Population structure of Hispanics in the United States: the multi-ethnic study of atherosclerosis

Using ∼60,000 SNPs selected for minimal linkage disequilibrium, we perform population structure analysis of 1,374 unrelated Hispanic individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with self-identification corresponding to Central America (n = 93), Cuba (n = 50), the Dominican Republic (n = 203), Mexico (n = 708), Puerto Rico (n = 192), and South America (n = 111). By projection of principal components (PCs) of ancestry to samples from the HapMap phase III and the Human Genome Diversity Panel (HGDP), we show the first two PCs quantify the Caucasian, African, and Native American origins, while the third and fourth PCs bring out an axis that aligns with known South-to-North geographic location of HGDP Native American samples and further separates MESA Mexican versus Central/South American samples along the same axis. Using k-means clustering computed from the first four PCs, we define four subgroups of the MESA Hispanic cohort that show close agreement with self-identification, labeling the clusters as primarily Dominican/Cuban, Mexican, Central/South American, and Puerto Rican. To demonstrate our recommendations for genetic analysis in the MESA Hispanic cohort, we present pooled and stratified association analysis of triglycerides for selected SNPs in the LPL and TRIB1 gene regions, previously reported in GWAS of triglycerides in Caucasians but as yet unconfirmed in Hispanic populations. We report statistically significant evidence for genetic association in both genes, and we further demonstrate the importance of considering population substructure and genetic heterogeneity in genetic association studies performed in the United States Hispanic population.     

Overview of interleukin-2 function, production and clinical applications

The existence of interleukin (IL)-2 has been recognized for over 25 years, and it remains one of the most extensively studied cytokines. Here we present a broad overview of IL-2 history, functional activities, biological sources, regulation and applications to disease treatment. IL-2 exerts a wide spectrum of effects on the immune system, and it plays crucial roles in regulating both immune activation and homeostasis. Both IL-2 and its multipartite receptor are prototypical of the Type I receptor superfamily, and both have been exploited in numerous ways in the clinic. Despite the wealth of information generated about IL-2 from in vitro culture systems, in vivo mouse knockout models, and clinical trials in humans, fascinating new aspects of its functions in the immune system continue to emerge.     

EVOLUTION OF LEAF FORM IN MARSILEACEOUS FERNS: EVIDENCE FOR HETEROCHRONY

Using an explicit phylogenetic framework, ontogenetic patterns of leaf form are compared among the three genera of marsileaceous ferns ( Marsilea , Regnellidium , and Pilularia ) with the outgroup Asplenium to address the hypothesis that heterochrony played a role in their evolution. We performed a Fourier analysis on a developmental sequence of leaves from individuals of these genera. Principal components analysis of the harmonic coefficients was used to characterize the ontogenetic trajectories of leaf form in a smaller dimensional space. Results of this study suggest that the evolutionary juvenilization observed in these leaf sequences is best described using a mixed model of heterochrony (accelerated growth rate and early termination at a simplified leaf form). The later stages of the ancestral, more complex, ontogenetic pattern were lost in Marsileaceae, giving rise to the simplified adult leaves of Marsilea , Regnellidium , and Pilularia . Life-history traits such as ephemeral and uncertain habitats, high reproductive rates, and accelerated maturation, which are typical for marsileaceous ferns, suggest that they may be r strategists. The evidence for heterochrony presented here illustrates that it has resulted in profound ecological and morphological consequences for the entire life history of Marsileaceae.     

