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Journal of Postdoctoral Research (JPR) - Vol. 5, No. 5, May 2017
 
EDITORIAL: Developing Antibiotics with “Selfish DNA” Plasmids
Aparna Rao, PhD, and Somdutta Saha, PhD
Bacterial plasmid addiction systems and their implications for antibiotic drug development
Jennifer Tsang, PhD
Jadomycins: A Study of Their Synthesis and Biological Evaluation
Ehesan U. Sharif, PhD, and George A. O’Doherty, PhD
The many roles of TET1 in the post-implantation mouse embryo
Rita Khoueiry, PhD
Adipose triglyceride lipolysis - adding fuel to the fire
Vidisha Raje, PhD
A Cross-Sectional Study to Assess Mental Health Awareness among Adolescents
Anjali P. Kumar, Manoj .P Jadhav, PhD
Sodium tungstate mimics insulin effect on nuclear translocation of FBPase in rat liver
Romina Bertinat, Francisco Nualart, Juan Carlos Slebe, Alejandro J. Yáñez
Addgene: a global scientific resource - Sponsored Article
Maria Soriano-Carot, PhD
Morphological Characterization of Bacteriogenic Manganese Oxides From Three Model Manganese (II/III) Oxidizing Bacterial Species
Wendy F. Smythe, PhD
Are Shwachman-diamond syndrome patients radiosensitive?
Nimrat Chatterjee, PhD
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Author(s)
Aparna Rao, PhD, and Somdutta Saha, PhD
Address
Dept. of Neurosurgery, University of Pittsburgh, Pittsburgh PA 15232, USA, 
Computational Biology, GSK R&D, 1250 South Collegeville Road, Pennsylvania 19426, USA
Abstract:

Plasmids are small circular double-stranded DNA molecules that are most commonly found in bacteria. They replicate independently of chromosomal DNA. Plasmids often encode genes that provide a survival advantage to the organisms(1). For instance, plasmids may carry genes that confer resistance to naturally occurring antibiotics, or may provide the organism the ability to selectively utilize particular nutrients that will aid in survival when food is scarce. However, the maintenance and replication of plasmids impose immense metabolic burden on the bacterial host, mainly in terms of reduced host growth and viability.


Author(s)
Jennifer Tsang, PhD
Address
Harvard Medical School/Beth Israel Deaconess Medical Cente, Boston, MA 02115, USA
Abstract:

Bacteria frequently carry mobile genetic elements capable of being passed to other bacterial cells. An example of this is the transfer of plasmids (small, circular DNA molecules) that often contain antibiotic resistance genes from one bacterium to another. Plasmids have evolved mechanisms to ensure their survival through generations by employing plasmids segregation and replication machinery and plasmid addiction systems. Plasmid addiction systems utilize a post-segregational killing of cells that have not received a plasmid. In this review, the types of plasmid addiction systems are described as well as their prevalence in antibiotic resistant bacteria. Lastly, the possibility of targeting these plasmid addiction systems for the treatment of antibiotic resistant bacterial infections is explored.


Author(s)
Ehesan U. Sharif, PhD, and George A. O’Doherty, PhD
Address
Arcus Biosciences, 3928 Point Eden Way, Hayward, CA 94545, USA
Northeastern University, Boston, MA 02125, USA
Abstract:

Jadomycins are anticancer antibiotics isolated from Streptomyces venezuelae. The core of these natural products consists of a dihydro-phenanthridine ring-system. Another unique feature built to the core is a fused 1,3-oxazolidine-5-one ring. Recent synthetic reports suggest a structural revision of the fused oxazolidinone ring in jadomycin S and jadomycin T. This review will focus on the synthetic efforts leading to the structural revision, and the semisynthetic approaches to generate new jadomycin analogs and their biological activity.


Author(s)
Rita Khoueiry, PhD
Address
KU Leuven Department of Development and Regeneration, 3000 Leuven, Belgium.
Abstract:

The TET dioxygenases mediate DNA demethylation in pre-implantation embryos and in primordial germ cells, yet limited studies address their contribution to the global gain of DNA methylation following implantation. Here, we discuss our recent study revealing that Tet1 is expressed and functions non-redundantly in the early post-implantation mouse embryo. Ablating TET1 affects the methylation status of primed epiblast cells; however, the majority of gene expression regulation by TET1 seems to be independent of any gain or loss in methylation/hydroxymethylation due to TET1 omission. Interestingly, we reveal a gene repressive effect of TET1. Moreover, we show that loss of TET1 leads to developmental defects resulting in embryonic lethality with different penetrance depending on the genetic background of the mice.  


Author(s)
Vidisha Raje, PhD
Address
Department of Pharmacology, UVa, 1340 Jefferson Park Avenue, Charlottesville, VA 22908, USA
Abstract:

Recent studies have shown the presence of functional brown adipose tissue (BAT) in adult humans and it role in thermogenesis. This study by Blondin et al published in Cell Metabolism shows that similar to rodents; adult human brown adipose tissue uses lipids as its cellular fuel during thermogenesis. Inhibition of triglyceride lipolysis was associated with a shift in the skeletal muscle mediated shivering instead and a shift in fuel utilization from lipids to glucose. This study provides yet another confirmatory role of a functional brown fat in adult humans that is fueled by fatty acids.


