Prevalent de novo somatic mutations in superantigen genes of mouse mammary tumor viruses in the genome of C57BL/6J mice and its potential implication in the immune system

<p>Abstract</p> <p>Background</p> <p>Superantigens (SAgs) of mouse mammary tumor viruses (MMTVs) play a crucial role in T cell selection in the thymus in a T cell receptor (TCR) Vβ-specific manner and SAgs presented by B cells activate T cells in the periphery. The peripheral T cell repertoire is dynamically shaped by the steady induction of T cell tolerance against self antigens throughout the lifespan. We hypothesize that <it>de novo </it>somatic mutation of endogenous MMTV SAgs contributes to the modulation of the peripheral T cell repertoire.</p> <p>Results</p> <p>SAg coding sequences were cloned from the genomic DNAs and/or cDNAs of various tissues of female C57BL/6J mice. A total of 68 unique SAg sequences (54 translated sequences) were identified from the genomic DNAs of liver, lungs, and bone marrow, which are presumed to harbor only three endogenous MMTV loci (<it>Mtv-8</it>, <it>Mtv-9</it>, and <it>Mtv-17</it>). Similarly, 69 unique SAg sequences (58 translated sequences) were cloned from the cDNAs of 18 different tissues. Examination of putative TCR Vβ specificity suggested that some of the SAg isoforms identified in this study have Vβ specificities different from the reference SAgs of <it>Mtv-8</it>, <it>Mtv-9</it>, or <it>Mtv-17</it>.</p> <p>Conclusion</p> <p>The pool of diverse SAg isoforms, generated by <it>de novo </it>somatic mutation, may play a role in the shaping of the peripheral T cell repertoire including the autoimmune T cell population.</p

Tropism, Cytotoxicity, and Inflammatory Properties of Two Envelope Genes of Murine Leukemia Virus Type-Endogenous Retroviruses of C57BL/6J Mice

Envelope (env) proteins of certain endogenous retroviruses (ERVs) participate in various pathophysiological processes. In this study, we characterized pathophysiologic properties of two murine leukemia virus-type ERV (MuLV-ERV) env genes cloned from the ovary of C57BL/6J mice. The two env genes (named ENVOV1 and ENVOV2), with 1,926 bp coding region, originated from two MuLV-ERV loci on chromosomes 8 and 18, respectively. ENVOV1 and ENVOV2 were ~75 kDa and predominantly expressed on the cell membrane. They were capable of producing pseudotype murine leukemia virus virions. Tropism trait and infectivity of ENVOV2 were similar to the polytropic env; however, ENVOV1 had very low level of infectivity. Overexpression of ENVOV2, but not ENVOV1, exerted cytotoxic effects and induced expression of COX-2, IL-1β, IL-6, and iNOS. These findings suggest that the ENVOV1 and ENVOV2 are capable of serving as an env protein for virion assembly, and they exert differential cytotoxicity and modulation of inflammatory mediators

Genome-wide expression profiles of endogenous retroviruses in lymphoid tissues and their biological properties

AbstractEndogenous retroviruses (ERVs) constitute approximately 8–10% of the human and mouse genome. Some autoimmune diseases are attributed to the altered expression of ERVs. In this study, we examined the ERV expression profiles in lymphoid tissues and analyzed their biological properties. Tissues (spleen, thymus, and lymph nodes [axillary, inguinal, and mesenteric]) from C57BL/6J mice were analyzed for differential murine ERV (MuERV) expression by RT-PCR examination of polymorphic U3 sequences. Each tissue had a unique profile of MuERV expression. A genomic map identifying 60 putative MuERVs was established using 22 unique U3s as probes and their biological properties (primer binding site, coding potential, transcription regulatory element, tropism, recombination event, and integration age) were characterized. Interestingly, 12 putative MuERVs retained intact coding potentials for all three polypeptides essential for virus assembly and replication. We suggest that MuERV expression is differentially regulated in conjunction with the transcriptional environment of individual lymphoid tissues

