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Treatment of cancers in the lung remains a critical challenge in the clinic for which gene therapy could offer valuable options. We describe an effective approach through systemic injection of engineered polymer/DNA nanoparticles that mediate tumor-specific expression of a therapeutic gene, under the control of the cancer-selective progression elevated gene 3 (PEG-3) promoter, to treat tumors in the lungs of diseased mice. A clinically tested, untargeted, polyethylenimine carrier was selected to aid rapid transition to clinical studies, and a CpG-free plasmid backbone and coding sequences were used to reduce inflammation. Intravenous administration of nanoparticles expressing murine single-chain interleukin 12, under the control of PEG-3 promoter, significantly improved the survival of mice in both an orthotopic and a metastatic model of lung cancer with no marked symptoms of systemic toxicity. These outcomes achieved using clinically relevant nanoparticle components raises the promise of translation to human therapy.

Plasma-derived polyclonal antibody therapeutics, such as intravenous immunoglobulin, have multiple drawbacks, including low potency, impurities, insufficient supply, and batch-to-batch variation. Here we describe a microfluidics and molecular genomics strategy for capturing diverse mammalian antibody repertoires to create recombinant multivalent hyperimmune globulins. Our method generates thousands-diverse mixtures of recombinant antibodies, enriched for specificity and activity against therapeutic targets. Each hyperimmune globulin product comprised thousands to tens of thousands of antibodies derived from convalescent or vaccinated human donors, or immunized mice. Using this approach, we generated hyperimmune globulins with potent neutralizing activity against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in under three months, Fc-engineered hyperimmune globulins specific for Zika virus that lacked antibody-dependent enhancement of disease, and hyperimmune globulins specific for lung pathogens present in patients with primary immune deficiency. To address the limitations of rabbit-derived anti-thymocyte globulin (ATG), we generated a recombinant human version and demonstrated its efficacy in mice against graft-versus-host disease.

Purpose: This paper describes the rationale, study design and procedures of the National Eye Survey of Trinidad and Tobago (NESTT). The main objective of this survey is to obtain prevalence estimates of vision impairment and blindness for planning and policy development.\ud \ud Methods: A population-based, cross-sectional survey was undertaken using random multistage cluster sampling, with probability-proportionate-to-size methods. Eligible participants aged 5 years and older were sampled from the non-institutional population in each of 120 cluster segments. Presenting distance and near visual acuity were screened in their communities. People aged 40 years and older, and selected younger people, were invited for comprehensive clinic assessment. The interview included information on potential risk factors for vision loss, associated costs and quality of life. The examination included measurement of anthropometrics, blood glucose, refraction, ocular biometry, corneal hysteresis, and detailed assessment of the anterior and posterior segments, with photography and optical coherence tomography imaging. Adult participants were invited to donate saliva samples for DNA extraction and storage.\ud \ud Results: The fieldwork was conducted over 13 months in 2013–2014. A representative sample of 10,651 individuals in 3410 households within 120 cluster segments identified 9913 people who were eligible for recruitment.\ud \ud Conclusion: The study methodology was robust and adequate to provide the first population-based estimates of the prevalence and causes of visual impairment and blindness in Trinidad and Tobago. Information was also gathered on risk factors, costs and quality of life associated with vision loss, and on normal ocular parameters for the population aged 40 years and older.

