An NF-κB–Dependent Role for JunB in the Induction of Proinflammatory Cytokines in LPS-Activated Bone Marrow–Derived Dendritic Cells

BACKGROUND: Dendritic cells (DCs) play a key role in the induction of adaptive and memory immune responses. Upon encounter with pathogens, they undergo a complex maturation process and migrate toward lymphoid organs where they stimulate immune effector cells. This process is associated with dramatic transcriptome changes, pointing to a paramount role for transcription factors in DC activation and function. The regulation and the role of these transcription factors are however ill-defined and require characterization. Among those, AP-1 is a family of dimeric transcription complexes with an acknowledged role in the control of immunity. However, it has not been studied in detail in DCs yet. METHODOLOGY/PRINCIPAL FINDINGS: Here, we have investigated the regulation and function of one of its essential components, JunB, in primary bone marrow-derived DCs induced to maturate upon stimulation by Escherichia coli lipopolysaccharide (LPS). Our data show fast and transient NF-kappaB-dependent transcriptional induction of the junb gene correlating with the induction of the TNFalpha, IL-6, and IL-12 proinflammatory cytokines. Inhibition of JunB protein induction by RNA interference hampered the transcriptional activation of the TNF-alpha, IL-6, and IL-12p40 genes. Consistently, chromatin immunoprecipitation experiments showed LPS-inducible binding of JunB at AP-1-responsive sites found in promoter regions of these genes. Concomitant LPS-inducible NF-kappaB/p65 binding to these promoters was also observed. CONCLUSIONS/SIGNIFICANCE: We identified a novel role for JunB--that is, induction of proinflammatory cytokines in LPS-activated primary DCs with NF-kappaB acting not only as an inducer of JunB, but also as its transcriptional partner

Study of the impact of the synergic line and the strategy of conception on Ti-6Al-4V wire arc additive manufacturing process (WAAM-CMT)

In additive manufacturing, technologies based on the fusion of a metallic wire using an electric arc represent an interesting alternative to current manufacturing processes, particularly for large metal parts, thanks to higher deposition rates and lower process costs than powder or wire-laser technologies. A versatile 3D printing device using a DED-W Arc (Direct Energy Deposition by wire-arc) station to melt a metallic filler wire is developed to build titanium parts by optimizing the process parameters and control the geometrical, metallurgical and the mechanical properties of produced parts. In this study, the impact of two different CMT synergic lines on the energetic and geometric behavior of Ti-6Al-4V single deposits is highlighted. These are related to first order parameters: wire feed speed (WFS) and travel speed (TS). The results show difference on energy, geometric of deposits and different deposition regime between these two law with identical process parameters. The second part of this study focuses on the transition from single deposits to walls and blocks. By first choosing the best set of process parameters to make the construction of thin walls (composed of stacked layers), and then the research the optimal horizontal step of deposition (overlapping) for thicker constructions, results obtained made it possible to validate transition from single deposits (1D) to thick walls (3D) without any weld pool collapse or lack of fusion

Additive manufacturing of Ti6Al4V with wire laser metal deposition process

Additive manufacturing (AM) using wire as an input material is currently in full swing, with very strong growth prospects thanks to the possibility of creating large parts, with high deposition rates, but also a low investment cost compared to the powder bed fusion machines. A versatile 3D printing device using a Direct Energy Deposition Wire-Laser (DED-W Laser) with Precitec Coaxprinter station to melt a metallic filler wire is developed to build titanium parts by optimizing the process parameters. The geometrical and metallurgical of produced parts are analyzed. In the literature, several authors agree to define wire feed speed, travel speed, and laser beam power as first-order process parameters governing laser-wire deposition. This study shows the relative importance of these parameters taking separately as well as the importance of their sequencing at the start of the process. Titanium deposit are obtained with powers never explored in bibliography (up to 5 kW), and wire feed speed up to 5 m.min-1 with a complete process repeatability

Trans-activation, post-transcriptional maturation, and induction of antibodies to HERV-K (HML-2) envelope transmembrane protein in HIV-1 infection

Background Human Endogenous Retroviruses (HERVs) comprise about 8% of the human genome and have lost their ability to replicate or to produce infectious particles after having accumulated mutations over time. We assessed the kinetics of expression of HERV-K (HML-2) Envelope mRNA transcript and surface unit (SU) and transmembrane (TM) subunit proteins during HIV-1 infection. We also mapped the specificity of the humoral response to HERV-K (HML-2) Envelope protein in HIV-1 infected subjects at different stages of disease, and correlated the response with plasma viral load. Results We found that HIV-1 modified HERV-K (HML-2) Env mRNA expression, resulting in the expression of a fully N-glycosylated HERV-K (HML-2) envelope protein on the cell surface. Serological mapping of HERV-K (HML-2) envelope protein linear epitopes revealed two major immunogenic domains, one on SU and another on the ectodomain of TM. The titers of HERV-K (HML-2) TM antibodies were dramatically increased in HIV-1 infected subjects (p \u3c 0.0001). HIV-1 infected adults who control HIV-1 in the absence of therapy (“elite” controllers) had a higher titer response against TM compared to antiretroviral-treated adults (p \u3c 0.0001) and uninfected adults (p \u3c 0.0001). Conclusions These data collectively suggest that HIV-1 infection induces fully glycosylated HERV-K (HML-2) envelope TM protein to which antibodies are induced. These anti-HERV-K (HML-2) TM antibodies are a potential marker of HIV-1 infection, and are at higher titer in elite controllers. HERV-K (HML-2) envelope TM protein may be a new therapeutic target in HIV-1 infection

