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Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent infection, and viral genes are poised to be transcribed in the latent chromatin. In the poised chromatins, KSHV latency-associated nuclear antigen (LANA) interacts with cellular chromodomain-helicase-DNA-binding protein 4 (CHD4) and inhibits viral promoter activation. CHD4 is known to regulate cell differentiation by preventing enhancers from activating promoters. Here, we identified a putative CHD4 inhibitor peptide (VGN73) from the LANA sequence corresponding to the LANA-CHD4 interaction surface. The VGN73 interacts with CHD4 at its PHD domain with a dissociation constant (K D) of 14 nM. Pre-treatment with VGN73 enhanced monocyte differentiation into macrophages and globally altered the repertoire of activated genes in U937 cells. Furthermore, the introduction of the peptide into the cancer cells induced caspase-mediated CHD4 cleavage, triggered cell death, and inhibited tumor growth in a xenograft mouse model. The VGN73 may facilitate cell differentiation therapy. [Display omitted] • VGN73 derived from KSHV LANA protein sequence interacts with and induces CHD4 cleavage • LANA peptide induces cell apoptosis and autophagy by CHD4 cleavage • VGN73 facilitates transcription reprogramming of monocytes • VGN73 prevents primary effusion lymphoma cell growth in a xenograft model Miura et al. identify a small peptide, derived from the KSHV LANA protein sequence, that enhances monocyte differentiation into macrophages. The introduction of the peptide into cancer cells induces CHD4 protein cleavage, triggers cell death, and inhibits tumor growth in a xenograft mouse model. [ABSTRACT FROM AUTHOR]

Kaposi’s sarcoma-associated herpesvirus (KSHV) belongs to the gamma-herpesvirus family and is a well-known human oncogenic virus. In infected cells, the viral genome of 165 kbp is circular DNA wrapped in chromatin. The tight control of gene expression is critical for latency, the transition into the lytic phase, and the development of viral-associated malignancies. Distal cis-regulatory elements, such as enhancers and silencers, can regulate gene expression in a position- and orientation-independent manner. Open chromatin is another characteristic feature of enhancers. To systematically search for enhancers, we cloned all the open chromatin regions in the KSHV genome downstream of the luciferase gene and tested their enhancer activity in infected and uninfected cells. A silencer was detected upstream of the latency-associated nuclear antigen promoter. Two constitutive enhancers were identified in the K12p-OriLyt-R and ORF29 Intron regions, where ORF29 Intron is a tissue-specific enhancer. The following promoters: OriLyt-L, PANp, ALTp, and the terminal repeats (TRs) acted as lytically induced enhancers. The expression of the replication and transcription activator (RTA), the master regulator of the lytic cycle, was sufficient to induce the activity of lytic enhancers in uninfected cells. We propose that the TRs that span about 24 kbp region serve as a “viral super-enhancer” that integrates the repressive effect of the latency-associated nuclear antigen (LANA) with the activating effect of RTA. Utilizing CRISPR activation and interference techniques, we determined the connections between these enhancers and their regulated genes. The silencer and enhancers described here provide an additional layer to the complex gene regulation of herpesviruses. IMPORTANCE In this study, we performed a systematic functional assay to identify cis-regulatory elements within the genome of the oncogenic herpesvirus, Kaposi’s sarcoma-associated herpesvirus (KSHV). Similar to other herpesviruses, KSHV presents both latent and lytic phases. Therefore, our assays were performed in uninfected cells, during latent infection, and under lytic conditions. We identified two constitutive enhancers, one of which seems to be a tissue-specific enhancer. In addition, four lytically induced enhancers, which are all responsive to the replication and transcription activator (RTA), were identified. Furthermore, a silencer was identified between the major latency promoter and the lytic gene locus. Utilizing CRISPR activation and interference techniques, we determined the connections between these enhancers and their regulated genes. The terminal repeats, spanning a region of about 24 kbp, seem like a “viral super-enhancer” that integrates the repressive effect of the latency-associated nuclear antigen (LANA) with the activating effect of RTA to regulate latency to lytic transition. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV; human herpesvirus 4; HHV-4) and Kaposi sarcoma-associated herpesvirus (KSHV; human herpesvirus 8; HHV-8) are human gammaherpesviruses that have oncogenic properties. EBV is a lymphocryptovirus, whereas HHV-8/KSHV is a rhadinovirus. As lymphotropic viruses, EBV and KSHV are associated with several lymphoproliferative diseases or plasmacytic/plasmablastic neoplasms. Interestingly, these viruses can also infect epithelial cells causing carcinomas and, in the case of KSHV, endothelial cells, causing sarcoma. EBV is associated with Burkitt lymphoma, classic Hodgkin lymphoma, nasopharyngeal carcinoma, plasmablastic lymphoma, lymphomatoid granulomatosis, leiomyosarcoma, and subsets of diffuse large B-cell lymphoma, post-transplant lymphoproliferative disorder, and gastric carcinoma. KSHV is implicated in Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease, and KSHV-positive diffuse large B-cell lymphoma. Pathogenesis by these two herpesviruses is intrinsically linked to viral proteins expressed during the lytic and latent lifecycles. This comprehensive review intends to provide an overview of the EBV and KSHV viral cycles, viral proteins that contribute to oncogenesis, and the current understanding of the pathogenesis and clinicopathology of their related neoplastic entities.

