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PubMed2025

A study of the link between food-water insecurities and self-reported psychotic experiences among young adults in Gaza Strip: What role does social support play under conditions of war and extreme suffering?

BACKGROUND: The war in Gaza, coupled with severe restrictions on humanitarian access and assistance, have led to a rapid and large-scale exacerbation of food insecurity (FI) and water insecurity (WI) in Gaza, which can cause a myriad of deleterious effects on both physical and mental health. Previous evidence suggests that environmental stressors (such as FI and WI), coupled with lack of support, can compromise coping ability and trigger psychosis. Elucidation of these pathways can inform efforts to reduce the incidence of psychosis in war settings in particular, and in global communities more generally. This study aimed to assess the mediating role of social support on the association between food-water insecurities and psychotic experiences (PEs). METHODS: This study was carried-out over a period of one month (September 2024) by using a free online form builder. Data were collected at a single time point using snowball sampling. A total of 476 adults aged 18–35 years and living in Gaza at the time of the survey took part in this study. The Prodromal Questionnaire- Brief, the Food Insecurity Experience Scale, the Four-Item Household Water Insecurity Experiences Scale, and the Single Item Measure of Social Supports have been administered to participants. RESULTS: A total of 110 participants (23.1%) reported low tangible social support (i.e., having no or 1 person in the social support network), 27.3% were classified as moderately-to-severely food insecure and 41% were categorized as water-insecure. The mediation analysis was adjusted for the following covariates: marital status, living arrangement and age. Higher food-water insecurity experiences were significantly associated with lower social support. Higher food-water insecurity experiences were also significantly associated with higher PEs. Higher social support was significantly associated with lower PEs. The results of the mediation analysis showed that social support mediated the link of FI (indirect effect: Beta = 0.06; Boot SE = 0.03; Boot CI 0.01; 0.12) and WI (indirect effect: Beta = 0.04; Boot SE = 0.02; Boot CI 0.01; 0.08) to PEs. CONCLUSION: Our findings support the case for bolstering social support networks in war-affected communities facing survival challenges such as FI and WI. This study points to the urgent need for increased food aid and improved water supplies in the short term, and sustainable food and water systems in the long term, to support mental health. In times of war, mental health prevention and interventions strategies might do well to increase social support and resources in order to help buffer such intense environmental stressors and prevent the emergence of psychosis. CLINICAL TRIAL NUMBER: Not applicable.

Humans↗

PubMed2026

Immunological, Inflammatory, and Microbiota Determinants of Carpal Tunnel Syndrome: Evidence from Mendelian Randomization.

INTRODUCTION: Carpal Tunnel Syndrome (CTS) is a common peripheral neuropathy, and immune dysregulation and microbial dysbiosis are believed to play a role in its development. However, the cause-and-effect relationships have yet to be clarified. METHODS: Using publicly available Genome-Wide Association Study (GWAS), there are 731 immune cell phenotypes, 91 inflammatory proteins, 150 skin microbiota taxon, and 473 gut microbiota taxon based on two-sample Mendelian Randomization (MR) analysis to test whether there is a causal relationship between them and CTS. The results from the study were shown to have some degree of stability as demonstrated by various sensitivity analyses, which included running heterogeneity tests, performing MR -PRESSO, and running MR-Egger regressions. On the other hand, reverse MR was performed to verify the direction of the association. In addition, a two-step MR mediation analysis was conducted to explore whether there was a mediation effect of gut microbiota and skin microbiota, respectively, of immune and inflammatory traits on CTS. RESULTS: 22 Immune cell traits, 4 Inflammatory proteins, 18 gut microbiota taxa, and 3 skin microbiota taxa are causally associated with CTS. Reverse MR suggested feedback effects of CTS on select immune traits and gut microbiota. Mediation analysis revealed 4 gut microbiota taxa that substantially mediated immune/inflammatory effects upon CTS, with mediation rates as high as 44%; however, skin microbiota did not demonstrate any mediation. DISCUSSION: The immune dysregulation, inflammation, and the gut microbiota that cause CTS are all revealed through this research. Mendelian randomization analysis suggests that traits and inflammatory proteins of immune cells directly increase the risk of CTS, and certain types of gut microbes partially mediate these effects. Therefore, the results show a central role of the immune-gut axis in CTS pathogenesis, and suggest a systemic, rather than a local, immune-microbial interaction in disease development. CONCLUSION: We provided the first causal evidence that immune cells, inflammatory proteins, and CTS risk are causally associated with some specific taxa of gut microbiota. This contributes to a better understanding of the immune-microbiome interactions in the process of occurrence and development of CTS, and also provides theoretical support for precision prevention and treatment.