Author(s)
Anjali P. Kumar, Manoj .P Jadhav, PhD
Address
Acton-Boxborough middle and high schools in Massachusetts, USA,and CRC Pharma, 333 Littleton Road, Suite # 302, Parsippany, New Jersey, USA
Abstract:

Suicide is among the top three leading causes of death in adolescents, and the rate of suicide-related deaths is on the rise. A systematic approach to address this challenge is warranted. This study aimed to assess how many students had awareness of or have had mental health issues, or knew someone who struggled with mental health. A cross-sectional, web-based survey was conducted at Acton-Boxborough middle and high schools in Massachusetts, USA. An electronic, self-administered survey with a total of 13 questions, including closed- and open-ended questions, was developed to collect feedback from students, teachers, counselors, and staff members. The survey was conducted between October 20 and November 13, 2016. The survey was posted on Facebook and was accessible to anyone with a Google email account linked to Acton-Boxborough schools. In this three–week survey, 623 completed responses were returned. The most frequent responders were middle school and younger students (n = 356; 57.1%), followed by high school students (n = 213; 34.2%), and college students (n = 39; 6.2%). A high number of participants (99%) considered mental health to be an important topic of discussion. 


Author(s)
Romina Bertinat, Francisco Nualart, Juan Carlos Slebe, Alejandro J. Yáñez
Address
Centro de Microscopía Avanzada, CMA Bío Bío, Universidad de Concepción, Concepción, Chile
Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Valdivia, Chile
Abstract:

Sodium tungstate (NaW) is an inorganic salt that has proven to be a potent insulin-mimetic agent, although the molecular events seems to differ. Inhibition of hepatic gluconeogenesis is one significant physiological action of insulin, therefore studying the effect of NaW on gluconeogenic enzymes will contribute to understand its elusive mechanism of action. Here, we show that NaW has no inhibitory effect over the gluconeogenic enzyme fructose 1,6-bisphosphatase (FBPase) in vitro, but mimics insulin in the induction of the nuclear translocation of FBPase in rat liver, which may have a negative impact on its activity. Then, at least in part, NaW may inhibit hepatic gluconeogenesis by inducing the proper subcellular distribution of FBPase, without directly interfering with its phosphatase activity. 


Author(s)
Maria Soriano-Carot, PhD
Address
75 Sidney St, Suite 550A, Cambridge, MA 02139, USA
Abstract:

Addgene • Addgene (http://www.addgene.org) is a nonprofit organization whose mission is to accelerate research and biomedical discovery by facilitating access to useful research materials and information. To fulfill this mission, Addgene maintains a repository that distributes >50,000 plasmids contributed by scientists coming from more than 3,000 different labs all over the world. The repository stores, quality controls, and annotates the data associated with the plasmids. Addgene also recently started providing ready-to-use viral particles produced from select plasmids in the repository. Researchers can use these viral particles directly in their experiments, thereby skipping the viral production process and accelerating their research. All plasmid data is made freely available to the public at Addgene.org. Members of the academic and nonprofit research community can request plasmids from the repository for a small fee. In addition, the organization creates useful educational materials covering topics from basic biology to the therapeutic applications of CRISPR for an audience ranging from undergraduate biologists to tenured professors. Every month Addgene distributes '11,000 plasmids, provides hundreds of viral particles, and publishes posts on a blog receiving >60,000 views per month. Addgene is an essential and global resource for the academic life sciences.  


Author(s)
Wendy F. Smythe, PhD
Address
BEACON Center for the Study of Evolution in Action, MSU, East Lansing, MI 48824
Abstract:

Currently there is limited knowledge as to the morphology of bacteriogenic manganese (Mn)-oxide minerals, making it difficult to identify Mn minerals from geologic deposits as being biotic or abiotically formed. When investigating mineral deposits it is critical to understand what environmental processes lead to mineral formation in order to accurately interpret the information locked inside each mineral. This study aims to characterize the morphology, structural variability, and microbe-mineral association of bacteriogenic Mn(III/IV) oxides produced by Mn(II/III)-oxidizing bacteria, using pure cultures of three known Mn-oxidizing bacteria. Morphology and localization of bacteriogenic Mn-oxides was characterized using high resolution scanning electron (HR-SEM) and transmission electron microscopy (TEM). We found that the morphology of bacteriogenic Mn-oxides varies between bacterial species, and that the localization of Mn oxidizing enzymes determines if Mn-oxides are closely associated with the cellular surface or form in exopolysaccharides (EPS). Knowledge acquired from this study illustrates the complexity of identifying bacteriogenic Mn-oxides and oxidation products from more complex natural environmental settings like ancient geologic deposits.


Author(s)
Nimrat Chatterjee, PhD
Address
Department of Biology, MIT, Cambridge 02139, USA
Abstract:

Mutations in the Schwachman-Bodian diamond syndrome (SBDS) gene—involved in ribosome biogenesis—cause Shwachman-diamond syndrome (SDS), a known bone marrow failure disorder. A dysfunctional ribosome biogenesis is postulated as a cause of phenotypes seen in SDS patients. Recently, lymphocytes from SDS patients with hypomorphic SBDS expression were shown to harbor significantly increased DNA damage and H2AX foci in response to X-rays or gamma rays. Additionally, SBDS knockdown in cells increases ROS (reactive oxygen species) levels and enhances proliferation defects in a p53 dependent manner. These new reports suggest that SBDS may have a novel and a yet unexplored role in DNA repair and damage response pathways. In this short opinion article, I will discuss these recent observations and delineate hypothesis to explain the potential new roles of SBDS. 

 
     
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