Kaposi sarcoma-associated herpesvirus (KSHV) establishes a latent infection in the cell nucleus, but where KSHV episomal genomes are tethered and the mechanisms underlying KSHV lytic reactivation are unclear. Here, we study the nuclear microenvironment of KSHV episomes and show that the KSHV latency-lytic replication switch is regulated via viral long non-coding (lnc)RNA-CHD4 (chromodomain helicase DNA binding protein 4) interaction. KSHV episomes localize with CHD4 and ADNP proteins, components of the cellular ChAHP complex. The CHD4 and ADNP proteins occupy the 5'-region of the highly inducible lncRNAs and terminal repeats of the KSHV genome together with latency-associated nuclear antigen (LANA). Viral lncRNA binding competes with CHD4 DNA binding, and KSHV reactivation sequesters CHD4 from the KSHV genome, which is also accompanied by detachment of KSHV episomes from host chromosome docking sites. We propose a model in which robust KSHV lncRNA expression determines the latency-lytic decision by regulating LANA/CHD4 binding to KSHV episomes.

El domingo, con su repetición semanal, marcaba la estructura básica para la medición temporal de los ciclos litúrgicos y del descanso laboral. Este día adquiría un peso crucial en la liturgia, ya que los domingos se celebraba el misterio pascual. A su vez, la resurrección de Jesucristo en esta misma jornada la convertía en un día privilegiado que habría de reunir a la comunidad de fieles. Quizá, la cotidianidad del domingo haya hecho que se le haya considerado como una festividad de menor entidad. No obstante, como veremos a lo largo del presente artículo para la Baja Edad Media y los primeros años de la modernidad, la actividad laboral debía detenerse para ser celebrado profusamente. Sunday, with its weekly repetition, marked the basic structure for measuring the temporal cycles of liturgy and work rest. This day acquired a crucial weight in the liturgy, as the Easter mystery was celebrated on Sundays. In turn, the resurrection of Jesus Christ on this same day made it a privileged day that would bring together the community of believers. Perhaps the everyday nature of Sunday has made it considered a less significant holiday. However, as we will see throughout this article for the Late Middle Ages and the early years of modernity, Sunday work activities had to stop in order for Sunday to be celebrated profusely. Igandea, bere asteroko errepikapenarekin, liturgia-zikloen eta lan-atsedenaren denbora-neurketarako oinarrizko egitura markatzen zuen. Egun honek berebiziko garrantzia hartzen zuen liturgian, igandeetan pazko misterioa ospatzen baitzen. Aldi berean, Jesukristoren berpizkundeak egun honetan eman zelako, fededunen komunitatea bilduko zen egun pribilegiatu honetan. Agian, igandeko egunerokotasunak eragin du jaiegun txikitzat hartzea. Hala ere, artikulu honetan ikusiko dugunez, Behe Erdi Aroari eta modernitatearen lehen urteei dagokienez lan-jarduera eten egin behar zen, igandea oparo ospatu ahal izateko.

El objetivo de este artículo es mostrar la contribución de dos mujeres a la cuestión femenina dentro del movimiento obrero: Virginia González, socialista, y Dolores Ibárruri, comunista. Para ello, nos centraremos en el primer tercio del siglo XX, mostrando primero cuál era la situación de la mujer dentro del movimiento obrero, y realizando después un recorrido por algunas de las aportaciones más importantes de ambas mujeres, centrándonos en la cuestión de la maternidad, el matrimonio y el trabajo. Langile-mugimenduaren barruan emakumezkoen gaiari dagokionez bi emakumek egindako ekarpena erakustea da artikulu honen helburua: Virginia González, sozialista, eta Dolores Ibárruri, komunista. Horretarako, XX. mendearen lehenengo herena hartuko dugu ardatz, lehenik emakumeak langile-mugimenduaren barruan zuen egoera zein zen erakutsiz, eta ondoren bi emakumeek egindako ekarpen garrantzitsuenen errepasoa eginez, amatasuna, ezkontza eta lana gai nagusitzat hartuta. The aim of this article is to show the contribution of the socialist Virginia González and the communist Dolores Ibárruri to the women issue inside the working class movement. We will focus on the first third of the tweentieh century. Firstly we will show how the woman was considered for the working class movement at that time; secondly we will show proposal of these two women in topics like motherhood, marriage and work.

