Miracle-dz/UniFAR-FTUs huggingface dataset:
Why is the 'healthy immigrant effect' different between European countries?

BACKGROUND Even if health status of immigrants constitutes an important public health issue, the literature provides contradictory results on the existence of a 'healthy migrant' effect in Europe. This study proposes to explore the heterogeneity of the health gap between migrants and natives across four European countries. DATA AND METHODS Based on several harmonized national health interview surveys, the association between migratory status and self-assessed health was firstly explored separately in Belgium, France, Spain and Italy. To explore whether differences in health gap between countries reflect differences in health status of immigrants between host countries or whether they are because of differences in health status of natives between host countries, the association between the host country and health was secondly analysed separately among a pooled sample of immigrants and one of natives, controlling for socio-economic status and country of origin. RESULTS After controlling for socio-economic status, immigrants report a poorer health status than natives in France, Belgium and Spain, whereas they report a better health status than natives in Italy, among both women and men. A North-South gradient in immigrants' health status appears: their health status is better in Italy and in Spain than in France and Belgium. Conversely, health status of natives is poorer in Italy and in Belgium than in France and in Spain. CONCLUSION Differences in health gap reflect differences in health status of both natives and immigrants between host countries. This suggests differences in health selection at migration and in immigrants' integration between European countries.
The shoulder to shoulder model-channeling medical volunteerism toward sustainable health change.

BACKGROUND Rapid growth in medical volunteerism in resource-poor countries presents an opportunity for improving global health. The challenge is to ensure that the good intentions of volunteers are channeled effectively into endeavors that generate locally acceptable, sustainable changes in health. METHODS Started in Honduras in 1990, Shoulder to Shoulder is a network of partnerships between family medicine training programs and communities in Honduras and other resource-poor countries. The program involves short-term volunteering by US health professionals collaborating with community health boards in the host countries. The program has been implemented in seven US family medicine training programs and is supported by a small international staff. RESULTS During the 16 years of program operation, more than 1,400 volunteers have made visits to host countries, which include Honduras, Ecuador, and Tanzania. Clinics have been established, school-based food programs and community-based water filtration programs developed, and cancer screening and pregnancy-care programs put in place. These and other programs have been implemented on a budget of less than $400,000, raised through donations and small grants. CONCLUSIONS The Shoulder to Shoulder model allows health care professionals to channel short-term medical volunteerism into sustainable health partnerships with resource-poor communities. The resulting network of partnerships offers a powerful resource available to governments and foundations, poised to provide innovative interventions and cost-effective services directly to poor communities.
The Interaction of Heparin Tetrasaccharides with Chemokine CCL5 Is Modulated by Sulfation Pattern and pH*

Background: Chemokine-glycosaminoglycan (GAG) binding regulates leukocyte migration. Results: Heparin tetrasaccharides are examined for their ability to inhibit CCL5-CCR1 binding, and key interactions between the heparin fragments and CCL5 are identified. Conclusion: Binding modes and inhibitory capabilities depend on the extent and pattern of sulfation of the heparin fragments. Significance: Inhibition of CCL5-CCR1 binding requires heparin to interact with specific residues on the CCL5 surface. Interactions between chemokines such as CCL5 and glycosaminoglycans (GAGs) are essential for creating haptotactic gradients to guide the migration of leukocytes into inflammatory sites, and the GAGs that interact with CCL5 with the highest affinity are heparan sulfates/heparin. The interaction between CCL5 and its receptor on monocytes, CCR1, is mediated through residues Arg-17 and -47 in CCL5, which overlap with the GAG-binding 44RKNR47 “BBXB” motifs. Here we report that heparin and tetrasaccharide fragments of heparin are able to inhibit CCL5-CCR1 binding, with IC50 values showing strong dependence on the pattern and extent of sulfation. Modeling of the CCL5-tetrasaccharide complexes suggested that interactions between specific sulfate and carboxylate groups of heparin and residues Arg-17 and -47 of the protein are essential for strong inhibition; tetrasaccharides lacking the specific sulfation pattern were found to preferentially bind CCL5 in positions less favorable for inhibition of the interaction with CCR1. Simulations of a 12-mer heparin fragment bound to CCL5 indicated that the oligosaccharide preferred to interact simultaneously with both 44RKNR47 motifs in the CCL5 homodimer and engaged residues Arg-47 and -17 from both chains. Direct engagement of these residues by the longer heparin oligosaccharide provides a rationalization for its effectiveness as an inhibitor of CCL5-CCR1 interaction. In this mode, histidine (His-23) may contribute to CCL5-GAG interactions when the pH drops just below neutral, as occurs during inflammation. Additionally, an examination of the contribution of pH to modulating CCL5-heparin interactions suggested a need for careful interpretation of experimental results when experiments are performed under non-physiological conditions.
African iron overload and hepatocellular carcinoma (HA‐7–0–080)

