana, Bombay College of Pharmacy, India, and College of Medicine, University of Florida, Gainesville, Flori
Abstract:
Background: The FDA issued guidance for the industry on the Oversight of Clinical Investigations-ARisk-Based Approach to Monitoring (RBM however the guidance lacks specificity on what successful implementations should look like and strategies that will address global adoption.

Purpose: To address current challenges with implementation of risk based approach to monitoring in the global research platform and suggest potential solutions.

Methods: Literature search was conducted followed by several discussion and brain storming sessions conducted to arrive at this brief write up.
Conclusions: Having a team science approach to implementation of the risk based approach to monitoring at the initial stage to ensure effective and efficient adoption across the industry in the global platform. This will eliminate inconsistencies in understanding as well as implementation of RBM by the investigational research sites.

Author(s)
Stephan C. Jahn, PhD.
Address
Departmentof Medicinal Chemistry and UF Health Cancer Center, UFL,Gainesville, FL  32610, USA
Abstract: This opinion piece looks at why negative results are viewed differently from other "positive" results, even though both are equally valid.  It argues that the practice of excluding negative data is outdated and is seen as odd and wasteful to those that are not a part of the academic culture.
 
     
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