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Journal of Postdoctoral Research (JPR) - Vol. 5, No. 9, September 2017
 
EDITORIAL: Targeting DNA repair as cancer therapy: TLS comes into focus
Jia Zhou, Ph.D.
Translesion Synthesis: An emerging new target during chemotherapy
Cynthia A. Harris and Nimrat Chatterjee, PhD
Understanding the Potential Barriers and Facilitators for Enrolling Postdoctoral Fellows: A Case Study of Medical Colleges in Malawi, Zambia, and Zimbabwe
Wilson L. Mandala, Ph.D., Amelia C. Challender, Margaret Maimbolwa, Exnevia Gomo, Moffat Nyirenda, Frances M.Cowan, Susan C. Connors
Natural Killer Cells in Cancer: An Overview
Aparna Rao,Ph.D., and Nduka Amankulor, Ph.D.
Does More Education Promote Civic Engagement?
Zhaogang Qiao, Ph.D., Ying Zhang, Ph.D., and Guodong Liang, Ph.D. 
Role of the Spindle and kinetochore associated (Ska) protein complex in mitotic progression
Sushama Sivakumar, Ph.D.
EDITORIAL: Metal Hydrides as Catalytic Intermediates
Sarah R. Soltau, Ph.D.
Metal Hydrides as Catalytic Intermediates: The Curious Case of Iron Carbonyl Clusters
Atefeh Taheri, Ph.D. and Louise A. Berben, Ph.D.
Chinese Anti-Corruption Policy Choices in a Transitional Stage
Zhaogang Qiao, Ph.D., and Ying Zhang, Ph.D.
Cyanobacterial biofactories: combining evolved and synthetic genetic regulatory mechanisms to yield carbon-neutral bioproducts
Logan A. Brand, and George W. Owttrim, Ph.D.
12

Author(s)
Jia Zhou, Ph.D.
Address
Department of Radiation Oncology, DFCI, Harvard Medical School, MA, 02115, USA. 
Abstract:

DNA repair plays critical roles in maintaining genome stability. There are six major DNA repair pathways that handle different types of DNA damages, namely base excision repair (BER), nucleotide excision repair (NER), mis-match repair (MMR), homologous recombination repair (HR), non-homologous end joining (NHEJ), and translesion synthesis (TLS). Numerous studies have shown that alteration in DNA repair genes, including deletions, mutations, and copy number alterations, and altered gene expression, is one of the major causes of mutagenesis and cancer. In fact, cancer cells are often defective in one of their six major DNA repair pathways. For example, approximately half of the epithelial ovarian cancers have alterations in genes that regulate HR, which accounts for their genomic instability and thus aggressiveness. The cancer risk dramatically increases in the population who carry mutations in HR genes, including the well-known breast cancer susceptibility genes (BRCA1 and BRCA2). 


Author(s)
Cynthia A. Harris and Nimrat Chatterjee, PhD
Address
Department of Biology, MIT, Cambridge 02139, USA
Abstract:

Translesion synthesis (TLS) is an important mechanism where a group of polymerases come together to orchestrate the bypass of aberrant DNA lesions. This process enables survival of those cells, which would have otherwise been committed to die because of these difficult to repair DNA lesions. Interestingly, siRNA knockdown of TLS polymerases in cancer cells was shown to sensitize cells to increased killing and reduced mutagenesis following treatment with chemotherapeutic drugs, which suggests an important role of TLS polymerases in chemoresistance and cancer relapse. Recent investigations showed that small molecule inhibitors (SMi) that specifically bind REV1 TLS polymerases and suppressed its protein-protein interactions with other TLS polymerases, also successfully sensitized cancer cells to enhanced killing and reduced mutagenesis. As such, the possibility of a SMi that specifically binds REV1 and inhibits TLS, will serve as a chemotherapy adjuvant and prevent chemoresistance and cancer relapse is now a promising possibility. In this mini-review, we will provide a brief discourse of the overarching importance of TLS polymerases in normal and cancer cells and describe characteristics of current and future TLS inhibitors that will potentially serve as clinical chemotherapeutic adjuvants.


Author(s)
Wilson L. Mandala, Ph.D., Amelia C. Challender, Margaret Maimbolwa, Exnevia Gomo, Moffat Nyirenda, Frances M.Cowan, Susan C. Connors
Address
Multiple universities across Malawi, Zambia, Zimbabwe, and the University of Colorado, Denver, USA.
Abstract:

In many countries, aspiring researchers compete for post-doctoral fellowships after PhD studies. The Southern Africa Consortium of Research Excellence (SACORE) had aimed to enrol eight post-doctoral fellows in the first phase but only appointed one. This study was conducted to explore barriers and potential facilitators for enrolment of post-doctoral fellows at three African schools of medicine. Individual interviews were conducted with 32 stakeholders from College of Medicine, Malawi; University of Zambia, School of Medicine; and University of Zimbabwe, College of Health Sciences. Interviewees included: university leaders and faculty (n = 15), Ministry leaders (n = 5), eligible fellowship candidates (n = 11), and a post-doctoral fellow (n = 1). Interview guides were developed for each stakeholder group; interviews were recorded, transcribed verbatim and coded for key themes. Post-doctoral fellowships were identified as potentially beneficial financially and for academic career development. Institutions felt they could benefit by developing relevant research, increasing the pool of mentors, and future research leaders. Lack of suitably qualified applicants and economic constraints of academia were the main challenges to recruitment. Post-doctoral fellowships benefits for individuals, institutions and countries, and the need to improve the recruitment process as well as to define research career pathways, were isolated.


