Does a New Polyomavirus Contribute to Merkel Cell Carcinoma?

A new technique designed to hunt for non-human transcripts has identified a novel SV40-like virus present in the majority of Merkel cell carcinomas. Here we examine what it will take to determine whether or not this virus contributes to carcinogenesis

Fabrication of a focusing soft X-ray collector payload

A large area X-ray focusing collector with arc minute resolution and a position sensitive detector capable of operating in the soft X-ray region was developed for use on sounding rockets in studying stellar X-ray sources. The focusing payload consists of the following components, which are described: (1) a crossed paraboloid mirror assembly; (2) an aspect camera and star tracker; (3) a focal plane assembly containing an imaging proportional counter and its preamplifiers, high voltage power supplies and gas system; (4) a fiducial system; and (5) housekeeping, data handling, instrumentation and telemetry electronics. The design, tests, and operation are described

Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus

Merkel cell polyomavirus (MCV) has been recently described as the cause for most human Merkel cell carcinomas. MCV is similar to simian virus 40 (SV40) and encodes a nuclear large T (LT) oncoprotein that is usually mutated to eliminate viral replication among tumor-derived MCV. We identified the hVam6p cytoplasmic protein involved in lysosomal processing as a novel interactor with MCV LT but not SV40 LT. hVam6p binds through its clathrin heavy chain homology domain to a unique region of MCV LT adjacent to the retinoblastoma binding site. MCV LT translocates hVam6p to the nucleus, sequestering it from involvement in lysosomal trafficking. A naturally occurring, tumor-derived mutant LT (MCV350) lacking a nuclear localization signal binds hVam6p but fails to inhibit hVam6p-induced lysosomal clustering. MCV has evolved a novel mechanism to target hVam6p that may contribute to viral uncoating or egress through lysosomal processing during virus replication

Merkel Cell Polyomavirus Small T Antigen Promotes Pro-Glycolytic Metabolic Perturbations Required for Transformation

An accurate analytic model describing the microscopic mechanism of high-harmonic generation (HHG) in solids is derived. Extensive first-principles simulations within a time-dependent density-functional framework corroborate the conclusions of the model. Our results reveal that (i) the emitted HHG spectra are highly anisotropic and laser-polarization dependent even for cubic crystals; (ii) the harmonic emission is enhanced by the inhomogeneity of the electron-nuclei potential; the yield is increased for heavier atoms; and (iii) the cutoff photon energy is driver-wavelength independent. Moreover, we show that it is possible to predict the laser polarization for optimal HHG in bulk crystals solely from the knowledge of their electronic band structure. Our results pave the way to better control and optimize HHG in solids by engineering their band structure

Relationships of Polychlorinated Biphenyls and Dichlorodiphenyldichloroethylene (p,p’-DDE) with Testosterone Levels in Adolescent Males

Background: Concern persists over endocrine-disrupting effects of persistent organic pollutants (POPs) on human growth and sexual maturation. Potential effects of toxicant exposures on testosterone levels during puberty are not well characterized. Objectives: In this study we evaluated the relationship between toxicants [polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p´-DDE), hexachlorobenzene (HCB), and lead] and testosterone levels among 127 Akwesasne Mohawk males 10 to \u3c 17 years of age with documented toxicant exposures. Methods: Data were collected between February 1996 and January 2000. Fasting blood specimens were collected before breakfast by trained Akwesasne Mohawk staff. Multivariable regression models were used to estimates associations between toxicants and serum testosterone, adjusted for other toxicants, Tanner stage, and potential confounders. Results: The sum of 16 PCB congeners (Σ16PCBs) that were detected in ≥ 50% of the population was significantly and negatively associated with serum testosterone levels, such that a 10% change in exposure was associated with a 5.6% decrease in testosterone (95% CI: –10.8, –0.5%). Of the 16 congeners, the more persistent ones (Σ8PerPCBs) were related to testosterone, whereas the less persistent ones, possibly reflecting more recent exposure, were not. When PCB congeners were subgrouped, the association was significant for the sum of eight more persistent PCBs (5.7% decrease; 95% CI: –11, –0.4%), and stronger than the sum of six less persistent congeners (3.1% decrease; 95% CI: –7.2, 0.9%). p,p´-DDE was positively but not significantly associated with serum testosterone (5.2% increase with a 10% increase in exposure; 95% CI: –0.5, 10.9%). Neither lead nor HCB was significantly associated with testosterone levels. Conclusions: Exposure to PCBs, particularly the more highly persistent congeners, may negatively influence testosterone levels among adolescent males. The positive relationship between p,p´-DDE and testosterone indicates that not all POPs act similarly