Copyright of Immaterial is the property of BAU, Centro Universitario de Diseno de Barcelona and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes life-long latent infection and is linked to several human malignancies. Latency-associated nuclear antigen (LANA) is highly expressed during latency, and is responsible for the replication and maintenance of the viral genome. The expression of LANA is regulated at transcriptional/translational levels through multiple mechanisms, including the secondary structures in the mRNA sequence. LANA mRNA has multiple G-quadruplexes (G4s) that are bound by multiple proteins to stabilize/destabilize these secondary structures for regulating LANA. In this manuscript, we demonstrate the role of Nucleolin (NCL) in regulating LANA expression through its interaction with G-quadruplexes of LANA mRNA. This interaction reduced LANA's protein expression through the sequestration of mRNA into the nucleus, demonstrated by the colocalization of G4-carrying mRNA with NCL. Furthermore, the downregulation of NCL, by way of a short hairpin, showed an increase in LANA translation following an alteration in the levels of LANA mRNA in the cytoplasm. Overall, the data presented in this manuscript showed that G-quadruplexes-mediated translational control could be regulated by NCL, which can be exploited for controlling KSHV latency. [ABSTRACT FROM AUTHOR]

In eukaryotic organisms, genomic DNA associates with histone proteins to form nucleosomes. Nucleosomes provide a basis for genome compaction, epigenetic markup, and mediate interactions of nuclear proteins with their target DNA loci. A negatively charged (acidic) patch located on the H2A-H2B histone dimer is a characteristic feature of the nucleosomal surface. The acidic patch is a common site in the attachment of various chromatin proteins, including viral ones. Acidic patch-binding peptides present perspective compounds that can be used to modulate chromatin functioning by disrupting interactions of nucleosomes with natural proteins or alternatively targeting artificial moieties to the nucleosomes, which may be beneficial for the development of new therapeutics. In this work, we used several computational and experimental techniques to improve our understanding of how peptides may bind to the acidic patch and what are the consequences of their binding. Through extensive analysis of the PDB database, histone sequence analysis, and molecular dynamic simulations, we elucidated common binding patterns and key interactions that stabilize peptide–nucleosome complexes. Through MD simulations and FRET measurements, we characterized changes in nucleosome dynamics conferred by peptide binding. Using fluorescence polarization and gel electrophoresis, we evaluated the affinity and specificity of the LANA1-22 peptide to DNA and nucleosomes. Taken together, our study provides new insights into the different patterns of intermolecular interactions that can be employed by natural and designed peptides to bind to nucleosomes, and the effects of peptide binding on nucleosome dynamics and stability. [ABSTRACT FROM AUTHOR]

Molecular mechanisms of Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation have been studied primarily by measuring the total or average activity of an infected cell population, which often consists of a mixture of both nonresponding and reactivating cells that in turn contain KSHVs at various stages of replication. Studies on KSHV gene regulation at the individual cell level would allow us to better understand the basis for this heterogeneity, and new preventive measures could be developed based on findings from nonresponding cells exposed to reactivation stimuli. Here, we generated a recombinant reporter virus, which we named "Rainbow-KSHV," that encodes three fluorescence-tagged KSHV proteins (mBFP2-ORF6, mCardinal-ORF52, and mCherry-LANA). Rainbow-KSHV replicated similarly to a prototype reporter-KSHV, KSHVr.219, and wild-type BAC16 virus. Live imaging revealed unsynchronized initiation of reactivation and KSHV replication with diverse kinetics between individual cells. Cell fractionation revealed temporal gene regulation, in which early lytic gene expression was terminated in late protein-expressing cells. Finally, isolation of fluorescence-positive cells from nonresponders increased dynamic ranges of downstream experiments 10-fold. Thus, this study demonstrates a tool to examine heterogenic responses of KSHV reactivation for a deeper understanding of KSHV replication.IMPORTANCE Sensitivity and resolution of molecular analysis are often compromised by the use of techniques that measure the ensemble average of large cell populations. Having a research tool to nondestructively identify the KSHV replication stage in an infected cell would not only allow us to effectively isolate cells of interest from cell populations but also enable more precise sample selection for advanced single-cell analysis. We prepared a recombinant KSHV that can report on its replication stage in host cells by differential fluorescence emission. Consistent with previous host gene expression studies, our experiments reveal the highly heterogenic nature of KSHV replication/gene expression at individual cell levels. The utilization of a newly developed reporter-KSHV and initial characterization of KSHV replication in single cells are presented.

Copyright of Industria Textila is the property of Institutul National de Cercetare-Dezvoltare pentru Textile si Pielarie and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Research & Development / Revista de Investigación & Desarrollo is the property of ECORFAN-Mexico S.C. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Kaposi's sarcoma (KS) is the second most common tumor in people infected with human immunodeficiency virus worldwide, but its pathogenesis is still unclear. In this study, we discovered that the expression of GATA‐binding protein 3 (GATA3) was lowly expressed in KS tissues and KSHV‐infected cells, while microRNA‐155 (miR‐155) was highly expressed in KS serum and KSHV‐infected cells. miR‐155 promoted the proliferation, migration and invasion of KSHV infection by targeting GATA3. Further, The KSHV‐encoded protein, the Latency associated nuclear antigen (LANA), promotes the proliferation, migration and invasion of KSHV‐infected cells by regulating the miR‐155/GATA3 axis. Regarding the molecular mechanism, c‐Jun and c‐Fos interact to form a complex. LANA upregulates the expression of c‐Jun and c‐Fos and enhances the formation of c‐Jun/c‐Fos complex. The complex binds to the −95∼−100 bp site of miR‐155 promoter and transcriptionally activates miR‐155. All in all, LANA enhances the c‐Jun/c‐Fos interaction, resulting in enhanced transcriptional regulation of miR‐155 by the c‐Jun/c‐Fos complex, thereby downregulating GATA3 and promoting the proliferation, migration and invasion of KSHV‐infected cells. The discovery of LANA/c‐Jun/c‐Fos/miR‐155/GATA3 further refines the pathogenesis of KS, potentially opening a new avenue for developing effective drugs against KS. [ABSTRACT FROM AUTHOR]

