Nuclear factor-kappa B localization and function within intrauterine tissues from term and preterm labor and cultured fetal membranes

Abstract Background The objective of this study was to quantify the nuclear localization and DNA binding activity of p65, the major transactivating nuclear factor-kappa B (NF-kappaB) subunit, in full-thickness fetal membranes (FM) and myometrium in the absence or presence of term or preterm labor. Methods Paired full-thickness FM and myometrial samples were collected from women in the following cohorts: preterm no labor (PNL, N = 22), spontaneous preterm labor (PTL, N = 21), term no labor (TNL, N = 23), and spontaneous term labor (STL, N = 21). NF-kappaB p65 localization was assessed by immunohistochemistry, and DNA binding activity was evaluated using an enzyme-linked immunosorbent assay (ELISA)-based method. Results Nuclear p65 labeling was rare in amnion and chorion, irrespective of clinical context. In decidua, nuclear p65 labeling was greater in the STL group relative to the TNL cohort, but there were no differences among the TNL, PTL, and PNL cohorts. In myometrium, diffuse p65 nuclear labeling was significantly associated with both term and preterm labor. There were no significant differences in ELISA-based p65 binding activity in amnion, choriodecidual, and myometrial specimens in the absence or presence of term labor. However, parallel experiments using cultured term fetal membranes demonstrated high levels of p65-like binding even the absence of cytokine stimulation, suggesting that this assay may be of limited value when applied to tissue specimens. Conclusions These results suggest that the decidua is an important site of NF-kappaB regulation in fetal membranes, and that mechanisms other than cytoplasmic sequestration may limit NF-kappaB activation prior to term

Synthetic RNA Silencing of Actinorhodin Biosynthesis in Streptomyces coelicolor A3(2)

We demonstrate the first application of synthetic RNA gene silencers in Streptomyces coelicolor A3(2). Peptide nucleic acid and expressed antisense RNA silencers successfully inhibited actinorhodin production. Synthetic RNA silencing was target-specific and is a new tool for gene regulation and metabolic engineering studies in Streptomyces.Peer reviewe

Depressive symptoms and smoking among young Turkish and Moroccan ethnic minority groups in the Netherlands: a cross-sectional study

ABSTRACT: BACKGROUND: Although evidence indicates a strong association between depressive symptoms and smoking among host and migrant adults, less is known about this relationship among young ethnic minority groups in Europe. This paper aims to assess the relationship between depressive symptoms and smoking among young Turkish and Moroccan migrants in the Netherlands. METHODS: Multiple logistic regression analyses was used to analyze cross-sectional data from a sample of 364 Turkish and Moroccan migrants aged 15 to 24 years. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to measure the presence of clinically significant depressive symptoms. Smoking behavior was measured by a number of questions. RESULTS: Of the respondents, 22% were smokers and 33% had depressive symptoms. The prevalence of depressive symptoms was significantly higher in smokers (42.9%) than in nonsmokers (29.5%). Respondents with depressive symptoms had increased odds of smoking even after adjusting for socioeconomic and cultural factors (OR = 2.68, 95% CI = 1.45-4.97). CONCLUSIONS: Depressive symptoms were significantly associated with smoking behavior in young Turkish and Moroccan migrants. In addition to other acknowledged factors, depressive symptoms should also be considered in relation to the smoking behavior of this group. Intervention programs for smoking behavior should take depressive symptoms into account for young Turkish and Moroccan migrant

Health-related characteristics and preferred methods of receiving health education according to dominant language among Latinos Aged 25 to 64 in a large Northern California health plan

