Project description:Septin family proteins are quite similar to each other both within and between eukaryotic species. Typically, multiple discrete septins co-assemble into linear heterooligomers (usually hexameric or octameric rods) with a variety of cellular functions. We know little about how incorporation of different septins confers different properties to such complexes. This issue is especially acute in human cells where 13 separate septin gene products (often produced in multiple forms arising from alternative start codons and differential splicing) are expressed in a tissue-specific manner. Based on sequence alignments and phylogenetic criteria, human septins fall into four distinct groups predictive of their interactions, that is, members of the same group appear to occupy the same position within oligomeric septin protomers, which are "palindromic" (have twofold rotational symmetry about a central homodimeric pair). Many such protomers are capable of end-to-end polymerization, generating filaments. Over a decade ago, a study using X-ray crystallography and single-particle electron microscopy deduced the arrangement within recombinant heterohexamers comprising representatives of three human septin groups-SEPT2, SEPT6, and SEPT7. This model greatly influenced subsequent studies of human and other septin complexes, including how incorporating a septin from a fourth group forms heterooctamers, as first observed in budding yeast. Two recent studies, including one in this issue of Cytoskeleton, provide clear evidence that, in fact, the organization of subunits within human septin heterohexamers and heterooctamers is inverted relative to the original model. These findings are discussed here in a broader context, including possible causes for the initial confusion.
Project description:Spiroketals organize small molecule structures into well-defined, three-dimensional configurations that make them good ligands of proteins. We recently discovered a tandem cycloisomerization-dimerization reaction of alkynyl hemiketals that delivered polycyclic, enol-ether-containing spiroketals. Here we describe rearrangements of those compounds, triggered by epoxidation of their enol ethers that completely remodel their structures, essentially turning them "inside out". Due to the high level of substitution on the carbon skeletons of the substrates and products, characterization resorted to X-ray crystallography and advanced computation and NMR techniques to solve the structures of representative compounds. In particular, a new proton-detected ADEQUATE NMR experiment (1,1-HD-ADEQUATE) enabled the unequivocal assignment of the carbon skeleton of one of the new compounds. Solution of the structures of the representative compounds allowed for the assignment of product structures for the other compounds in two separate series. Both the rearrangement and the methods used for structural determination of the products are valuable tools for the preparation of characterization of new small molecule compounds.
Project description:Tumors are complex collections of heterogeneous cells with recruited vasculature, inflammatory cells, and stromal elements. Neoplastic cells frequently display a hierarchy in differentiation status. Recent studies suggest that brain tumors have a limited population of neoplastic cells called cancer stem cells with the capacity for sustained self-renewal and tumor propagation. Brain tumor stem cells contribute to therapeutic resistance and tumor angiogenesis. In this minireview, we summarize recent data regarding critical signaling pathways involved in brain tumor stem cell biology and discuss how targeting these molecules may contribute to the development of novel anti-glioma therapies.
Project description:Filamentous fungi are found in virtually every marine and terrestrial habitat. Vital to this success is their ability to secrete a diverse range of molecules, including hydrolytic enzymes, organic acids, and small molecular weight natural products. Industrial biotechnologists have successfully harnessed and re-engineered the secretory capacity of dozens of filamentous fungal species to make a diverse portfolio of useful molecules. The study of fungal secretion outside fermenters, e.g., during host infection or in mixed microbial communities, has also led to the development of novel and emerging technological breakthroughs, ranging from ultra-sensitive biosensors of fungal disease to the efficient bioremediation of polluted environments. In this review, we consider filamentous fungal secretion across multiple disciplinary boundaries (e.g., white, green, and red biotechnology) and product classes (protein, organic acid, and secondary metabolite). We summarize the mechanistic understanding for how various molecules are secreted and present numerous applications for extracellular products. Additionally, we discuss how the control of secretory pathways and the polar growth of filamentous hyphae can be utilized in diverse settings, including industrial biotechnology, agriculture, and the clinic.
Project description:The microbiota of the built environment is linked to usage, materials and, perhaps most importantly, human health. Many studies have attempted to identify ways of modulating microbial communities within built environments to promote health. None have explored how these complex communities assemble initially, following construction of new built environments. This study used high-throughput targeted sequencing approaches to explore bacterial community acquisition and development throughout the construction of a new build. Microbial sampling spanned from site identification, through the construction process to commissioning and use. Following commissioning of the building, bacterial richness and diversity were significantly reduced (P < 0.001) and community structure was altered (R2 = 0.14; P = 0.001). Greater longitudinal community stability was observed in outdoor environments than indoor environments. Community flux in indoor environments was associated with human interventions driving environmental selection, which increased 10.4% in indoor environments following commissioning. Increased environmental selection coincided with a 12% reduction in outdoor community influence on indoor microbiomes (P = 2.00 × 10-15). Indoor communities became significantly enriched with human associated genera including Escherichia, Pseudomonas, and Klebsiella spp. These data represent the first to characterize the initial assembly of bacterial communities in built environments and will inform future studies aiming to modulate built environment microbiota.
Project description:The built environment microbiota initially resembles the outdoors before human associated interventions drive development toward functionally specific communities
Project description:Locational data, logged on portable GPS units and matched with accelerometer data, was used to examine associations of the built environment with physical activity and sedentary behaviors of adolescent females. In a sample of 293 adolescent females aged 15 to 18 years old in Minneapolis and San Diego, the built environment around each GPS point and its corresponding sedentary, light, and moderate-to-vigorous intensity physical activity was examined using random intercept multinomial logistic regression models. The odds of higher physical activity intensity (3-level outcome: sedentary, light, MVPA) were higher in places with parks, schools, and high population density, during weekdays, and lower in places with more roads and food outlets. Understanding the places where physical activity and sedentary behaviors occur appears to be a promising strategy to clarify relationships and inform policy aimed at increasing physical activity and reducing sedentary behaviors.
Project description:Meniscus repair over resection, when feasible, should be strongly considered in an effort to preserve meniscus integrity and function, especially in younger patients. Currently, a number of techniques and implants may be used to achieve a successful result. Although all-inside meniscus repair devices have evolved significantly since their introduction and have become the repair technique of choice for many surgeons, the classic inside-out repair technique is still very useful to have in one's armamentarium. Though less popular because of the ease of current-generation fixators, the inside-out technique can still offer advantages for those surgeons who are proficient. With the versatility to address most tear patterns, the ability to deliver sutures with smaller needle diameters, and proven long-term results, it has been considered the gold standard in meniscus repair. We review the inside-out repair technique for both a medial and lateral meniscus tear with some helpful tips when performing the technique, and we present a video demonstration of the lateral meniscus repair technique.