La raza ovina Ideal o Polwarth originaria de Australia se cría en el centro del Litoral argentino proveyendo ingresos a sus productores a través de la venta de lana y carne. Criadores de esa región, interesados en afinar las lanas, aumentar o al menos mantener el peso de vellón y aumentar los pesos corporales de sus ovinos Ideal formaron la sociedad “Cabañas Integradas” e implementaron en el año 2003 un programa de mejoramiento genético. El objetivo del presente trabajo fue evaluar el resultado de ese programa cumplidos quince años de ejecución. El programa de mejoramiento se basó en la formación de un núcleo con las mejores ovejas de los criadores y la provisión de carneros nacidos en el núcleo a los planteles individuales de sus establecimientos. Después de la introducción inicial de carneros todos los reemplazos de carneros y ovejas se basó en candidatos nacidos en el propio núcleo o en los planteles individuales. Para la selección de reemplazos se usaron índices de selección basados en una función objetivo con valores de cría de caracteres de interés ponderados por su importancia económica. Los caracteres fueron el peso al destete (PCD) y el peso a la esquila, peso de vellón y diámetro medio a la primera (PCE1, PVS1 y PDF1) y segunda esquila (PCE2, PVS2 y PDF2). La importancia económica se determinó como beneficio marginal, precio menos costo, por unidad de cambio en la característica. Los valores de cría expresados como diferencias esperadas en la progenie (DEPs) se obtuvieron de análisis mixtos multicarácter con propiedades BLUP del servicio de evaluación genética de ovinos “Provino Avanzado” operado por el INTA. Para su cálculo se utilizaron parámetros genéticos y fenotípicos calculados de la propia población. Las tendencias genéticas resultaron similares para los tres pesos corporales (PCD, PCE1 y PCE2) con tasas de 0,12 a 0,14 kg por año. Las ganancias genéticas acumuladas en los 15 años llegaron a los 2,5 kg. No se logró mejora genética en los pesos de vellón (PVS1 y PVS2), pero se logró afinar la lana (PDF1 y PDF2) en cerca de un micrón. Las tendencias genéticas en los siete caracteres se resumen en el incremento del ingreso económico de aproximadamente 1% por año. Las tendencias fenotípicas resultaron con bajo coeficiente de determinación, pero en las direcciones deseadas. Tomando el promedio de los primeros y últimos tres años del programa y en el caso de borregos/as el peso corporal a la primera esquila aumentó unos 3,1 kg y el diámetro medio de fibras se redujo 1,5 µm. Sería deseable que más criadores Ideal comiencen sus propios programas de mejoramiento basados en evaluaciones Provino Avanzado, eventualmente vinculándose a Cabañas Integradas para su evaluación genética conjunta y así aprovechar mejor la variabilidad genética existente en la raza.

Copyright of Archivio Giuridico is the property of Mucchi Editore and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

ABSTRACT The past decade illuminated the H2A-H2B acidic patch as a cornerstone for both nucleosome recognition and chromatin structure regulation. Higher-order folding of chromatin arrays is mediated by interactions of histone H4 tail with an adjacent nucleosome acidic patch. Dynamic chromatin folding ensures a proper regulation of nuclear functions fundamental to cellular homeostasis. Many cellular factors have been shown to act on chromatin by tethering nucleosomes via an arginine anchor binding to the acidic patch. This tethering mechanism has also been described for several viral proteins. In this minireview, we will discuss the structural basis for acidic patch engagement by viral proteins and the implications during respective viral infections. We will also discuss a model in which acidic patch occupancy by these non-self viral proteins alters the local chromatin state by preventing H4 tail-mediated higher-order chromatin folding.