Abstract: Although HLA‐linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, iron overload in Africa is not thought to be etiologically related to this malignancy. To determine if African iron overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular iron. Subjects were stratified according to hepatocellular iron grades of 0–2+ (normal levels to mild siderosis; n=183) and grades of 3+ and 4+ (distinctly elevated levels consistent with iron overload; n=32). Thirty‐six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between iron overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p=0.041). The odds of hepatocellular carcinoma in subjects with iron overload was 3.1 (95% confidence interval of 1.05–9.4) times that of subjects without iron overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that iron overload may be a risk factor for hepatocellular carcinoma in Africa.
Intracellular MUC1 Peptides Inhibit Cancer Progression

Purpose: During cancer progression, the oncoprotein MUC1 binds β-catenin while simultaneously inhibiting the degradation of the epidermal growth factor receptor (EGFR), resulting in enhanced transformation and metastasis. The purpose of this study was to design a peptide-based therapy that would block these intracellular protein-protein interactions as a treatment for metastatic breast cancer. Experimental Design: The amino acid residues responsible for these interactions lie in tandem in the cytoplasmic domain of MUC1, and we have targeted this sequence to produce a MUC1 peptide that blocks the protumorigenic functions of MUC1. We designed the MUC1 inhibitory peptide (MIP) to block the intracellular interactions between MUC1/β-catenin and MUC1/EGFR. To allow for cellular uptake we synthesized MIP adjacent to the protein transduction domain, PTD4 (PMIP). Results: We have found that PMIP acts in a dominant-negative fashion, blocking both MUC1/β-catenin and MUC1/EGFR interactions. In addition, PMIP induces ligand-dependent reduction of EGFR levels. These effects correspond to a significant reduction in proliferation, migration, and invasion of metastatic breast cancer cells in vitro, and inhibition of tumor growth and recurrence in an established MDA-MB-231 immunocompromised (SCID) mouse model. Importantly, PMIP also inhibits genetically driven breast cancer progression, as injection of tumor-bearing MMTV-pyV mT transgenic mice with PMIP results in tumor regression and a significant inhibition of tumor growth rate. Conclusions: These data show that intracellular MUC1 peptides possess significant antitumor activity and have important clinical applications in the treatment of cancer.
Clinical implications of expression of ETS‐1 in relation to angiogenesis in ovarian cancers

ETS‐1 has been identified as a transcription factor involved in tumor angiogenesis, which is essential for the growth, invasion, and metastasis of solid tumors. This result prompted us to study whether ETS‐1 works as an angiogenic mediator in ovarian cancers. Immunohistochemical staining revealed that ETS‐1 was expressed in vascular endothelial cells and in cancer cells of ovarian cancers. There was a significant correlation between microvessel counts and both ETS‐1 histoscores and ets‐1 mRNA levels in ovarian cancers. Both ETS‐1 histoscores and ets‐1 mRNA levels increased with the progression of ovarian cancers. Furthermore, the 24‐month survival rate of 30 patients with high ets‐1 (high ETS‐1 histoscores and high ets‐1 mRNA levels) was 30%, while that of 30 other patients with low ets‐1 (low ETS‐1 histoscores and ets‐1 mRNA levels) was 70%. There was a significant difference between the 24‐month survival rates of the 30 patients with high ets‐1 and the 30 with low ets‐1. This indicates that ETS‐1 might act as an angiogenic mediator in, and be a prognostic factor for, ovarian cancers.
The Assessment of the Symmetric and Asymmetric Effects of Exchange Rate Volatility on the Flow of Iranian-Chinese Industrial Trade

