Seroprevalence of Zika virus in wild African green monkeys and baboons

ABSTRACT Zika virus (ZIKV) has recently spread through the Americas and has been associated with a range of health effects, including birth defects in children born to women infected during pregnancy. Although the natural reservoir of ZIKV remains poorly defined, the virus was first identified in a captive “sentinel” macaque monkey in Africa in 1947. However, the virus has not been reported in humans or nonhuman primates (NHPs) in Africa outside Gabon in over a decade. Here, we examine ZIKV infection in 239 wild baboons and African green monkeys from South Africa, the Gambia, Tanzania, and Zambia using combinations of unbiased deep sequencing, quantitative reverse transcription-PCR (qRT-PCR), and an antibody capture assay that we optimized using serum collected from captive macaque monkeys exposed to ZIKV, dengue virus, and yellow fever virus. While we did not find evidence of active ZIKV infection in wild NHPs in Africa, we found variable ZIKV seropositivity of up to 16% in some of the NHP populations sampled. We anticipate that these results and the methodology described within will help in continued efforts to determine the prevalence, natural reservoir, and transmission dynamics of ZIKV in Africa and elsewhere. IMPORTANCE Zika virus (ZIKV) is a mosquito-borne virus originally discovered in a captive monkey living in the Zika Forest of Uganda, Africa, in 1947. Recently, an outbreak in South America has shown that ZIKV infection can cause myriad health effects, including birth defects in the children of women infected during pregnancy. Here, we sought to investigate ZIKV infection in wild African primates to better understand its emergence and spread, looking for evidence of active or prior infection. Our results suggest that up to 16% of some populations of nonhuman primate were, at some point, exposed to ZIKV. We anticipate that this study will be useful for future studies that examine the spread of infections from wild animals to humans in general and those studying ZIKV in primates in particular. Podcast: A podcast concerning this article is available

Lie detector

Novel, semicrystalline polyamides and copolyamides were synthesized from a new carbohydrate-based diamine, namely isoidide-2,5-dimethyleneamine (IIDMA). In combination with 1,6-hexamethylene diamine (1,6-HDA) as well as the biobased sebacic acid (SA) or brassylic acid (BrA), the desired copolyamides were obtained via melt polymerization of the nylon salts followed by a solid-state polycondensation (SSPC) process. Depending on the chemical compositions, the number average molecular weights (Mn) of the polyamides were in the range of 4000–49000 g/mol. With increasing IIDMA content in the synthesized copolyamides, their corresponding glass transition temperatures (Tg) increased from 50 °C to approximately 60–67 °C while the melting temperatures (Tm) decreased from 220 to 160 °C. The chemical structures of the polyamides were analyzed by NMR and FT-IR spectroscopy. Both differential scanning calorimetry (DSC) and wide-angle X-ray diffraction (WAXD) analyses revealed the semicrystalline character of these novel copolyamides. Variable-temperature (VT) 13C{1H} cross-polarization/magic-angle spinning (CP/MAS) NMR and FT-IR techniques were employed to study the crystal structures as well as the distribution of IIDMA moieties over the crystalline and amorphous phases of the copolyamides. The performed ab initio calculations reveal that the stability of the IIDMA moieties is due to a pronounced boat conformation of the bicyclic rings. The incorporation of methylene segments in between the isohexide group and the amide groups enables the hydrogen bonds formation and organization of the polymer chain fragments. Given the sufficiently high Tm values (200 °C) of the copolyamides containing less than 50% of IIDMA, these biobased semicrystalline copolyamides can be useful for engineering plastic applications

Tailoring the mechanical and degradation performance of Mg-2.0Zn-0.5Ca-0.4Mn alloy through microstructure design

A novel Mg-2.0Zn-0.5Ca-0.4Mn alloy has been formulated and processed through melt spinning and hot extrusion to enhance its mechanical and degradation properties. Microstructural characterization of rapidly solidified alloy ribbons consolidated by extrusion revealed a fine and fully recrystallized microstructure with average size of 4 µm. The conventionally extruded alloy consisted of several course second-phase strips as coarse as 100 µm, while the extrusion-consolidated ribbons were devoid of any second phases larger than 100 nm. Rapid solidification followed by extrusion processing resulted in significantly randomized texture where the majority of the basal planes were tilted toward transverse and extrusion directions. Such a weak texture resulted in higher activity of basal planes and thereby considerably improved the fracture elongation from 4% to 19%, while retaining relatively high tensile strength of 294 MPa. In addition to high strength and ductility due to the reduced activity of deformation twining during compression, the extrusion-consolidated alloy ribbons showed lower yielding asymmetric ratio than that measured for the conventionally extruded alloy (1.25 versus 1.61). Electrochemical measurements and immersion tests indicated that application of rapid solidification followed by extrusion remarkably reduced the corrosion rate from 2.49 mm/year to 0.37 mm/year due to recrystallization completion and suppression of coarse second-phase formation