<p>Abstract</p> <p>Background</p> <p>Latinos are a fast growing segment of the U.S. health care population. Acculturation factors, including English fluency, result in an ethnic group heterogeneous with regard to SES, health practices, and health education needs. This study examined how demographic and health-related characteristics of Spanish-dominant (SD), Bilingual (BIL), and English-dominant (ED) Latino men and women aged 25–64 differed among members of a large Northern California health plan.</p> <p>Methods</p> <p>This observational study was based on data from cohorts of 171 SD (requiring an interpreter), 181 BIL, and 734 ED Latinos aged 25–64 who responded to random sample health plan member surveys conducted 2005–2006. Language groups were compared separately by gender on education, income, behavioral health risks (smoking, obesity, exercise frequency, dietary practices, health beliefs), health status (overall health and emotional health, diabetes, hypertension, high cholesterol, heartburn/acid reflux, back pain, depression), computer and Internet access, and health education modality preferences.</p> <p>Results</p> <p>Compared with ED Latinos, higher percentages of the SD and BIL groups had very low educational attainment and low income. While groups were similar in prevalence of diabetes, hypertension, and high cholesterol, SD were less likely than ED Latinos to rate overall health and emotional well-being as good, very good, or excellent and more likely to report heartburn and back pain (women only). The groups were similar with regard to smoking and obesity, but among women, SD were more likely to be physically inactive than ED, and BIL were less likely than SD and ED groups to eat <3 servings of fruit/vegetables per day. SD and BIL of both genders were significantly less likely than ED Latinos to believe that health practices had a large impact on health. Compared to ED men and women, SD and BIL Latinos had significantly lower Internet and computer access. As a result, SD Latinos had a greater preference for lower technology health education modalities such as videos and taped phone messages.</p> <p>Conclusion</p> <p>There are important differences among Latinos of different English language proficiency with regard to education, income, health status, health behaviors, IT access, and health education modality preferences that ought to be considered when planning and implementing health programs for this growing segment of the U.S. population.</p

Reliability of orthostatic beat-to-beat blood pressure tests: implications for population and clinical studies

Objective: To assess the test–retest reliability of orthostatic beat-to-beat blood pressure responses to active standing and related clinical definitions of orthostatic hypotension. Methods: A random sample of community-dwelling older adults from the pan-European Survey of Health, Ageing and Retirement in Europe, Ireland underwent a health assessment that mimicked that of the Irish Longitudinal Study on Ageing. An active stand test was performed using continuous blood pressure measurements. Participants attended a repeat assessment 4–12 weeks after the initial measurement. A mixed-effects regression model estimated the reliability and minimum detectable change while controlling for fixed observer and time of day effects. Results: A total of 125 individuals underwent repeat assessment (mean age 66.2 ± 7.5 years; 55.6% female). Mean time between visits was 84.3 ± 23.3 days. There was no significant mean difference in heart rate or blood pressure recovery variables between the first and repeat assessments. Minimum detectable change was noted for changes from resting values in systolic blood pressure (26.4 mmHg) and diastolic blood pressure (13.7 mmHg) at 110 s and for changes in heart rate (10.9 bpm) from resting values at 30 s after standing. Intra-class correlation values ranged from 0.47 for nadir values to 0.80 for heart rate and systolic blood pressure values measured 110 s after standing. Conclusion: Continuous orthostatic beat-to-beat blood pressure and related clinical definitions show low to moderate reliability and substantial natural variation over a 4–12-week period. Understanding variation in measures is essential for study design or estimating the effects of orthostatic hypotension, while clinically it can be used when evaluating longer term treatment effects

Base-Pairing Versatility Determines Wobble Sites in tRNA Anticodons of Vertebrate Mitogenomes

