Editorial: Nanomaterials for the diagnosis and therapy of viral infections

[no abstract available

CRISPR/Cas system: an emerging technology in stem cell research

The identification of new and even more precise technologies for modifying and manipulating the genome has been a challenge since the discovery of the DNA double helix. The ability to modify selectively specific genes provides a powerful tool for characterizing gene functions, performing gene therapy, correcting specific genetic mutations, eradicating diseases, engineering cells and organisms to achieve new and different functions and obtaining transgenic animals as models for studying specific diseases. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology has recently revolutionized genome engineering. The application of this new technology to stem cell research allows disease models to be developed to explore new therapeutic tools. The possibility of translating new systems of molecular knowledge to clinical research is particularly appealing for addressing degenerative diseases. In this review, we describe several applications of CRISPR/Cas9 to stem cells related to degenerative diseases. In addition, we address the challenges and future perspectives regarding the use of CRISPR/Cas9 as an important technology in the medical sciences

Control of the autophagy pathway in osteoarthritis: key regulators, therapeutic targets and therapeutic strategies

Autophagy is involved in different degenerative diseases and it may control epigenetic modifications, metabolic processes, stem cells differentiation as well as apoptosis. Autophagy plays a key role in maintaining the homeostasis of cartilage, the tissue produced by chondrocytes; its impairment has been associated to cartilage dysfunctions such as osteoarthritis (OA). Due to their location in a reduced oxygen context, both differentiating and mature chondrocytes are at risk of premature apoptosis, which can be prevented by autophagy. AutophagomiRNAs, which regulate the autophagic process, have been found differentially expressed in OA. AutophagomiRNAs, as well as other regulatory molecules, may also be useful as therapeutic targets. In this review, we describe and discuss the role of autophagy in OA focusing mainly on the control of autophagomiRNAs in OA pathogenesis and on their potential therapeutic applications

HLA-C increases HIV-1 infectivity and is associated with gp120

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Finite-temperature relativistic Landau problem and the relativistic quantum Hall effect

This paper presents a study of the free energy and particle density of the relativistic Landau problem, and their relevance to the quantum Hall effect. We study first the zero temperature Casimir energy and fermion number for Dirac fields in a 2+1-dimensional Minkowski space-time, in the presence of a uniform magnetic field perpendicular to the spatial manifold. Then, we go to the finite-temperature problem, with a chemical potential, introduced as a uniform zero component of the gauge potential. By performing a Lorentz boost, we obtain Hall's conductivity in the case of crossed electric and magnetic fields.Comment: Final version, to appear in Journal of Physics A: Mathematical and Genera

Analysis of colorectal cancers for human cytomegalovirus presence

<p>Abstract</p> <p>Background</p> <p>A possible association between human cytomegalovirus (HCMV) infection and colorectal cancer progression has been inferred by the identification in tumour tissues of HCMV antigens and specific viral DNA or RNA sequences. To further investigate the relationship between HCMV and colorectal cancers we developed qualitative and quantitative PCR assay to detect HCMV DNA in 56 formalin-fixed paraffin-embedded (FFPE) tissue samples from patients belonging to 4 different histological phenotypes: adenoma; poorly, moderately and well differentiated adenocarcinomas.</p> <p>Results</p> <p>Of the 56 FFPE tested tissue samples, 6 (11%) were positive for HCMV nested PCR amplification, and more precisely 1 (5%) of 20 cases of adenoma and 5 (21%) of 24 cases of moderately differentiated adenocarcinoma. No PCR positivity was obtained in samples from well and poorly differentiated adenocarcinomas.</p> <p>Conclusion</p> <p>Our observations suggest that there is no evidence of a direct association between HCMV and colorectal cancer. Moreover, the results obtained are not supportive of a causal role of HCMV in the processes of carcinogenesis and/or progression of colorectal cancer. However, the fact that the virus may present a "hit and run" like-mechanism and HCMV can thus only be detectable at a particular stage of a processing adenocarcinoma, suggests that a significant number of colorectal cancers might have been the subject of HCMV infection that could contribute to trigger the oncogenic differentiation. Our analysis does not exclude the possibility of HCMV infection subsequent viral clearance.</p

The emerging role of the RBM20 and PTBP1 ribonucleoproteins in heart development and cardiovascular diseases

Alternative splicing is a regulatory mechanism essential for cell differentiation and tissue organization. More than 90% of human genes are regulated by alternative splicing events, which participate in cell fate determination. The general mechanisms of splicing events are well known, whereas only recently have deep-sequencing, high throughput analyses and animal models provided novel information on the network of functionally coordinated, tissue-specific, alternatively spliced exons. Heart development and cardiac tissue differentiation require thoroughly regulated splicing events. The ribonucleoprotein RBM20 is a key regulator of the alternative splicing events required for functional and structural heart properties, such as the expression of TTN isoforms. Recently, the polypyrimidine tract-binding protein PTBP1 has been demonstrated to participate with RBM20 in regulating splicing events. In this review, we summarize the updated knowledge relative to RBM20 and PTBP1 structure and molecular function; their role in alternative splicing mechanisms involved in the heart development and function; RBM20 mutations associated with idiopathic dilated cardiovascular disease (DCM); and the consequences of RBM20-altered expression or dysfunction. Furthermore, we discuss the possible application of targeting RBM20 in new approaches in heart therapies

HTLV ANTISENSE PROTEINS ROLE IN THE NF-\u3baB MODULATION.

