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10 recordsLinked to original sources
PubMed1991

Psychophysical measurement of spectral sensitivity and color vision in red-light-reared tree shrews (Tupaia belangeri).

The role of the spectral lighting environment on the post-natal development of spectral sensitivity and color vision was studied in tree shrews (Tupaia belangeri) that were born and reared to adulthood in cyclic red light. Normal tree shrews are dichromats, possessing short-wavelength-sensitive (SWS) and long-wavelength-sensitive (LWS) cone receptors and a small population of rods. Red-light-rearing (RLR) produced differential stimulation of the cone types by effectively eliminating photic stimulation of the SWS cones, without depriving the LWS cones. Spectral sensitivity and color vision were measured behaviorally for RLR shrews and normal shrews under different ambient light levels. Spectral sensitivity functions were deutan-like, exhibiting maxima at ca 450 and 550 nm and a minimum at 510 nm. No significant differences in spectral sensitivity were observed between RLR and control animals. Furthermore, all animals demonstrated deutan-type dichromatic color vision evidenced by their ability to discriminate monochromatic lights from equally-bright achromatic lights except for a "neutral point" near 505 nm. These results demonstrate that a population of functional SWS cones survived the lack of post-natal photic stimulation. However, RLR shrews differed from controls in that they were poorer at making chromatic/achromatic discriminations. While no severe disorganization of color vision was evident, the poorer discrimination displayed by the RLR animals is likely the result of changes in post-receptoral visual mechanisms.

Animals↗
PubMed2025

Dengue Virus Replicative-Form dsRNA Is Recognized by Both RIG-I and MDA5 to Activate Innate Immunity.

RIG-I like receptors (RLRs) are a family of cytosolic RNA sensors that sense RNA virus infection to activate innate immune response. It is generally believed that different RNA viruses are recognized by either RIG-I or MDA5, two important RLR members, depending on the nature of pathogen-associated molecular patterns (PAMPs) that are generated by RNA virus replication. Dengue virus (DENV) is an important RNA virus causing serious human diseases. Despite extensive investigations, the molecular basis of the DENV PAMP recognized by the host RLR has been poorly defined. Here, we demonstrated that the DENV infection-induced interferon response is dependent upon both RIG-I and MDA5, with RIG-I playing a predominant role. Next we purified the DENV PAMP RNA from the DENV-infected cells, and demonstrated that the purified DENV PAMP is viral full-length double-stranded RNA bearing 5'ppp modifications, likely representing the viral replicative-form RNA. Finally, we confirmed the nature of the DENV PAMP by reconstituting the viral replicative-form RNA from in vitro synthesized DENV genomic RNA. In conclusion, our work not only defined the molecular basis of the RLR-PAMP interaction during DENV infection, but also revealed the previously underappreciated recognition of a distinct moiety of the same PAMP by different RLRs in innate immunity against RNA viruses.

Interferon-Induced Helicase, IFIH1↗
PubMed1988

The effect of pyrophosphate on the reaction of myosin with 2,4,6-trinitrobenzene sulphonate.

Myosin was reacted with 2,4,6-trinitrobenzene sulphonate (TNBS) in the presence or absence of Mg-pyrophosphate. The reaction led to trinitrophenylation of lysyl residues which could be divided on the basis of the reaction into three classes: (i) two rapidly reacting lysyl residues (RLR), one residing on each head of myosin, whose rate of reaction depends on the presence of Mg-pyrophosphate; (ii) two lysyl residues which react with intermediate rate (ILR) and reside on the rod segment of myosin; and (iii) the remaining lysyl residues of myosin which react slowly with TNBS. The rate of the trinitrophenylation of RLR was followed spectrophotometrically and enzymatically, measuring an absorbance change at 345 nm, and also changes in K+ (EDTA)-, Mg2+- and Ca2+-activated ATPase activities, respectively. According to analysis of the kinetics of the reaction, Mg-pyrophosphate inhibited the rate of trinitrophenylation in both heads of myosin, not in one head only as was suggested by Miyanishi et al. (J. Biochem Tokyo 85; 1979). Myosin heads (myosin subfragment-1, S-1) were prepared by digesting myosin trinitrophenylated in the absence and presence of Mg-pyrophosphate with chymotrypsin. S-1, with trinitrophenylated RLR, was separated from non-trinitrophenylated S-1 by DEAE cellulose column chromatography. The trinitrophenylated S-1 had a high Mg2+- and a low K+(EDTA)-activated ATPase while the non-trinitrophenylated species had the usual high K+(EDTA)- and low Mg2+-ATPase activity. This results excluded the possibility suggested by Miyanishi et al., that the myosin head, which is resistant to trinitrophenylation in the presence of Mg-pyrophosphate, did not possess K+(EDTA)-activated ATPase activity. The presence of Mg-pyrophosphate during trinitrophenylation substantially affected the enzymic characteristics of the modified myosin. The myosin trinitrophenylated in the presence of Mg-pyrophosphate had a higher K+(EDTA)- and a lower Mg2+-ATPase activity. SH1 (Cys-707) also probably becomes a target of the reaction if myosin is trinitrophenylated in the presence of Mg-pyrophosphate. This is deduced from the following findings: (i) the addition of dithiothreitol after trinitrophenylation partially reversed the loss in the K+(EDTA)-ATPase activity; and (ii) the specific alkylation of the SH1 thiol by 1,5-IAEDANS prior to trinitrophenylation prevented the effect of dithiothreitol on the ATPase activity of myosin. The results indicated that Mg-pyrophosphate induced structural changes in the myosin molecule which influenced the course and possibly the target(s) of trinitrophenylation.