Background Recent emergence of Zika virus (ZIKV), and the global spread of dengue (DENV), chikungunya (CHIKV) and West Nile viruses (WNV) raised urgent need of accurate and affordable molecular diagnosis of these clinically indistinguishable arboviral infections. Objectives We established a pentaplex real-time reverse transcription PCR (rRT-PCR) assay (CII-ArboViroPlex rRT-PCR) for specific and sensitive detection of the African and American genotypes of ZIKV, all four serotypes of DENV, CHIKV, WNV and a housekeeping gene as internal control in single reaction. Study design Specific primers and probe sets were designed for ZIKV, DENV, CHIKV, WNV and RNase P (housekeeping gene) and tested for in-vitro transcribed RNA standards, virus cultures, clinical samples positive for ZIKV, DENV, CHIKV and WNV and limit of detection (LOD) were determined for each. Results Using ten-fold serially diluted in-vitro transcribed RNA, CII- ArboViroPlex rRT-PCR assay has LOD of 100 RNA copies/reaction (Rn) for ZIKV in serum or urine, 100 RNA copies/Rn for DENV in serum, and 10 RNA copies/Rn for CHIKV and WNV in serum. LODs from sera spiked with quantitated viral stocks were 2.6 × 102 GEQ/Rn for ZIKV, 2.2 × 101 GEQ/Rn for DENV-1, 9.4 × 100 GEQ/Rn for DENV-2, 2.3 × 102 GEQ/Rn for DENV-3, 1.4 × 103 GEQ/Rn for DENV-4, 2.7 × 102 GEQ/Rn for CHIKV, and 1.05 × 101 GEQ/Rn for WNV. Conclusions The CII-ArboViroPlex rRT-PCR assay is a quantitative one-step pentaplex rRT-PCR assay for the molecular detection and differential diagnosis of ZIKV, DENV, CHIKV, WNV and a human housekeeping gene control in a single- PCR reaction.

Vampire bat-transmitted human rabies was first recognized in Trinidad during a major outbreak during the first half of the 20th century. To date, Trinidad is the only Caribbean island with vampire bat-transmitted rabies. Herein, we summarized the epidemiological situation of rabies in Trinidad during the period 1971–2015 through the analysis of field and laboratory records. During the study period, 259 domestic and wild animal rabies cases were laboratory confirmed with an annual median of 2 animal rabies cases. Over the 45 years, five significant epizootic events occurred (in 1974, 1997–1998, 2000, 2010 and 2012–2013) over which there was a significant increasing trend for the occurrence of rabies cases. The highest number of cases (87 cases) occurred during the 1997–1998 event, and the rabies positive proportion, was highest (0.7, 95% CI 0.52-0.84) for the year 2000. Rabies risk was highest for cattle (negative binomial parameter estimate 4.84, 95% CI 3.45–6.76), although numerous rabies cases were seen in the caprine population during the study period. In light of this finding, consideration should be given to including the small ruminant population in the national rabies vaccination program. Outbreaks affected mainly the counties of St. Patrick and St. George East, with epidemic progression outwards, and these areas should be prioritized for prevention and control efforts.

Yellow fever virus (YFV) is historically one of the most important viruses to affect human populations. Despite the existence of highly effective vaccines for over 70 years, yellow fever remains a significant and re-emerging cause of morbidity and mortality in endemic and high-risk regions of South America and Africa. The virus may be maintained in sylvatic enzootic/epizootic, transitional and urban epidemic transmission cycles with geographic variation in terms of levels of genetic diversity, the nature of transmission cycles and patterns of outbreak activity. In this review we consider evolutionary and ecological factors underlying YFV emergence, maintenance and spread, geographic distribution and patterns of epizootic/epidemic activity.

The CD45 antigen is essential for normal antigen receptor-mediated signalling in lymphocytes, and different patterns of splicing of CD45 are associated with distinct functions in lymphocytes. Abnormal CD45 splicing has been recognized in humans, caused by a C77G transversion in the gene encoding CD45 (PTPRC). Recently the C77G polymorphism has been associated with multiple sclerosis and increased susceptibility to HIV-1 infection. These studies suggest that the regulation of CD45 splicing may be critical for the proper function of the immune system. Because of these data we examined the frequency of the C77G allele in African and Asian populations from countries with high or low prevalence of HIV infection. Here we report that the variant CD45 C77G allele is absent in African populations. We further show that populations living in the Pamir mountains of Central Asia have a very high prevalence of the C77G variant.

