How can you help athletes prevent and treat shin splints?

Encourage patients who are concerned about shin splints to decrease the intensity of their running; suggest rest and ice and foot orthoses, to treat the condition. Reducing running intensity probably reduces lower extremity soft tissue injuries (strength of recommendation [SOR]: B, low-quality randomized controlled trials [RCTs]), although doing stretching exercises doesn't

When should you order a Lyme titer?

Lyme titers should be ordered for patients with signs or symptoms of disseminated Lyme disease, but who do not have the pathognomonic erythema migrans rash (strength of recommendation [SOR]: C, based on expert opinion). Symptomatic patients with erythema migrans should be treated without being tested, given the high probability of having Lyme disease

A Public Spirit: George H. Atkinson’s Written Legacy

George Henry Atkinson (1819-89) was a son of New England who arrived in the Oregon Territory in 1848, sent by the American Home Missionary Society. Although his commission from the Society specified that his work was to be ecclesiastical and educational, he took an approach to that assignment which went well beyond his mandate. Well-informed and energetic, he made an impact on the Congregational churches of the Northwest, while using that base of action to spread his influence far beyond the churches that were his primary area of responsibility. He believed that a successful future for his adopted region required productive, intelligent, moral communities. This broad perspective led him to assume—and maintain for four decades—public leadership in subjects as diverse and significant as railroads, prisons, public and private schools, Native American relationships, agriculture, engineering, commerce, and meteorology. He left an impressive written legacy, in personal correspondence and in print. This volume contains a number of Atkinson’s longer writings. Most were published in the state’s leading newspaper, the Oregonian, although several appeared in other publications or reports. Two were included in the records of the State Legislature and two were submitted to the Centennial Exposition in Philadelphia in 1876. Taken together, his writings tell us much about the man George Henry Atkinson, and about the times and places where he implemented his vision.https://commons.pacificu.edu/beetree/1000/thumbnail.jp

Adapting the Library Repository to Accommodate Research Data, Publications, and Partnering with Researchers

Brown University Library originally created the Brown Digital Repository (BDR) in 2011 to serve the digital content storage and dissemination needs of its Special Collections and Center for Digital Scholarship (CDS). Since then, the BDR has evolved to serve a broader group of stakeholders, including the science librarians, who deposit researchers’ data along with the supplementary materials underlying their publications, collections of data to comply with a grant-funder’s requirements for data sharing, and faculty publications. Some university library systems have created separate repositories for data, such as the Universities of Michigan and Minnesota. However, for libraries at smaller institutions, having a separate system for images, publications, and data may not be the most-feasible or affordable short-term solution. Over the last year, Brown’s science librarians and developers have been planning to make enhancements and changes to the BDR to improve its ingest, dissemination, and overall capabilities for preserving the long-term access of research data as well as make the necessary adaptations to the way that the BDR collects faculty publications, with the aim of it being a resource to help researchers with retaining their final approved manuscripts and complying with their funders’ public access policies. These shifts, from a focus on ingesting and displaying images to a focus on data and publications have exposed many issues and challenges that librarians considering adapting their existing repositories to accommodate data and public access mandates should hear. At the same time, the Library has been working with the Brown Center for Biomedical Informatics to integrate its science librarians and repository infrastructure into grant-funded projects, such as an NLM Administrative Supplement for Informationist Services. In the second half of the session, Dr. Neil Sarkar, the Director of the Brown Center for Biomedical Informatics, and Principal Investigator on the NLM Administrative Supplement, will provide a keynote address, which will cover: (1) faculty perspectives academic libraries should have in mind while adapting their repositories for tracking and making available their faculty’s scholarly output; (2) ways libraries can develop infrastructure to partner with their faculty on research projects and grant-funded initiatives, such as clinical and translational science; (3) ways that libraries could integrate their repositories into existing systems for recording scholarly output, such as My NCBI’s My Bibliography as well as systems for displaying researcher and scholarship ontologies such as VIVO; and (4) ways that libraries can adapt their repositories to provide meaningful analytics and metrics for measuring the impact of their researcher communities

Fishy Business: Fish in the United States Serial Set

The United States Congressional Serial Set contains a wide variety of historical documents relating to natural resources and their history in the United States. It is an excellent resource for those researching historical data concerning fisheries, from extant species and ecology to economic issues. Information on resources outside the United States is also available due to the U.S. history of explorations and expansions. Charts, maps and tables are found within many of the papers and reports. There are also numerous scientific illustrations

Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene

G protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH β-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH(2)-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH β-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH(2)-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH β-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression

A Novel Regulatory Mechanism of Map Kinases Activation and Nuclear Translocation Mediated by Pka and the Ptp-Sl Tyrosine Phosphatase

Protein tyrosine phosphatase PTP-SL retains mitogen-activated protein (MAP) kinases in the cytoplasm in an inactive form by association through a kinase interaction motif (KIM) and tyrosine dephosphorylation. The related tyrosine phosphatases PTP-SL and STEP were phosphorylated by the cAMP-dependent protein kinase A (PKA). The PKA phosphorylation site on PTP-SL was identified as the Ser231 residue, located within the KIM. Upon phosphorylation of Ser231, PTP-SL binding and tyrosine dephosphorylation of the MAP kinases extracellular signal–regulated kinase (ERK)1/2 and p38α were impaired. Furthermore, treatment of COS-7 cells with PKA activators, or overexpression of the Cα catalytic subunit of PKA, inhibited the cytoplasmic retention of ERK2 and p38α by wild-type PTP-SL, but not by a PTP-SL S231A mutant. These findings support the existence of a novel mechanism by which PKA may regulate the activation and translocation to the nucleus of MAP kinases