Humans↗

PubMed2004

SPSS and SAS procedures for estimating indirect effects in simple mediation models.

Researchers often conduct mediation analysis in order to indirectly assess the effect of a proposed cause on some outcome through a proposed mediator. The utility of mediation analysis stems from its ability to go beyond the merely descriptive to a more functional understanding of the relationships among variables. A necessary component of mediation is a statistically and practically significant indirect effect. Although mediation hypotheses are frequently explored in psychological research, formal significance tests of indirect effects are rarely conducted. After a brief overview of mediation, we argue the importance of directly testing the significance of indirect effects and provide SPSS and SAS macros that facilitate estimation of the indirect effect with a normal theory approach and a bootstrap approach to obtaining confidence intervals, as well as the traditional approach advocated by Baron and Kenny (1986). We hope that this discussion and the macros will enhance the frequency of formal mediation tests in the psychology literature. Electronic copies of these macros may be downloaded from the Psychonomic Society's Web archive at www.psychonomic.org/archive/.

Humans↗

PubMed2026

Retinal microstructural alterations as early phenotypes of depression in radiogenomics analysis.

BACKGROUND: With the increasing prevalence of depression, there is an urgent clinical need for early screening in depression. The retina offers a promising window for early screening in depression due to its rapid, non-invasive, objective, eye-brain correlated characteristics, but previous research has yielded conflicting alterations in retinal microstructure in depression. METHODS: We screened retinal optical coherence tomography and brain magnetic resonance imaging data in the UK Biobank to enroll 23,225 participants for retinal study of depression occurrence, and 1475 participants for the eye-brain association study. We also used genetic data (ID: ebi-a-GCST90014267 and ukb-d-20,448) from the Integrative Epidemiology Unit Open Genome-Wide Association Study for Mendelian randomization analysis. We used Cox regression to assess the association between retinal microstructure and depression risk, Mendelian randomization to infer causality, and mediation analysis to explore retina-brain pathway association. RESULTS: The Cox regression analysis showed that retinal ganglion cell-inner plexiform layer (GCIPL) thickness remained a significant predictor of depression. The Mendelian randomization analysis indicated a positive statistical association between GCIPL thickness and depression. Moreover, there was a significant positive correlation (all p < 0.001) between the volume of specific depression-related brain regions and the GCIPL thickness. Adjusting for age, sex, and head size, the mediation analysis provided preliminary evidence for a potential anatomical pathway linking retinal GCIPL thickness to depression-related brain regions through primary visual cortex and secondary visual cortex volumes. CONCLUSION: Thickened retinal GCIPL is a potential early phenotype of depression and has a potential association pathway with depression-related brain regions using a radiogenomics approach.

Humans↗

PubMed1984

The analysis of arachidonic acid metabolites in normal, uninvolved and lesional psoriatic skin.

Collection of exudate from suction bullae is a commonly used method for sampling human skin for mediator analysis. It is satisfactory on skin of normal structure but is unreliable on lesional psoriatic skin in which there are major structural changes and excessive scaling. Collection of exudates from abraded sites was found to be a suitable alternative method for psoriatic skin. Arachidonic acid and 12-HETE, but not PGE2, were significantly higher in exudate from abraded lesional psoriatic skin (494 +/- 88, 45.9 +/- 4.2 and 9.6 +/- 1.8 ng/ml respectively, mean +/- sem, n = 5) compared to uninvolved skin (154 + 38, 18.5 + 5.1 and 7.7 + 1.9 ng/ml) or skin of normal volunteers (119 +/- 37, 14.5 +/- 6.7 and 4.5 +/- 1.6 ng/ml, n = 7) which were similar. The coefficient of variation for exudate collection and mediator analysis was usually less than 55%. The analysis of lipoxygenase and cyclooxygenase products was simplified by the use of chlorobutane to extract preferentially arachidonic acid and HETEs from neutral aqueous solutions.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed2026

Genetic-epigenetic interactions (meQTLs) in orofacial clefts etiology.