Identification of FAM111A as an SV40 Host Range Restriction and Adenovirus Helper Factor

The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT

Pengaruh Absensi Fingerprint Terhadap Kinerja Pegawai Pada Badan Pengelolaan Pajak Daerah (BPPD) Kota Palembang

ABSTRACT   This study aims to determine the effect of fingerprint attendance on employee performance at the Regional Tax Management Agency (BPPD) of Palembang City. The data used is primary data. Data collection techniques are questionnaires, observation and documentation. The analytical technique used in this research is simple linear regression analysis, correlation coefficient analysis, coefficient of determination analysis and hypothesis testing assisted by the Statistical Program For Special Science (SPSS) version 25. Based on the results and data analysis that has been done, it shows that Fingerprint Attendance Partial has a positive and significant effect on the Performance of BPPD Employees in Palembang City. Based on the analysis of the correlation coefficient, the correlation coefficient (R) between Fingerprint Attendance on Employee Performance is very strong or has a ridge of 0.868. From the results of the analysis, it is known that the coefficient of determination R2 = 0.749 or 74.9% so that it can be concluded that the Fingerprint Attendance Variable (X) affects the Employee Performance Variable (Y).   Keywords: Fingerprint Attendance, Employee Performance   ABSTRAK   Penelitian ini bertujuan untuk mengetahui pengaruh absensi fingerprint terhadap kinerja pegawai pada Badan Pengelolaan Pajak Daerah (BPPD) Kota Palembang. Data yang digunakan adalah data primer. Teknik pengumpulan data adalah kuesioner, observasi dan dokumentasi. Teknik analisis yang digunakan dalam penelitian ini adalah analisis regresi linear sederhana, analisis koefisien korelasi, analisis koefisien determinasi dan uji hipotesis dibantu oleh Statistical Program For Special Science (SPSS) versi 25. Berdasarkan hasil dan analisis data yang telah dilakukan menunjukkan secara Parsial Absensi Fingerprint berpengaruh positif dan signifikan terhadap Kinerja Pegawai BPPD Kota Palembang . Berdasarkan analisis koefisien korelasi koefisien korelasi (R) antara Absensi Fingerprint terhadap Kinerja Pegawai sangat kuat atau mempunyai bubungan sebesar 0,868. Dari hasil analisis diketahui bahwa koefisen determinasi R2 = 0,749 atau 74,9% sehingga dapat disimpulkan Variabel Absensi Fingerprint (X) mempengaruhi Variabel Kinerja Pegawai (Y).   Kata Kunci: Absensi Fingerprint,Kinerja Pegawai

The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-kB by Merkel Polyomavirus small Tumour antigen

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-B) signalling and a modulator of the host anti-viral response. Here we demonstrate that regulation of NF-B activation involves a previously undocumented interaction between tAg and regulatory sub-unit 1 of protein phosphatase 4 (PP4R1). Formation of a complex with PP4R1 and PP4c is required to bridge MCPyV tAg to the NEMO adaptor protein, allowing deactivation of the NF-B pathway. Mutations in MCPyV tAg that fail to interact with components of this complex, or siRNA depletion of PP4R1, prevents tAg-mediated inhibition of NF-B and pro-inflammatory cytokine production. Comparison of tAg binding partners from other human polyomavirus demonstrates that interactions with NEMO and PP4R1 are unique to MCPyV. Collectively, these data identify PP4R1 as a novel target for virus subversion of the host anti-viral response

Does a new polyomavirus contribute to Merkel cell carcinoma?

A new polyomavirus has been discovered in Merkel cell carcinomas, but does it contribute to carcinogenesis