Faktor Predisposisi, Pemungkin dan Penguat serta pengaruhnya terhadap Konseling dan Testing pada Pekerja Seks Komersial di Kabupaten Grobogan

ABSTRACT Background: Human Immunodeficiency Virus (HIV) infection is a global public health issue. Global AIDS Response Progress Reporting (GARP) reported that in 2015, about 36.7 million people worldwide suffered from HIV-AIDS in all age groups. The highest number of HIV/AIDS cases occured in East Africa and South Africa. This study aimed to examine the effects of predisposing, enabling, and reinforcing factors on the uptake of voluntary counselling and testing (VCT) among female sex workers in Grobogan, Central Java. Subjects and Method: This was an analytical observational study with cross-sectional design. It was conducted in Grobogan, Central Java, in July 2017. A sample of 142 female sex workers were selected for this study by exhaustive sampling. The dependent variable was uptake of VCT. The independent variables were attitude, perceived benefit, external motivation from others, and social support. The data were collected by a questionnaire and analyzed by multiple logistic regression. Results: Positive attitude towards HIV status (OR= 6.09; 95% CI= 0.968 to 38.38; p= 0.054), positive perceived benefit (OR= 10.58; 95% CI= 1.48 to 76.93; p= 0.019), external motivation (OR= 8.30; 95% CI= 1.21 to 56.82; p= 0.031), and social support (OR= 9.45; 95% CI= 1.46 to 60.83; p= 0.018), positively affected uptake of VCT. Conclusion: Positive attitude towards HIV status, positive perceived benefit, external motivation, and social support, positively affect uptake of VCT

Tinjauan Yuridis Atas Hak Pencipta Lagu yang Diaransemen di Media Sosial Tanpa Izin Pencipta

Perkembangan musik dalam masa pandemik sekarang ini mau tidak mau kita harus berdampingan dengan dunia online yaitu menggunakan internet khususnya media sosial, belakangan ini banyak sekali penyanyi-penyanyi baru yang bermunculan di media sosial yang menyanyikan atau mengcover lagu pencipta tanpa izin atau tanpa hak dengan memperoleh hak ekonomi secara individu atau secara bersama. Sehingga di dalam penelitian ini tentu ditemukan permasalahan yaitu ada kerugian dan pelanggaran di dalamnya. Hak cipta yang diatur di dalam Undang-Undang Nomor 28 Tahun 2014 Tentang Hak Cipta, ternyata belum memenuhi keinginan dari sang pencipta lagu, tentunya di dalam menyanyikan ulang atau mengaransemen ulang lagu yang dinyanyikan oleh penyanyi harus memperoleh izin terlebih dahulu dari pencipta lagu. Meskipun sudah mendapatkan perlindungan sejak karyanya diwujudkan dalam bentuk nyata, sebaiknya jika dilakukan pencatatan terhadap hak cipta tersebut agar memiliki bukti yang formal. Penyelesaian sengketa terhadap hak cipta dapat diselesaikan melalui dua cara. Cara yang pertama melalui jalur non litigasi dan kedua melalui jalur litigasi. Penyelesaian melalui jalur non litigasi dibagi menjadi beberapa bagian yaitu konsultasi, mediasi, negosiasi, konsiliasi, dan arbitrase. Sedangkan jika melalui jalur litigasi, dapat ditempuh melalui dua cara yaitu upaya perdata dan upaya pidana

Corporate Social Responsibility (Csr) Dan Good Corporate Governance (Gcg) Sebagai Indikator Dalam Menilai Nilai Perusahaan

Berbagai macam pendekatan dalam pengukuran nilai perusahaan sudah banyak digunakan dalam berbagai penelit ianpenelitian ilmiah. Hal ini menunjukkan berbagai pemikiran tentang nilai perusahaan, suatu nilai perusahaan yang menggambarkan kondisi suatu perusahaan selama beroperasi. Nilai perusahaan pent ing diketahui karena semakin t inggi nilai perusahaan menunjukkan kemakmuran para pemegang saham.  Tulisan ini memcoba untuk menulis kembali pemaparan tentang Corporate Social Responsibilit y (CSR) dan Good CorporateGovernance (GCG) sebagai salah satu indikator pengukuran nilai perusahaan. Suatu pendekatan yang bisa mempresentasikan makna yang lebih besar dari gambaran kondisi suatu perusahaan, sehingga sampai saat ini CSR dan GCG masih menjadi indikator bagi penelit i dalam pengukuran nilai perusahaan

The nuclear structural protein NuMA is a negative regulator of 53BP1 in DNA double-strand break repair

