Postdoc Journal

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...

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...

Recent studies have demonstrated that leptin can prolong life chronically in rats with poorly-controlled type 1 diabetes (T1D). Multiple explanations have been proposed to explain leptin's chronic antihyperglycemic effect, including suppression of glucagon release and/or signaling, reductions in hyperphagia and ectopic lipid content, and improvements in insulin sensitivity; it is leptin's ability to reduce plasma glucose relies on all of these effects. In addition, leptin reverses hyperglycemia and diabetic ketoacidosis (DKA) acutely, within 6 hours of leptin infusion, by suppressing hypothalamic-pituitary-adrenal (HPA) axis activity in insulinopenic rats...

Glycolysis is highly upregulated in head and neck squamous cell carcinoma (HNSCC). HNSCC glycolysis is an important contributor to disease progression and decreases sensitivity to radiation or chemotherapy. Despite therapeutic advances, the survival rates for HNSCC patients remain low. Understanding glycolysis regulation in HNSCC will facilitate the development of effective therapeutic strategies for this disease. In this review, we will evaluate the regulation of altered HNSCC glycolysis and possible therapeutic approaches by targeting glycolytic pathways...

Conventional microbiological methods have been readily taken over by newer molecular techniques due to the ease of use, reproducibility, sensitivity and speed of working with nucleic acids. These tools allow high throughput analysis of complex and diverse microbial communities, such as those in soil, freshwater, saltwater, or the microbiota living in collaboration with a host organism (plant, mouse, human, etc). For instance, these methods have been robustly used for characterizing the plant (rhizosphere), animal and human microbiome specifically the complex intestinal microbiota...

Mx1 (Myxovirus (Influenza virus) resistance 1, interferon-inducible protein p78) gene has been implicated in the resistance to a wide range of RNA viruses including influenza A in several species such as Sus scrofa. In the present study a 28-bp deletion in exon 14 of the Mx1 gene has been identified in Iberian domestic pigs but not in other domestic breeds neither in wild boars. The mutation produces a frameshift giving a protein with 6 amino acid substitutions and the extension of the C-terminal region with additional 20 amino acids with respect to the wild type MX1 protein...

Ever since video games were available to the general public, they have intrigued brain researchers for many reasons. There is an enormous amount of diversity in the video game research, ranging from types of video games used, the amount of time spent playing video games, the definition of video gamer versus non-gamer to the results obtained after playing video games. In this paper, our goal is to provide a critical discussion of these issues, along with some steps towards generalization using the discussion of an article published by Clemenson and Stark (2005) as the starting point...

RNA therapeutics refers to the use of oligonucleotides to target primarily ribonucleic acids (RNA) for therapeutic efforts or in research studies to elucidate functions of genes. Oligonucleotides are distinct from other pharmacological modalities, such as small molecules and antibodies that target mainly proteins, due to their mechanisms of action and chemical properties. Nucleic acids come in two forms: deoxyribonucleic acids (DNA) and ribonucleic acids (RNA). Although DNA is more stable, RNA offers more structural variety ranging from messenger RNA (mRNA) that codes for protein to non-coding RNAs, microRNA (miRNA), transfer RNA (tRNA), short interfering RNAs (siRNAs), ribosomal RNA (rRNA), and long-noncoding RNAs (lncRNAs)...

Almost 20 incurable neurodegenerative disorders are caused by trinucleotide repeat (TNR) expansion beyond a certain threshold, with disease time of onset and severity positively correlating with repeat length. Typically, long TNRs display a bias toward further expansion and repeats continue to expand not only during germline transmissions from parents to offspring, but also remain highly unstable in somatic tissues of patients. Hence, understanding TNR instability mechanisms sheds light on underlying disease pathology...

Imaging mass spectrometry (IMS) has emerged as a powerful analytical tool enabling the direct molecular mapping of many types of tissue. Specifically, matrix-assisted laser desorption/ ionization (MALDI) represents one of the most broadly applicable IMS technologies. In recent years, advances in solid state laser technology, mass spectrometry instrumentation, computer technology, and experimental methodology have produced IMS systems capable of unprecedented data acquisition speeds (>50 pixels/second). In applications of this technology, throughput is an important consideration when designing an IMS experiment...

Ohio State University researchers have made a leap forward in disease research by creating an eraser sized human "brain" in a petri dish1 . Although lacking a circulatory system their brain model includes spinal cord, cortex, midbrain, brain stem, and even the beginnings of an eye- aiding in the effectiveness of research on complex neurological disease. To create their new brain model, the researchers converted adult skin cells into pluripotent stem cells, which afforded the opportunity to build the multiple nervous cell types required for such a complex system...

