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Journal of Postdoctoral Research (JPR) - Vol. 6, No. 3, March 2018
 
Editorial: Leptin - The Central Regulator of Starvation
Vidisha Raje, PhD
The Role of Leptin in Maintaining Plasma Glucose During Starvation
Rachel J. Perry and Gerald I. Shulman
Circadian-tumor suppressor crosstalk: Emerging opportunities in cancer chronotherapy
Tetsuya Gotoh, Xianlin Zou, Carla V. Finkielstein
Editorial: Injecting new life into intracellular delivery methods
Kathy Myers Gschweng, Ph.D.
Recent Advances in Mammalian Cell Transfection Techniques
Andy Tay, PhD, and Nicholas Melosh, PhD.
Stock Risk Assessment via Multi-Objective Genetic Programming
Amirhessam Tahmassebi, Amir H. Gandomi, Anke Meyer-Baese
Therapeutic Potential of Biologically Active Resin Glycoside Natural Products
Ehesan U. Sharif, PhD.
Assignment of Absolute Stereochemistry of Hydroxyl Centre Using Mandalate Ester: An Anisotropic Effect of Phenyl Group on Remote Protons
Ganapathy S. Sankaran, Vasantha R, Dandamudi V. Lenin, Sivaraman Balasubramaniam
EDITORIAL: Mining gold to treat the untreatable: Design, Synthesis and Characterization of Gold Based Nucleosidic Compounds
Sharmistha Mitra, PhD
6-Mercaptopurine Nucleoside Complexes of Gold(I): Synthesis and Cytotoxicity
Ayan Maity, Nihal Deligonul, Anthony J. Berdis, and Thomas G. Gray
12

Author(s)
Vidisha Raje, PhD
Address
Department of Pharmacology, UVA, Charlottesville, Virginia 22903, USA
Abstract:

Humans have evolved to store energy in three major forms: carbohydrate, fat, and protein. In the liver, insulin triggers the storage of circulating glucose as glycogen, which can be readily mobilized to glucose and is the fuel of choice where instantaneous energy is required, such as during conditions of stress and the onset of starvation. However, liver glycogen accounts for <1% of the total stored energy. Skeletal muscle is also a major site of storage of glycogen (about 2/3 of the total glycogen) and protein and accounts for 15% of the total stored energy. The majority of energy stores, >80%, are in the form of fat, stored as lipid droplets in adipocytes1. Teleologically, this makes a lot of sense given that humans have been hunter-gatherers and had to go for prolonged periods of starvation in search of food. On the contrary, the modern man is exposed to a much more nutrient replete environment. The human body, however, is still adapted for efficiently storing any ingested nutrients as energy reserves in different tissues for periods of critical need such as starvation. 


Author(s)
Rachel J. Perry and Gerald I. Shulman
Address
Departments of Internal Medicine and Cellular & Molecular Physiology
Yale University School of Medicine
Howard Hughes Medical Institute

Abstract:

For 20 years it has been known that concentrations of leptin, a hormone produced by the white adipose tissue (WAT) largely in proportion to body fat, drops precipitously with starvation, particularly in lean humans and animals. The role of leptin to suppress the thyroid and reproductive axes during a prolonged fast has been well defined; however, the impact of leptin on metabolic regulation has been incompletely understood. However emerging evidence suggests that, in starvation, hypoleptinemia increases activity of the hypothalamic-pituitary-adrenal axis, promoting WAT lipolysis, increasing hepatic acetyl-CoA concentrations, and maintaining euglycemia. In addition, leptin may be largely responsible for mediating a shift from a reliance upon glucose metabolism (absorption and glycogenolysis) to fat metabolism (lipolysis increasing gluconeogenesis) which preserves substrates for the brain, heart, and other critical organs. In this way a leptin-mediated glucose-fatty acid cycle appears to maintain glycemia and permit survival in starvation.


Author(s)
Tetsuya Gotoh, Xianlin Zou, Carla V. Finkielstein
Address
Biocomplexity Institute, Virginia Tech, Blacksburg, VA, USA.
Institute for Protein Research, Osaka University, Osaka, Japan 
Abstract:

Previously, cancer treatment modalities relied primarily on chemotherapeutic agents; nowadays, advances in rationally-designed drugs and targeted therapies have enabled the manipulation of cancer-specific regulatory molecules that are frequently mutated and globally identified in various cancers. Regardless the approach, the objective for controlling cancer progression has always been to attenuate, eliminate, or control the neomorphic activity of target driver mutations in tumors by maintaining steady levels of therapeutic agents. As precision medicine gains momentum, so does the possibility of customizing individual patients’ treatments to the “time-of-day” when tumor cells exhibit the highest susceptibility to therapeutics (1). However, a gap exists in our knowledge regarding the times at which therapeutically-targeted molecules are likely to be most susceptible to drugs and yield the greatest cellular effect. As a result, there is a need to unveil “when” and “where” druggable targets are in the cell and “to what extent” the tumor’s time-keeping system differs from normal tissue (Fig. 1A). Defining priorities that address those needs across the hierarchical system of organization will allow researchers to find the best time-windows where delivery of treatment modalities can be most effective. 