Genome-wide changes in expression profile of murine endogenous retroviruses (MuERVs) in distant organs after burn injury

<p>Abstract</p> <p>Background</p> <p>Previous studies have shown that burn-elicited stress signals alter expression of certain murine endogenous retroviruses (MuERVs) in distant organs of mice. These findings suggest that MuERVs may participate in a network of pathophysiologic events during post-burn systemic response. To gain a better understanding of the biological roles of MuERVs in post-burn systemic response, we examined the genome-wide changes in the MuERV expression profiles in distant organs and the biological properties of the putative-burn related MuERVs were characterized.</p> <p>Results</p> <p>Female C57BL/6J mice were subjected to an approximately 18 % total body surface area flame burn and tissues (liver, lung, and kidney) were harvested at 3 hours and 24 hours after injury. The changes in the MuERV expression profiles in these tissues were examined by RT-PCR using a primer set flanking the non-ecotropic MuERV U3 promoter region within the 3' long terminal repeat. There were differential changes in the expression profiles of MuERV U3 regions after injury in all three tissues examined. Subsequently, a total of 31 unique U3 promoter sequences were identified from the tissues of both burn and no burn mice. An analysis of viral tropisms revealed that putative MuERVs harboring these U3 promoter sequences were presumed to be either xenotropic or polytropic. Some putative transcription regulatory elements were present predominantly in U3 promoter sequences isolated from burn and no burn mice, respectively. In addition, <it>in silico </it>mapping using these U3 sequences as a probe against the mouse genome database identified 59 putative MuERVs. The biological properties (coding potentials for retroviral polypeptides, primer binding sites, tropisms, branching ages, recombination events, and neighboring host genes) of each putative MuERV were characterized. In particular, 16 putative MuERVs identified in this study retained intact coding potentials for all three retroviral polypeptides (<it>gag, pol</it>, and <it>env</it>). None of the putative MuERVs identified in this study were mapped to the coding sequences of host genes.</p> <p>Conclusion</p> <p>In this study, we identified and characterized putative MuERVs whose expression might be altered in response to burn-elicited systemic stress signals. Further investigation is needed to understand the role of these MuERVs in post-burn systemic pathogenesis, in particular, via characterization of their interaction with host genes, MuERV gene products, and viral activities.</p

Facile synthesis of NiAl layered double hydroxide nanoplates for high-performance asymmetric supercapacitor

Layered double hydroxide (LDH) is a promising electrode material for supercapacitor owing to its versatility in compositions, high theoretical capacitance, environmental benignity, and low cost. However, capacity fading of LDH hinders its application in energy storage. Herein, we develop a facile approach to synthesize NiAl-LDH nanoplates possessing high electrochemical activity and desirable morphology to improve ion diffusion kinetics and reduce charge transfer resistance, leading to enhanced specific capacitance compared to pristine NiAl-LDH. Scanning electron microscopy shows that the LDH nanoplates are as thin as ∼30 nm with a mean lateral dimension of ∼150 nm. The NiAl-LDH nanoplates electrode delivers remarkably high specific capacitance of 1713.2 F g−1 at 1 A g−1 and good cycling ability of 88% capacitance retention over 5000 cycles compared to only 757.1 F g−1 at 1 A g−1 and 76.4% of the pristine NiAl-LDH. An asymmetric supercapacitor (ASC) is assembled using NiAl-LDH nanoplates and graphene as positive and negative electrodes, respectively. The ASC operating at 1.4 V delivers a high specific capacitance of 125 F g−1 at 1 A g−1 with a high energy density of 34.1 Wh kg−1 at a power density of 700 W kg−1 and outstanding cyclic stability (91.8% capacitance retention after 5000 cycles)

High-performance solid-state flexible supercapacitor based on reduced graphene oxide/hierarchical core-shell Ag nanowire@NiAl layered double hydroxide film electrode