Problem-based learning (PBL) and concept mapping have been shown to promote active and meaningful learning.To design a method of PBL that includes concept mapping and examine students' perceptions of this form of PBL.We designed a 5-phase method of PBL which produced three clearly identifiable mapping phases that reflected the learning activities during the tutorial: (1) the initial understanding of the clinical problem, (2) students' prior knowledge of the problem, (3) the final understanding of the problem following self-directed study. The process of developing the second and third phases of the map involved the students answering questions that they generated on two occasions to give the entire process a 5-phase approach. Each student was exposed to both methods of PBL: a conventional 7-step method (Maastricht type) and the modified PBL (5-phase) method. We used a questionnaire to evaluate the students' perceptions of the two methods in four learning domains.The students' ratings for the 5-phase method were significantly higher than for the 7-step method (paired t-test) on all items on the questionnaire.The students perceived the 5-phase method as promoting their passion for learning, and developing their cognitive, metacognitive and interpersonal skills.

Interactions of killer cell immunoglobulin-like receptors (KIRs) with major histocompatibility complex (MHC) class I ligands diversify natural killer cell responses to infection. By analyzing sequence variation in diverse human populations, we show that the KIR3DL1/S1 locus encodes two lineages of polymorphic inhibitory KIR3DL1 allotypes that recognize Bw4 epitopes of protein">HLA-A and HLA-B and one lineage of conserved activating KIR3DS1 allotypes, also implicated in Bw4 recognition. Balancing selection has maintained these three lineages for over 3 million years. Variation was selected at D1 and D2 domain residues that contact HLA class I and at two sites on D0, the domain that enhances the binding of KIR3D to HLA class I. HLA-B variants that gained Bw4 through interallelic microconversion are also products of selection. A worldwide comparison uncovers unusual KIR3DL1/S1 evolution in modern sub-Saharan Africans. Balancing selection is weak and confined to D0, KIR3DS1 is rare and KIR3DL1 allotypes with similar binding sites predominate. Natural killer cells express the dominant KIR3DL1 at a high frequency and with high surface density, providing strong responses to cells perturbed in Bw4 expression.

Local transmission of Chikungunya virus (CHIKV) was first documented in Trinidad and Tobago (T&T) in July 2014 preceding a large epidemic. At initial presentation, it is difficult to distinguish chikungunya fever (CHIKF) from other acute undifferentiated febrile illnesses (AUFIs), including life-threatening dengue disease. We characterised and compared dengue virus (DENV) and CHIKV infections in 158 patients presenting with suspected dengue fever (DF) and CHIKF at a major hospital in T&T, and performed phylogenetic analyses on CHIKV genomic sequences recovered from 8 individuals. The characteristics of patients with and without PCR-confirmed CHIKV were compared using Pearson’s χ2 and student’s t-tests, and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were determined using logistic regression. We then compared signs and symptoms of people with RT-qPCR-confirmed CHIKV and DENV infections using the Mann-Whitney U, Pearson’s χ2 and Fisher’s exact tests. Among the 158 persons there were 8 (6%) RT-qPCR-confirmed DENV and 30 (22%) RT-qPCR-confirmed CHIKV infections. Phylogenetic analyses showed that the CHIKV strains belonged to the Asian genotype and were most closely related to a British Virgin Islands strain isolated at the beginning of the 2013/14 outbreak in the Americas. Compared to persons who were RT-qPCR-negative for CHIKV, RT-qPCR-positive individuals were significantly more likely to have joint pain (aOR: 4.52 [95% CI: 1.28–16.00]), less likely to be interviewed at a later stage of illness (days post onset of fever—aOR: 0.56 [0.40–0.78]) and had a lower white blood cell count (aOR: 0.83 [0.71–0.96]). Among the 38 patients with RT-qPCR-confirmed CHIKV or DENV, there were no significant differences in symptomatic presentation. However when individuals with serological evidence of recent DENV or CHIKV infection were included in the analyses, there were key differences in clinical presentation between CHIKF and other AUFIs including DF, which can be used to triage patients for appropriate care in the clinical setting., Author Summary Chikungunya virus (CHIKV) recently emerged in the Americas and caused a major epidemic of chikungunya fever (CHIKF). While not usually life threatening, CHIKF is a debilitating and often chronic illness resulting in major morbidity and economic losses. It is difficult to distinguish CHIKF from other viral illnesses that cause acute fevers including dengue fever (DF), an important consideration since DF can be life-threatening and early identification and treatment of cases is key to reducing mortality. In this study we investigated individuals presenting to a major hospital in Trinidad and Tobago (T&T) with suspected DF or CHIKF, and identified signs and symptoms that distinguish these two illnesses. We also recovered complete genome sequences for CHIKV and show that the etiologic strain in T&T is a closely related descendent of the strain first isolated from the British Virgin Islands at the beginning of the outbreak in the Americas.