Hypoxic reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) refers to the phenomenon under low oxygen where the virus goes from latent to lytic replication. Typically, healthy cells generally cease cell division and DNA replication under hypoxic conditions due to limited resources, and the presence of physiological inhibitors. This restricted replication under hypoxic conditions is considered an employed strategy of the cell to minimize energy consumption. However, cancerous cells continuously replicate and divide in hypoxic conditions by reprogramming several aspects of their cell physiology, including but not limited to metabolism, cell cycle, DNA replication, transcription, translation, and the epigenome. KSHV infection, similar to cancerous cells, is known to bypass hypoxia-induced restrictions and undergo reactivation to produce progeny viruses. In previous studies we have mapped several aspects of cell physiology that are manipulated by KSHV through its latent antigens during hypoxic conditions, which allows for a permissive environment for its replication. We discuss the major strategies utilized by KSHV to bypass hypoxia-induced repression. We also describe the KSHV-encoded antigens responsible for modulating these cellular processes important for successful viral replication and persistence in hypoxia., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

„Saggio delli Commerciali Rapporti di Veneziani colle Ottomane Scale di Durazzo ed Albania" by Giovanni Antonio Maria Morana, printed in Venice in 1816, is used in this study as a first class source in attempt to track significant changes in local businesses of the the so-called Turkish Albania, within the general framework of Venetian economy, in the circumstances that followed the abolition of the Republic in 1797. Document offers concrete answers to the question, whether this area, with Durrës as an export port, could be a compatible partner to the Venetian economy. At the time this treatise was published, the region came under the rule of Austria. [ABSTRACT FROM AUTHOR]

ABSTRACT Hypoxia signaling is a key regulator in the development and progression of many types of human malignancies, including viral cancers. The latency-associated nuclear antigen (LANA), encoded by Kaposi’s sarcoma-associated herpesvirus (KSHV) during latency, is a multifunctional protein that plays an essential role in viral episome maintenance and lytic gene silencing for inducing tumorigenesis. Although our previous studies have shown that LANA contains a SUMO-interacting motif (LANASIM), and hypoxia reduces SUMOylated KAP1 association with LANASIM, the physiological proteomic network of LANASIM-associated cellular proteins in response to hypoxia is still unclear. In this study, we individually established cell lines stably expressing wild-type LANA (LANAWT) and its SIM-deleted mutant (LANAdSIM) and treated them with or without hypoxia, followed by coimmunoprecipitation and mass spectrometry analysis to systemically identify the hypoxia-responsive profile of LANASIM-associated cellular proteins. We found that in hypoxia, the number of cellular proteins associated with LANAWT instead of LANAdSIM was dramatically increased. Functional network analysis revealed that two major pathways, which included cytoskeleton organization and DNA/RNA binding and processing pathways, were significantly enriched for 28 LANASIM-associated proteins in response to hypoxia. HNRNPU was one of the proteins consistently identified that interacted with LANASIM in different proteomic screening systems and responded to hypoxia. This study provides a proteomic profile of LANASIM-associated proteins in hypoxia and facilitates our understanding of the role of the collaboration between viral infection and the hypoxia response in inducing viral persistence and tumorigenesis. IMPORTANCE Kaposi’s sarcoma-associated herpesvirus (KSHV) has been reported to be involved in the regulation of host proteins in response to hypoxic stress. LANA, one of the key latent proteins, contains a SUMO-interacting motif (LANASIM) and reduces the association with SUMOylated KAP1 upon hypoxic treatment. However, the physiological systematic network of LANASIM-associated cellular proteins in hypoxia is still unclear. Here, we revealed two major pathways, which included cytoskeleton organization and DNA/RNA binding and processing pathways, that were significantly enriched for 28 LANASIM-associated proteins in hypoxia. This discovery not only provides a proteomic profile of LANASIM-associated proteins in hypoxia but also facilitates our understanding of the collaboration between viral infection and hypoxic stress in inducing viral persistence and tumorigenesis.

Kaposi sarcoma (KS) is the most common cancer in persons living with HIV. It is caused by KS-associated herpesvirus (KSHV). There exists no animal model for KS. Pronuclear injection of the 170,000-bp viral genome induces early-onset, aggressive angiosarcoma in transgenic mice. The tumors are histopathologically indistinguishable from human KS. As in human KS, all tumor cells express the viral latency-associated nuclear antigen (LANA). The tumors transcribe most viral genes, whereas endothelial cells in other organs only transcribe the viral latent genes. The tumor cells are of endothelial lineage and exhibit the same molecular pattern of pathway activation as KS, namely phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR, interleukin-10 (IL-10), and vascular endothelial growth factor (VEGF). The KSHV-induced tumors are more aggressive than Ha-ras -induced angiosarcomas. Overall survival is increased by prophylactic ganciclovir. Thus, whole-virus KSHV-transgenic mice represent an accurate model for KS and open the door for the genetic dissection of KS pathogenesis and evaluation of therapies, including vaccines. [Display omitted] • Kaposi sarcoma (KS)-associated herpesvirus transgenic mice develop angiosarcomas • The murine angiosarcomas resemble human KS based on protein and RNA-seq analysis • All latent and some lytic viral genes are transcribed in murine KS Kaposi sarcoma (KS)-associated herpesvirus causes KS. Sin et al. create an immunocompetent mouse model of KS using the entire 170,000 bp herpesvirus genome as transgene. Latent and some lytic viral genes are expressed in the tumor. By histology, protein markers, and RNA-seq, the murine angiosarcomas resemble human KS. [ABSTRACT FROM AUTHOR]

In the buoyant Valencia of the VX century Italians were the biggest and most dynamic foreign community. Amongst them stood out the Lombards, behind the Ligures and Tuscans. Our objective is to analyze Prato’s family trajectory, native from Mombaruzzo, during their stay in the Valencia of the second half of the XV century, who was amongst the most actives families in the Lombarda colony. The documentation allows us to recover their economic activities, but also aspects of their daily life like material and religious culture. The bulk of their sales in Valencia and Castilla was the glasto (pastel grass), where they acquired wool, that they exported to Italy. Their stay was always temporal and their level of integration in Valencian society scarce.

