Birth Outcomes of Latin Americans in Two Countries with Contrasting Immigration Admission Policies: Canada and Spain

Background

We delved into the selective migration hypothesis on health by comparing birth outcomes of Latin American immigrants giving birth in two receiving countries with dissimilar immigration admission policies: Canada and Spain. We hypothesized that a stronger immigrant selection in Canada will reflect more favourable outcomes among Latin Americans giving birth in Canada than among their counterparts giving birth in Spain.

Materials and Methods

We conducted a cross-sectional bi-national comparative study. We analyzed birth data of singleton infants born in Canada (2000–2005) (N = 31,767) and Spain (1998–2007) (N = 150,405) to mothers born in Spanish-speaking Latin American countries. We compared mean birthweight at 37–41 weeks gestation, and low birthweight and preterm birth rates between Latin American immigrants to Canada vs. Spain. Regression analysis for aggregate data was used to obtain Odds Ratios and Mean birthweight differences adjusted for infant sex, maternal age, parity, marital status, and father born in same source country.

Results

Latin American women in Canada had heavier newborns than their same-country counterparts giving birth in Spain, overall [adjusted mean birthweight difference: 101 grams; 95% confidence interval (CI): 98, 104], and within each maternal country of origin. Latin American women in Canada had fewer low birthweight and preterm infants than those giving birth in Spain [adjusted Odds Ratio: 0.88; 95% CI: 0.82, 0.94 for low birthweight, and 0.88; 95% CI: 0.84, 0.93 for preterm birth, respectively].

Conclusion

Latin American immigrant women had better birth outcomes in Canada than in Spain, suggesting a more selective migration in Canada than in Spain.     

Targeting Artificial Tumor Stromal Targets for Molecular Imaging of Tumor Vascular Hypoxia

Developed and tested for many years, a variety of tumor hypoxia detection methods have been inconsistent in their ability to predict treatment outcomes or monitor treatment efficacy, limiting their present prognostic capability. These variable results might stem from the fact that these approaches are based on inherently wide-ranging global tumor oxygenation levels based on uncertain influences of necrotic regions present in most solid tumors. Here, we have developed a novel non-invasive and specific method for tumor vessel hypoxia detection, as hypoxemia (vascular hypoxia) has been implicated as a key driver of malignant progression, therapy resistance and metastasis. This method is based on high-frequency ultrasound imaging of α-pimonidazole targeted-microbubbles to the exogenously administered hypoxia marker pimonidazole. The degree of tumor vessel hypoxia was assessed in three mouse models of mammary gland carcinoma (4T1, SCK and MMTV-Wnt-1) and amassed up to 20% of the tumor vasculature. In the 4T1 mammary gland carcinoma model, the signal strength of α-pimonidazole targeted-microbubbles was on average 8-fold fold higher in tumors of pimonidazole-injected mice than in non-pimonidazole injected tumor bearing mice or non-targeted microbubbles in pimonidazole-injected tumor bearing mice. Overall, this provides proof of principle for generating and targeting artificial antigens able to be ‘created’ on-demand under tumor specific microenvironmental conditions, providing translational diagnostic, therapeutic and treatment planning potential in cancer and other hypoxia-associated diseases or conditions.     

Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus

BackgroundZika virus (ZIKV), a mosquito-borne flavivirus, is a re-emerging virus that constitutes a public health threat due to its recent global spread, recurrent outbreaks, and infections that are associated with neurological abnormalities in developing fetuses and Guillain-Barré syndrome in adults. To date, there are no approved vaccines against ZIKV infection. Various preclinical and clinical development programs are currently ongoing in an effort to bring forward a vaccine for ZIKV.Methodology/Principle findingsWe have developed a ZIKV vaccine candidate based on Virus-Like-Particles (VLPs) produced in HEK293 mammalian cells using the prM (a precursor to M protein) and envelope (E) structural protein genes from ZIKV. Transient transfection of cells via plasmid and electroporation produced VLPs which were subsequently purified by column chromatography yielding approximately 2mg/L. Initially, immunogenicity and efficacy were evaluated in AG129 mice using a dose titration of VLP with and without Alhydrogel 2% (alum) adjuvant. We found that VLP with and without alum elicited ZIKV-specific serum neutralizing antibodies (nAbs) and that titers correlated with protection. A follow-up immunogenicity and efficacy study in rhesus macaques was performed using VLP formulated with alum. Multiple neutralization assay methods were performed on immune sera including a plaque reduction neutralization test, a microneutralization assay, and a Zika virus Renilla luciferase neutralization assay. All of these assays indicate that following immunization, VLP induces high titer nAbs which correlate with protection against ZIKV challenge.Conclusions/SignificanceThese studies confirm that ZIKV VLPs could be efficiently generated and purified. Upon VLP immunization, in both mice and NHPs, nAb was induced that correlate with protection against ZIKV challenge. These studies support translational efforts in developing a ZIKV VLP vaccine for evaluation in human clinical trials.     