Gender as a determinant of responses to a self-screening questionnaire on anxiety and depression by patients with coronary artery disease

Background: Because patients with coronary artery disease (CAD) could benefit from interventions to decrease psychological distress, it is important to identify these individuals. Both salivary cortisol level and the Hospital Anxiety and Depression Scale (HADS) are recognized measures of stress/anxiety and depression.Objectives: This study was designed to determine whether there is an association between anxiety and depression, as measured by the HADS, and salivary cortisol levels among patients with CAD, and whether this association is affected by gender.Methods: All adult residents of Alberta, Canada, undergoing their first cardiac catheterization for CAD (≥50% occlusion of ≥2 coronary arteries) were eligible for participation in this study. A 14-question survey (the HADS) and 3 saliva-collection devices (a 1-day supply) were sent to the participants' home within 1 week of their initial cardiac catheterization. Participants were asked to take saliva samples for determination of cortisol levels on waking and at 30 and 60 minutes after waking, and then return the completed questionnaire and saliva samples using a prepaid express mailing envelope.Results: Seventy-one adults (52 men and 19 women) participated in the study. Mean (SD) ages were 68.4 (4.6) years for men and 69.1 (4.4) years for women. Among the women, significant negative correlations were found between the HADS anxiety score and the wake-up and 30-minute cortisol levels (higher HADS scores were associated with lower cortisol levels) (all, P < 0.05). Also among women, negative correlations were found between the HADS depression score and the salivary cortisol values, but the differences were not statistically significant. Conversely, among the men, nonsignificant positive correlations were found between the HADS anxiety scores and the salivary cortisol levels (higher HADS scores were associated with higher cortisol levels), and statistically significant positive correlations were observed between the HADS depression scores and all 3 salivary cortisol values (all, P < 0.05).Conclusions: Our findings suggest that the HADS is an appropriate screening instrument for anxiety and depression in patients with CAD. In particular, the scale appears to be sensitive for measuring anxiety in women and depression in men. When the HADS is used clinically as a screening tool, it should be examined through a “gender-based lens.”.     

Update on Best Practice Recommendations for Anesthetic Perioperative Care and Pain Management in Weight Loss Surgery, 2004–2007

To reevaluate and update evidence‐based best practice recommendations published in 2004 for anesthetic perioperative care and pain management in weight loss surgery (WLS), we performed a systematic search of English‐language literature on anesthetic perioperative care and pain management in WLS published between April 2004 and May 2007 in MEDLINE and the Cochrane Library. We identified relevant abstracts by using key words, retrieved full text articles, and stratified the resulting evidence according to systems used in established evidence‐based models. We updated prior evidence‐based best practice recommendations based upon interim literature. In instances of controversial or inadequate scientific evidence, the task force reached consensus recommendations following evaluation of the best available information and expert opinion. The search yielded 1,788 abstracts, with 162 potentially relevant titles; 45 were reviewed in detail. Despite more information on perioperative management of patients with obstructive sleep apnea (OSA), evidence to support preoperative testing and treatment or to guide perioperative monitoring is scarce. New evidence on appropriate intraoperative dosing of muscle relaxants allows for greater precision in their use during WLS. A novel application of α?2 agonists for perioperative anesthetic care is emerging. Key elements that may enhance patient safety include integration of the latest evidence on WLS, obesity, and collaborative multidisciplinary care into clinical care. However, large gaps remain in the evidence base.     

Chick growth rates in Charadriiformes: comparative analyses of breeding climate, development mode and parental care

The rate at which a young bird grows is highly diverse across taxa. We investigated the influences of ecological variables on growth rates of shorebirds, gulls and their allies (order Charadriiformes) using comparative analyses of 68 species. We investigated three hypotheses: (1) exposure to cold temperatures results in reduced growth rate due to the increased energy expenditure required for thermoregulation, (2) fast growth rates allow offspring to complete development in habitats with short periods of fair ecological conditions, and (3) parental feeding allows the offspring to grow faster than self-feeding offspring. Charadriiform species are suitable for testing these hypotheses, because they breed in diverse environmental conditions that include Arctic and Antarctic habitats, temperate zones and tropics, and in some species the offspring feed themselves (precocial) whereas in others they are fed by the parents (semi-precocial). First, we tested the influence of ambient temperature on growth rate and we found that species breeding in cold habitats had faster growth rates than species breeding in warm temperatures. The relationship between growth rate and ambient temperature was not significantly different between precocial and semi-precocial offspring. Second, we tested the influence of the length of the breeding season on growth rate, and we found that species with shorter breeding seasons had faster growth rates than species with longer breeding seasons. Finally, we show that precocial offspring grew slower than semi-precocial offspring, and this relationship remains significant when the influences of ambient temperature and breeding season length are statistically controlled. In conclusion, our work, using phylogenetically corrected models, confirms that ambient environment and developmental mode of young together influence the growth of Charadriiform chicks, and their effects are additive.     

