The identity and activity of several anti-HIV soluble factor(s) secreted by CD8 and CD4 T lymphocytes have been determined; however, some of them still await definition. We have established an HIV-1-resistant, transformed CD4 T cell line that secretes HIV-1 resistance protein(s). Our studies indicate that this protein(s), called HIV-1 resistance factor (HRF), inhibits transcription of the virus by interfering with the activity of NF-κB. In the present report we identified the site at which HRF exerts this inhibition by evaluating a set of discrete events in NF-κB action. We tested the κB oligonucleotide binding activity in nuclei of resistant cells, nuclear translocation and binding to the HIV-1 long terminal repeat of p65 and p50 proteins from susceptible cells after exposure to HRF, and the binding of recombinant p50 to the κB oligonucleotide in vitro as affected by prior or simultaneous exposure to HRF. The results of this experimental schema indicate that HRF interacts with p50 after it enters the nucleus, but before its binding to DNA and that this interaction impedes the formation of an NF-κB-DNA complex required for the promotion of transcription. These findings suggest that HRF mediates a novel innate immune response to virus infection.
BackgroundThe combination of blue dye and radioisotope is most widely used to identify sentinel lymph nodes (SLNs) in patients with breast cancer. However, some individual studies suggested that dual tracers did not have an advantage over radioisotope alone in detecting SLNs. We performed a systematic review to investigate the added value of blue dye in addition to radioisotope.MethodsWe searched Pubmed and Embase. Prospective studies that compared the combination of radioisotope and blue dye with radioisotope alone were selected. The identification rate of SLNs and the false-negative rate were the main outcomes of interest. The odds ratios (ORs) and 95 % confidential intervals (CIs) were calculated by using random-effects model.ResultsTwenty-four studies were included. The combination of radioisotope and blue dye showed higher identification rate than radioisotope alone (OR = 2.03, 95 % CI 1.53–2.69, P < 0.05). However, no statistically significant difference was revealed for patients after neoadjuvant chemotherapy (OR = 1.64, 95 % CI 0.82–3.27, P > 0.05), or for studies with high proportion of patients with positive lymphoscintigraphy (OR = 1.41, 95 % CI 0.83–2.39, P > 0.05). Dual tracers did not significantly lower the false-negative rate compared with radioisotope alone (OR = 0.76, 95 % CI 0.44–1.29, P > 0.05).ConclusionsAlthough the combination of blue dye and radioisotope outperformed radioisotope alone in SLN detection, the superiority for dual tracers may be limited for patients with positive lymphoscintigraphy or for those after neoadjuvant chemotherapy. Besides, the combined modality did not help lower the false-negative rate.
We analyzed climate proxies from loessic-soil sections of the southern Chinese Loess Plateau. The early Holocene paleosol, S0, is 3.2 m thick and contains six sub-soil units. Co-eval soils from the central Loess Plateau are thinner (~ 1 m). Consequently higher-resolution stratigraphic analyses can be made on our new sections and provide more insight into Holocene temporal variation of the East Asian monsoon. Both summer and winter monsoon evolution signals are recorded in the same sections, enabling the study of phase relationships between the signals. Our analyses consist of (i) measurements of magnetic properties sensitive to the production of fine-grained magnetic minerals which reflect precipitation intensity and summer monsoon strength; and (ii) grain-size analyses which reflect winter monsoon strength. Our results indicate that the Holocene precipitation maximum occurred in the mid-Holocene, ~ 7.8–3.5 cal ka BP, with an arid interval at 6.3–5.3 cal ka BP. The winter monsoon intensity declined to a minimum during 5.0–3.4 cal ka BP. These results suggest that the East Asian summer and winter monsoons were out of phase during the Holocene, possibly due to their different sensitivities to ice and snow coverage at high latitudes and to sea-surface temperature at low latitudes.
BackgroundGenetic modification of plant cell walls has been implemented to reduce lignocellulosic recalcitrance for biofuel production. Plant glycoside hydrolase family 9 (GH9) comprises endo-β-1,4-glucanase in plants. Few studies have examined the roles of GH9 in cell wall modification. In this study, we independently overexpressed two genes from GH9B subclasses (OsGH9B1 and OsGH9B3) and examined cell wall features and biomass saccharification in transgenic rice plants.ResultsCompared with the wild type (WT, Nipponbare), the OsGH9B1 and OsGH9B3 transgenic rice plants, respectively, contained much higher OsGH9B1 and OsGH9B3 protein levels and both proteins were observed in situ with nonspecific distribution in the plant cells. The transgenic lines exhibited significantly increased cellulase activity in vitro than the WT. The OsGH9B1 and OsGH9B3 transgenic plants showed a slight alteration in three wall polymer compositions (cellulose, hemicelluloses, and lignin), in their stem mechanical strength and biomass yield, but were significantly decreased in the cellulose degree of polymerization (DP) and lignocellulose crystalline index (CrI) by 21–22%. Notably, the crude cellulose substrates of the transgenic lines were more efficiently digested by cellobiohydrolase (CBHI) than those of the WT, indicating the significantly increased amounts of reducing ends of β-1,4-glucans in cellulose microfibrils. Finally, the engineered lines generated high sugar yields after mild alkali pretreatments and subsequent enzymatic hydrolysis, resulting in the high bioethanol yields obtained at 22.5% of dry matter.ConclusionsOverproduction of OsGH9B1/B3 enzymes should have specific activity in the postmodification of cellulose microfibrils. The increased reducing ends of β-1,4-glucan chains for reduced cellulose DP and CrI positively affected biomass enzymatic saccharification. Our results demonstrate a potential strategy for genetic modification of cellulose microfibrils in bioenergy crops.Electronic supplementary materialThe online version of this article (10.1186/s13068-018-1351-1) contains supplementary material, which is available to authorized users.
We have recently described the molecular basis of HIV-1 resistance factor (HRF)-mediated anti-viral activity in primary and transformed CD4 T cells. HRF(+) cell culture supernatants or partially purified HRF were found to incapacitate the formation of the NF-jB/DNA complex, which is indispensable for long terminal promoter-driven transcription of virus genes. In this study, we tested whether HRF might have much broader activity against other organisms whose pathogenesis is linked to NF-jB activation. Specifically, we tested the effects of HRF on the NF-jB-mediated responses of primary macrophages to HIV-1 or several bacterial antigens. We found that exposure to HRF inhibited HIV-1 expression in macrophages and also induced the production of HRF-like activity by macrophages, which prevented replication of virus in HIV-1-infected peripheral blood lymphocytes cultured in the adjacent compartment. We investigated the mechanism of this inhibition and found that HRF impeded NF-jB/ DNA binding in macrophages induced by either HIV-1 or lipopolysaccharide from several bacteria species, resulting in impaired tumor necrosis factor-alpha responses to these organisms.
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