Identification of a new pebp2 alpha A2 isoform from zebrafish runx2 capable of inducing osteocalcin gene expression in vitro

Introduction: RUNX2 (also known as CBFA1/Osf2/AML3/PEBP2 alpha A) is a transcription factor essential for bone formation in mammals, as well as for osteoblast and chondrocyte differentiation, through regulation of expression of several bone- and cartilage-related genes. Since its discovery, Runx2 has been the subject of intense studies, mainly focused in unveiling regulatory targets of this transcription factor in high vertebrates. However, no single study has been published addressing the role of Runx2 in bone metabolism of low vertebrates. While analyzing the zebrafish (Danio rerio) runx2 gene, we identified the presence of two orthologs of RUNX2, which we named runx2a and runx2b and cloned a pebp2 alpha A-like transcript of the runx2b gene, which we named pebp2 alpha A2. Materials and Methods: Zebrafish runx2b gene and cDNA were isolated by RT-PCR and sequence data mining. The 3D structure of runx2b runt domain was modeled using mouse Runx1 runt as template. The regulatory effect of pebp2 alpha A2 on osteocalcin expression was analyzed by transient co-transfection experiments using a luciferase reporter gene. Phylogenetic analysis of available Runx sequences was performed with TREE-PUZZLE 5.2. and MrBayes. Results and Conclusions: We showed that the runx2b gene structure is highly conserved between mammals and fish. Zebrafish runx2b has two promoter regions separated by a large intron. Sequence analysis suggested that the runx2b gene encodes three distinct isoforms, by a combination of alternative splicing and differential promoter activation, as described for the human gene. We have cloned a pebp2 alpha A-like transcript of the runx2b gene, which we named pebp2 alpha A2, and showed its high degree of sequence similarity with the mammalian pebp2 alpha A. The cloned zebrafish osteocalcin promoter was found to contain three putative runx2-binding elements, and one of them, located at -221 from the ATG, was capable of mediating pebp2 alpha A2 transactivation. In addition, cross-species transactivation was also confirmed because the mouse Cbfa1 was able to induce the zebrafish osteocalcin promoter, whereas the zebrafish pebp2 alpha A2 activated the murine osteocalcin promoter. These results are consistent with the high degree of evolutionary conservation of these proteins. The 3D structure of the runx2b runt domain was modeled based on the runt domain of mouse Runx1. Results show a high degree of similarity in the 3D configuration of the DNA binding regions from both domains, with significant differences only observed in non-DNA binding regions or in DNA-binding regions known to accommodate considerable structure flexibility. Phylogenetic analysis was used to clarify the relationship between the isoforms of each of the two zebrafish Runx2 orthologs and other Runx proteins. Both zebrafish runx2 genes clustered with other Runx2 sequences. The duplication event seemed, however, to be so old that, whereas Runx2b clearly clusters with the other fish sequences, it is unclear whether Runx2a clusters with Runx2 from higher vertebrates or from other fish.info:eu-repo/semantics/publishedVersio

The Transcriptional Cofactor Nab2 Is Induced by TGF-β and Suppresses Fibroblast Activation: Physiological Roles and Impaired Expression in Scleroderma

By stimulating collagen synthesis and myofibroblasts differentiation, transforming growth factor-β (TGF- β) plays a pivotal role in tissue repair and fibrosis. The early growth response-1 (Egr-1) transcription factor mediates profibrotic TGF-β responses, and its expression is elevated in biopsies from patients with scleroderma. NGF1-A-binding protein 2 (Nab2) is a conserved transcriptional cofactor that directly binds to Egr-1 and positively or negatively modulates Egr-1 target gene transcription. Despite the recognized importance of Nab2 in governing the intensity of Egr-1-dependent responses, the regulation and function of Nab2 in the context of fibrotic TGF-β signaling is unknown. Here we show that TGF-β caused a time-dependent stimulation of Nab2 protein and mRNA in normal fibroblasts. Ectopic expression of Nab2 in these cells blocked Egr-1-dependent transcriptional responses, and abrogated TGF-β-induced stimulation of collagen synthesis and myofibroblasts differentiation. These inhibitory effects of Nab2 involved recruitment of the NuRD chromatin remodeling complex to the COL1A2 promoter and were accompanied by reduced histone H4 acetylation. Mice with targeted deletion of Nab2 displayed increased collagen accumulation in the dermis, and genetic or siRNA-mediated loss of Nab2 in fibroblasts was associated with constitutively elevated collagen synthesis and accentuation of Egr-1-dependent TGF-β responses in vitro. Expression of Nab2 was markedly up-regulated in skin biopsies from patients with scleroderma, and was localized primarily to epidermal keratinocytes. In contrast, little Nab2 could be detected in dermal fibroblasts. These results identify Nab2 as a novel endogenous negative regulator of Egr-1-dependent TGF-β signaling responsible for setting the intensity of fibrotic responses. Defective Nab2 expression or function in dermal fibroblasts might play a role in persistent fibrotic responses in scleroderma