Adenosine Triphosphatases↗
PubMed1987

Measurement of interprotein distances in the acto-subfragment 1 rigor complex.

Using enzymatic labeling, we have conjugated the fluorescence probe dansylcadaverine (DNC) to Gln-41 of rabbit skeletal muscle actin with the intention of utilizing the dansyl chromophore as a donor in fluorescence resonance energy transfer (FRET) distance measurements. The fluorescence decay of DNC-actin was found to consist of two decay constants (8.23 and 21.2 ns) that were associated with two different but partially overlapping spectra of the dye. Three different chemical points on myosin subfragment 1 (S1) were labeled with suitable acceptors: reactive thiol 1 (SH1) and Cys-136 on LC3 were modified with tetramethylrhodamine 5- (and 6-) iodoacetamide (ITMR); Lys-83 (RLR) was derivatized with trinitrobenzenesulfonate. In the rigor complex of the two labeled proteins, fluorescence resonance energy transfer took place, the efficiency of which was 10.9, 9.28, and 3.73% for the transfer from Gln-41 to SH1, Cys-136 (LC3), and RLR, respectively. The limits of the Förster critical distance for each pair were obtained from the analysis of the polarization spectra of the donor and of the acceptors. The kappa 2(2/3) distances from actin Gln-41 to the three points on S1 were 63, 66, and greater than 37 A for SH1, Cys-136 (LC3), and RLR, respectively.

Actins↗
PubMed1989

Relationship of nocturnal bronchoconstriction to sleep stages.

The possible role of sleep stages in the pathogenesis of nocturnal asthmatic attacks is still under debate because previous studies suffered methodologic limitations that prevented the possibility of providing a clear-cut answer to the question. To evaluate the relationship of nocturnal asthma to sleep, eight asthmatics with unstable asthma (seven with history of nocturnal wheeze) and four reference subjects were submitted to all-night polysomnography, including the continuous evaluation of esophageal and supraglottic pressure (with two catheters) as well as of airflow (with a face mask), so as to derive total lung resistance, supraglottic resistance, and, by subtraction lower respiratory resistance (Rlr). Stage 3-4 was characterized by the highest peaks in Rlr and by longer episodes of bronchoconstriction; conversely, neither the onset nor the remission of the latter were specifically related to any sleep stage. Considering episodes remitted with an awakening. Stage 3-4 was marked by higher Rlr peaks than during REM sleep. We conclude that sleep plays a contributory role in the multifactorial pathogenesis of nocturnal asthma, with a higher susceptibility during slow-wave sleep, probably related to a decreased responsivity to resistive loads.

Adult↗
PubMed2026

Transcriptomic analysis provides molecular insights into the innate immune defense of Mactra veneriformis against Vibrio alginolyticus infection.