The hypoxic microenvironment and metabolic reprogramming are two major contributors to the phenotype of oncogenic virus-infected cells. Infection by Kaposi's sarcoma-associated herpesvirus (KSHV) stabilizes hypoxia-inducible factor 1a (HIF1a) and reprograms cellular metabolism. We investigated the comparative transcriptional regulation of all major genes involved in fatty acid and amino acid metabolism in KSHV-positive and -negative cells grown under normoxic or hypoxic conditions. We show a distinct regulation of genes involved in both fatty acid and amino acid metabolism in KSHV-positive cells grown in either normoxic or hypoxic conditions, with a particular focus on genes involved in the acetyl coenzyme A (acetyl-CoA) pathway. The fatty acid binding protein (FABP) family of genes, specifically FABP1, FABP4, and FABP7, was also observed to be synergistically upregulated in hypoxia by KSHV. This pattern of FABP gene expression was also seen in naturally infected KSHV BC3 or BCBL1 cells when compared to KSHV-negative DG75 or BL41 cells. Two KSHV-encoded antigens, which positively regulate HIF1a, the viral G-protein coupled receptor (vGPCR), and the latency-associated nuclear antigen (LANA) were shown to drive upregulation of the FABP gene transcripts. Suppression of FABPs by RNA interference resulted in an adverse effect on hypoxia-dependent viral reactivation. Overall, this study provides new evidence, which supports a rationale for the inhibition of FABPs in KSHV-positive cells as potential strategies, for the development of therapeutic approaches targeting KSHV-associated malignancies. [ABSTRACT FROM AUTHOR]

Copyright of Mediterranea - Ricerche Storiche is the property of Mediterranea-Ricerche Storiche and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

KSHV latency can be envisioned as an outcome that is balanced between factors that promote viral gene expression and lytic replication against those that facilitate gene silencing and establish or maintain latency. A large body of work has focused on the activities of the key viral regulatory proteins involved in KSHV latent or lytic states. Moreover, recent studies have also begun to document the importance of epigenetic landscape evolution of the KSHV viral genome during latency and reactivation. However, one area of KSHV molecular virology that remains largely unanswered is the precise role of post-translational modifications on the activities of viral factors that function during latency and reactivation. In this review, we will summarize the post-translational modifications associated with three viral factors whose activities contribute to the viral state. The viral proteins discussed are the two major KSHV encoded transcription factors, K-Rta (KSHV replication and transcriptional activator) and K-bZIP (KSHV basic leucine zipper) and the viral latency-associated nuclear antigen (LANA). A special emphasis will be placed on the role of the sumoylation pathway in the modulation of the KSHV lifecycle. Newly uncovered small ubiquitin-like modifier (SUMO)-associated properties of LANA and K-Rta will also be presented, namely LANA histone targeting SUMO E3 ligase activity and K-Rta SUMO-targeted ubiquitin ligase function.

With the realization of the industrial plant of Pile, Dubrovnik inaugurated in 1416 the production of fabrics according to the standards of Italian manufacture. In the organization of the putting-out system, the use of water resources for cleaning and dyeing required experimentation of the ever-changing forms of management. This article examines both the firms and the artisans who managed the hydraulic factories in the first twenty years of the textile manufacturing in Dubrovnik. This period witnessed a mix of public and private investments, import of significant foreign human resources, and the rise and fall of various dyers. [ABSTRACT FROM AUTHOR]

On the surface of the nucleosome, there are many regions for interaction with chromatin proteins, but an acidic patch, a negatively charged region formed by the residues of the histone H2A/H2B dimer, is especially prominent. The acidic patch is a target for anticancer drugs and an interaction locus for various pathogens. For instance, it was shown that this region is the binding site of the LANA protein of human gammaherpesvirus 8 and tethers the virus episomes to mitotic chromosomes. The development of methods for analyzing the binding of various compounds to nucleosomes is necessary both for understanding the mechanisms of chromatin regulation and for therapeutic agents' design. In this work, we propose a technique and measure the binding constant of the LANA protein fragment to the nucleosome. In contrast to previous studies, the measurements were carried out at a physiological salt concentration in the buffer solution. The proposed technique is based on the signal detection from the fluorescently labeled peptides after the separation of complexes of nucleosomes with peptides by gel electrophoresis. The paper also discusses mathematical models for analyzing the interaction between peptides and nucleosome and possible factors that can affect it. [ABSTRACT FROM AUTHOR]