Understanding how genetic variants influence disease risk through molecular mechanisms remains a central challenge in complex disease genetics. Nonsyndromic orofacial clefts (OFCs) exemplify this challenge, with most risk loci residing in non-coding regions. We hypothesized that common genetic variants influence OFC risk by modulating DNA methylation at regulatory elements through methylation quantitative trait loci (meQTLs). We analyzed 10 OFC-associated SNPs against genome-wide DNA methylation profiles in 409 cases and 456 controls, identifying 23 potential meQTLs. Findings were validated using 358 cleft-discordant sibling pairs with MethyLight assays. We performed formal mediation analysis, genotype-tissue interaction and cross-referenced with the mQTL Database to assess developmental timing. Nine meQTLs were validated, including rs987525 (8q24)-cg16561172 (MYC) (P = 9.6 × 10⁻⁶), which mapped to a mesendoderm-active enhancer upstream of MYC. Genotype × tissue interaction confirmed tissue-specificity (P = 1.00 × 10- 3), with stronger effects in oral-derived tissue (saliva). Additional validated SNP-CpG associations involved MAFB-PLCG1, NOG-PPM1E, FOXE1-FRZB, and SPRY2-LGR4. While effect sizes correlated between tissues (r = 0.81), formal mediation analysis indicated individual CpG sites do not fully mediate SNP-phenotype relationships, suggesting coordinated epigenetic mechanisms. Most associations showed peak effects during childhood, while 8q24 showed unique adult-specific patterns. We identified genetic variants influencing methylation at craniofacial regulatory elements, and provided a mechanistic link for a major risk locus, 8q24, with tissue-specific effects in saliva. While individual CpG sites did not fully mediate the genetic risk, our findings identified specific regulatory regions where coordinated epigenetic changes may contribute to OFC susceptibility.

Humans↗

PubMed2026

The role of ferroptosis in juvenile idiopathic arthritis: Causal inference and mediation by immune phenotypes.

This study employed a bidirectional 2-step, two-sample Mendelian randomization approach to investigate the causal relationships between ferroptosis-related genes and juvenile idiopathic arthritis (JIA) and to explore the mediating role of immune cells. Ferroptosis genes were identified from the deCODE database and matched with protein quantitative trait locus data as exposures to evaluate their causal effects on JIA, while immune cell traits were similarly assessed. For genes showing positive Mendelian randomization results, further analyses were conducted to determine whether immune cells mediated the effects on JIA, with mediation analysis performed only in the presence of causal associations. Data were sourced from the GWAS, FerrDb, and other public repositories. Nine ferroptosis-related genes were found to have causal links with JIA: HSPB1, DECR1, LIFR, and CTSB increased JIA risk, whereas PIEZO1, DPP4, BID, and others were protective. Forty immune cell traits were also causally associated with JIA. Mediation analysis revealed that several immune cells, including CD127- CD8+ T cells, partially mediated the genetic effects, with mediation proportions reaching up to 18.6%. Collectively, these results point to a ferroptosis-immune-JIA axis, suggesting that ferroptosis-related genes contribute to JIA pathogenesis through immune cell mediation and offering new mechanistic insights and potential therapeutic targets.

Arthritis, Juvenile↗

PubMed2026

Associations of Illness Perception, Resignation Coping, and Social Support With Self-Regulatory Fatigue in Patients With Type 2 Diabetes: A Cross-Sectional Study.

