Induction and repression of mammalian achaete-scute homologue (MASH) gene expression during neuronal differentiation of P19 embryonal carcinoma cells

MASH1 and MASH2, mammalian homologues of the Drosophila neural determination genes achaete-scute, are members of the basic helix-loop-helix (bHLH) family of transcription factors. We show here that murine P19 embryonal carcinoma cells can be used as a model system to study the regulation and function of these genes. MASH1 and MASH2 display complementary patterns of expression during the retinoic-acid-induced neuronal differentiation of P19 cells. MASH1 mRNA is undetectable in undifferentiated P19 cells but is induced to high levels by retinoic acid coincident with neuronal differentiation. In contrast, MASH2 mRNA is expressed in undifferentiated P19 cells and is repressed by retinoic acid treatment. These complementary expression patterns suggest distinct functions for MASH1 and MASH2 in development, despite their sequence homology. In retinoic-acid-treated P19 cells, MASH1 protein expression precedes and then overlaps expression of neuronal markers. However, MASH1 is expressed by a smaller proportion of cells than expresses such markers. MASH1 immunoreactivity is not detected in differentiated cells displaying a neuronal morphology, suggesting that its expression is transient. These features of MASH1 expression are similar to those observed in vivo, and suggest that P19 cells represent a good model system in which to study the regulation of this gene. Forced expression of MASH1 was achieved in undifferentiated P19 cells by transfection of a cDNA expression construct. The transfected cells expressing exogenous MASH1 protein contained E-box-binding activity that could be super-shifted by an anti-MASH1 antibody, but exhibited no detectable phenotypic changes. Thus, unlike myogenic bHLH genes, such as MyoD, which are sufficient to induce muscle differentiation, expression of MASH1 appears insufficient to promote neurogenesis

Human Trafficking and Air Transportation

Human trafficking may seem like something that only happens somewhere far away, but it happens right here in Indiana and elsewhere in the Midwest. Human trafficking is different from smuggling (moving people) because trafficking involves exploitation. Come learn more about human trafficking and what airports can do to help stop it

XATH-1,a Vertebrate Homolog ofDrosophila atonal,Induces Neuronal Differentiation within Ectodermal Progenitors

AbstractXATH-1,a basic/helix-loop-helix transcription factor and a homolog ofDrosophila atonaland mammalianMATH-1,is expressed specifically in the dorsal hindbrain duringXenopusneural development. In order to investigate the role ofXATH-1in the neuronal differentiation process, we have examined the effects ofXATH-1overexpression duringXenopusdevelopment.XATH-1induces the expression of neuronal differentiation markers, such asN-tubulin,within the neural plate as well as within nonneural ectodermal progenitor populations, resulting in the appearance of process-bearing neurons within the epidermis. The related basic/helix-loop-helix genesneurogenin-related-1andneuroDare not induced in response toXATH-1overexpression within the embryo, suggesting thatXATH-1may activate an alternate pathway of neuronal differentiation. In further contrast toneurogenin-related-1andneuroD,high-level expression of general neural markers expressed earlier in development, such asN-CAM,is not induced byXATH-1overexpression. Competent ectodermal progenitors therefore respond to ectopicXATH-1expression by initiating a distinct program of neuronal differentiation

The Dynamic Proliferation of CanSINEs Mirrors the Complex Evolution of Feliforms

Background: Repetitive short interspersed elements (SINEs) are retrotransposons ubiquitous in mammalian genomes and are highly informative markers to identify species and phylogenetic associations. Of these, SINEs unique to the order Carnivora (CanSINEs) yield novel insights on genome evolution in domestic dogs and cats, but less is known about their role in related carnivores. In particular, genome-wide assessment of CanSINE evolution has yet to be completed across the Feliformia (cat-like) suborder of Carnivora. Within Feliformia, the cat family Felidae is composed of 37 species and numerous subspecies organized into eight monophyletic lineages that likely arose 10 million years ago. Using the Felidae family as a reference phylogeny, along with representative taxa from other families of Feliformia, the origin, proliferation and evolution of CanSINEs within the suborder were assessed. Results: We identified 93 novel intergenic CanSINE loci in Feliformia. Sequence analyses separated Feliform CanSINEs into two subfamilies, each characterized by distinct RNA polymerase binding motifs and phylogenetic associations. Subfamily I CanSINEs arose early within Feliformia but are no longer under active proliferation. Subfamily II loci are more recent, exclusive to Felidae and show evidence for adaptation to extant RNA polymerase activity. Further, presence/absence distributions of CanSINE loci are largely congruent with taxonomic expectations within Feliformia and the less resolved nodes in the Felidae reference phylogeny present equally ambiguous CanSINE data. SINEs are thought to be nearly impervious to excision from the genome. However, we observed a nearly complete excision of a CanSINEs locus in puma (Puma concolor). In addition, we found that CanSINE proliferation in Felidae frequently targeted existing CanSINE loci for insertion sites, resulting in tandem arrays. Conclusions: We demonstrate the existence of at least two SINE families within the Feliformia suborder, one of which is actively involved in insertional mutagenesis. We find SINEs are powerful markers of speciation and conclude that the few inconsistencies with expected patterns of speciation likely represent incomplete lineage sorting, species hybridization and SINE-mediated genome rearrangement