Le Forum, Vol. 41 No. 1

https://digitalcommons.library.umaine.edu/francoamericain_forum/1090/thumbnail.jp

Invest Ophthalmol Vis Sci

PURPOSE. Albinism is a group of genetic disorders that includes several conditions related to a defect in melanin production. There is a broad phenotypic and genotypic variability between the different forms. The aim of this study was to assess the ophthalmologic characteristics according to patients' genotypes in a cohort followed in the Reference Center for oculocutaneous albinism (OCA) of Bordeaux University Hospital, France.METHODS. A retrospective observational study was conducted in a cohort of patients with OCA seen in consultation in the ophthalmology department between 2017 and 2021 in whom a genetic analysis was performed.RESULTS. In total, 127 patients with OCA were included in this study and matched with the results of the genetic analysis. In the population aged over 6 years, there was no statistical difference in binocular visual acuity between the OCA1, OCA2, and OCA4 forms (P = 0.27). There was difference in ametropia between the three forms (P = 0.003). A twoby-two comparison using the Bonferroni correction showed a significant difference in ametropia between the OCA2 and OCA4 forms (P = 0.007) and between the OCA1 and OCA2 forms (P = 0.0075). Regardless of the form, most patients (75.4%) had grade 4 foveal hypoplasia. There was no association between the grade of foveal hypoplasia and the gene involved (P = 0.87).CONCLUSIONS. We described a genotype-phenotype correlation for the three most represented forms of albinism in our cohort. This study allowed assessing the degree of visual deficiency in young children with OCA

A study of lambda Bootis type stars in the wavelength region beyond 7000A

The group of lambda Bootis type stars comprises late B- to early F-type, Population I objects which are basically metal weak, in particular the Fe group elements, but with the clear exception of C, N, O and S. One of the theories to explain the abundance pattern of these stars involves circumstellar or interstellar matter around the objects. Hence, we have compiled all available data from the literature of well established members of the lambda Bootis group redward of 7000A in order to find evidence for matter around these objects. Furthermore, we present unpublished ISO as well as submillimeter continuum and CO (2-1) line measurements to complete the data set. In total, measurements for 34 (26 with data redward of 20 mu m) well established lambda Bootis stars are available. There is evidence for an infrared excesses in six stars (HD 31295, HD 74873, HD 110411, HD 125162, HD 198160/1 and HD 210111) and two are doubtful cases (HD 11413 and HD 192640) resulting in a percentage of 23% (excluding the two doubtful cases). Dust models for these objects show fractional dust luminosities comparable to the Vega-type stars and slightly higher dust temperatures. ISO-SWS spectroscopy for HD 125162 and HD 192640 resulted in the detection of pure stellar HI lines ruling out an active accretion disk (as found for several Herbig Ae/Be stars) around these objects. The submillimeter measurements gave only upper limits for the line and continuum fluxes.Comment: 16 pages, 5 figures, accepted by A&

A Crucial Role for Infected-Cell/Antibody Immune Complexes in the Enhancement of Endogenous Antiviral Immunity by Short Passive Immunotherapy

Antiviral monoclonal antibodies (mAbs) represent promising therapeutics. However, most mAbs-based immunotherapies conducted so far have only considered the blunting of viral propagation and not other possible therapeutic effects independent of virus neutralization, namely the modulation of the endogenous immune response. As induction of long-term antiviral immunity still remains a paramount challenge for treating chronic infections, we have asked here whether neutralizing mAbs can, in addition to blunting viral propagation, exert immunomodulatory effects with protective outcomes. Supporting this idea, we report here that mice infected with the FrCasE murine retrovirus on day 8 after birth die of leukemia within 4–5 months and mount a non-protective immune response, whereas those rapidly subjected to short immunotherapy with a neutralizing mAb survive healthy and mount a long-lasting protective antiviral immunity with strong humoral and cellular immune responses. Interestingly, the administered mAb mediates lysis of infected cells through an antibody-dependent cell cytotoxicity (ADCC) mechanism. In addition, it forms immune complexes (ICs) with infected cells that enhance antiviral CTL responses through FcγR-mediated binding to dendritic cells (DCs). Importantly, the endogenous antiviral antibodies generated in mAb-treated mice also display the same properties, allowing containment of viral propagation and enhancement of memory cellular responses after disappearance of the administered mAb. Thus, our data demonstrate that neutralizing antiviral mAbs can act as immunomodulatory agents capable of stimulating a protective immunity lasting long after the end of the treatment. They also show an important role of infected-cells/antibody complexes in the induction and the maintenance of protective immunity through enhancement of both primary and memory antiviral T-cell responses. They also indicate that targeting infected cells, and not just viruses, by antibodies can be crucial for elicitation of efficient, long-lasting antiviral T-cell responses. This must be considered when designing antiviral mAb-based immunotherapies

Les ostraca de Lakis conservés à Londres

Michaud Henri. Les ostraca de Lakis conservés à Londres . In: Syria. Tome 34 fascicule 1-2, 1957. pp. 39-60