Author(s)
Aparna Rao,Ph.D., and Nduka Amankulor, Ph.D.
Address
Department of Neurological Surgery, U Pitt, Pittsburgh, PA 15232, USA.
Abstract:

Natural Killer cells (NK cells) are cells of the innate immune system that are important players in mounting an immune response against viral infections and tumors. NK cells have a variety of mechanisms in order to detect and attack their target cells. In this review, the roles of NK cells in anti-tumor immunity have been discussed. NK cells use a combination of cell surface receptors and secreted factors in order to attack tumor cells and prevent tumor growth. In addition, NK cells act as an important mediator in the activation of the adaptive immune system, thereby resulting in a sustained anti-tumor immune response. Thus a high NK cell number in the tumor is indicative of a positive prognosis. Therefore, NK cell proportion is an important readout in order to evaluate the efficacy of novel anti-tumor therapies. However, a novel subset of NK cells .....


Author(s)
Zhaogang Qiao, Ph.D., Ying Zhang, Ph.D., and Guodong Liang, Ph.D. 
Address
Community Training and Assistance Center, Boston, MA, University of Maryland, College Park, MD 20742, USA
Abstract:

Education has long been regarded as a predicator for a strong understanding of civics, implying that civic participation will increase with more education. In this work, we model the relationship between schooling and a broad range of civic outcomes by using data from the National Civic Engagement Survey (NCES I) of Spring, 2002. By using Child labor laws as instruments and controlling for a number of factors such as age, gender, and occupation status, we estimated the contribution education makes in promoting civic participation. Our results suggest that education has a positive impact on voting, volunteering, and citizens’ group participation.


Author(s)
Sushama Sivakumar, Ph.D.
Address
UTSMC, Dallas, TX, 75390 USA.
Abstract:

The Spindle and Kinetochore Associated (Ska) protein complex is a heterotrimeric complex involved in mitotic progression. Depletion of Ska1, Ska2 or Ska3 by RNAi causes delays in chromosome alignment followed by a long metaphase arrest that results in Cohesion fatigue. Ska1 and Ska3 have been shown to bind microtubules both in vitro and in vivo. Ska1 directly recruits the protein phosphatase PP1 to kinetochores during mitosis. The Ska complex has also been implicated is regulating the localization of Anaphase promoting complex/cyclosome (APC/C) to chromosomes. Aurora B kinase has been shown to phosphorylate and regulate kinetochore recruitment of Ska proteins. The Ska complex, in addition to being substrate of Aurora B, also directly activates Aurora B and regulates kinetochore microtubule stability to ensure proper chromosome bi-orientation. The master mitotic kinase Cdk1 phosphorylates Ska3 and regulates Ska complex localization to kinetochores. Cdk1 kinase does not affect spindle localization of the Ska complex suggesting that distinct pathways exist to recruit Ska complex to defined mitotic substructures. Herein we discuss these findings and postulate their implications on Ska complex function during mitosis.    


Author(s)
Sarah R. Soltau, Ph.D.
Address
Department of Chemical Sciences, Bridgewater State University, Bridgewater, MA 02325, United States
Abstract:

Metal hydrides are essential intermediates for many important processes in alternative energy production such as hydrogen (H2) production or H2 oxidation, electrochemical reduction of carbon dioxide (CO2) to carbon based fuels, and the hydrogenation of CO2 and carbon monoxide.  These processes are the future of the alternative energy landscape and necessary developments to combat global climate change.  Development of catalysts that can be better tuned particular chemical reactions will increase the efficiency and success of the chemical processes necessarily for alternative energy production. The review by Drs. Taheri and Berben in this issue discusses the efforts to prepare catalysts that selectively perform CO2 reduction rather than favoring H2 production.  In their review, a selection of iron carbonyl cluster catalysts that vary in their ability to reduce CO2 or produce H2 based on their structure and hydricity are discussed (Taheri and Berben 2017).


Author(s)
Atefeh Taheri, Ph.D. and Louise A. Berben, Ph.D.
Address
Department of Chemistry, UC Davis, California 95616, United States
Abstract:

Here, we discuss recent efforts during the last 5 years for the development of molecular electrocatalysts involving metal hydride intermediates with particular attention to iron carbonyl clusters. This review begins with a brief description of thermodynamic properties (hydricity) of metal hydride intermediates and methods of hydricity measurements, specifically for iron carbonyl clusters. We then discuss two important reactions by iron carbonyl clusters relevant to solar fuel catalysis: electrocatalytic reduction of CO2 to formate and proton reduction to hydrogen. These examples are included because they provide valuable mechanistic insights into the design of catalysts that produce hydrogenated products selectively from CO2.


Author(s)
Zhaogang Qiao, Ph.D., and Ying Zhang, Ph.D.

Address
Community Training and Assistance Center, Boston. USA, and UMD, College Park. USA
Abstract:

With rapid economic development, corruption has become more and more serious in China. This paper has set up an optimal utility model to analyze the factors leading to corruption in China. The model illustrates how higher salary, lower income from corruption, lower preparation costs, higher probability and degree of punishment can help to reduce corruption. Considering these findings, this paper provided some policy discussions in the end.  


Author(s)
Logan A. Brand, and George W. Owttrim, Ph.D.
Address
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2E9.
Abstract:

While cyanobacteria hold the promise of producing useful bioproducts from little more than sunlight and carbon dioxide, their economic feasibility hinges on developing better mechanisms to manipulate gene expression in order to divert photosynthate towards product formation. A recent report demonstrates how combining simple feedback loops can improve the dynamic range of target gene expression while utilizing progressively lower concentrations of chemical inducers. As an extension of this work, we propose that utilizing regulatory elements that respond to changing temperatures could circumvent the need for exogenous chemical inducers, maintaining low background expression under non-induced conditions, and enhancing dynamic range via temperature induction of cyanobacterial cultures on an industrial scale.

 
     
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