The cerebellum ages slowly according to the epigenetic clock

Studies that elucidate why some human tissues age faster than others may shed light on how we age, and ultimately suggest what interventions may be possible. Here we utilize a recent biomarker of aging (referred to as epigenetic clock) to assess the epigenetic ages of up to 30 anatomic sites from supercentenarians (subjects who reached an age of 110 or older) and younger subjects. Using three novel and three published human DNA methylation data sets, we demonstrate that the cerebellum ages more slowly than other parts of the human body. We used both transcriptional data and genetic data to elucidate molecular mechanisms which may explain this finding. The two largest superfamilies of helicases (SF1 and SF2) are significantly over-represented (p=9.2x10-9) among gene transcripts that are over-expressed in the cerebellum compared to other brain regions from the same subject. Furthermore, SNPs that are associated with epigenetic age acceleration in the cerebellum tend to be located near genes from helicase superfamilies SF1 and SF2 (enrichment p=5.8x10-3). Our genetic and transcriptional studies of epigenetic age acceleration support the hypothesis that the slow aging rate of the cerebellum is due to processes that involve RNA helicases

Zoonotic potential of simian arteriviruses

Wild nonhuman primates are immediate sources and long-term reservoirs of human pathogens. However, ethical and technical challenges have hampered the identification of novel blood-borne pathogens in these animals. We recently examined RNA viruses in plasma from wild African monkeys and discovered several novel, highly divergent viruses belonging to the family Arteriviridae. Close relatives of these viruses, including simian hemorrhagic fever virus, have caused sporadic outbreaks of viral hemorrhagic fever in captive macaque monkeys since the 1960s. However, arterivirus infection in wild nonhuman primates had not been described prior to 2011. The arteriviruses recently identified in wild monkeys have high sequence and host species diversity, maintain high viremia, and are prevalent in affected populations. Taken together, these features suggest that the simian arteriviruses may be “preemergent” zoonotic pathogens. If not, this would imply that biological characteristics of RNA viruses thought to facilitate zoonotic transmission may not, by themselves, be sufficient for such transmission to occur

Genome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms.

Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carried out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 single-nucleotide polymorphisms. Of the ~1100 families, 972 were informative for further analyses, and mean information content was 0.86 after pruning for linkage disequilibrium. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with bipolar II disorder (BPII) and 702 subjects with recurrent major depression. Three affection status models (ASMs) were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus recurrent major depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (non-parametric pairs LOD 3.4 for rs1046943 at 119 cM) and 9q21 (non-parametric pairs logarithm of odds (LOD) 3.4 for rs722642 at 78 cM) using only BPI and schizoaffective (SA), BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis, we observed 59 parametric LODs of 2 or greater, many of which are likely to be close to maximum possible scores. Although some linkage findings may be false positives, the results could help prioritize the search for rare variants using whole exome or genome sequencing

BRCA1 mutations in women with familial or early-onset breast cancer and BRCA2 mutations in familial cancer in Estonia

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to identify BRCA1 and BRCA2 mutations in the Estonian population. We analyzed genetic data and questionnaire from 64 early-onset (< 45 y) breast cancer patients, 47 familial cases (patients with breast or ovarian cancer and a case of these cancers in the family), and 33 predictive cases (patients without breast or ovarian cancer, with a family history of such diseases) from Estonia for mutations in the BRCA1 gene. A sub-set of familial cases and predictive cases were also analyzed for mutations in the BRCA2 gene.</p> <p>Methods</p> <p>For mutation detection, we used the Polymerase Chain Reaction-Single Stranded Conformation Polymorphism Heteroduplex Analysis (PCR-SSCP-HD), followed by direct DNA sequencing.</p> <p>Results</p> <p>We identified three clinically important mutations in the BRCA1 gene, including seven occurrences of the c.5382insC mutation, three of c.4154delA, and one instance of c.3881_3882delGA. We also detected six polymorphisms: c.2430T>C, c.3232A>G, c.4158A>G, c.4427T>C, c.4956A>G, and c.5002T>C. Four sequence alterations were detected in introns: c.560+64delT, c.560+ [36-38delCTT, 52-63del12], c.666-58delT, and c.5396+60insGTATTCCACTCC. In the BRCA2 gene, two clinically important mutations were found: c.9610C>T and c.6631delTTAAATG. Additionally, two alterations (c.7049G>T and c.7069+80delTTAG) with unknown clinical significance were detected.</p> <p>Conclusions</p> <p>In our dataset, the overall frequency of clinically important BRCA1 mutations in early-onset patients, familial cases, and predictive testing was 7.6% (144 cases, 11 mutation carriers). Pathogenic mutations were identified in 4 of the 64 early-onset breast cancer cases (6.3%). In familial cases, clinically important mutations in the BRCA1 gene were found in 6 of the 47 individuals analyzed (12.8%). In predictive cases, 1 clinically important mutation was detected in 33 individuals studied (3%). The occurrence of clinically important mutations in BRCA2 in familial cases of breast cancer was 2 of the 16 individuals analyzed (12.5%).</p