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. planktonic cells. Some of these peptides have also been shown to act in synergy with antibiotics commonly used in the clinic to prevent biofilm formation and eradicate pre-existing biofilms. Recently, the mechanism of action of one of these peptides (i.e., 1018) was shown to involve binding to and causing degradation of the second messenger stress response nucleotide ppGpp, which plays an important role in biofilm formation and maintenance. Here, we review recent progress in the field of anti-biofilm peptides and propose future directions to further develop these therapeutic agents.
Glycated hemoglobin is a clinically established important biomarker that provides retrospective value of blood glucose concentration over the preceding 2-3 months. Owing to the biochemical specificity and multiplexing capability, Raman spectroscopy has emerged as a promising tool for detection and quantification of blood constituents in a label-free and non-destructive manner. Here, we critically review the Raman spectroscopy-based approach to detect and quantify this important biomarker. The potential of this spectroscopy-based approach and its possible clinical translation from the current optical bench will be also briefly discussed along with the future prospects.
This comparative study used the latest Trends in International Mathematics and Science Study (TIMSS) data sets and examined the relationship between professional development and student achievement. It found that although the national levels of access for students at the fourth and eighth grade levels to teachers who participated in professional learning in the United States were higher than the other countries, one third to one half of the fourth grades were taught by teachers who had no professional learning focusing on math instruction or curriculum. In addition, teachers’ participation in professional development was positively associated with higher student math achievement. This cross-national study provided empirical evidence highlighting the importance of investing in teacher learning for improving national educational quality.
Department of Cellular and Molecular Pharmacology. UCSF, 600 16th Street, MC 2140, CA 94158-2140, USA
Aging is a degenerative process associated with several phenotypes among which are increases in accumulation of misfolded and damaged proteins. Several studies have shown associations of altered mitochondrial DNA and structure, oxidative phosphorylation function, and ROS production with aging. In this study, Zhou et al explore the role of mitochondria in regulating protein aggregate distribution during cell division. This is in fact the first account of a framework mechanism for proteome quality control and its role in aging and cell rejuvenation.
Department of Medicinal Chemistryand UF Health Cancer Center, UFL, Gainesville, FL 32610, USA
Dichloroacetate (DCA) has been used for many years as an investigational drug to treat children born with mitochondrial disorders. Through its inhibition of Pyruvate Dehydrogenase Kinase (PDK), a key component of the pyruvate dehydrogenase complex, DCA has shown promise in facilitating oxidative phosphorylation in cell mitochondria. Recently, DCA has received more attention as a possible treatment for numerous forms of cancer. In this research highlight, we will discuss a paper from Dunbar et al. in which a Phase 1 trial for DCA was run in adults with recurrent malignant brain tumors (RMBTs). These tumors often carry a poor prognosis. As DCA has the ability to pass through the blood-brain barrier, it is being investigated as a possible treatment for RMBTs. The goal of the trial was to establish dose ranges that are safe to administer to patients with recurrent malignant gliomas.
Department of Pharmacology, UVA, 1300 Jefferson Park Avenue, Charlottesville, VA 22908, USA
The global epidemic of obesity is increasing at an alarming rate, posing a severe threat to human health. The accumulation of excess white adipose tissue in obese individuals increases their risk for type 2 diabetes, cardiovascular diseases, hypertension, stoke and even cancer. Current efforts manifest the need to identify potential anti-obesity therapeutics. One promising approach is increasing the activity of ‘brown like’ adipocytes in white adipose depots, which has been shown to improve the overall metabolic phenotype of the organism. This report by Moisan and coworkers demonstrates a novel and a promising approach by inhibiting JAK kinases to induce browning in white adipose tissue.
Perelman School of Medicine, 415 Curie Blvd, Philadelphia,PA 19104, USA
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.
Division of Hematology/Oncology, PO Box 100278 Gainesville, Florida32610, USA
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.