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David Klatzmann
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November 2017: Human Gene Therapy
Cai Zhang, Joonbae Seo, Takahisa Nakamura
In mammals, there are four Argonaute (Ago) family proteins that play crucial roles in RNA silencing, a process wherein microRNA (miRNA) mediates inhibition of target mRNA translation. Among the Ago proteins, Argonaute2 (Ago2) uniquely possesses an endoribonuclease (slicer) activity that is critical for the biogenesis of specific miRNAs and mRNA cleavage. This Ago2 slicer activity is required for postnatal development. Despite its important roles, there are still gaps in our understanding of the mechanistic basis of Ago2's unique functions in vivo due to a limited availability of experimental tools...
2018: Methods in Molecular Biology
Chun Shik Park, H Daniel Lacorazza
Hematopoietic stem cells (HSCs) represent an important target cell population in bone marrow transplantation, cell and gene therapy applications, and the development of leukemia models for research. Because the hematopoietic progeny carries the genetic information of HSCs and replenishes the blood and immune system, corrective gene transfer into HSCs provides an ideal therapeutic approach for many monogenic hematological diseases and a useful tool for studies of HSC function and blood formation in normal and malignant hematopoiesis...
2018: Methods in Molecular Biology
Thalita Camêlo da Silva Ferreira, Maria Alice Freitas Queiroz, Gustavo Adolfo Argañaraz, Ricardo Ishak, Antonio Carlos Rosário Vallinoto, Enrique Roberto Argañaraz
OBJECTIVES: The present study investigated the association of alpha-1-antrypsin deficiency (S and Z polymorphisms), with HIV-1 and HTLV-1 infection. METHODS: Blood samples from 201 HIV-1 and 115 HTLV-1 infected individuals were examined and compared with 300 healthy controls. Genotyping of A1AT (S and Z) and quantification of plasma viral load were performed using RT-PCR and TCD4+/CD8+ cell count was determined by flow cytometry. RESULTS: The wild-type MM genotype showed a higher frequency in the three groups investigated...
October 10, 2017: International Journal of Infectious Diseases: IJID
François E Dufrasne, Mara Lucchetti, Anandi Martin, Emmanuel André, Géraldine Dessilly, Benoit Kabamba, Patrick Goubau, Jean Ruelle
The HIVs have evolved by selecting means to hijack numerous host cellular factors. HIVs exploit the transcription factor NF-κB to ensure efficient LTR-driven gene transcription. However, NF-κB is primarily known to act as a key regulator of the proinflammatory and antiviral responses. Interestingly, retroviruses activate NF-κB during early stages of infection to initiate proviral genome expression while suppressing it at later stages to restrain expression of antiviral genes. During HIV-1 infection, diverse viral proteins such as Env, Nef and Vpr have been proposed to activate NF-κB activity, whereas Vpu has been shown to inhibit NF-κB activation...
October 10, 2017: Virology
Zhilan Guo, Luyang Che, Jingzhe Li, Zhenxiao Sun, Changzhen Liu
To quantify the transcriptional activity of NF-κB and to screen drugs related to the regulation of NF-κB activation, we constructed a recombinant plasmid through deleting the original CMV promoter of retrovirus vector pQCXIP and inserting the NF-κB enhancer and NanoLuc luciferase sequence into the vector. Then, using the recombinant plasmid we constructed a cell line in which the expression of NanoLuc luciferase (NLuc) was regulated by NF-κB. The inserted sequences were verified by restriction endonuclease digestion and sequencing...
October 25, 2016: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
George A Yendewa, Robert A Salata
The introduction of combination antiretroviral therapy (ART) in the 1990s has fundamentally transformed the landscape of HIV medicine, greatly improved disease morbidity and mortality, and reduced transmission rates across all demographic groups. Central to this success was the idea that to achieve best disease outcomes and minimize the development of drug resistance, at least three antiretroviral agents should be used for HIV treatment. This therapeutic strategy is a core tenet of HIV medicine, backed by incontrovertible scientific evidence, and made easy to deploy by the high compliance levels with once-daily coformulations, which have generally been well tolerated...