Redox-Active Nanomaterials For Nanomedicine Applications

Nanomedicine utilizes the remarkable properties of nanomaterials for the diagnosis, treatment, and prevention of disease. Many of these nanomaterials have been shown to have robust antioxidative properties, potentially functioning as strong scavengers of reactive oxygen species. Conversely, several nanomaterials have also been shown to promote the generation of reactive oxygen species, which may precipitate the onset of oxidative stress, a state that is thought to contribute to the development of a variety of adverse conditions. As such, the impacts of nanomaterials on biological entities are often associated with and influenced by their specific redox properties. In this review, we overview several classes of nanomaterials that have been or projected to be used across a wide range of biomedical applications, with discussion focusing on their unique redox properties. Nanomaterials examined include iron, cerium, and titanium metal oxide nanoparticles, gold, silver, and selenium nanoparticles, and various nanoscale carbon allotropes such as graphene, carbon nanotubes, fullerenes, and their derivatives/variations. Principal topics of discussion include the chemical mechanisms by which the nanomaterials directly interact with biological entities and the biological cascades that are thus indirectly impacted. Selected case studies highlighting the redox properties of nanomaterials and how they affect biological responses are used to exemplify the biologically-relevant redox mechanisms for each of the described nanomaterials

Are upright lateral cervical radiographs in the obtunded trauma patient useful? A retrospective study

BACKGROUND: The best method for radiographic "clearance" of the cervical spine in obtunded patients prior to removal of cervical immobilization devices remains debated. Dynamic radiographs or MRI are thought to demonstrate unstable injuries, but can be expensive and cumbersome to obtain. An upright lateral cervical radiograph (ULCR) was performed in selected patients to investigate whether this study could provide this same information, to enable removal of cervical immobilization devices in the multiple trauma patient. METHODS: We retrospectively reviewed our experience with ULCR in 683 blunt trauma victims who presented over a 3-year period, with either a Glasgow Coma Score <13 or who were intubated at the time of presentation. RESULTS: ULCR was performed in 163 patients. Seven patients had studies interpreted to be abnormal, of which six were also abnormal, by either CT or MRI. The seventh patient's only abnormality was soft tissue swelling; MRI was otherwise normal. Six patients had ULCR interpreted as normal, but had abnormalities on either CT or MRI. None of the missed injuries required surgical stabilization, although one had a vertebral artery injury demonstrated on subsequent angiography. ULCR had an apparent sensitivity of 45.5% and specificity of 71.4%. CONCLUSION: ULCR are inferior to both CT and MRI in the detection of cervical injury in patients with normal plain radiographs. We therefore cannot recommend the use of ULCR in the obtunded trauma patient

Progression of foot deformity in charcot neuropathic osteoarthropathy

BACKGROUND: Charcot neuropathic osteoarthropathy associated foot deformity can result in joint instability, ulceration, and even amputation. The purpose of the present study was to follow patients with and without active Charcot osteoarthropathy for as long as two years to examine the magnitude and timing of foot alignment changes. METHODS: We studied fifteen subjects with Charcot osteoarthropathy and nineteen subjects with diabetes mellitus and peripheral neuropathy without Charcot osteoarthropathy for one year; eight of the subjects with osteoarthropathy and five of the subjects with diabetes and peripheral neuropathy were followed for two years. Bilateral weight-bearing radiographs of the foot were made at baseline for all subjects, with repeat radiographs being made at six months for the osteoarthropathy group and at one and two years for both groups. Radiographic measurements included the Meary angle, cuboid height, calcaneal pitch, and hindfoot-forefoot angle. RESULTS: The Meary angle, cuboid height, and calcaneal pitch worsened in feet with Charcot osteoarthropathy over one year as compared with the contralateral, uninvolved feet and feet in patients with diabetes and peripheral neuropathy. Cuboid height continued to worsen over the two-year follow-up in the feet with Charcot osteoarthropathy. These feet also had a greater change in the hindfoot-forefoot angle at one year as compared with the feet in patients with diabetes and peripheral neuropathy and at two years as compared with the contralateral, uninvolved feet. CONCLUSIONS: In patients with Charcot neuropathic osteoarthropathy, radiographic alignment measurements demonstrate the presence of foot deformity at the time of the initial clinical presentation and evidence of progressive changes over the first and second years. The six-month data suggest worsening of medial column alignment prior to lateral column worsening. This radiographic evidence of worsening foot alignment over time supports the need for aggressive intervention (conservative bracing or surgical fixation) to attempt to prevent limb-threatening complications. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence