The hRPC62 subunit of human RNA polymerase III displays helicase activity.

In Eukaryotes, tRNAs, 5S RNA and U6 RNA are transcribed by RNA polymerase (Pol) III. Human Pol III is composed of 17 subunits. Three specific Pol III subunits form a stable ternary subcomplex (RPC62-RPC39-RPC32α/β) being involved in pre-initiation complex formation. No paralogues for subunits of this subcomplex subunits have been found in Pols I or II, but hRPC62 was shown to be structurally related to the general Pol II transcription factor hTFIIEα. Here we show that these structural homologies extend to functional similarities. hRPC62 as well as hTFIIEα possess intrinsic ATP-dependent 3'-5' DNA unwinding activity. The ATPase activities of both proteins are stimulated by single-stranded DNA. Moreover, the eWH domain of hTFIIEα can replace the first eWH (eWH1) domain of hRPC62 in ATPase and DNA unwinding assays. Our results identify intrinsic enzymatic activities in hRPC62 and hTFIIEα

Forward Analysis and Model Checking for Trace Bounded WSTS

We investigate a subclass of well-structured transition systems (WSTS), the bounded---in the sense of Ginsburg and Spanier (Trans. AMS 1964)---complete deterministic ones, which we claim provide an adequate basis for the study of forward analyses as developed by Finkel and Goubault-Larrecq (Logic. Meth. Comput. Sci. 2012). Indeed, we prove that, unlike other conditions considered previously for the termination of forward analysis, boundedness is decidable. Boundedness turns out to be a valuable restriction for WSTS verification, as we show that it further allows to decide all $\omega$-regular properties on the set of infinite traces of the system

Incidence of fracture in adjacent levels in patients treated with balloon kyphoplasty: a review of the literature

The available evidence suggests that the treatment of painful vertebral compression fractures (VCFs) secondary to osteoporosis or multiple myeloma, by cement augmentation with balloon kyphoplasty (BK), is both safe and effective. However, there is uncertainty in the literature concerning the potential of the procedure to influence the risk for adjacent segment fracture. The aim of this article is to review the available peer-reviewed literature, regarding adjacent vertebral body fractures after kyphoplasty augmentation

Quaternary structure of a G-protein coupled receptor heterotetramer in complex with Gi and Gs

Background: G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling units. Despite the exponential growth in the number of solved GPCR crystal structures, the structural properties of heteromers remain unknown. Results: We used single-particle tracking experiments in cells expressing functional adenosine A1-A2A receptors fused to fluorescent proteins to show the loss of Brownian movement of the A1 receptor in the presence of the A2A receptor, and a preponderance of cell surface 2:2 receptor heteromers (dimer of dimers). Using computer modeling, aided by bioluminescence resonance energy transfer assays to monitor receptor homomerization and heteromerization and G-protein coupling, we predict the interacting interfaces and propose a quaternary structure of the GPCR tetramer in complex with two G proteins. Conclusions: The combination of results points to a molecular architecture formed by a rhombus-shaped heterotetramer, which is bound to two different interacting heterotrimeric G proteins (Gi and Gs). These novel results constitute an important advance in understanding the molecular intricacies involved in GPCR function

Percutaneous vertebral compression fracture management with polyethylene mesh-contained morcelized allograft bone

Study design    A comprehensive systematic review of the literature. Objectives To assess the modern literature on the use of polyethylene mesh-contained morcelized allograft (PMCMA) bone for spinal fusion and vertebral compression fracture management. Summary of background data    There are presently no systematic reviews of PMCMA. Methods    A systematic literature review was performed within three databases (OVID, PubMed, and Google Scholar) using the following keyword search terms: vertebroplasty, kyphoplasty, vertebral compression fracture, percutaneous, polyethylene mesh, and osteoporosis. Results    The initial search identified 764 items, from which two pertinent technique-based articles were identified. There were no published scientific peer-reviewed or case series reporting the clinical results of this technique. The use of PMCMA in the management of vertebral compression fractures (VCFs) is similar to vertebroplasty and kyphoplasty. This novel, percutaneous system uses the properties of granular mechanics to establish a conforming, semirigid graft that is purportedly capable of withstanding physiologic loads. Discussion    PMCMA is a novel percutaneous technology for the management of VCF and possibly for use as a conforming interbody graft. The available published literature lacks outcome data of the use of PMCMA. Careful, independent research is needed to assess the viability of this technology and its long-term results

Evaluation of the antigen-antibody complex vaccine of Gumboro disease administered in ovo in broiler chickens challenged with F52/70 strain