October 11, 2017: AIDS Reviews
Chunting Wu, Jiahui Zhao, Guangfa Zhu, Yan Huang, Liyan Jin
Acute lung injury (ALI) is a condition of acute respiratory failure, characterized by diffuse pulmonary infiltrates and severe hypoxemia. During ALI, the acute phase of inflammation induces the recruitment of activated inflammatory cells, including macrophages and lymphocytes, to the damaged lesions. Nuclear factor (NF)‑κB is a key protein in many signal transduction pathways, over‑activation of which is followed by an approach of inflammation cells and release of pre‑inflammation cytokines. The aim of the present study was to explore the effect of NF‑κB P65 siRNA retroviruses on the activation of NF‑κB signaling pathway and release of pro‑inflammatory cytokines in THP‑1 cells...
October 4, 2017: Molecular Medicine Reports
Tomohiro Tobita, Daiji Kiyozumi, Masahito Ikawa
The placenta is an essential organ for embryo development in the uterus of eutherian mammals. Large contributions in unveiling molecular mechanisms and physiological functions underlying placental formation were made by analyzing mutant and transgenic animals. However, it had been difficult to elucidate whether the placental defects observed in such animals originate from the placenta itself or from the fetus, as both placental and fetal genomes are modified. Therefore strategies to modify the placental genome without affecting the "fetal genome" had been needed...
September 28, 2017: Placenta
Sheli R Radoshitzky, Veronica Soloveva, Dima Gharaibeh, Jens H Kuhn, Sina Bavari
The majority of viruses causing hemorrhagic fever in humans are Risk Group 3 or 4 pathogens and, therefore, can only be handled in biosafety level 3 or 4 (BSL-3/4) containment laboratories. The restricted number of such laboratories, the substantial financial requirements to maintain them, and safety concerns for the laboratory workers pose formidable challenges for rapid medical countermeasure discovery and evaluation. BSL-2 surrogate systems are a less challenging, cheap, and fast alternative to the use of live high-consequence viruses for dissecting and targeting individual steps of viral lifecycles with a diminished threat to the laboratory worker...
2018: Methods in Molecular Biology
Daniel Esau
In 1964, Epstein, Barr, and Achong published a report outlining their discovery of viral particles in lymphoblasts isolated from a patient with Burkitt lymphoma. The Epstein-Barr virus (EBV) was the first human cancer virus to be described, and its discovery paved the way for further investigations into the oncogenic potential of viruses. In the decades following the discovery of EBV, multinational research efforts led to the discovery of further viral causes of various human cancers. Lymphomas are perhaps the cancer type that is most closely associated with oncogenic viruses: infection with EBV, human T-lymphotropic virus 1 (HTLV-1), human immunodeficiency virus (HIV), Kaposi sarcoma-associated herpesvirus/human herpesvirus 8, and hepatitis C virus have all been associated with lymphomagenesis...
2017: Virology: Research and Treatment
Attila Szűcs, Norbert Moldován, Dóra Tombácz, Zsolt Csabai, Michael Snyder, Zsolt Boldogkői
Here, we present the complete genome sequence of a porcine endogenous retrovirus determined by Pacific Biosciences sequencing. A comparison of the genome of this isolate with those of other strains revealed the operation of a mechanism resulting in the selective accumulation of G and C bases in the viral DNA.
October 5, 2017: Genome Announcements
Eloy Gonzales-Gustavson, N Timoneda, X Fernandez-Cassi, A Caballero, J F Abril, M Buti, F Rodriguez-Frias, R Girones
Hepatitis is a general term meaning inflammation of the liver, which can be caused by a variety of viruses. However, a substantial number of cases remain with unknown aetiology. We analysed the serum of patients with clinical signs of hepatitis using a metagenomics approach to characterize their viral species composition. Four pools of patients with hepatitis without identified aetiological agents were evaluated. Additionally, one pool of patients with hepatitis E (HEV) and pools of healthy volunteers were included as controls...
2017: PloS One
Eun Ji Lee, Ji Hae Seo, Ji-Hyeon Park, Tam Thuy Lu Vo, Sunho An, Sung-Jin Bae, Hoang Le, Hye Shin Lee, Hee-Jun Wee, Danbi Lee, Young-Hwa Chung, Jeong A Kim, Myoung-Kuk Jang, Soo Hyung Ryu, Ensil Yu, Se Hwan Jang, Zee Yong Park, Kyu-Won Kim
SAM domain and HD domain containing protein 1 (SAMHD1) is a deoxynucleotide triphosphohydrolase (dNTPase) that inhibits retroviruses by depleting intracellular deoxynucleotide triphosphates (dNTPs) in non-cycling myeloid cells. Although SAMHD1 is expressed ubiquitously throughout the human body, the molecular mechanisms regulating its enzymatic activity and function in non-immune cells are relatively unexplored. Here, we demonstrate that the dNTPase activity of SAMHD1 is regulated by acetylation, which promotes cell cycle progression in cancer cells...
