A mouse DRG genetic toolkit reveals morphological and physiological diversity of somatosensory neuron subtypes.

Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG neuron subtypes relay neural signals from the periphery to the CNS has been challenging with existing tools. Here, we develop and curate a mouse genetic toolkit that allows for interrogating the properties and functions of distinct cutaneous targeting DRG neuron subtypes. These tools have enabled a broad morphological analysis, which revealed distinct cutaneous axon arborization areas and branching patterns of the transcriptionally distinct DRG neuron subtypes. Moreover, in vivo physiological analysis revealed that each subtype has a distinct threshold and range of responses to mechanical and/or thermal stimuli. These findings support a model in which morphologically and physiologically distinct cutaneous DRG sensory neuron subtypes tile mechanical and thermal stimulus space to collectively encode a wide range of natural stimuli.

Murine bone marrow mesenchymal stromal cells have reduced hematopoietic maintenance ability in sickle cell disease.

Sickle cell disease (SCD) is characterized by hemolytic anemia, which can trigger oxidative stress, inflammation, and tissue injury that contribute to disease complications. Bone marrow mesenchymal stromal cells (MSCs) tightly regulate hematopoietic stem cell (HSC) homeostasis in health and disease, but their functionality in SCD remains unclear. We identified for the first time that murine SCD MSCs have altered gene signatures, reduced stem cell properties, and increased oxidative stress, due in part to hemolysis. Murine SCD MSCs had lower HSC maintenance ability in vitro and in vivo, as manifested by increased HSC mobilization and decreased HSC engraftment after transplant. Activation of Toll-like receptor-4 through p65 in MSCs further contributed to MSC dysfunction. Transfusions led to an improved MSC and HSC oxidative state in SCD mice. Improving the regulation between MSCs and HSCs has vital implications for enhancing clinical HSC transplantation and gene therapy outcomes and for identification of new molecular targets for alleviating SCD complications.

A DRG genetic toolkit reveals molecular, morphological, and functional diversity of somatosensory neuron subtypes.

Mechanical and thermal stimuli acting on the skin are detected by morphologically and physiologically distinct sensory neurons of the dorsal root ganglia (DRG). Achieving a holistic view of how this diverse neuronal population relays sensory information from the skin to the central nervous system (CNS) has been challenging with existing tools. Here, we used transcriptomic datasets of the mouse DRG to guide development and curation of a genetic toolkit to interrogate transcriptionally defined DRG neuron subtypes. Morphological analysis revealed unique cutaneous axon arborization areas and branching patterns of each subtype. Physiological analysis showed that subtypes exhibit distinct thresholds and ranges of responses to mechanical and/or thermal stimuli. The somatosensory neuron toolbox thus enables comprehensive phenotyping of most principal sensory neuron subtypes. Moreover, our findings support a population coding scheme in which the activation thresholds of morphologically and physiologically distinct cutaneous DRG neuron subtypes tile multiple dimensions of stimulus space.

Antioxidant properties of apple juice and its protection against Cr(VI)-induced cellular injury.

Reactive oxygen species (ROS) have been shown to cause a broad spectrum of damage to the biological system. ROS-mediated reactions are believed to play a key role in Cr(VI)-induced carcinogenesis. Using electron spin resonance (ESR) spin trapping, the present study shows that apple juice efficiently scavenged hydroxyl radicals generated by Cr(VI) reduction catalyzed byglutathione reductase/NADPH. Apple juice reduced Cr(VI)-induced lipid peroxidation, DNA damage, cell apoptosis, and NF-kappaB activation in human lung epithelial A549 cells. The lipid peroxidation was measured by a colorimetric assay, DNA damage by single cell gel electrophoresis assay, induction of cell apoptosis by flow cytometry, and activation of NF-kappaB by luciferase assay. The results show that through its antioxidant properties, apple juice can protect Cr(VI)-induced cellular injury and may help reduce its carcinogenic potentiaL

Anesthetic evaluation and perioperative management in a patient with new onset mediastinal mass syndrome presenting for emergency surgery.

Mediastinal mass syndrome (MMS) is a complex case that poses many challenges to the anesthesiologist. The cornerstone of management focuses on the potential hemodynamic changes associated with this syndrome. We describe the anesthetic management of a patient with a previously undiagnosed mediastinal mass presenting for emergency neurosurgical surgery.

Synthetic gene networks that count.

Synthetic gene networks can be constructed to emulate digital circuits and devices, giving one the ability to program and design cells with some of the principles of modern computing, such as counting. A cellular counter would enable complex synthetic programming and a variety of biotechnology applications. Here, we report two complementary synthetic genetic counters in Escherichia coli that can count up to three induction events: the first, a riboregulated transcriptional cascade, and the second, a recombinase-based cascade of memory units. These modular devices permit counting of varied user-defined inputs over a range of frequencies and can be expanded to count higher numbers.