All-solid-state flexible supercapacitor (AFSC) is a promising energy storage device due to its high flexibility, security, and environmental friendliness. However, high electrical resistance and low specific capacitance of electrodes limit its application for potential portable electronic devices. In this study, we design a novel hybrid film electrode composed of reduced graphene oxide (rGO)/silver nanowire (Ag NW)@nickel aluminum layered double hydroxide (NiAl LDH; herein, GAL) possessing high electrochemical performance by using hydrothermal and vacuum filtration techniques. The Ag NW@NiAl LDH (AL) composites with hierarchical core-shell structure are utilized to increase electroactive surface area and improve electrical conductivity, while the rGO nanosheets serve as a prominent carbon material with outstanding electrical conductivity and mechanical flexibility. The freestanding GAL electrode shows high specific capacitance of 1148 F g−1 at 1 A g−1 compared with rGO/NiAl LDH (GL) of 765.2 F g−1 at 1 A g−1. Furthermore, the bind-free symmetric AFSC device is successfully prepared using GAL hybrid film as electrodes and PVA-KOH as solid-state gel electrolyte. The GAL//GAL AFSC device delivers a superior specific capacitance of 127.2 F g−1 at 1 A g−1, a high energy density of 35.75 mWh cm−3 at a power density of 1.01 W cm−3, and great cycling ability of 83.2% over 10,000 cycles at 5 A g−1. This study introduces a novel design of flexible electrode structure for advanced energy storage applications

Apoptosis and remodeling in adriamycin-induced cardiomyopathy rat model

PurposeThe mechanism for the pathogenesis of adriamycin (ADR)-induced cardiomyopathy is not yet known. Different hypotheses include the production of free radicals, an interaction between ADR and nuclear components, and a disruption in cardiac-specific gene expression. Apoptosis has also been proposed as being involved in cardiac dysfunction. The purpose of this study was to determine if apoptosis might play a role in ADR-induced cardiomyopathy.MethodsMale Sprague-Dawley rats were separated into 2 groups: the control group (C group) and the experimental group (ADR 5 mg/wk for 3 weeks through intraperitoneal injections; A group). Echocardiographic images were obtained at week 3. Changes in caspase-3, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), interleukin (IL)-6, tumor necrosis factor-α, brain natriuretic peptide (BNP), troponin I, collagen 1, and collagen 3 protein expression from the left ventricle tissues of C and A group rats were determined by Western blot.ResultsAscites and heart failure as well as left ventricular hypertrophy were noted in the A group. Ejection fraction and shortening fraction were significantly lower in the A group by echocardiography. The expression of caspase-3, Bax, IL-6, BNP, collagen 1, and collagen 3 were significantly higher in the A group as compared with the C group. Protein expression of Bcl-2 decreased significantly in the A group compared with the C group.ConclusionADR induced an upregulation of caspase-3, Bax, IL-6, and collagen, as well as a depression in Bcl-2. Thus, apoptosis and fibrosis may play an important role in ADR-induced cardiomyopathy

Synthesis of Eu-doped (Gd,Y) 2 O 3 transparent optical ceramic scintillator

A novel process for transparent oxide ceramic scintillator with a composition of Gd 1.94-x Y x Eu 0.06 O 3 was developed. The process consists of a glycine-nitrate combustion synthesis of nano-sized starting powder and subsequent controlled sintering and annealing steps. The organic molecules remaining in the as-combusted powder were efficiently removed by the combined heat-treatment at vacuum and air atmospheres. Hot-pressed ceramic scintillators show transparent optical state and high light output. Transparent optical ceramic scintillator with a high content of Gd (up to 80 mol%) was fabricated by the process. The measured light output of Gd 1.54 Y 0.4 Eu 0.06 O 3 ceramic scintillator was about two times higher that that of CdWO 4 single crystal. In a typical radiation detection system, the scintillator plays the key role of converting the incident energy of ionizing radiation into scintillation light photons, then the emitted lights are collected by the under-laid photosensor. This specific application requires an ideal scintillator that has high light output, fast decay property, low afterglow, and so forth. Recently, a large number of new scintillator systems has been reviewed, 1 resulting, in part, with the development of a new class of scintillator: the polycrystalline ceramic scintillator