AIMS: To examine the associations among illness perception, resignation coping, social support, and self-regulatory fatigue (SRF) in patients with Type 2 diabetes mellitus. The study specifically explores whether resignation coping and social support exhibit indirect associations with SRF in the context of illness perception. DESIGN: A cross-sectional study. METHODS: From November 2024 to October 2025, a convenience sample of 302 adult patients with T2DM was recruited from a tertiary general hospital in China. Participants completed validated instruments with established psychometric properties, namely the Brief Illness Perception Questionnaire, the Medical Coping Modes Questionnaire, the Perceived Social Support Scale, and the Self-Regulatory Fatigue Scale. Statistical analyses included Spearman correlation and serial mediation analysis using the PROCESS Macro (Model 6) with bias-corrected bootstrapping. RESULTS: SRF was positively correlated with negative illness perception (r = 0.579, p < 0.01) and resignation coping (r = 0.612, p < 0.01), and negatively correlated with social support (r = -0.598, p < 0.01). Serial mediation analysis revealed that illness perception was associated with SRF through indirect pathways involving resignation coping and social support. Resignation coping and social support mediated the association between illness perception and self-regulatory fatigue, both individually and sequentially. CONCLUSIONS: Negative illness perception correlates with higher SRF. This observed correlation is additionally linked to indirect pathways involving resignation coping and lower social support. Collectively, these findings highlight a pattern of interrelated cognitive (illness perception), behavioural (resignation coping), and resource (social support) factors that are associated with self-regulatory fatigue in this cross-sectional study. IMPLICATIONS FOR THE PROFESSION: The findings offer a clear, evidence-based framework for nursing practice. They highlight the potential value of integrated assessment and intervention that simultaneously addresses patients' illness beliefs, maladaptive coping strategies, and social support systems, which are associated with lower SRF and better diabetes self-management. REPORTING METHOD: This study adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cross-sectional studies. PATIENT OR PUBLIC CONTRIBUTION: Patients participated solely as research participants by providing survey data. They were not involved in the study design, implementation, data analysis, interpretation, or manuscript preparation. All patients provided written informed consent prior to questionnaire completion.

Humans↗

PubMed2005

Rainbow trout (Oncorhynchus mykiss) brain cells biosynthesize novel docosahexaenoic acid-derived resolvins and protectins-Mediator lipidomic analysis.

Docosahexaenoic acid (DHA; C22:6 n-3) is an abundant fatty acid in fish phospholipids. In the present study, we employed liquid chromatography-ultraviolet spectrometry-tandem mass spectrometry and dissociated rainbow trout (Oncorhynchus mykiss) brain cells to determine whether fish utilize endogenous DHA to produce the recently uncovered novel lipid mediators termed the resolvins and protectins, generated by mammalian cells [Serhan CN, Hong S, Gronert K, et al. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 2002; 196:1025-37; Hong S, Gronert K, Devchand P, Moussignac R-L, Serhan, CN. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. J Biol Chem 2003;278:14677-87]. Trout brain cells biosynthesize a range of recently identified di- and tri-hydroxy-containing bioactive products from endogenous sources of DHA when challenged in vitro. We identified neuroprotectin D1, resolvin D5, resolvin D1 and resolvin D2 from trout brain cells. Each compound was identified on the basis of its characteristic physical chemical properties that included MS, MS-MS, UV spectra and chromatographic behavior. The monohydroxy products from DHA, signatures of DHA conversion by lipoxygenases, were also identified. These included both 14S-hydroxy-docosahexaenoic acid and 17S-hydroxy-docosahexaenoic acid. The biosynthesis of these novel bioactive lipid mediators, namely resolvins and protectins, by fish cells provides the first evidence for the conservation of these structures from fish to humans as chemical signals in diverse biological systems.

Animals↗

PubMed2024

The role of co-occurring conditions and genetics in the associations of eating disorders with attention-deficit/hyperactivity disorder and autism spectrum disorder.

