Alzheimer’s disease (AD) is a devastating illness with unknown etiology and no cure. The predominant model for studying AD has been transgenic mice with human mutant amyloid-ß (Aß) protein designed to reflect inherited familial forms of AD (fAD). However, this approach only reflects a small percentage of the AD population and has not lead to successful therapeutics. There is recent and compelling evidence that the Aß is not simply a misfolded protein that accumulates to eventual AD, but instead a protein with physiological roles that responds to several pathological contexts. If we better understand the contexts that stimulate Aß accumulation, and the character of its response, we can refocus research on targets upstream of Aß. In order to do this, the field needs models of late-onset AD (LOAD) that do not rely on human transgenes in mice. This perspective outlines models of contextually-driven Aß accumulation, animals with naturally elevated Aß and a potential human organ model that may be employed to better understand the role of Aß in AD.
In this discussion we present a course in cancer biology and therapeutics that we have taught for high school students the past five summers. Course content as well as data quantifying student learning are presented. Our hope is to provide guidance to those teaching similar courses or a template to teach the same course elsewhere.
One of the most influencing theories in numerical cognition proposes a specialized cognitive system for extracting number out of visual displays. This system has been suggested to map number onto a mental representation of space, the mental number line. While initially number extraction was said to occur independent of visual features, recent evidences challenge this view. After introducing the basics of numerical cognition, the current article will briefly outline this ongoing dispute based on literature coming from the line bisection task. Finally, directions for future research are proposed.
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. Having this tissue model will assist researchers in developing new disease models, and thus, facilitate the development of novel clinical interventions.
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. Challenges for gastrointestinal gene therapy include identifying gene targets, optimizing gene delivery, and target cell selection. Researchers are now beginning to tackle the later of the two challenges with AAV, and the same AAV technology can be used to identify novel gene targets in the future. Continued efforts to understand AAV delivery and improve vector design are essential for therapeutic development. This review summarizes the current knowledge about AAV delivery to the ENS.
Acetate assimilation in C. reinhardtii leads to bicarbonate and CO2aq formation in heterotrophic growth condition. Bicarbonate and CO2aq thus formed under this condition remain in equilibrium with the action of carbonic anhydrases. Carbonic anhydrase catalyzes reversible hydration of carbon dioxide and dehydration of bicarbonate. In this article we report that the rapid exchange catalyzed by extracellular carbonic anhydrase causes a large magnetization (saturation) transfer effect on the 13C signal of bicarbonate at 161.01 ppm when the resonance of the carbon dioxide (aq) at 125.48 ppm is irradiated with RF pulses. In C. reinhardtii extracellular space the unidirectional, pseudo first-order rate constant of this exchange in the dehydration direction was determined to be 0.011 ± 0.005 sec-1. The presence of highly specific carbonic anhydrase inhibitor acetazolamide, was also shown to drastically attenuate the observed 13C magnetization transfer effect of the carbon dioxide–bicarbonate exchange in C. reinhardtii. We have demonstrated the utility of 13C saturation transfer for determining the exchange rate between bicarbonate and carbon dioxide catalyzed by extracellular carbonic anhydrase in C. reinhardtii extracellular space.This study for the first time reports the dehydration rate of bicarbonate to CO2 in live C. reinhardtii cells.
Macrophages contribute decisively to the initiation and progression of atherosclerosis. Although most studies conclude that plaque macrophages derive from circulating monocytes, there is growing evidence that vascular-resident smooth muscle cells (SMCs) may also differentiate into macrophages and contribute to the growing pool of foam cells in the atherosclerotic plaque. Understanding of SMC-to-macrophage differentiation has been clouded by inadequate fate-mapping studies and potentially inaccurate staining of SMC- or macrophage-specific markers. A new study published in Nature Medicine by Shankman et al., used a novel fate-mapping technique to label SMCs early in atherosclerosis and definitively assess their cellular fate throughout the progression of disease. The authors conclude that SMCs make up a striking number of cells in the atherosclerotic plaque, but lose several SMC-specific markers masking their inclusion in previous studies. Although this research illustrates the plasticity of SMCs and the importance of SMC retention in ameliorating atherosclerosis, it, unfortunately, does not confirm that SMCs differentiate into functional macrophages nor provide proof that SMC-to-macrophage differentiation is important for the progression of atherosclerosis.
Structural DNA nanotechnology explores various nanoscale structural and functional properties of DNA to develop probes at nanoscale for diverse applications. Three dimensional architectures based on DNA like various polyhedra, boxes, and DNA-based dendrimers, have raised particular interest in biomedical applications. Some of these DNA architectures have been recently explored as nano containers for functional molecules and as molecular scaffolds to site specifically display biological ligands. Such DNA nanostructures have been demonstrated to interact with cell-surface markers and trigger signalling pathways in biological systems via specific targets. These recent studies highlight the emerging potential of DNA devices in biomedical applications that could enable targeted delivery of molecular payloads within living systems.
High-throughput RNA and DNA sequencing approaches continue to yield informative data that provides insights into genomic patterns and variations that influence disease susceptibility and therapy outcome in cancer. The field is currently in need of high-throughput functional assays to test the impact of genetic variations identified by these next generation genomic techniques. Such methods are essential to identify mutations and genetic patterns that drive cancer or impact response to treatment. Since a majority of diseases associated with genome instability are driven by dysfunctional DNA repair pathways, there is an urgent need for assays that can effectively characterize mutations in DNA repair genes. This review outlines salient DNA repair pathways and functional repair assays described in literature that have clinical applications.
The CRISPR technology has recently received extensive attention from the research and medical community due to its remarkable genome-editing capacity. In particular, the therapeutic potential of translating the CRISPR technology into clinical interventions for various human diseases has brought bright hopes for patients around the world. In the current Commentary, I shall scrutinize recent advances in manipulating and improving the CRISPR technology for viral diseases and genetic disorders in humans. Key challenges to realize the full clinical potential of the CRISPR technology will also be discussed.