BACKGROUND: Vertebrate mitochondrial genomes typically have one transfer RNA (tRNA) for each synonymous codon family. This limited anticodon repertoire implies that each tRNA anticodon needs to wobble (establish a non-Watson-Crick base pairing between two nucleotides in RNA molecules) to recognize one or more synonymous codons. Different hypotheses have been proposed to explain the factors that determine the nucleotide composition of wobble sites in vertebrate mitochondrial tRNA anticodons. Until now, the two major postulates--the "codon-anticodon adaptation hypothesis" and the "wobble versatility hypothesis"--have not been formally tested in vertebrate mitochondria because both make the same predictions regarding the composition of anticodon wobble sites. The same is true for the more recent "wobble cost hypothesis". PRINCIPAL FINDINGS: In this study we have analyzed the occurrence of synonymous codons and tRNA anticodon wobble sites in 1553 complete vertebrate mitochondrial genomes, focusing on three fish species with mtDNA codon usage bias reversal (L-strand is GT-rich). These mitogenomes constitute an excellent opportunity to study the evolution of the wobble nucleotide composition of tRNA anticodons because due to the reversal the predictions for the anticodon wobble sites differ between the existing hypotheses. We observed that none of the wobble sites of tRNA anticodons in these unusual mitochondrial genomes coevolved to match the new overall codon usage bias, suggesting that nucleotides at the wobble sites of tRNA anticodons in vertebrate mitochondrial genomes are determined by wobble versatility. CONCLUSIONS/SIGNIFICANCE: Our results suggest that, at wobble sites of tRNA anticodons in vertebrate mitogenomes, selection favors the most versatile nucleotide in terms of wobble base-pairing stability and that wobble site composition is not influenced by codon usage. These results are in agreement with the "wobble versatility hypothesis"

Expression and Cellular Immunogenicity of a Transgenic Antigen Driven by Endogenous Poxviral Early Promoters at Their Authentic Loci in MVA

CD8+ T cell responses to vaccinia virus are directed almost exclusively against early gene products. The attenuated strain modified vaccinia virus Ankara (MVA) is under evaluation in clinical trials of new vaccines designed to elicit cellular immune responses against pathogens including Plasmodium spp., M. tuberculosis and HIV-1. All of these recombinant MVAs (rMVA) utilize the well-established method of linking the gene of interest to a cloned poxviral promoter prior to insertion into the viral genome at a suitable locus by homologous recombination in infected cells. Using BAC recombineering, we show that potent early promoters that drive expression of non-functional or non-essential MVA open reading frames (ORFs) can be harnessed for immunogenic expression of recombinant antigen. Precise replacement of the MVA orthologs of C11R, F11L, A44L and B8R with a model antigen positioned to use the same translation initiation codon allowed early transgene expression similar to or slightly greater than that achieved by the commonly-used p7.5 or short synthetic promoters. The frequency of antigen-specific CD8+ T cells induced in mice by single shot or adenovirus-prime, rMVA-boost vaccination were similarly equal or marginally enhanced using endogenous promoters at their authentic genomic loci compared to the traditional constructs. The enhancement in immunogenicity observed using the C11R or F11L promoters compared with p7.5 was similar to that obtained with the mH5 promoter compared with p7.5. Furthermore, the growth rates of the viruses were unimpaired and the insertions were genetically stable. Insertion of a transgenic ORF in place of a viral ORF by BAC recombineering can thus provide not only a potent promoter, but also, concomitantly, a suitable insertion site, potentially facilitating development of MVA vaccines expressing multiple recombinant antigens

Amyloid-β aggregates activate peripheral monocytes in mild cognitive impairment

\ua9 The Author(s) 2024. The peripheral immune system is important in neurodegenerative diseases, both in protecting and inflaming the brain, but the underlying mechanisms remain elusive. Alzheimer’s Disease is commonly preceded by a prodromal period. Here, we report the presence of large Aβ aggregates in plasma from patients with mild cognitive impairment (n = 38). The aggregates are associated with low level Alzheimer’s Disease-like brain pathology as observed by 11C-PiB PET and 18F-FTP PET and lowered CD18-rich monocytes. We characterize complement receptor 4 as a strong binder of amyloids and show Aβ aggregates are preferentially phagocytosed and stimulate lysosomal activity through this receptor in stem cell-derived microglia. KIM127 integrin activation in monocytes promotes size selective phagocytosis of Aβ. Hydrodynamic calculations suggest Aβ aggregates associate with vessel walls of the cortical capillaries. In turn, we hypothesize aggregates may provide an adhesion substrate for recruiting CD18-rich monocytes into the cortex. Our results support a role for complement receptor 4 in regulating amyloid homeostasis