Using DNA extracted from 112 parasitised blood blots, we screened for the population marker of chloroquine resistance (CQR) pfcrt K76T in Plasmodium falciparum infections from Guyana. Pfmdr1 mutations S1034C, N1042D, and D1246Y also associated with CQR were surveyed as well in 15 isolates for which the in vitro responses to CQ were known. Results indicate that the pfcrt K76T is ubiquitous in this environment, and confirmatory sequencing of codons 72 and 76 revealed two novel allelic sequences SVMIT and RVMNT in addition to the previously identified CVMNT and SVMNT haplotypes. The frequency of the pfcrt K76T despite its presence in both CQR and CQS (chloroquine sensitive) infections measured in vivo and in vitro, suggests that it is a useful population marker in this low-transmission setting of sweeping CQR.

We sequenced the E gene and adjacent prM/M and NS1 junctions (1940 bp) of 48 Dengue-4 (DEN-4) isolates collected between 1981 and 1999 from 8 Caribbean islands and from 7 South and Central American countries. Phylogenetic analysis confirms a single introduction in the early 1980s and a high degree of gene flow resulting in a pattern of evolution defined more by time period than geographic origin, especially within the Caribbean basin. A modern Caribbean clade consisting of four distinct lineages has arisen, comprised of isolates from Caribbean islands and nearby regions of South America. This clade is defined by three amino acid substitutions in the E (aa 163 and 351) and NS1 (aa 52) proteins. These findings highlight the importance of migration and gene flow in dengue viral change and suggest that efforts to understand disease dynamics in the Caribbean basin need to focus at regional, rather than local scales.

Natural killer (NK) and some T cells express killer cell immunoglobulin-like receptors (KIRs), which interact with HLA class I expressed by target cells and consequently regulate cytolytic activity. The number of KIR loci can vary and so a range of genetic profiles is observed. We have determined the KIR genetic profiles from one African (n = 62) and two South Asian (n = 108, n = 78) populations. Several of the KIRs are present at significantly different frequencies between the two major ethnic groups (eg KIR2DS4 gene frequency 0.82 African, 0.47 S Asian. Pc < 1 × 10−6) and this is due to uneven distribution of two KIR haplotype families ‘A’ and ‘B’. All three populations described here displayed a greater degree of diversity of KIR genetic profiles than other populations investigated, which indicates further complexity of underlying haplotypes; in this respect we describe two individuals who appear homozygous for a large deletion including the previously ubiquitous 2DL4. We have also reanalysed three populations that we studied previously, for the presence of a KIR which is now known to be an indicator of the ‘B’ haplotype. South Asians had the highest overall frequencies of all KIR loci characteristic of ‘B’ haplotypes (Pc < 0.0001 to < 0.004). Furthermore, gene frequency independent deviances in the linkage disequilibrium were apparent between populations.