The exchange rate is important because of the interaction with other internal and external variables and exchange ratevolatility will have important economic implications. The relationship between exchange rate volatility and trade flows is one of the important issues in international economics. The effect of increasing the exchange rate volatility on trade flows may be different from the decrease of exchange rate volatility on trade, so the main objective of this research is to evaluate the symmetric and asymmetric effects of exchange rate volatility on industrial trade flows in Iran. In this research, the symmetric and asymmetric effects of exchange rate volatility on Iran's export and import industries (for the 9 export industries to China and 12 industries imported from China) are estimated in the years 2016-1992. Linear ARDL has been used to evaluate the symmetric effects and nonlinear ARDL approach has been used to evaluate the asymmetric effects. The results show that out of the 21 industries, almost half of the imported and exported industries have asymmetric effects of exchange rate volatility surveyed. The results of this study show that the asymmetric effects vary by industry. Also, most of the investigated industries in this study use the exchange rate volatility as a factor for profitability and, despite volatility in exchange rates, increase their business. Therefore, this research is confirmed in most of the approved surveyed industries the risk theory is a portfolio.
Effect of renal nerve stimulation, renal blood flow and adrenergic blockade on plasma renin activity in the cat

1. The effect of electrical stimulation of the distal cut ends of the renal nerves of unilaterally nephrectomized, anaesthetized cats was studied. Using stimulation parameters of 15 pulses per second (pps), 15 V and 0·2 msec duration, there was an immediate sharp drop in renal blood flow, as determined by an electromagnetic flowmeter, which was maintained for about 2 min. Flow gradually returned to control values over approximately the next 10 min in spite of continued stimulation for up to 30 min.
Treml4, an Ig Superfamily Member, Mediates Presentation of Several Antigens to T Cells In Vivo, Including Protective Immunity to HER2 Protein

Members of the triggering expressed on myeloid cells (Trem) receptor family fine-tune inflammatory responses. We previously identified one of these receptors, called Treml4, expressed mainly in the spleen, as well as at high levels by CD8α+ dendritic cells and macrophages. Like other Trem family members, Treml4 has an Ig-like extracellular domain and a short cytoplasmic tail that associates with the adaptor DAP12. To follow up on our initial results that Treml4-Fc fusion proteins bind necrotic cells, we generated a knockout mouse to assess the role of Treml4 in the uptake and presentation of dying cells in vivo. Loss of Treml4 expression did not impair uptake of dying cells by CD8α+ dendritic cells or cross-presentation of cell-associated Ag to CD8+ T cells, suggesting overlapping function between Treml4 and other receptors in vivo. To further investigate Treml4 function, we took advantage of a newly generated mAb against Treml4 and engineered its H chain to express three different Ags (i.e., OVA, HIV GAGp24, and the extracellular domain of the breast cancer protein HER2). OVA directed to Treml4 was efficiently presented to CD8+ and CD4+ T cells in vivo. Anti–Treml4-GAGp24 mAbs, given along with a maturation stimulus, induced Th1 Ag-specific responses that were not observed in Treml4 knockout mice. Also, HER2 targeting using anti-Treml4 mAbs elicited combined CD4+ and CD8+ T cell immunity, and both T cells participated in resistance to a transplantable tumor. Therefore, Treml4 participates in Ag presentation in vivo, and targeting Ags with anti-Treml4 Abs enhances immunization of otherwise naive mice.
The Small Ubiquitin-like Modifier (SUMO) Protein Modification System in Arabidopsis