Author(s)
Kathy Myers Gschweng, Ph.D.
Address
Department of Psychiatry, Semel Institute of Neuroscience and Human Behavior, UCLA, Los Angeles 90095, USA.
Abstract:

Effective methods for intracellular delivery of nucleic acid, protein or other cargo presents an ongoing challenge for both basic research needs and clinical applications. With the expansion of CRISPR/Cas9 gene editing for research and therapeutic purposes (Fellmann, Gowen et al. 2017) and with recent clinical successes of genetically modified cell therapies for cancer treatment (Brudno and Kochenderfer 2018), improvements to existing gene delivery technologies have been highly sought after (Singh, Shi et al. 2017). The main approaches can be generally categorized as viral, chemical, or physical techniques. In their review, Tay and Melosh describe these different approaches for cellular transduction in mammalian systems with a focus on technological improvements made within the last year to each (Tay and Melosh, 2018).


Author(s)
Andy Tay, PhD, and Nicholas Melosh, PhD.
Address
Dept. of Materials Science and Engineering, Stanford, CA 94305;
Dept. of Biomedical Engineering, NUS, Singapore 117583

Abstract:

Cell transfection is an essential step for gene editing and intracellular delivery of cargoes such as mRNA and proteins. Significant improvements have been made to reduce the cytotoxicity and to improve efficiency associated with transfection over the few decades. Nevertheless, with new, exciting biological questions, the demand for the ideal transfection technique with high throughput, single cell transfection ability and control of cargo dosage has increased. This review focuses on recent innovations in cell transfection techniques, and discusses the pros and cons of each method.


Author(s)
Amirhessam Tahmassebi, Amir H. Gandomi, Anke Meyer-Baese
Address
Department of Scientific Computing, FSU, Tallahassee, FL 32306-4120, USA
School of Business, SIT, Hoboken, New Jersey 07030, USA
Abstract:

Recent exponential growth of investors in stock markets brings the idea to develop a predictive model to forecast the total risk of investment in stock markets. In this paper, an evolutionary approach was proposed to predict the total risk in stock investment based on an S&P 500 database in a time period of 1991-2010 employing a multi-objective genetic programming along with an adaptive regression by mixing algorithm. The reasonable results suggest that the proposed model can be applied to various stock databases to assess the total risk of investment. The proposed model along with stock selection decision support systems can overcome the disadvantages of weighted scoring stock selection.


Author(s)
Ehesan U. Sharif, PhD.
Address
Department of Chemistry, Arcus Biosciences, 3928 Point Eden Way, Hayward, CA 94545, USA
Abstract:

Resin glycosides are naturally occurring oligosaccharides, primarily found in the morning glory plants (convolvulaceous family). The unique structural feature of this class of natural products is the presence of a macrolactone ring. The hydrophobic side-chain of the macrolactone maintains a fine balance on the highly polar polysaccharide backbone, making them amphiphilic. Various parts of the morning glory plant have been used as folk medicines for centuries throughout the world.  The commentary bellow emphasizes on the potential application of resin glycosides in the development of new therapies. 


Author(s)
Ganapathy S. Sankaran, Vasantha R, Dandamudi V. Lenin, Sivaraman Balasubramaniam
Address
UMass Medical School, Worcester, MA-02464, USA
School of Chemical Sciences, Central University of Gujarat, Gandhinagar, India-382030  
Abstract:

An absolute configuration of a hydroxy center is assigned by using methoxy mandelic acid taking the advantage of anisotropic effect phenyl group. The enantiomeric excess and absolute configuration of unknown compounds is determined by using simple 1H NMR spectra. The influence of anisotropic effect of phenyl ring on remote protons is revealed.


Author(s)
Sharmistha Mitra, PhD
Address
Department of Pediatrics, Division of Neurology, UTSMC, Dallas, TX 75390, USA.
Abstract:

The current field of anticancer therapy is dominated by organic molecules. However, after FDA approval of the platimum based drug Cisplatin in 1978 and its positive effects to treat testicular and ovarian cancer, there came an urge to design more metal based anticancer drugs which would be more selective, non-toxic to non-targeting cells and will have reduced side effects. Following the success of Cisplatin, came the gold based anti cancer drug Auranofin, which showed immunosuppressory properties as well. Gold’s oxidation state +3 is similar in chemical configation as platinum and on the top gold complexes show antiinflammatory and immunospressory properties5. Therefore, there were several reports afterwards which emphasized the synthesis and use of gold based complexes as potetial drugs against cancer. Most of the gold complexes described so far targets enzymes or proteins inside the cells. Gold complexes targeting DNA are rare. 


Author(s)
Ayan Maity, Nihal Deligonul, Anthony J. Berdis, and Thomas G. Gray
Address
MIT, Cambridge, MA 02139.
Case Western Reserve University, Cleaveland, OH 44106.
Cleveland State University, Cleveland, OH 44115, USA,
Abstract:

Molecular gold compounds have shown intermittent promise as human pharmaceuticals, mostly in in vitro as-says.  Rational approaches to gold prodrugs are essential for desired cytotoxicity.  This work describes non-natural nucleosides of 6-mercaptopurine.  Binding to (organophosphine)- and (N-heterocyclic carbene)gold(I) proceeds in high-yield reactions at room temperature.  Three such metallonucleosides were prepared.  They dif-fer in the phosphine or carbene ligand on gold.  New compounds are characterized by multinuclear NMR spec-troscopy, mass spectrometry, and elemental analysis.  One complex is crystallographically characterized; gold(I) is bound to the sulfur atom of the mercaptopurine moiety, and aurophilic interactions are absent.  Experiments in human cell lines showed evidence of mitochondrial swelling, programmed cell death, and inhibition of rat liver thioredoxin reductase.

 
     
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