Summary A serosurvey of antibodies against selected flaviviruses and alphaviruses in 384 bats (representing 10 genera and 14 species) was conducted in the Caribbean island of Trinidad. Sera were analysed using epitope‐blocking enzyme‐linked immunosorbent assays (ELISAs) specific for antibodies against West Nile virus (WNV), Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV), all of which are zoonotic viruses of public health significance in the region. Overall, the ELISAs resulted in the detection of VEEV‐specific antibodies in 11 (2.9%) of 384 bats. Antibodies to WNV and EEEV were not detected in any sera. Of the 384 sera, 308 were also screened using hemagglutination inhibition assay (HIA) for antibodies to the aforementioned viruses as well as St. Louis encephalitis virus (SLEV; which also causes epidemic disease in humans), Rio Bravo virus (RBV), Tamana bat virus (TABV) and western equine encephalitis virus (WEEV). Using this approach, antibodies to TABV and RBV were detected in 47 (15.3%) and 3 (1.0%) bats, respectively. HIA results also suggest the presence of antibodies to an undetermined flavivirus(es) in 8 (2.6%) bats. Seropositivity for TABV was significantly (P

2 Abstract Trinidadians of South Asian origin have a high prevalence of cardiovascular disease and diabetes compared to Trinidadians of African ori- gin. The degree to which these differences are related to genetic and/or envi- ronmental factors is unclear. To determine whether there might be a genetic basis for this difference in prevalence of deleterious phenotypes we exam- ined allele frequencies for candidate genes in atherosclerosis and diabetes. We genotyped 81 consecutive neonates of African origin and 103 consecu- tive neonates of South Asian origin. We evaluated common polymorphisms in 11 candidate genes for atherosclerosis and diabetes. We found differences between the two subpopulations in the allele frequencies of several candidate genes, including APOE, LIPC, APOC3, PON1, PON2, and PPP1R3. Howev- er, the differences in the allele frequencies were not all consistent with the pattern of CHD expression between these two ethnic groups in adulthood. Thus, differences in genetic architecture alone may not explain the wide dis- parities in disease prevalence between these two subpopulations. It is very likely that environmental factors, or unmeasured genetic factors, influence the genetic susceptibility to disease in these subpopulations.

Changes in Dengue virus (DENV) disease patterns in the Americas over recent decades have been attributed, at least in part, to repeated introduction of DENV strains from other regions, resulting in a shift from hypoendemicity to hyperendemicity. Using newly sequenced DENV-1 and DENV-3 envelope (E) gene isolates from 11 Caribbean countries, along with sequences available on GenBank, we sought to document the population genetic and spatiotemporal transmission histories of the four main invading DENV genotypes within the Americas and investigate factors that influence the rate and intensity of DENV transmission. For all genotypes, there was an initial invasion phase characterized by rapid increases in genetic diversity, which coincided with the first confirmed cases of each genotype in the region. Rapid geographic dispersal occurred upon each genotype's introduction, after which individual lineages were locally maintained, and gene flow was primarily observed among neighboring and nearby countries. There were, however, centers of viral diversity (Barbados, Puerto Rico, Colombia, Suriname, Venezuela, and Brazil) that were repeatedly involved in gene flow with more distant locations. For DENV-1 and DENV-2, we found that a "distance-informed" model, which posits that the intensity of virus movement between locations is inversely proportional to the distance between them, provided a better fit than a model assuming equal rates of movement between all pairs of countries. However, for DENV-3 and DENV-4, the more stochastic "equal rates" model was preferred.

Trinidad, like many other American regions, experiences repeated epizootics of yellow fever virus (YFV). However, it is unclear whether these result from in situ evolution (enzootic maintenance) or regular reintroduction of YFV from the South American mainland. To discriminate between these hypotheses, we carried out a Bayesian phylogeographic analysis of over 100 prM/E gene sequences sampled from 8 South American countries. These included newly sequenced isolates from the recent 2008-2009 Trinidad epizootic and isolates derived from mainland countries within the last decade. The results indicate that the most recent common ancestor of the 2008-2009 epizootic existed in Trinidad 4.2 years prior to 2009 (95% highest probability density [HPD], 0.5 to 9.0 years). Our data also suggest a Trinidad origin for the progenitor of the 1995 Trinidad epizootic and support in situ evolution of YFV between the 1979 and 1988-1989 Trinidad epizootics. Using the same phylogeographic approach, we also inferred the historical spread of YFV in the Americas. The results suggest a Brazilian origin for YFV in the Americas and an overall dispersal rate of 182 km/year (95% HPD, 52 to 462 km/year), with Brazil as the major source population for surrounding countries. There is also strong statistical support for epidemiological links between four Brazilian regions and other countries. In contrast, while there were well-supported epidemiological links within Peru, the only statistically supported external link was a relatively weak link with neighboring Bolivia. Lastly, we performed a complete analysis of the genome of a newly sequenced Trinidad 2009 isolate, the first complete genome for a genotype I YFV isolate.