Gene therapy to the gastrointestinal tract has remarkable potential for treating gastrointestinal disorders that currently lack effective treatments. Adeno-associated viral vectors (AAVs) have been extensively applied to the central nervous system, and have repeatedly demonstrated safety and efficacy in animal models. The enteric nervous system (ENS) represents a vast collection of neurons and glial cells that may also be subject to treatment by AAV, however little work has been conducted on AAV delivery to the ENS...

This review will focus on strategies to develop new treatments that target the biofilm mode of growth and that can be used to treat biofilm infections. These approaches aim to reduce or inhibit biofilm formation, or to increase biofilm dispersion. Many antibiofilm compounds are not bactericidal but render the cells in a planktonic growth state, which are more susceptible to antibiotics and more easily cleared by the immune system. Novel compounds are being developed with antibiofilm activity that includes antimicrobial peptides, natural products, small molecules and polymers...

Phosphoinositide 3-kinases (PI3Ks) are central regulators of cellular responses to extracellular stimuli, and are involved in growth, proliferation, migration, and metabolism. The Class I PI3Ks are activated by Receptor Tyrosine Kinases (RTKs) or G Protein-Coupled Receptors (GPCRs), and their signaling is commonly deregulated in disease conditions. Among the class I PI3Ks, the p110β isoform is unique in being activated by both RTKs and GPCRs, and its ability to bind Rho-GTPases and Rab5. Recent studies have characterized these p110β interacting partners, defining the binding mechanisms and regulation, and thus provide insight into the function of this kinase in physiology and disease...

Host defense (antimicrobial) peptides (HDPs) are produced by virtually all organisms and have an important role in protection against microbial infections. Some naturally occurring peptides such as the human cathelicidin LL-37 and the bovine peptide indolicidin have been shown to inhibit bacterial biofilm development. Rearrangement and substantial modification of the amino acid sequence of these and other HDPs has led to the identification of small synthetic peptides with increased, broad-spectrum anti-biofilm activity that is independent of activity vs...

Diabetes is a long-standing disease that leads to secondary complications of capillaries such as retinopathy, nephropathy and neuropathy. Emerging evidence suggests that diabetes may also affect the cerebromicrovasculature, the blood-brain barrier (BBB), and lead to changes in the brain that affect cognition and mood. Therefore, it is important to identify natural compounds that may have therapeutic benefit for reducing BBB dysfunction and improve patient quality of life. Preclinical evidence suggests that sesamol, a natural antioxidant in sesame seed oil, could have therapeutic benefit for treating BBB dysfunction during diabetes...

The development of leadership and project management skills is increasingly important to the evolution of translational science and team-based endeavors. Team science is dependent upon individuals at various stages in their careers, inclusive of postdocs. Data from case histories, as well as from interviews with current and former postdocs, and those supervising postdocs, indicate six essential tasks required of project managers in multidisciplinary translational teams, along with eight skill-related themes critical to their success...

IL2-inducible T-cell kinase (ITK), a member of the Tec family tyrosine kinases, is the predominant Tec kinase in T cells and natural killer (NK) cells mediating T cell receptor (TCR) and Fc receptor (Fc R) initiated signal transduction. ITK deficiency results in impaired T and NK cell functions, leading to various disorders including malignancies, inflammation, and autoimmune diseases. In this mini-review, the role of ITK in T cell signaling and the development of small molecule inhibitors of ITK for the treatment of T-cell related disorders is examined...

CCL20 or MIP3α is a small ~8 kDa protein primarily expressed in the liver, colon, prostate, cervix, and skin. The cellular receptor for CCL20 is CCR6. CCl20 unlike many other cytokines only binds CCR6, making the CCL20/CCR6 pathway an attractive drug target. Since the initial discovery of CCL20 in the early 1990's, there has been an increase in the evidence implicating the chemokine and its receptor in a number of diseases, including rheumatoid arthritis and human immunodeficiency virus infection. CCL20 has also been linked to malignancies such as ovarian, colorectal and pancreatic cancers...

Osteosarcoma (OS) is the most common non-hematologic primary tumor of bone in children and adults. High-dose cytotoxic chemotherapy and surgical resection have improved prognosis, with long-term survival for non-metastatic disease approaching 70%. However, most OS tumors are high grade and tend to rapidly develop pulmonary metastases. Despite clinical advances, patients with metastatic disease or relapse have a poor prognosis. Here the cell biology of OS is reviewed with a special emphasis on mouse models as well as the roles of the cell of origin and cancer stem cells...