P53-binding protein 1 (53BP1) mediates DNA repair pathway choice and promotes checkpoint activation. Chromatin marks induced by DNA double-strand breaks and recognized by 53BP1 enable focal accumulation of this multifunctional repair factor at damaged chromatin. Here, we unveil an additional level of regulation of 53BP1 outside repair foci. 53BP1 movements are constrained throughout the nucleoplasm and increase in response to DNA damage. 53BP1 interacts with the structural protein NuMA, which controls 53BP1 diffusion. This interaction, and colocalization between the two proteins in vitro and in breast tissues, is reduced after DNA damage. In cell lines and breast carcinoma NuMA prevents 53BP1 accumulation at DNA breaks, and high NuMA expression predicts better patient outcomes. Manipulating NuMA expression alters PARP inhibitor sensitivity of BRCA1-null cells, end-joining activity, and immunoglobulin class switching that rely on 53BP1. We propose a mechanism involving the sequestration of 53BP1 by NuMA in the absence of DNA damage. Such a mechanism may have evolved to disable repair functions and may be a decisive factor for tumor responses to genotoxic treatments

Single Molecule In Vivo Analysis of Toll-Like Receptor 9 and CpG DNA Interaction

Toll-like receptor 9 (TLR9) activates the innate immune system in response to oligonucleotides rich in CpG whereas DNA lacking CpG could inhibit its activation. However, the mechanism of how TLR9 interacts with nucleic acid and becomes activated in live cells is not well understood. Here, we report on the successful implementation of single molecule tools, constituting fluorescence correlation/cross-correlation spectroscopy (FCS and FCCS) and photon count histogram (PCH) with fluorescence lifetime imaging (FLIM) to study the interaction of TLR9-GFP with Cy5 labeled oligonucleotide containing CpG or lacking CpG in live HEK 293 cells. Our findings show that i) TLR9 predominantly forms homodimers (80%) before binding to a ligand and further addition of CpG or non CpG DNA does not necessarily increase the proportion of TLR9 dimers, ii) CpG DNA has a lower dissociation constant (62 nM±9 nM) compared to non CpG DNA (153 nM±26 nM) upon binding to TLR9, suggesting that a motif specific binding affinity of TLR9 could be an important factor in instituting a conformational change-dependant activation, and iii) both CpG and non CpG DNA binds to TLR9 with a 1∶2 stoichiometry in vivo. Collectively, through our findings we establish an in vivo model of TLR9 binding and activation by CpG DNA using single molecule fluorescence techniques for single cell studies

HER2 induced EMT and tumorigenicity in breast epithelial progenitor cells is inhibited by coexpression of EGFR.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The members of the epidermal growth factor receptor (EGFR) kinase family are important players in breast morphogenesis and cancer. EGFR2/HER2 and EGFR expression have a prognostic value in certain subtypes of breast cancer such as HER2-amplified, basal-like and luminal type B. Many clinically approved small molecular inhibitors and monoclonal antibodies have been designed to target HER2, EGFR or both. There is, however, still limited knowledge on how the two receptors are expressed in normal breast epithelium, what effects they have on cellular differentiation and how they participate in neoplastic transformation. D492 is a breast epithelial cell line with stem cell properties that can undergo epithelial to mesenchyme transition (EMT), generate luminal- and myoepithelial cells and form complex branching structures in three-dimensional (3D) culture. Here, we show that overexpression of HER2 in D492 (D492(HER2)) resulted in EMT, loss of contact growth inhibition and increased oncogenic potential in vivo. HER2 overexpression, furthermore, inhibited endogenous EGFR expression. Re-introducing EGFR in D492(HER2) (D492(HER2/EGFR)) partially reversed the mesenchymal state of the cells, as an epithelial phenotype reappeared both in 3D cultures and in vivo. The D492(HER2/EGFR) xenografts grow slower than the D492(HER2) tumors, while overexpression of EGFR alone (D492(EGFR)) was not oncogenic in vivo. Consistent with the EGFR-mediated epithelial phenotype, overexpression of EGFR drove the cells toward a myoepithelial phenotype in 3D culture. The effect of two clinically approved anti-HER2 and EGFR therapies, trastuzumab and cetuximab, was tested alone and in combination on D492(HER2) xenografts. While trastuzumab had a growth inhibitory effect compared with untreated control, the effect of cetuximab was limited. When administered in combination, the growth inhibitory effect of trastuzumab was less pronounced. Collectively, our data indicate that in HER2-overexpressing D492 cells, EGFR can behave as a tumor suppressor, by pushing the cells towards epithelial differentiation.Landspitali University Hospital Science Fund, University of Iceland Research Fund, Science and Technology Policy Council Research Fund and Grant of Excellence, ‘Göngum saman’, a supporting group for breast cancer research in Iceland

Evaluation of a Multiparametric Immunofluorescence Assay for Standardization of Neuromyelitis Optica Serology