Mactra veneriformis is an economically important bivalve mollusc in China, but its aquaculture is frequently threatened by Vibrio infections, particularly Vibrio alginolyticus. To investigate the molecular immune response of M. veneriformis to V. alginolyticus, we performed RNA-seq analysis of hepatopancreatic tissues collected at 48 h post-infection, the peak mortality time point, with PBS-injected individuals used as controls. Infection with V. alginolyticus caused severe histopathological damage in the hepatopancreas and resulted in a cumulative mortality of 53.3% over 14 d, compared with 3.3% in the control group. Transcriptomic analysis identified 2623 differentially expressed genes (DEGs), including 1585 significantly up-regulated genes and 1038 down-regulated genes. KEGG enrichment analysis demonstrated that DEGs were significantly enriched in immune related and metabolism pathways, including the JAK-STAT signaling pathway, RIG-I-like receptor (RLR) signaling pathway, and cytochrome P450 (CYP450) signaling pathway. Collectively, these findings revealed candidate immune related genes (tlr3, tlr5, myd88, nfkb1, il-17d, and ifi44l), a putative TLR-MyD88-NF-κB signaling axis, and KEGG signaling pathways, including JAK-STAT, RLR and CYP450, that may be involved in the innate immune response of M. veneriformis to V. alginolyticus infection. These results provide a transcriptomic basis for understanding host-pathogen interactions in this species and highlight candidate genes and pathways for future functional validation and potential application in disease-resistance breeding.

Animals↗
PubMedDate not supplied

[Development of a new quantitative rheumatoid factor test].

A new simple identification of rheumatoid factor on nitrocellulose was developed that allows quantitative detection. Verification of the results was done by comparison with the established Waaler-Rose-Test and Latextest: Correlation coefficient of linear regression for Latextest rLR = 0.717 and for Waaler-Rose-Test rLR = 0.665; Spearman rank correlation coefficient for Latextest rs = 0.798 and for Waaler-Rose-Test rs = 0.700. The interday and intraday variations showed good results. The histograms for different patient groups showed significant distributions. The nitrocellulose-test satisfies ARA-criterium No. 6.

Adult↗
PubMed2025

Expression of intron-containing HIV-1 RNA induces NLRP1 inflammasome activation in myeloid cells.

Despite the success of antiretroviral therapy in suppressing plasma viremia in people living with human immunodeficiency virus type-1 (HIV-1), persistent viral RNA expression in tissue reservoirs is observed and can contribute to HIV-1-induced immunopathology and comorbidities. Infection of long-lived innate immune cells, such as tissue-resident macrophages and microglia may contribute to persistent viral RNA production and chronic inflammation. We recently reported that de novo cytoplasmic expression of HIV-1 intron-containing RNA (icRNA) in macrophages and microglia leads to MDA5 and MAVS-dependent innate immune sensing and induction of type I IFN responses, demonstrating that HIV icRNA is a pathogen-associated molecular pattern (PAMP). In this report, we show that cytoplasmic expression of HIV-1 icRNA also induces NLRP1 inflammasome activation and IL-1β secretion in macrophages and microglia in an RLR- and endosomal TLR-independent manner. Infection of both macrophages and microglia with either replication-competent or single-cycle HIV-1 induced IL-1β secretion, which was attenuated when cytoplasmic expression of viral icRNA was prevented. While IL-1β secretion was blocked by treatment with caspase-1 inhibitors or knockdown of NLRP1 or caspase-1 expression in HIV-infected macrophages, overexpression of NLRP1 significantly enhanced IL-1β secretion in an HIV-icRNA-dependent manner. Immunoprecipitation analysis revealed interaction of HIV-1 icRNA, but not multiply-spliced HIV-1 RNA, with NLRP1, suggesting that HIV-1 icRNA sensing by NLRP1 is sufficient to trigger inflammasome activation. Together, these findings reveal a pathway of NLRP1 inflammasome activation induced by de novo expressed HIV icRNA in HIV-infected myeloid cells.

HIV-1↗
PubMed2025

An adjuvant database for preclinical evaluation of vaccines and immunotherapeutics.

Adjuvants are immunostimulators used to enhance vaccine efficacy against infectious diseases. However, current methods for evaluating their efficacy and safety are limited, hindering large-scale screening. To address this, we developed a prototype Adjuvant Database (ADB) containing transcriptome data, generated using the same protocols as the widely used Open TG-GATEs (OTG) toxicogenomics database, covering 25 adjuvants across multiple species, organs, time points, and doses. This enabled cross-database integration of ADB and OTG. Transcriptomic patterns successfully distinguished each adjuvant regardless of organs or species. Using both databases, we built machine learning models to predict adjuvanticity and hepatotoxicity. Notably, we identified colchicine's adjuvant activity and FK565's liver toxicity through data-driven analysis. Overall, ADB combined with OTG offers a framework for transcriptomics-based, data-driven screening of adjuvant candidates.

Animals↗