Molecular mechanisms of Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation have been studied primarily by measuring the total or average activity of an infected cell population, which often consists of a mixture of both nonresponding and reactivating cells that in turn contain KSHVs at various stages of replication. Studies on KSHV gene regulation at the individual cell level would allow us to better understand the basis for this heterogeneity, and new preventive measures could be developed based on findings from nonresponding cells exposed to reactivation stimuli. Here, we generated a recombinant reporter virus, which we named "Rainbow-KSHV," that encodes three fluorescence-tagged KSHV proteins (mBFP2-ORF6, mCardinal-ORF52, and mCherry-LANA). Rainbow-KSHV replicated similarly to a prototype reporter-KSHV, KSHVr.219, and wild-type BAC16 virus. Live imaging revealed unsynchronized initiation of reactivation and KSHV replication with diverse kinetics between individual cells. Cell fractionation revealed temporal gene regulation, in which early lytic gene expression was terminated in late protein-expressing cells. Finally, isolation of fluorescence-positive cells from nonresponders increased dynamic ranges of downstream experiments 10-fold. Thus, this study demonstrates a tool to examine heterogenic responses of KSHV reactivation for a deeper understanding of KSHV replication. [ABSTRACT FROM AUTHOR]

Copyright of Industria Textila is the property of Institutul National de Cercetare-Dezvoltare pentru Textile si Pielarie and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The human DNA tumor viruses Epstein–Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human papillomavirus (HPV) share the common property of persisting as multicopy episomes in the nuclei of rapidly dividing host cells. These episomes form the molecular basis for viral latency and are etiologically linked to virus-associated cancers. Episome maintenance requires epigenetic programming to ensure the proper control of viral gene expression, DNA replication, and genome copy number. For these viruses, episome maintenance requires a dedicated virus-encoded episome maintenance protein (EMP), namely LANA (KSHV), EBNA1 (EBV), and E2 (HPV). Here, we review common features of these viral EMPs and discuss recent advances in understanding how they contribute to the epigenetic control of viral episome maintenance during latency. Viruses have evolved elaborate mechanisms to maintain their genomes as passengers in host cells The oncogenic human herpesviruses, EBV and KSHV, and the small DNA tumor virus, HPV, persist as multicopy episomes EBV, KSHV, and HPV have dedicated EMPs that bind their viral genomes and tether to cellular metaphase chromosomes EMPs contribute to the epigenetic programming of latent viral genomes [ABSTRACT FROM AUTHOR]

Higher-order genome structure influences the transcriptional regulation of cellular genes through the juxtaposition of regulatory elements, such as enhancers, close to promoters of target genes. While enhancer activation has emerged as an important facet of Kaposi sarcoma-associated herpesvirus (KSHV) biology, the mechanisms controlling enhancer-target gene expression remain obscure. Here, we discover that the KSHV genome tethering protein latency-associated nuclear antigen (LANA) potentiates enhancer-target gene expression in primary effusion lymphoma (PEL), a highly aggressive B cell lymphoma causally associated with KSHV. Genome-wide analyses demonstrate increased levels of enhancer RNA transcription as well as activating chromatin marks at LANA-bound enhancers. 3D genome conformation analyses identified genes critical for latency and tumorigenesis as targets of LANA-occupied enhancers, and LANA depletion results in their downregulation. These findings reveal a mechanism in enhancer-gene coordination and describe a role through which the main KSHV tethering protein regulates essential gene expression in PEL. [Display omitted] • KSHV LANA is enriched on cellular enhancers in PEL cells • LANA occupancy is associated with higher enhancer activity and gene expression • Loss of LANA reduces enhancer-promoter contacts and gene expression Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic DNA virus. Ye et al. uncover a role of the KSHV tethering protein LANA in the regulation of cellular gene expression through the manipulation of enhancer biology. [ABSTRACT FROM AUTHOR]

This is a proposal to encode the Lanna script in the international character encoding standard Unicode. The name of the script was changed to "Tai Tham" by consensus of users in different countries. Tai Tham was published in Unicode Standard version 5.2 in October 2009. Tai Tham is used to write Northern Thai, Lue, and Khün, which are spoken in Northern Thailand, Myanmar, China and surrounding areas. It is also used for Lao Tham (Old Lao). The script is known by various names: Old Xishuangbanna Dai or Old Tai Lue in China, Khün in Myanmar, and Tua Mueang, Lanna, or Yuan in Thailand. Several changes have been made to the script since the proposal was written, so users should check the latest code charts, accessible from , and section 16.7 in the Unicode Standard.