Smallubiquitin-like modifier (SUMO) is a member of the superfamily of ubiquitin-like polypeptides that become covalently attached to various intracellular target proteins as a way to alter their function, location, and/or half-life. Here we show that the SUMO conjugation system operates in plants through a characterization of theArabidopsis SUMO pathway. An eight-gene family encoding the SUMO tag was discovered as were genes encoding the various enzymes required for SUMO processing, ligation, and release. A diverse array of conjugates could be detected, some of which appear to be SUMO isoform-specific. The levels of SUMO1 and -2 conjugates but not SUMO3 conjugates increased substantially following exposure of seedlings to stress conditions, including heat shock, H2O2, ethanol, and the amino acid analog canavanine. The heat-induced accumulation could be detected within 2 min from the start of a temperature upshift, suggesting that SUMO1/2 conjugation is one of the early plant responses to heat stress. Overexpression of SUMO2 enhanced both the steady state levels of SUMO2 conjugates under normal growth conditions and the subsequent heat shock-induced accumulation. This accumulation was dampened in an Arabidopsis line engineered for increased thermotolerance by overexpressing the cytosolic isoform of the HSP70 chaperonin. Taken together, the SUMO conjugation system appears to be a complex and functionally heterogeneous pathway for protein modification in plants with initial data indicating that one important function may be in stress protection and/or repair.
C-Reactive Protein Distribution and Correlates among Men and Women with Chronic Coronary Heart Disease

Background: C-reactive protein (CRP) elevated in inflammation is associated with atherosclerotic disease. We describe the distribution of CRP and its association with coronary heart disease (CHD) risk factors in a large CHD patient group. Methods: This analysis comprises 2,723 male and 256 female CHD patients, included in the Bezafibrate Infarction Prevention (BIP) study. High sensitive CRP levels were determined in frozen plasma samples. Results: CRP distribution, was normalized upon log transformation. Levels among women were higher than in men in the entire group (4.4 vs. 3.5 mg/l) and in each age group. Co-morbidities, smoking, lower education level, and use of cardiovascular drugs, were associated with elevated CRP levels in both sexes. The correlation between CRP and body mass index (BMI), insulin and glucose was stronger among women. The explained variability in CRP level was larger in women (20%) compared to men (13%). Among women, BMI explained 10% of CRP variability, whereas the contribution of each variable among men was significantly smaller. Conclusions: Among men and women with CHD, CRP level was correlated with traditional risk factors and to a lesser degree to manifestation of CHD. BMI is the main contributor to CRP variability, explained by these factors among women.
Absolute Values of Dendritic Cell Subsets in Bone Marrow, Cord Blood, and Peripheral Blood Enumerated by a Novel Method

Dendritic cells (DCs) are pivotal in inducing immunity or alternatively downregulating immune reactivity. In humans, the opposing phenotypic subsets of CD11c+/CD123− “myeloid” DCs and CD123+/CD11c− “lymphoid” DCs have been proposed to orchestrate these immune responses. In this study we determined the absolute numbers of both subsets in three resting hematopoietic tissues by employing a novel flow cytometry method, eliminating processing steps and calculations based on mononuclear cell percentages. Internal bead standards along with the cells of interest were simultaneously acquired directly from unmanipulated whole blood specimens. We found significant differences (p < 0.001) between the mean absolute numbers of CD123+/CD11c− lymphoid DCs among the three sources, with the fewest present in peripheral blood (8.2/μl), about 50% more in cord blood (12.2/μl), and fivefold more in bone marrow (40.2/μl). Cord blood and bone marrow CD11c+/CD123− myeloid DC counts did not differ from each other (23.5/μl and 28.9/μl, respectively) but peripheral blood contained significantly fewer (15.5/μl, p = 0.006). CD11c+/CD123− DCs had significantly higher surface expression of HLA‐DR (p < 0.001) in all three sources. To test for association with the DC subsets, T, B, and natural killer (NK) lymphocytes were also enumerated. In bone marrow only, significant correlations were found between the size of the CD123+/CD11c− lymphoid DC pool and NK cells (p = 0.0029) and B cells (p = 0.0033). These data support the hypothesis that a common CD123+/CD11c− DC, NK cell, and B cell progenitor is resident in marrow, and this cell may be identical to the common lymphoid progenitor previously described in mice and/or the human CD34+/Lin−/CD10+ progenitor.
Vestibular ganglion neurons survive hair cell defects in jerker, shaker, and varitint‐waddler mutants and downregulate calretinin expression