Eating disorders (EDs) commonly co-occur with other psychiatric and neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD); however, the pattern of family history and genetic overlap among them requires clarification. This study investigated the diagnostic, familial, and genetic associations of EDs with ADHD and ASD. The nationwide population-based cohort study included all individuals born in Denmark, 1981-2008, linked to their siblings and cousins. Cox regression was used to estimate associations between EDs and ADHD or ASD, and mediation analysis was used to assess the effects of intermediate mood or anxiety disorders. Polygenic scores (PGSs) were used to investigate the genetic association between anorexia nervosa (AN) and ADHD or ASD. Significantly increased risk for any ED was observed following an ADHD or ASD diagnosis. Mediation analysis suggested that intermediate mood or anxiety disorders could account for 44%-100% of the association between ADHD or ASD and ED. Individuals with a full sibling or maternal half sibling with ASD had increased risk of AN compared to those with siblings without ASD. A positive association was found between ASD-PGS and AN risk whereas a negative association was found between AN-PGS and ADHD. In this study, positive phenotypic associations between EDs and ADHD or ASD, mediation by mood or anxiety disorder, and genetic associations between ASD-PGS and AN and between AN-PGS and ADHD were observed. These findings could guide future research in the development of new treatments that can mitigate the development of EDs among individuals with ADHD or ASD.

Humans↗

PubMed2003

Construction of a gamete-enriched gene pool and RNAi-mediated functional analysis in Dictyostelium discoideum.

Macrocysts in Dictyostelium discoideum possess prototypic features of sexual reproduction and are useful for understanding the basic mechanisms of the reproductive process. Here, we randomly analyzed 1,071 gamete cDNAs, and then constructed a gamete-specific subtraction library, FC-IC. Nucleotide sequences of all 903 FC-IC clones were determined and clustered into 272 independent genes. Expression analysis based on real-time RT-PCR revealed 67 gamete-enriched genes, among which those involved in 'signal transduction' and 'multicellular organization' are prevalent. One of them, FC-IC0003, appeared also to be mating-type specific, and was named gmsA. RNAi-mediated silencing as well as disruption of gmsA reduced the cellular competency for sexual cell fusion, indicating the involvement of this gene in the sexual development of D. discoideum.

Amino Acid Sequence↗

PubMed1990

[An analysis of mediator secretion in the active zone of the motor nerve ending].

The topography of transmitter release sites at the motor-nerve terminal of the cutaneous-pectoris frog muscle has been determined using three extracellular electrodes. It is shown that release sites are united in groups arranged transversally to the nerve endings and reflecting the transmitter release in the active zones (AZ) of the nerve terminal. The quantitative analysis of revealed groups has permitted concluding that the maximal level of secretion is at the centre of AZ, decreasing to the edge and aside from AZ. At the low extracellular Ca2+ concentration all the AZ take part in the spontaneous release process, while in the evoked one--only some of AZ. Advantages of the three-microelectrode method over the two-microelectrode one are analyzed. It is found that the transmitter secretion in spatially isolated AZ leads to the polymodality in uniquantal signal amplitude distribution at extracellular recording. The role of AZ in the transmitter release process is discussed.

Animals↗

PubMed1992

The role of insulin receptor kinase domain autophosphorylation in receptor-mediated activities. Analysis with insulin and anti-receptor antibodies.

The role of specific tyrosine autophosphorylation sites in the human insulin receptor kinase domain (Tyr1158, Tyr1162, and Tyr1163) was analyzed using in vitro mutagenesis to replace tyrosine residues individually or in combination. Each of the three single-Phe, the three possible double-Phe a triple-Phe and a triple-Ser mutant receptors, stably expressed in Chinese hamster ovary cells, were compared with the wild-type receptor in their ability to mediate stimulation of receptor kinase activity, glycogen synthesis, and DNA synthesis by insulin or the human-specific anti-receptor monoclonal antibody 83-14. At a concentration of 0.1 nM insulin which produced approximately half-maximal responses with wild-type receptor, DNA synthesis and glycogen synthesis mediated by the three single-Phe mutants ranged from 52 to 88% and from 32 to 79% of the wild-type receptor, respectively. The corresponding figures for the double-Phe mutants averaged 15 and 6%, whereas the triple-mutants were unresponsive in both assays. The level of biological function approximately paralleled the insulin-stimulated tyrosine kinase activity in the intact cell as estimated by tyrosine phosphorylation of the insulin receptor and its endogenous substrate pp 185/IRS-1. Interestingly, all mutants showed a marked decrease in insulin-stimulated receptor internalization. Anti-receptor antibody stimulated receptor kinase activity and mimicked insulin action in these cells. In general, the impairment of the metabolic response was greater and impairment of the growth response was less when antibody was the stimulus. These experiments show that the level and specific sites of autophosphorylation are critical determinants of receptor function. The data are consistent with a requirement for the receptor tyrosine kinase either as an obligatory step or a modulator, in both metabolic and growth responses, and demonstrate the important role of the level of insulin receptor kinase domain autophosphorylation in regulating insulin sensitivity.