Background: Neuromyelitis optica (NMO) is a severely disabling autoimmune disorder of the central nervous system, which predominantly affects the optic nerves and spinal cord. In a majority of cases, NMO is associated with antibodies to aquaporin-4 (AQP4) (termed NMO-IgG). Aims: In this study, we evaluated a new multiparametric indirect immunofluorescence (IIF) assay for NMO serology. Methods: Sera from 20 patients with NMO, 41 patients with multiple sclerosis (MS), 30 healthy subjects, and a commercial anti-AQP4 IgG antibody were tested in a commercial composite immunofluorescence assay ("Neurology Mosaic 17"; Euroimmun, Germany), consisting of five different diagnostic substrates (HEK cells transfected with AQP4, non-transfected HEK cells, primate cerebellum, cerebrum, and optic nerve tissue sections). Results: We identified AQP4 specific and non-specific fluorescence staining patterns and established positivity criteria. Based on these criteria, this kit yielded a high sensitivity (95%) and specificity (100%) for NMO and had a significant positive and negative likelihood ratio (LR+ = ∞, LR- = 0.05). Moreover, a 100% inter- and intra-laboratory reproducibility was found. Conclusions: The biochip mosaic assay tested in this study is a powerful tool for NMO serology, fast to perform, highly sensitive and specific for NMO, reproducible, and suitable for inter-laboratory standardization as required for multi-centre clinical trials

LMTK3 confers chemo-resistance in breast cancer

Lemur tyrosine kinase 3 (LMTK3) is an oncogenic kinase that is involved in different types of cancer (breast, lung, gastric, colorectal) and biological processes including proliferation, invasion, migration, chromatin remodeling as well as innate and acquired endocrine resistance. However, the role of LMTK3 in response to cytotoxic chemotherapy has not been investigated thus far. Using both 2D and 3D tissue culture models, we found that overexpression of LMTK3 decreased the sensitivity of breast cancer cell lines to cytotoxic (doxorubicin) treatment. In a mouse model we showed that ectopic overexpression of LMTK3 decreases the efficacy of doxorubicin in reducing tumor growth. Interestingly, breast cancer cells overexpressing LMTK3 delayed the generation of double strand breaks (DSBs) after exposure to doxorubicin, as measured by the formation of γH2AX foci. This effect was at least partly mediated by decreased activity of ataxia-telangiectasia mutated kinase (ATM) as indicated by its reduced phosphorylation levels. In addition, our RNA-seq analyses showed that doxorubicin differentially regulated the expression of over 700 genes depending on LMTK3 protein expression levels. Furthermore, these genes were found to promote DNA repair, cell viability and tumorigenesis processes / pathways in LMTK3-overexpressing MCF7 cells. In human cancers, immunohistochemistry staining of LMTK3 in pre- and postchemotherapy breast tumor pairs from four separate clinical cohorts revealed a significant increase of LMTK3 following both doxorubicin and docetaxel based chemotherapy. In aggregate, our findings show for the first time a contribution of LMTK3 in cytotoxic drug resistance in breast cancer

Mediated Plastid RNA Editing in Plant Immunity

[EN] Plant regulatory circuits coordinating nuclear and plastid gene expression have evolved in response to external stimuli. RNA editing is one of such control mechanisms. We determined the Arabidopsis nuclear-encoded homeodomain-containing protein OCP3 is incorporated into the chloroplast, and contributes to control over the extent of ndhB transcript editing. ndhB encodes the B subunit of the chloroplast NADH dehydrogenase-like complex (NDH) involved in cyclic electron flow (CEF) around photosystem I. In ocp3 mutant strains, ndhB editing efficiency decays, CEF is impaired and disease resistance to fungal pathogens substantially enhanced, a process recapitulated in plants defective in editing plastid RNAs encoding NDH complex subunits due to mutations in previously described nuclear-encoded pentatricopeptide-related proteins (i.e. CRR21, CRR2). Furthermore, we observed that following a pathogenic challenge, wild type plants respond with editing inhibition of ndhB transcript. In parallel, rapid destabilization of the plastidial NDH complex is also observed in the plant following perception of a pathogenic cue. Therefore, NDH complex activity and plant immunity appear as interlinked processes.This work was supported by the Spanish MICINN (CONSOLIDER and BFU2012 to PV), and Generalitat Valenciana (Prometeo2010/020 to PV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.García-Andrade Serrano, J.; Ramirez Garcia, V.; López Sánchez, A.; Vera Vera, P. (2013). Mediated Plastid RNA Editing in Plant Immunity. PLoS Pathogens. 9(10):1003713-1003713. https://doi.org/10.1371/ journal.ppat.1003713S1003713100371391