Phage Display Selection of Cyclic Peptides That Inhibit Andes Virus Infection

Specific therapy is not available for hantavirus cardiopulmonary syndrome caused by Andes virus (ANDV). Peptides capable of blocking ANDV infection in vitro were identified using antibodies against ANDV surface glycoproteins Gn and Gc to competitively elute a cyclic nonapeptide-bearing phage display library from purified ANDV particles. Phage was examined for ANDV infection inhibition in vitro, and nonapeptides were synthesized based on the most-potent phage sequences. Three peptides showed levels of viral inhibition which were significantly increased by combination treatment with anti-Gn- and anti-Gc-targeting peptides. These peptides will be valuable tools for further development of both peptide and nonpeptide therapeutic agents.Andes virus (ANDV), an NIAID category A agent linked to hantavirus cardiopulmonary syndrome (HCPS), belongs to the family Bunyaviridae and the genus Hantavirus and is carried by Oligoryzomys longicaudatus rodents (11). HCPS is characterized by pulmonary edema caused by capillary leak, with death often resulting from cardiogenic shock (9, 16). ANDV HCPS has a case fatality rate approaching 40%, and ANDV is the only hantavirus demonstrated to be capable of direct person-to-person transmission (15, 21). There is currently no specific therapy available for treatment of ANDV infection and HCPS.Peptide ligands that target a specific protein surface can have broad applications as therapeutics by blocking specific protein-protein interactions, such as preventing viral engagement of host cell receptors and thus preventing infection. Phage display libraries provide a powerful and inexpensive tool to identify such peptides. Here, we used selection of a cyclic nonapeptide-bearing phage library to identify peptides capable of binding the transmembrane surface glycoproteins of ANDV, Gn and Gc, and blocking infection in vitro.To identify peptide sequences capable of recognizing ANDV, we panned a cysteine-constrained cyclic nonapeptide-bearing phage display library (New England Biolabs) against density gradient-purified, UV-treated ANDV strain CHI-7913 (a gift from Hector Galeno, Santiago, Chile) (17, 18). To increase the specificity of the peptides identified, we eluted phage by using monoclonal antibodies (Austral Biologicals) prepared against recombinant fragments of ANDV Gn (residues 1 to 353) or Gc (residues 182 to 491) glycoproteins (antibodies 6B9/F5 and 6C5/D12, respectively). Peptide sequences were determined for phage from iterative rounds of panning, and the ability of phage to inhibit ANDV infection of Vero E6 cells was determined by immunofluorescent assay (IFA) (7). Primary IFA detection antibodies were rabbit polyclonal anti-Sin Nombre hantavirus (SNV) nucleoprotein (N) antibodies which exhibit potent cross-reactivity against other hantavirus N antigens (3). ReoPro, a commercially available Fab fragment which partially blocks infection of hantaviruses in vitro by binding the entry receptor integrin β₃ (5), was used as a positive control (80 μg/ml) along with the original antibody used for phage elution (5 μg/ml). As the maximum effectiveness of ReoPro in inhibiting hantavirus entry approaches 80%, we set this as a threshold for maximal expected efficacy for normalization. The most-potent phage identified by elution with the anti-Gn antibody 6B9/F5 bore the peptide CPSNVNNIC and inhibited hantavirus entry by greater than 60% (61%) (Table ​(Table1).1). From phage eluted with the anti-Gc antibody 6C5/D12, those bearing peptides CPMSQNPTC and CPKLHPGGC also inhibited entry by greater than 60% (66% and 72%, respectively).

TABLE 1.

Peptide-bearing phage eluted from ANDV