The retrovirus HTLV-1 is the causative agent of adult T-cell leukemia, whereas the genetically related sierotype HTLV-2 is sporadically associated with neurological diseases. The HTLV-1 genome encodes regulatory proteins, such as the oncoprotein Tax and the antisense proteins HBZ, involved into T-cells proliferation and transformation. Tax-1, HBZ, and the HTLV-2 homologs, Tax-2 and APH-2 interact with many host cell factors imparing cell signaling pathways involved in the mechanisms of survival, and proliferation, including the NF-\u3baB pathway. The aim of this study is to investigate the involvement of the regulatory proteins HBZ and APH-2 in the constitutively Tax-mediated NF-\u3baB activation. We demonstrated that HBZ and APH-2 differ in the NF-\u3baB promoter suppression. The APH-2 protein, differently from HBZ, localizes into the cytoplasm in presence of Tax, where it prevents the degradation of the inhibitor I\u3baB, hindering the nuclear translocation of p65. Unlike HBZ, we found that APH-2 interacts with the E3 ubiquitin ligase TRAF3, an upstream inhibitor of the alternative NF-\u3baB pathway. By generating a TRAF3-KO cell line applying the CRISPR/Cas9 technique, we are investigating the HBZ and APH-2 activity on the alternative NF-\u3baB cell signaling. This study may provide insight into the effect of host-viral interactions in human viral oncogenesis

HTLV-1 BASIC LEUCIN ZIPPER FACTOR AND ITS HOMOLOGOUS APH-2 IMPAIR NF-\u3baB ACTIVATION MEDIATED BY THE VIRAL ONCOPROTEIN TAX.

HTLV-1 and HTLV-2 are complex retroviruses which share a similar genomic organization but differ in their pathobiology. HTLV-1, the first human retrovirus discovered, is the causal agent of an aggressive adult T-cell leukemia, whereas HTLV-2 is associated with a few cases of neurological disease. Both virus genomes encode an oncogenic protein, Tax, required for viral replication and capable to induce cell transformation. In addition, HTLV-1 and -2 generate an antisense transcript, named HBZ and APH-2, respectively, crucial for viral infection. Comparative studies between HTLV-1 regulatory proteins, Tax-1 and HBZ, and the HTLV-2 homologs, Tax-2 and APH-2, may highlight the contribution of viral proteins to oncogenesis. The purpose of this study is to investigate the functional role of the viral regulatory proteins HBZ and APH-2 in the NF-\u3baB cell signaling, which is constitutively activated by Tax in infected cells. We demonstrated that APH-2 and HBZ differ in their suppression of the NF-\u3baB promoter activity. Unlike HBZ, the APH-2 protein is recruited by Tax in cytoplasmic structures and prevents the degradation of the inhibitor I\u3baB, impairing p65 nuclear translocation. Furthermore, we found that APH-2, but not HBZ, forms complexes with the adaptor protein TRAF3, an upstream inhibitor of the alternative NF-\u3baB pathway. We generated a TRAF3-KO cell line applying the CRISPR/Cas9 technique, which will allow us to investigate the HBZ and APH-2 role in modulating the alternative NF-\u3baB cell signaling. This study may provide insight into the effect of host-viral interactions in human viral oncogenesis

A CRISPR/Cas9 based approach to study the implication of HTLV regulatory proteins in the NF-κB modulation.

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive form of T-cell malignancy with no cure. The HTLV-1 oncoprotein Tax plays a key role in CD4+ T-cell transformation, mainly through constitutive activation of both the canonical and the alternative NF-κB pathways. The HTLV-1 basic zipper protein (HBZ), encoded by the antisense viral genome strand, plays an essential role in the oncogenic process in concert with Tax, mediating T-cell proliferation. Unlike HTLV-1, the genetically related retrovirus HTLV-2 is not associated with ATL diseases. Functional comparisons between HTLV-1 regulatory proteins, Tax-1 and HBZ, and the HTLV-2 homologs, Tax-2 and APH-2, may highlight different mechanisms of their oncogenic potential. The aim of this study is to investigate how the antisense proteins HBZ and APH-2 impaired the NF-κB pathway activation. We found that both HBZ and APH-2 antagonized the NF-κB promoter activity mediated by Tax, but not in the same extent. Analyzing the intracellular distribution of the antisense proteins, we found that APH-2 is retained in cytoplasm complexes, whereas HBZ is mainly distributed into the nucleus. We observed that in presence of APH-2 and Tax-2, the degradation of the IκB-α inhibitor was reduced. Moreover, we found that unlike HBZ, APH-2 formed complexes with an upstream inhibitor of the alternative NF-κB pathway, the TNF receptor-associated factor 3, TRAF3. We generated a TRAF3 knock-out cell line applying the CRISPR/Cas9-mediated genome editing. By luciferase assays, we showed that TRAF3 is not required for Tax mediated NFκB promoter activation. Analyses are in progress to test the inhibitory effect of the antisense HBZ and APH-2 proteins on NF-κB promoter activity in absence of TRAF3. The results of this study may contribute to clarify the effect of the alternative NF-κB viral deregulation pathway in the expression of proinflammatory genes