Animals↗

PubMed1980

[Electrophysiologic analysis of mediator stores and release in smooth muscle synapses of the nictitating membrane in cats].

At the adrenergic junction of the sympathetic nerve with the medial smooth muscle of the cat nictitating membrane, blocking of the reuptake of noradrenaline with phenoxibenzamine suppressed the amplitude of rhythmic excitatory synaptic potentials. Stimulation of postganglionic sympathetic nerve (10/sec) made the time constant of the first component of the potential 60 sec whereas that of the second component--600 sec. The depression of amplitude seems to be connected with possible decrease in the noradrenaline release and partial exhaustion of its storage. The analysis of the transmitter function showed the release of noradrenaline to a single impulse to be in the reverse relation to the stimulation frequency and at 10/sec to constitute about 3 x 10(-4) (at 20/sec -1.9 X 10(-4)) of the transmitter storage. The replenishment of the transmitter (4 x 10(-6) of the initial operating pool of noradrenaline to a single impulse at 10/sec) was intensified parallel to the increased frequency of adrenergic neurons firing and was able to provide for afferent synaptic transmission within the working frequencies of the afferent part of the sympathetic reflex arch.

Animals↗

PubMed2005

Temperature-mediated heteroduplex analysis for the detection of drug-resistant gene mutations in clinical isolates of Mycobacterium tuberculosis by denaturing HPLC, SURVEYOR nuclease.

Denaturing high-performance liquid chromatography (DHPLC) is a relatively new technique, which utilizes heteroduplex formation between wild-type and mutated DNA strands to identify point mutations. Heteroduplex molecules are separated from homoduplex molecules by ion-pair, reverse-phase liquid chromatography on a special column matrix with partial heat denaturation of the DNA strands. In order to investigate the application of this method for point mutation detection in drug-resistant genes of Mycobacterium tuberculosis, katG, rpoB, embB, gyrA, pncA and rpsL genes, which are responsible for isoniazid, rifampicin, ethambutol, fluoroquinolone, pyrazinamide and streptomycin resistance, respectively, were detected by temperature-mediated DHPLC in 10 multidrug-resistant and 10 drug-susceptible clinical isolates. The DHPLC data were compared with those from a conventional MIC test. The results show that DHPLC is cost-effective with high capacity and accuracy, and is potentially useful for genotypic screening for mutations associated with anti-tuberculosis drug resistance.

Antitubercular Agents↗

PubMed1972

P22-mediated transduction analysis of the rough A (rfa) region of the chromosome of Salmonella typhimurium.

Seven temperature-sensitive rough mutants of Salmonella typhimurium were found to be sensitive to smooth-specific phages at low temperature (25 C, 30 C) and resistant or partially resistant to rough-specific phages, whereas at high temperatures (37 C, 45 C) they were resistant or partially resistant to smooth-specific phages but sensitive to rough-specific phages. These data indicate that at low temperature each strain makes lipopolysaccharide which is relatively normal, but at high temperatures O-specific side chains are not added to the lipopolysaccharide. At 45 C, these strains have the R-res-1 or R-res-2 phage sensitivity phenotype, and their genetic lesions map by P22-mediated transduction in the rfa gene cluster between cysE-pyrE, suggesting a mutation in genes with transferase functions. P22-mediated joint transduction with temperature-sensitive rfa mutants, leaky rfa mutants, and rfa P22 lysogens have shown the following order of genes in the S. typhimurium linkage map: xyl-mtlA-mtlB-cysE-rfaF-rfaG-pyrE. An rfaE allele was not jointly transduced in the cysE-pyrE segment.

