Hubbardhamrick6200

Circular DNA aptamers are powerful candidates for therapeutic applications given their dramatically enhanced biostability. Herein we report the first effort to evolve circular DNA aptamers that bind a human protein directly in serum, a complex biofluid. Targeting human thrombin, this strategy has led to the discovery of a circular aptamer, named CTBA4T-B1, that exhibits very high binding affinity (with a dissociation constant of 19 pM), excellent anticoagulation activity (with the half maximal inhibitory concentration of 90 pM) and high stability (with a half-life of 8 h) in human serum, highlighting the advantage of performing aptamer selection directly in the environment where the application is intended. CTBA4T-B1 is predicted to adopt a unique structural fold with a central two-tiered guanine quadruplex capped by two long stem-loops. This structural arrangement differs from all known thrombin binding linear DNA aptamers, demonstrating the added advantage of evolving aptamers from circular DNA libraries. The method described here permits the derivation of circular DNA aptamers directly in biological fluids and could potentially be adapted to generate other types of aptamers for therapeutic applications.Deletions in mitochondrial DNA (mtDNA) are associated with diverse human pathologies including cancer, aging and mitochondrial disorders. Large-scale deletions span kilobases in length and the loss of these associated genes contributes to crippled oxidative phosphorylation and overall decline in mitochondrial fitness. There is not a united view for how mtDNA deletions are generated and the molecular mechanisms underlying this process are poorly understood. This review discusses the role of replication and repair in mtDNA deletion formation as well as nucleic acid motifs such as repeats, secondary structures, and DNA damage associated with deletion formation in the mitochondrial genome. We propose that while erroneous replication and repair can separately contribute to deletion formation, crosstalk between these pathways is also involved in generating deletions.Aging-related changes in gut microbiome changes impacts host health. The interactive relationship between the microbiome and physiological systems in an aged body system remains to be clearly defined, particularly in the context of inflammation. Therefore, we aimed to evaluate systemic inflammation, microbial translocation (MT) and differences between fecal and mucosal microbiomes. Ascending colon mucosal biopsies, fecal and blood samples from healthy young and old female vervet monkeys were collected for 16S rRNA gene sequencing, MT and cytokine analyses, respectively. To demonstrate microbial co-occurrence patterns, we used Kendall's tau correlation measure of interactions between microbes. We found elevated levels of plasma LBP-1, MCP-1 and CRP in old monkeys, indicative of higher MT and systemic inflammation. Microbiome analysis revealed significant differences specific to age. At the phylum level, abundances of pathobionts such as Proteobacteria were increased in the mucosa of old monkeys. At the family level, Helicobacteriaceae was highly abundant in mucosal samples (old); in contrast, Ruminococcaceae were higher in fecal samples old monkeys. Tamoxifen molecular weight We found significantly lower FirmicutesBacteroidetes ratio and lower abundance of butyrate-producing microbes in old monkeys, consistent with less healthy profiles. Microbial community co-occurrence analysis on mucosal samples revealed 13 nodes and 41 associations in the young monkeys, but only 12 nodes and 21 associations in the old monkeys. Our findings provided novel insights into systemic inflammation and gut microbial interactions, highlights the importance of the mucosal niche, and facilitates further understanding of the decline in the stability of the microbial community with aging.Vulvodynia is chronic perineal pain in women. Repercussions of this disorder can have a negative effect on women's health and lifestyle. The origin is often multifactorial, including pelvic and lower extremity somatic dysfunctions. If left untreated, these somatic dysfunctions can directly alter ligamentous tension on the pelvic floor and surrounding regions, resulting in perineal pain. Management of vulvodynia must be individualized due to the multifactorial etiology and complicated structure and function of the pelvic floor muscles. The authors present a case of vulvodynia in which osteopathic manipulative treatment was an effective management technique.Glypican-1 and its heparan sulfate (HS) chains play important roles in modulating many biological processes including growth factor signaling. Glypican-1 is bound to a membrane surface via a glycosylphosphatidylinositol (GPI)-anchor. In this study, we used all-atom molecular modeling and simulation to explore the structure, dynamics, and interactions of GPI-anchored glypican-1, three HS chains, membranes, and ions. The folded glypican-1 core structure is stable, but has substantial degrees of freedom in terms of movement and orientation with respect to the membrane due to the long unstructured C-terminal region linking the core to the GPI-anchor. With unique structural features depending on the extent of sulfation, high flexibility of HS chains can promote multi-site interactions with surrounding molecules near and above the membrane. This study is a first step toward all-atom molecular modeling and simulation of the glycocalyx, as well as its modulation of interactions between growth factors and their receptors.

The effectiveness of osteopathic manipulative treatment (OMT) on the lumbar spine has been studied qualitatively, but quantitative measurement of the effects of OMT has not been thoroughly investigated.

To quantitatively measure the palpated improvements of OMT on the lumbar spine using ultrasonography (US) and correlate palpatory diagnosis with US measurements of lumbar asymmetry.

From September to November 2018, we recruited 20 adult participants 18 years of age or older. Lumbar somatic dysfunction (SD) was identified via osteopathic palpation. US was then performed on all participants with standard machine settings (frequency, 7 MHz; depth, 7 cm; dynamic range, 60; tissue harmonic imaging; and single-image focus). Longitudinal images of each lumbar transverse process were recorded and saved bilaterally by an experienced radiologist and a medical student. The participant's SD was then managed using OMT, including Still technique, myofascial release, muscle energy technique, high-velocity low-amplitude technique, functional positional release, balanced ligamentous tension, and counterstrain.