Characterizing dispersal patterns in a threatened seabird with limited genetic structure

Genetic assignment methods provide an appealing approach for characterizing dispersal patterns on ecological time scales, but require sufficient genetic differentiation to accurately identify migrants and a large enough sample size of migrants to, for example, compare dispersal between sexes or age classes. We demonstrate that assignment methods can be rigorously used to characterize dispersal patterns in a marbled murrelet (Brachyramphus marmoratus) population from central California that numbers approximately 600 individuals and is only moderately differentiated (F_ST～ 0.03) from larger populations to the north. We used coalescent simulations to select a significance level that resulted in a low and approximately equal expected number of type I and II errors and then used this significance level to identify a population of origin for 589 individuals genotyped at 13 microsatellite loci. The proportion of migrants in central California was greatest during winter when 83% of individuals were classified as migrants compared to lower proportions during the breeding (6%) and post‐breeding (8%) seasons. Dispersal was also biased toward young and female individuals, as is typical in birds. Migrants were rarely members of parent‐offspring pairs, suggesting that they contributed few young to the central California population. A greater number of migrants than expected under equilibrium conditions, a lack of individuals with mixed ancestry, and a small number of potential source populations (two), likely allowed us to use assignment methods to rigorously characterize dispersal patterns for a population that was larger and less differentiated than typically thought required for the identification of migrants.     

Widespread Abundance of Functional Bacterial Amyloid in Mycolata and Other Gram-Positive Bacteria

Until recently, extracellular functional bacterial amyloid (FuBA) has been detected and characterized in only a few bacterial species, including Escherichia coli, Salmonella, and the gram-positive organism Streptomyces coelicolor. Here we probed gram-positive bacteria with conformationally specific antibodies and revealed the existence of FuBA in 12 of 14 examined mycolata species, as well as six other distantly related species examined belonging to the phyla Actinobacteria and Firmicutes. Most of the bacteria produced extracellular fimbriae, sometimes copious amounts of them, and in two cases large extracellular fibrils were also produced. In three cases, FuBA was revealed only after extensive removal of extracellular material by saponification, indicating that there is integrated attachment within the cellular envelope. Spores of species in the genera Streptomyces, Bacillus, and Nocardia were all coated with amyloids. FuBA was purified from Gordonia amarae (from the cell envelope) and Geodermatophilus obscurus, and they had the morphology, tinctorial properties, and β-rich structure typical of amyloid. The presence of approximately 9-nm-wide amyloids in the cell envelope of G. amarae was visualized by transmission electron microscopy analysis. We conclude that amyloid is widespread among gram-positive bacteria and may in many species constitute a hitherto overlooked integral part of the spore and the cellular envelope.The gram-positive bacterial group mycolata (mycolic acid-containing actinomycetes) comprises a number of genera with disease-causing species, including the severely pathogenic organisms Corynebacterium diphtheriae and Mycobacterium tuberculosis. The latter species is the leading cause of death due to a single infectious agent globally (17). Furthermore, mycolata have great environmental and economical impact, since several species (e.g., Gordonia spp.) may lead to unwanted foaming in wastewater treatment plants (10, 27, 43). M. tuberculosis was recently shown to use long entangled pili (MTP) to adhere to endothelium, eventually invading and infecting human and animal tissue (1). MTP''s morphology and tinctorial properties are very similar to those of the amyloid-like curli fibrils found in Escherichia coli and Salmonella species (7), although it has not been determined whether they contain the characteristic cross-β structure with β-strands perpendicular to the long fibril axis (44). In higher organisms, amyloid occurs mainly as an aberrant product of protein misfolding in, e.g., neurodegeneration and systemic amyloidosis, but bacteria are adept at turning amyloid to good use. In addition to the two bacteria mentioned above, functional bacterial amyloid (FuBA) has also been reported for streptomycetes (8) and xanthomonads (35). These examples are only the tip of the iceberg. Our recent in situ studies using WO2 antibodies specific for the amyloid conformation (36) in conjunction with 16S rRNA-targeted oligonucleotide probes for identification of the microbes revealed that amyloid-like adhesins are widespread in many phyla in environmental biofilms (29). In view of the occurrence of potential amyloid-like fibrils in one species belonging to the mycolata and the observed link between infection by a mycolata genus (Nocardia) and neurodegenerative Parkinson''s disease (13, 25, 26, 47), we have investigated this group of bacteria more closely for the presence of amyloid. Here we show that 12 of 14 different species of mycolata, as well as 6 of 6 other gram-positive bacteria, harbor amyloid. Furthermore, in some cases the amyloid can be visualized only after harsh saponification procedures which remove surrounding lipid molecules, indicating that the amyloid is deeply embedded in the cell envelope. Thus, amyloid may play a hitherto unappreciated central role in the composition of the bacterial envelope in many gram-positive bacteria.     

