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Background/Aims To evaluate the intra- and interrater reliability (I-IR) of sagittal spinopelvic parameters from digital full-spine plain radiographs with basic software tools in an unselected adult population with degenerative spinal complaints who were evaluated for surgery. Methods Forty-nine adult full-spine digital radiographs were measured twice by 3 independent observers, including an experienced spine surgeon, an experienced radiologist, and a resident orthopedic surgeon. Clinical picture archiving and communication system workstations and software tools were used and landmarks were set manually. The I-IR of the sagittal vertical axis (SVA), pelvic tilt (PT), pelvic incidence (PI), sacral slope (SS), and thoracic kyphosis in T4–T12 (TK) were assessed. Results The intrarater intraclass correlation coefficient (ICC) scores varied from 0.82 to 0.99. The interrater ICC scores ranged from 0.78 to 0.99. The intrarater standard error of measurement (SEM) values for SS, PT, PI, and TK varied from 0.8° to 5.0°, and the interrater SEM values ranged from 2.5° to 6.2°, depending on the parameter and the reading round. The I-IR SEM values for SVA varied from 2.2 to 5.7 mm and from 4.6 to 5.0 mm, respectively. Kappa values were >0.88 for all readers. The intrarater variability was the smallest for the most experienced rater. Conclusion The I-IR of measuring sagittal spinopelvic parameters on digital full-spine images with basic software tools was high. Parameters consisting of several anatomic landmarks were more liable to error. Rater experience had a positive influence on reliability and repeatability. Reader experience should be assessed before accepting measurements for surgical planning and the interpretation of surgical correction during postoperative follow-up.

Kaposi sarcoma is a tumor consisting of Kaposi sarcoma herpesvirus (KSHV)-infected tumor cells that express endothelial cell (EC) markers and viral genes like v-cyclin, vFLIP, and LANA. Despite a strong link between KSHV infection and certain neoplasms, de novo virus infection of human primary cells does not readily lead to cellular transformation. We have studied the consequences of expression of v-cyclin in primary and immortalized human dermal microvascular ECs. We show that v-cyclin, which is a homolog of cellular D-type cyclins, induces replicative stress in ECs, which leads to senescence and activation of the DNA damage response. We find that antiproliferative checkpoints are activated upon KSHV infection of ECs, and in early-stage but not late-stage lesions of clinical Kaposi sarcoma specimens. These are some of the first results suggesting that DNA damage checkpoint response also functions as an anticancer barrier in virally induced cancers.

A disintegrin and metalloproteinases (ADAMs) constitute a protein family essential for extracellular signaling and regulation of cell adhesion. Catalytic activity of ADAMs and their predicted potential for Src-homology 3 (SH3) domain binding show a strong correlation. Here we present a comprehensive characterization of SH3 binding capacity and preferences of the catalytically active ADAMs 8, 9, 10, 12, 15, 17, and 19. Our results revealed several novel interactions, and also confirmed many previously reported ones. Many of the identified SH3 interaction partners were shared by several ADAMs, whereas some were ADAM-specific. Most of the ADAM-interacting SH3 proteins were adapter proteins or kinases, typically associated with sorting and endocytosis. Novel SH3 interactions revealed in this study include TOCA1 and CIP4 as preferred partners of ADAM8, and RIMBP1 as a partner of ADAM19. Our results suggest that common as well as distinct mechanisms are involved in regulation and execution of ADAM signaling, and provide a useful framework for addressing the pathways that connect ADAMs to normal and aberrant cell behavior.

Monoclonal and recombinant antibodies are ubiquitous tools in diagnostics, therapeutics, and biotechnology. However, their biochemical properties lack optimal robustness, their bacterial production is not easy, and possibilities to create multifunctional fusion proteins based on them are limited. Moreover, the binding affinities of antibodies towards their antigens are suboptimal for many applications where they are commonly used. To address these issues we have made use of the concept of creating high binding affinity based on multivalent target recognition via exploiting some of the best features of immunoglobulins (Ig) and non-Ig-derived ligand-binding domains. We have constructed a small protein, named Neffin, comprised of a 118 aa llama Ig heavy chain variable domain fragment (VHH) fused to a ligand-tailored 57 aa SH3 domain. Neffin could be readily produced in large amounts (>18 mg/L) in the cytoplasm of E. coli, and bound with a subpicomolar affinity (K(d) 0.54 pM) to its target, the HIV-1 Nef protein. When expressed in human cells Neffin could potently inhibit Nef function. Similar VHH-SH3 fusion proteins could be targeted against many other proteins of interest and could have widespread use in diverse medical and biotechnology applications where biochemical robustness and strong binding affinity are required.

Today, anthropologists, ethnomusicologists, cultural, and gender scholars are interested in culture not only as it is performed, but as it is continuously done, constructed, maintained through acting, musicking, talking, dancing together. Culture lives, and its elements—or aspects, if you wish—are constantly converging, and articulating into new, moving and shifting formations. In this paper Järviluoma discusses the different ways of understanding the concept of culture, interweaving the ideas with the early twentieth century forms of music making in her own grandmother’s home village in northern Finland. She discusses how the new ‘culture’, within the ‘civilising’ social movements converged with the old ways of life and musicking.

Nucleophosmin (NPM) is a multifunctional nuclear phosphoprotein and a histone chaperone implicated in chromatin organization and transcription control. Oncogenic Kaposi's sarcoma herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). In the infected host cell KSHV displays two modes of infection, the latency and productive viral replication phases, involving extensive viral DNA replication and gene expression. A sustained balance between latency and reactivation to the productive infection state is essential for viral persistence and KSHV pathogenesis. Our study demonstrates that the KSHV v-cyclin and cellular CDK6 kinase phosphorylate NPM on threonine 199 (Thr199) in de novo and naturally KSHV-infected cells and that NPM is phosphorylated to the same site in primary KS tumors. Furthermore, v-cyclin-mediated phosphorylation of NPM engages the interaction between NPM and the latency-associated nuclear antigen LANA, a KSHV-encoded repressor of viral lytic replication. Strikingly, depletion of NPM in PEL cells leads to viral reactivation, and production of new infectious virus particles. Moreover, the phosphorylation of NPM negatively correlates with the level of spontaneous viral reactivation in PEL cells. This work demonstrates that NPM is a critical regulator of KSHV latency via functional interactions with v-cyclin and LANA.