Bipolar neurons (BNs) in the vestibular ganglion (VG) connect vestibular hair cells with the central nervous system (CNS). Disturbed function and cell loss in central vestibular target areas or in the vestibular periphery involve BNs either retro‐ or anterogradely. However, the impact of central vestibular disturbances or hair cell defects on the maintenance of BNs is poorly understood. In the present study the volume of the VG, the size and total number of BNs, and the number of BNs expressing the calcium‐binding protein calretinin (Calr) were quantified stereologically in the cerebellar mutants purkinje cell degeneration (pcd/pcd), weaver (wv/wv), and Lurcher (Lc/+), and in the vestibular mutants jerker (je/je), shaker‐1 (sh/sh), and Varitint‐waddler (Va/+). In all the different mutant mice investigated the total number of BNs did not differ from that of wildtypes. In contrast, the number of Calr‐positive BNs was significantly reduced in je/je (23%) and sh/sh (33%) mutants. Reduced cell size was apparent in sh/sh mutants and the volume of the VG significantly decreased in je/je mice. Calr was virtually absent from calyx endings in the vestibular periphery of je/je, sh/sh, and Va/+ mutants, whereas in wildtypes and cerebellar mutants many calyces displayed intense Calr labeling. These results imply that the survival of BNs is apparently unaffected by the peripheral and central target defects found in the mutants investigated. Whether the decrease in Calr expression may reflect biochemical adaptations in response to input disturbances or a specific loss of large BNs is discussed. J. Comp. Neurol. 504:418–426, 2007. © 2007 Wiley‐Liss, Inc.
Purification and Characterization of a Pineapple Crown Leaf Thiol Protease

Abstract A thiol protease was isolated and purified from the crown leaf of pineapple, Ananas comosus (L.) Merr. cv. Queen, by an immunoaffinity procedure. After the purification to electrophoretic homogeneity, the enzyme was characterized with respect to some of its physico‐chemical and kinetic properties. The molecular weight of the protease (22.4–22.9 kDa), K m (97 µM) and k cat (8.8 s−1) for its esterolytic cleavage of the synthetic protease substrate N α‐CBZ‐L‐lysine p‐nitrophenyl ester, the concentration of its thiol activator L‐cysteine required for half maximal activation A 0.5 (9.9 µM), optimum pH (6.5) for its proteolytic action on azocasein, T 1/2 (60°C) for inactivation by heating the enzyme (35.5 µg protein/mL) in citrate buffer pH 6.0 for 15 min, and SH‐group content (0.98 mol/mol enzyme) were determined. Most of these physico‐chemical and kinetic properties were found to be similar to those of the already well‐characterized stem bromelain (EC 3.4.22.32). Thus, the immunoaffinity purified crown leaf protease appeared to be closely related to stem bromelain.
Multicomponent Moraxella catarrhalis outer membrane vesicles induce an inflammatory response and are internalized by human epithelial cells

Moraxella catarrhalis is an emerging human respiratory pathogen in patients with chronic obstructive pulmonary disease (COPD) and in children with acute otitis media. The specific secretion machinery known as outer membrane vesicles (OMVs) is a mechanism by which Gram‐negative pathogens interact with host cells during infection. We identified 57 proteins in M. catarrhalis OMVs using a proteomics approach combining two‐dimensional SDS‐PAGE and MALDI‐TOF mass spectrometry analysis. The OMVs contained known surface proteins such as ubiquitous surface proteins (Usp) A1/A2, and Moraxella IgD‐binding protein (MID). Most of the proteins are adhesins/virulence factors triggering the immune response, but also aid bacteria to evade the host defence. FITC‐stained OMVs bound to lipid raft domains in alveolar epithelial cells and were internalized after interaction with Toll‐like receptor 2 (TLR2), suggesting a delivery to the host tissue of a large and complex group of OMV‐attributed proteins. Interestingly, OMVs modulated the pro‐inflammatory response in epithelial cells, and UspA1‐bearing OMVs were found to specifically downregulate the reaction. When mice were exposed to OMVs, a pulmonary inflammation was clearly seen. Our findings indicate that Moraxella OMVs are highly biologically active, transport main bacterial virulence factors and may modulate the epithelial pro‐inflammatory response.