Mitochondrial proteomics on human fibroblasts for identification of metabolic imbalance and cellular stress

Background  

Mitochondrial proteins are central to various metabolic activities and are key regulators of apoptosis. Disturbance of mitochondrial proteins is therefore often associated with disease. Large scale protein data are required to capture the mitochondrial protein levels and mass spectrometry based proteomics is suitable for generating such data. To study the relative quantities of mitochondrial proteins in cells from cultivated human skin fibroblasts we applied a proteomic method based on nanoLC-MS/MS analysis of iTRAQ-labeled peptides.     

Genomic linkage map of the human blood fluke Schistosoma mansoni

Background  

Schistosoma mansoni is a blood fluke that infects approximately 90 million people. The complete life cycle of this parasite can be maintained in the laboratory, making this one of the few experimentally tractable human helminth infections, and a rich literature reveals heritable variation in important biomedical traits such as virulence, host-specificity, transmission and drug resistance. However, there is a current lack of tools needed to study S. mansoni's molecular, quantitative, and population genetics. Our goal was to construct a genetic linkage map for S. mansoni, and thus provide a new resource that will help stimulate research on this neglected pathogen.     

Population history and genetic structure of a circumpolar species: the arctic fox

The circumpolar arctic fox Alopex lagopus thrives in cold climates and has a high migration rate involving long-distance movements. Thus, it differs from many temperate taxa that were subjected to cyclical restriction in glacial refugia during the Ice Ages. We investigated population history and genetic structure through mitochondrial control region variation in 191 arctic foxes from throughout the arctic. Several haplotypes had a Holarctic distribution and no phylogeographical structure was found. Furthermore, there was no difference in haplotype diversity between populations inhabiting previously glaciated and unglaciated regions. This suggests current gene flow among the studied populations, with the exception of those in Iceland, which is surrounded by year-round open water. Arctic foxes have often been separated into two ecotypes: 'lemming' and 'coastal'. An analysis of molecular variance suggested particularly high gene flow among populations of the 'lemming' ecotype. This could be explained by their higher migration rate and reduced fitness in migrants between ecotypes. A mismatch analysis indicated a sudden expansion in population size around 118 000 BP, which coincides with the last interglacial. We propose that glacial cycles affected the arctic fox in a way opposite to their effect on temperate species, with interglacials leading to short-term isolation in northern refugia.  © 2005 The Linnean Society of London, Biological Journal of the Linnean Society , 2005, 84 , 79–89.     

Release from tonic inhibition of T cell activation through transient displacement of C-terminal Src kinase (Csk) from lipid rafts

In resting peripheral T cells, Csk is constitutively present in lipid rafts through an interaction with the Csk SH2-binding protein, PAG, also known as Cbp. Upon triggering of the T cell antigen receptor (TCR), PAG/Cbp is rapidly dephosphorylated leading to dissociation of Csk from lipid rafts. However, tyrosine phosphorylation of PAG/Cbp resumes after 3--5 min, at which time Csk reassociates with the rafts. Cells overexpressing a mutant Csk that lacks the catalytic domain, but displaces endogenous Csk from lipid rafts, have elevated basal levels of TCR-zeta-chain phosphorylation and spontaneous activation of an NFAT-AP1 reporter from the proximal interleukin-2 promoter as well as stronger and more sustained responses to TCR triggering than controls. We suggest that a transient release from Csk-mediated inhibition by displacement of Csk from lipid rafts is important for normal T cell activation.