Natural killer (NK) cells contribute to the essential functions of innate immunity and reproduction. Various genes encode NK cell receptors that recognize the major histocompatibility complex (MHC) Class I molecules expressed by other cells. For primate NK cells, the killer-cell immunoglobulin-like receptors (KIR) are a variable and rapidly evolving family of MHC Class I receptors. Studied here isKIR3DL1/S1, which encodes receptors for highly polymorphic human HLA-A and -B and comprises three ancient allelic lineages that have been preserved by balancing selection throughout human evolution. While the 3DS1 lineage of activating receptors has been conserved, the two 3DL1 lineages of inhibitory receptors were diversified through inter-lineage recombination with each other and with 3DS1. Prominent targets for recombination were D0-domain polymorphisms, which modulate enhancer function, and dimorphism at position 283 in the D2 domain, which influences inhibitory function. In African populations, unequal crossing over between the3DL1and3DL2genes produced a deletedKIRhaplotype in which the telomeric “half” was reduced to a single fusion gene with functional properties distinct from its3DL1and3DL2parents. Conversely, in Eurasian populations, duplication of theKIR3DL1/S1locus by unequal crossing over has enabled individuals to carry and express alleles of all threeKIR3DL1/S1lineages. These results demonstrate how meiotic recombination combines with an ancient, preserved diversity to create new KIR phenotypes upon which natural selection acts. A consequence of such recombination is to blur the distinction between alleles and loci in the rapidly evolving humanKIRgene family.

Dengue virus type 4 (DENV-4) was first reported in the Americas in 1981, where it caused epidemics of dengue fever throughout the region. In the same year, the region's first epidemic of dengue hemorrhagic fever was reported, caused by an Asian strain of dengue virus type 2 (DENV-2) that was distinct from the American subtype circulating previously. Despite the importance of these epidemics, little is known about the rates or determinants of viral spread among island and mainland populations or their directions of movement. We employed a Bayesian coalescent approach to investigate the transmission histories of DENV-2 and DENV-4 since their introduction in 1981 and a parsimony method to assess patterns of strain migration. For both viruses there was an initial invasion phase characterized by an exponential increase in the number of DENV lineages, after which levels of genetic diversity remained constant despite reported fluctuations in DENV-2 and DENV-4 activity. Strikingly, viral lineage numbers increased far more rapidly for DENV-4 than DENV-2, indicative of a more rapid rate of exponential population growth in DENV-4 or a higher rate of geographic dispersal, allowing this virus to move more effectively among localities. We propose that these contrasting dynamics may reflect underlying differences in patterns of host immunity. Despite continued gene flow along particular transmission routes, the overall extent of viral traffic was less than expected under panmixis. Hence, DENV in the Americas has a clear geographic structure that maintains viral diversity between outbreaks.