September 15, 2017: Oncotarget
Andrea Izquierdo-Bouldstridge, Alberto Bustillos, Carles Bonet-Costa, Patricia Aribau-Miralbés, Daniel García-Gomis, Marc Dabad, Anna Esteve-Codina, Laura Pascual-Reguant, Sandra Peiró, Manel Esteller, Matthew Murtha, Lluís Millán-Ariño, Albert Jordan
Histone H1 has seven variants in human somatic cells and contributes to chromatin compaction and transcriptional regulation. Knock-down (KD) of each H1 variant in breast cancer cells results in altered gene expression and proliferation differently in a variant specific manner with H1.2 and H1.4 KDs being most deleterious. Here we show combined depletion of H1.2 and H1.4 has a strong deleterious effect resulting in a strong interferon (IFN) response, as evidenced by an up-regulation of many IFN-stimulated genes (ISGs) not seen in individual nor in other combinations of H1 variant KDs...
August 28, 2017: Nucleic Acids Research
Christophe Penno, Romika Kumari, Pavel V Baranov, Douwe van Sinderen, John F Atkins
RNA dependent DNA-polymerases, reverse transcriptases, are key enzymes for retroviruses and retroelements. Their fidelity, including indel generation, is significant for their use as reagents including for deep sequencing. Here, we report that certain RNA template structures and G-rich sequences, ahead of diverse reverse transcriptases can be strong stimulators for slippage at slippage-prone template motif sequence 3' of such 'slippage-stimulatory' structures. Where slippage is stimulated, the resulting products have one or more additional base(s) compared to the corresponding template motif...
September 29, 2017: Nucleic Acids Research
Gkikas Magiorkinis, Aris Katzourakis, Pagona Lagiou
A retrovirus that infected our ancestors 100 million years ago became a human gene that is expressed in embryos and cancers, and can be detected in the blood of pregnant women. Accumulating evidence suggests potential roles for endogenous retroviruses in early life events, which may affect adult health.
September 21, 2017: Trends in Microbiology
Wenjing Wu, Yajun Yin, Jie Zhong, Yongjia Peng, Shuncai Li, Libin Zheng, Hong Cao, Jin Zhang
BACKGROUND: Lipoprotein lipase (LPL) deficiency is an autosomal recessive genetic disorder characterized by extreme hypertriglyceridemia, with no cure presently available. The purpose of this study was to test the possibility of using cell therapy to alleviate LPL deficiency. METHODS: The LPL coding sequence was cloned into the MSCV retrovirus vector, after which MSCV-hLPL and MSCV (empty construct without LPL coding sequence) virion suspensions were made using the calcium chloride method...
October 2, 2017: Lipids in Health and Disease
Anurag Kulkarni, Manuel Mateus, Cyrille C Thinnes, James S McCullagh, Christopher J Schofield, Graham P Taylor, Charles R M Bangham
The human retrovirus HTLV-1 causes a hematological malignancy or neuroinflammatory disease in ∼10% of infected individuals. HTLV-1 primarily infects CD4(+) T lymphocytes and persists as a provirus integrated in their genome. HTLV-1 appears transcriptionally latent in freshly isolated cells; however, the chronically active anti-HTLV-1 cytotoxic T cell response observed in infected individuals indicates frequent proviral expression in vivo. The kinetics and regulation of HTLV-1 proviral expression in vivo are poorly understood...
September 6, 2017: Cell Chemical Biology
Corinne N Simonti, Mihaela Pavlicev, John A Capra
Transposable element (TE)-derived sequences make up approximately half of most mammalian genomes, and many TEs have been co-opted into gene regulatory elements. However, we lack a comprehensive tissue- and genome-wide understanding of how and when TEs gain regulatory activity in their hosts. We evaluated the prevalence of TE-derived DNA in enhancers and promoters across hundreds of human and mouse cell lines and primary tissues. Promoters are significantly depleted of TEs in all tissues compared to their overall prevalence in the genome (P < 0...
August 14, 2017: Molecular Biology and Evolution
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