El objetivo del presente estudio fue evaluar la protección y seguridad del complejo vacunal antígeno-anticuerpo administrado in ovo frente a un desafío experimental con la cepa F52/70 de la Enfermedad de Gumboro en pollos de carne. Se utilizaron 450 pollos de la línea Cobb Vantress, de un día de edad, distribuidos en tres grupos: Grupo A, vacunado, vía agua de bebida, a los 9 días con la cepa intermedia suave tipo Lukert y revacunado a los 19 días con la cepa intermedia intermedia 2512; grupo B, vacunado vía in ovo a los 18 días de incubación con el complejo vacunal antígeno-anticuerpo; y grupo C, control no vacunado. A los 35 días de edad, 20 aves de cada grupo fueron desafiadas, vía ocular, con la cepa F52/70 de la enfermedad de Gumboro. La seguridad del complejo vacunal se evaluó semanalmente hasta los 47 días de edad mediante la determinación del índice bursal, lesiones macroscópicas, lesiones histopatológicas de bursa y respuesta serológica. Las lesiones post desafío se caracterizaron por edema y hemorragias petequiales en la bursa. El grupo B presentó la mejor protección con 75% comparado con el grupo A (68%) y el grupo control (30%). Las lesiones post desafío se caracterizaron por edema y hemorragias petequiales en la bursa. En las aves no desafiadas no se observó diferencias significativas entre los grupos A y B para el índice bursal y lesiones histopatológicas hasta los 28 días de edad; sin embargo, a partir de los 35 días el grupo A fue significativamente diferente de los grupos B y C (p<0.05). Al final del estudio el grupo A obtuvo títulos de 1948 y 2047 más de anticuerpos que el grupo B y el control, respectivamente.The objective of the study was to evaluate the protection and safety for in ovo vaccination against Infection Bursal Disease. Cobb Vantress broilers of one day of age (n=450) were distributed in three groups: Group A, vaccinated at 9 and 19 days with two commercial live vaccines containing Lukert and 2512 strains, respectively; group B, vaccinated in ovo with the antigen-antibody complex at 18 days of incubation; and group C, unvaccinated. At 35 days of age, 20 birds from each group were challenged, ocular via, with the F52/70 strain of Gumboro disease. The security of the complex vaccine was evaluated weekly until 47 days of age by determining the bursal index, gross lesions, histopathological lesions of the bursa, and serological response. Group B showed the best protection with 75% as compared with groups A (68%) and C (30%). Injuries after challenge were characterized by swelling, bleeding, and petechiae in the bursa. In non-challenged birds were none significant differences between groups A and B for the index and bursal histopathology lesions until 28 days of age; however, group A differed from groups B and C at 35 days of age (p<0.05). At the end of the study, group A had 1948 and 2047 antibodies titers higher than groups B and control respectively

MLN51 Stimulates the RNA-Helicase Activity of eIF4AIII

The core of the exon-junction complex consists of Y14, Magoh, MLN51 and eIF4AIII, a DEAD-box RNA helicase. MLN51 stimulates the ATPase activity of eIF4AIII, whilst the Y14-Magoh complex inhibits it. We show that the MLN51-dependent stimulation increases both the affinity of eIF4AIII for ATP and the rate of enzyme turnover; the K (M) is decreased by an order of magnitude and k (cat) increases 30 fold. Y14-Magoh do inhibit the MLN51-stimulated ATPase activity, but not back to background levels. The ATP-bound form of the eIF4AIII-MLN51 complex has a 100-fold higher affinity for RNA than the unbound form and ATP hydrolysis reduces this affinity. MLN51 stimulates the RNA-helicase activity of eIF4AIII, suggesting that this activity may be functionally important

Widespread Treponema pallidum Infection in Nonhuman Primates, Tanzania

We investigated Treponema pallidum infection in 8 nonhuman primate species (289 animals) in Tanzania during 2015–2017. We used a serologic treponemal test to detect antibodies against the bacterium. Infection was further confirmed from tissue samples of skin-ulcerated animals by 3 independent PCRs (polA, tp47, and TP_0619). Our findings indicate that T. pallidum infection is geographically widespread in Tanzania and occurs in several species (olive baboons, yellow baboons, vervet monkeys, and blue monkeys). We found the bacterium at 11 of 14 investigated geographic locations. Anogenital ulceration was the most common clinical manifestation; orofacial lesions also were observed. Molecular data show that nonhuman primates in Tanzania are most likely infected with T. pallidum subsp. pertenue–like strains, which could have implications for human yaws eradication

BRG-1 is required for RB-mediated cell cycle arrest

The antiproliferative action of the retinoblastoma tumor suppressor protein, RB, is disrupted in the majority of human cancers. Disruption of RB activity occurs through several disparate mechanisms, including viral oncoprotein binding, deregulated RB phosphorylation, and mutation of the RB gene. Here we report disruption of RB-signaling in tumor cells through loss of a critical cooperating factor. We have previously reported that C33A cells fail to undergo cell cycle inhibition in the presence of constitutively active RB (PSM-RB). To determine how C33A cells evade RB-mediated arrest, cell fusion experiments were performed with RB-sensitive cells. The resulting fusions were arrested by PSM-RB, indicating that C33A cells lack a factor required for RB-mediated cell cycle inhibition. C33A cells are deficient in BRG-1, a SWI/SNF family member known to stimulate RB activity. Consistent with BRG-1 deficiency underlying resistance to RB-mediated arrest, we identified two other BRG-1-deficient cell lines (SW13 and PANC-1) and demonstrate that these tumor lines are also resistant to cell cycle inhibition by PSM-RB and p16ink4a, which activates endogenous RB. In cell lines lacking BRG-1, we noted a profound defect in RB-mediated repression of the cyclin A promoter. This deficiency in RB-mediated transcriptional repression and cell cycle inhibition was rescued through ectopic coexpression of BRG-1. We also demonstrate that 3T3-derived cells, which inducibly express a dominant-negative BRG-1, arrest by PSM-RB and p16ink4a in the absence of dominant-negative BRG-1 expression; however, cell cycle arrest was abrogated on induction of dominant-negative BRG-1. These findings demonstrate that BRG-1 loss renders cells resistant to RB-mediated cell cycle progression, and that disruption of RB signaling through loss of cooperating factors occurs in cancer cells