Chromosome Mapping↗

PubMed2005

In vivo DNase I-mediated footprinting analysis along the human bradykinin B1 receptor (BDKRB1) gene promoter: evidence for cell-specific regulation.

By applying in vivo dimethyl sulphate and UV light type C-footprinting analysis, we previously showed that specific DNA sequences in the -1349/+42 core promoter region of the inducible human BDKRB1 (bradykinin B1 receptor) gene correlated with its transcriptional activity. In the present study we used the highly sensitive DNase I in vivo footprinting approach to delineate more precisely the functional domains of the BDKRB1 gene promoter in human SMCs (smooth muscle cells). Human lymphocytes that do not express a functional BDKRB1 were also studied as a reference using dimethyl sulphate, UV light type C and DNase I treatments. An obvious difference was found in the DNase I-footprinting patterns between cellular systems that express a functional BDKRB1 (SMCs) in comparison with human lymphocytes, where randomly distributed nucleosome-like footprinting patterns were found in the bulk of the core promoter region studied. Gel-shift assays and expression studies pointed to the implication of the YY1 and a TBP/TFIIB (TATA-box-binding protein/transcription factor IIB) transcription factor in the regulation of BDKRB1 gene expression in SMCs and possible YY1 involvement in the mechanisms of nuclear factor kappaB-mediated regulation of the receptor expression. No significant changes in the promoter foot-printing pattern were found after treatment with interleukin-1beta or serum (known BDKRB1 gene inducers), indicating that definite regulatory motifs could exist outside the BDKRB1 gene core promoter region studied.

Base Sequence↗

PubMed1985

The role of serologically defined epitopes on mumps virus HN-glycoprotein in the induction of virus-dependent cell-mediated cytotoxicity. Analysis with monoclonal antibodies.

The importance of virus structural proteins for the induction of virus-dependent cellular cytotoxicity (VDCC) was studied by means of monoclonal antibodies raised in mice against mumps virions. Antibodies against the viral glycoprotein bearing the haemagglutination and neuraminidase activities (HN) inhibited VDCC but not the natural cytotoxicity (NK) displayed by the lymphocytes in the absence of virus. Antibodies to the fusion factor, the membrane protein or the nucleoprotein were inactive. These results confirmed our previous conclusion, that the only viral component required for VDCC induction is the HN protein. To clarify the role of this protein in VDCC further, the inhibitory activity of 13 HN-specific monoclonals, all of IgG isotype and directed against 9 distinct determinants, was studied in detail. Seven antibodies reacting with 3 different determinants of the peptide moiety of the HN protein were strongly inhibitory. The remaining antibodies, specific for 5 additional peptide epitopes, had intermediate or weak inhibitory effects. One carbohydrate specific anti-HN antibody was inactive although its antigen-binding capacity was of the same magnitude as that of a good inhibitory antibody. The anti-HN antibodies inhibited VDCC regardless of their IgG subclass. Moreover, VDCC inhibition was not correlated with the capacity of the antibodies to inhibit haemagglutination, haemolysis, neuraminidase activity, or the infectivity of the virus. These results suggest that full expression of VDCC requires the interaction of more than one of the serologically defined structures of the HN polypeptide with virus receptors on the lymphocytes and probably also on the target cells. These structures may be different at least in part from those involved in other known biological activities of the virus. Treatment of lymphocytes with virus increases both the number of target-binding cells (TBC) and the number of cytotoxic effector cells. However, when treated under conditions which gave optimal VDCC inhibition, none of the inhibitory antibodies reduced the virus-mediated increase in TBC. This indicates either that the anti-HN antibodies decreased the efficiency of effector-target cell interaction necessary for VDCC induction, or that they blocked a post-binding step required for triggering of cytotoxicity.

Animals↗