Los caprinos de Angora, productores de la fibra mohair utilizada desde tiempos remotos en la confección de prendas de lujo, se diseminaron desde el Medio Oriente a varios países incluyendo a la Argentina. En el norte de la Patagonia su cría proporciona medios de vida a una gran cantidad de pequeños productores. Una revisión bibliográfica, una recopilación de testimonios e información no publicada permiten apreciar las particularidades del origen e historia del Angora, como así también permiten resumir las acciones que contribuyeron a su desarrollo en el país. En ese sentido debe resaltarse la acción del Instituto Nacional de Tecnología Agropecuaria en cuanto al mejoramiento genético y a la extensión. Con el tiempo los productores organizados y empoderados lograron apoyos adicionales que se enmarcaron en el denominado Programa Mohair que a su vez generó la base para la promulgación de una Ley Caprina nacional. Problemas en la producción y prospectivas de comercialización mundial del mohair indican que a pesar de precios favorables sostenidos la producción de Angoras enfrenta varios desafíos para mantenerse en el tiempo.

Argentina counts on continuous introduction of sheep of different breed and/or types of animals, mainly wool farmers. Some areas of the country are characterized for having standardized the sheep while others have preserved the heterogeneity. Having in consideration that the north of La Pampa province was part of this process, and that there are not recent antecedent of the type of wool production of the flock, additionally to the existent of promotion laws that favoured new sheep farms, it was considered necessary to evaluate the existence genetic resources. A study was conducted to evaluate the sheep biotype in relation to wool production in order to know the quality of wool flocks distributed to the region. From 2011 to 2012 was develop a population survey of 8 flocks contained 1021 sheep of the north area of La Pampa. Morphology, conformation, coverage and colour phenotype were evaluated, and 400 wool samples were sent to the laboratory in order to be washed and classified by quality criteria as finesse (FM), type of fleece (TM) and bulk (BK). It was detected significant differences in classes of flock and wool type. In conclusion, the native sheep population of the north area of La Pampa produce wool of high quality for carpet purpose.

The article presents a synthesis of international research aimed at studying the use of natural and renewable resources such as sheep's wool with / without plant waste in order to improve the thermal and acoustic performance of construction materials in which it is incorporated. During the research programs, samples were made from the mixture of wool with mortars, concretes or clay; these were tested to determine the mechanical, thermal and acoustic properties and to highlight the positive contribution of wool. [ABSTRACT FROM AUTHOR]

Copyright of Industria Textila is the property of Institutul National de Cercetare-Dezvoltare pentru Textile si Pielarie and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Internacional de los Estudios Vascos is the property of Sociedad de Estudios Vascos and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Chicken feathers and sheep wool are at present considered two major agro-industrial residues which are hard to be disposed. Therefore finding applications for these residues is interesting from the viewpoint of Circular Economy. The knowledge of the properties and characteristics of keratins, which are the main constituent of these materials, can help designing final applications for them. This report presents the results of the comparative analysis of the molecular weights of keratins from Lachas heep (Ovis aries) and consumer chicken (Gallus domesticus) obtained by reductive extraction with sodium tioglycolate inalkalyne media. The analysis was carried out trough polyacrylamide gel electrophoresis and showed that wool keratin has molecular weightfractions of 56, 47, 14, 10 y 8 KDa, higher on average than those of the feathers, only with lower molecular weight fractions, in the range of 8-6 KDa. [ABSTRACT FROM AUTHOR]

Copyright of Investigaciones Historicas is the property of Universidad de Valladolid, Facultad de Filosofia y Letras and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Este artículo analiza el Programa de Asistentes Personales, que brinda cuidados en domicilio para personas con dependencia severa del Sistema Nacional de Cuidados en Uruguay. Se busca examinar las condiciones en las que el trabajo de cuidados a domicilio es provisto y cómo ello impacta tanto en la garantía del derecho a ser cuidado, como en la reproducción de desigualdades de género. La hipótesis principal plantea que, dadas las características del trabajo remunerado de cuidados a domicilio y sus elevados requerimientos técnicos, un modelo público de atención que contemple este tipo de prestación requiere no solo de formación específica en cuidados de quienes realizan la atención, sino también de la provisión de soporte técnico institucional en el marco de condiciones laborales dignas. [ABSTRACT FROM AUTHOR]

Copyright of Estudios de Historia de España is the property of Pontificia Universidad Catolica Argentina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Primary effusion lymphoma (PEL) is a B cell lymphoma that is always associated with Kaposi's sarcoma-associated herpesvirus (KSHV) and in many cases also with Epstein-Barr virus (EBV); however, the requirement for EBV coinfection is not clear. Here, we demonstrate that adding exogenous EBV to KSHV+ single-positive PEL leads to increased KSHV genome maintenance and KSHV latency-associated nuclear antigen (LANA) expression. To show that EBV was necessary for naturally coinfected PEL, we nucleofected KSHV+/EBV+ PEL cell lines with an EBV-specific CRISPR/Cas9 plasmid to delete EBV and observed a dramatic decrease in cell viability, KSHV genome copy number, and LANA expression. This phenotype was reversed by expressing Epstein-Barr nuclear antigen 1 (EBNA-1) in trans, even though EBNA-1 and LANA do not colocalize in infected cells. This work reveals that EBV EBNA-1 plays an essential role in the pathogenesis of PEL by increasing KSHV viral load and LANA expression. [ABSTRACT FROM AUTHOR]