The human leukocyte receptor complex (LRC) of Chromosome 19q13.4 encodes polymorphic and highly homologous genes that are expressed by cells of the immune system and regulate their function. There is an enormous diversity at the LRC, most particularly the variable number of killer cell immunoglobulin-like receptor (KIR) genes. KIR have been associated with several disease processes due to their interaction with polymorphic human leukocyte antigen class I molecules. We have assessed haplotype compositions, linkage disequilibrium patterns and allele frequencies in two Caucasoid population samples (n=54, n=100), using a composite of single-nucleotide polymorphism (SNP) markers and high-resolution, allele-specific molecular genotyping. Particular KIR loci segregated with SNP and other markers, forming two blocks that were separated by a region with a greater history of recombination. The KIR haplotype composition and allele frequency distributions were consistent with KIR having been subject to balancing selection (Watterson's F: P=0.001). In contrast, there was a high inter-population heterogeneity measure for the LRC-encoded leukocyte immunoglobulin-like receptor A3 (LILRA3), indicating pathogen-driven disruptive selection (Wright's FST=0.32). An assessment of seven populations representative of African, Asian and Caucasoid ethnic groups (total n=593) provided little evidence for long-range LRC haplotypes. The different natural selection pressures acting on each locus may have contributed to a lack of linkage disequilibrium between them.

Using polymerase chain reaction–sequence-specific primer (PCR-SSP) typing, this study determined the frequency of human leukocyte antigen (HLA) DR- and -DQ alleles and haplotypes in individuals of African (n = 75), South Asian (n = 98), and mixed (n = 102) ancestry from the Caribbean island of Trinidad. We detected 19 different haplotypes containing DRB3, 8 containing DRB4, 6 containing DRB5, and 6 different haplotypes without DRB3/4/5 genes. Twenty-nine haplotypes were identified in Africans, 24 in the South Asians, and 32 in the mixed group. We detected significant differences between the populations, principally at the DQA1 and DQB1 loci, although the allele frequency for DRB1*0901 was highest in the Africans (pc < 0.05). Trinidad African and mixed groups were generally more diverse than the South Asians and displayed a wider range of DRB1-DQB1 associations; DQB1*02 and DQB1*0301 each associated with five to six different DRB1 alleles in the Africans and mixed group but only two in South Asians. In the Africans and the mixed group, DQB1*04 was found with DRB1*0302 and DRB1*04, but only with DRB1*08 in the South Asians. Trinidad Africans revealed consistencies with populations in Western, Central, and Northern Africa, but differed considerably from individual populations on the African continent. Trinidad South Asians displayed similar allele frequencies and associations to other populations from Northern India.

Pancreatic lipase (EC 3.1.1.3) is an exocrine secretion that hydrolyzes dietary triglycerides in the small intestine. We developed genomic amplification primers to sequence the 13 exons of PNLIP, which encodes pancreatic lipase, in order to screen for possible mutations in cell lines of four children with pancreatic lipase deficiency (OMIM 246600). We found no missense or nonsense mutations in these samples, but we found three silent single-nucleotide polymorphisms (SNPs), namely, 96A/C in exon 3, 486C/T in exon 6, and 1359C/T in exon 13. In 50 normolipidemic Caucasians, the PNLIP 96C and 486T alleles had frequencies of 0.083 and 0.150, respectively. The PNLIP 1359T allele was absent from Caucasian, Chinese, South Asian, and North American aboriginal samples, but had a frequency of 0.085 in an African sample, suggesting that it is a population-specific variant. In an association analysis of 185 African neonates, the PNLIP 1359C/T SNP genotype was significantly associated with concentrations of plasma lipoproteins. These associations were most likely due to linkage disequilibrium with another functional variant at or near PNLIP. Thus, we report three new SNPs for the PNLIP, which may serve as markers for association analyses and for pharmacogenetic studies of pancreatic lipase inhibitors.

We are investigating the binding of a series of monoclonal antibodies to native and detergent-treated human T-lymphotropic virus I (HTLV-I) envelope proteins to explore their conformation. A comparison of our data with previously published findings suggests that a central neutralization domain (aa 175–200) is folded such that only short stretches are exposed at the surface of the native envelope protein complex. However, the complete domain becomes accessible after treatment with mild non-ionic detergents, suggesting that envelope subunit interaction may partially obscure this domain. We further provide immunochemical evidence that a region containing a heptad repeat in the extracellular part of the transmembrane protein is folded towards the interior of the HTLV-I envelope complex.