Satellite-based tracking of migratory waterfowl is an important tool for understanding the potential role of wild birds in the long-distance transmission of highly pathogenic avian influenza. However, employing this technique on a continental scale is prohibitively expensive. This study explores the utility of stable isotope ratios in feathers in examining both the distances traveled by migratory birds and variation in migration behavior. We compared the satellite-derived movement data of 22 ducks from 8 species captured at wintering areas in Bangladesh, Turkey, and Hong Kong with deuterium ratios (?D) of these and other individuals captured at the same locations. We derived likely molting locations from the satellite tracking data and generated expected isotope ratios based on an interpolated map of ?D in rainwater. Although ?D was correlated with the distance between wintering and molting locations, surprisingly, measured ?D values were not correlated with either expected values or latitudes of molting sites. However, population-level parameters derived from the satellite-tracking data, such as mean distance between wintering and molting locations and variation in migration distance, were reflected by means and variation of the stable isotope values. Our findings call into question the relevance of the rainfall isotope map for Asia for linking feather isotopes to molting locations, and underscore the need for extensive ground truthing in the form of feather-based isoscapes. Nevertheless, stable isotopes from feathers could inform disease models by characterizing the degree to which regional breeding populations interact at common wintering locations. Feather isotopes also could aid in surveying wintering locations to determine where high-resolution tracking techniques (e.g. satellite tracking) could most effectively be employed. Moreover, intrinsic markers such as stable isotopes offer the only means of inferring movement information from birds that have died as a result of infection. In the absence of feather based-isoscapes, we recommend a combination of isotope analysis and satellite-tracking as the best means of generating aggregate movement data for informing disease models.
The role of molecular methods in the diagnosis of head and neck cancer is rapidly evolving and holds great potential for improving outcomes for all patients who suffer from this diverse group of malignancies . However, there is considerable debate as to the best clinical approaches, particularly for Next Generation Sequencing (NGS). The choices of NGS methods such as whole exome, whole genome, whole transcriptomes (RNA-Seq) or multiple gene resequencing panels, each have strengths and weakness based on data quality, the size of the data, the turnaround time for data analysis, and clinical actionability. There have also been a variety of gene expression signatures established from microarray studies that correlate with relapse and response to treatment, but none of these methods have been implemented as standard of care for oropharyngeal squamous cell carcinoma (OPSCC). Because many genomic methodologies are still far from the capabilities of most clinical laboratories, we chose to explore the use of a combination of off the shelf targeted mutation analysis and gene expression analysis methods to complement standard anatomical pathology methods. Specifically, we have used the Ion Torrent AmpliSeq cancer panel in combination with the NanoString nCounter Human Cancer Reference Kit on 8 formalin-fixed paraffin embedded (FFPE) OPSCC tumor specimens, (4) HPV-positive and (4) HPV-negative. Differential expression analysis between HPV-positive and negative groups showed that expression of several genes was highly likely to correlate with HPV status. For example, WNT1, PDGFA and OGG1 were all over-expressed in the positive group. Our results show the utility of these methods with routine FFPE clinical specimens to identify potential therapeutic targets which could be readily applied in a clinical trial setting for clinical laboratories lacking the instrumentation or bioinformatics infrastructure to support comprehensive genomics workflows. To the best of our knowledge, these preliminary experiments are among the earliest to combine both mutational and gene expression profiles using Ion Torrent and NanoString technologies. This reports serves as a proof of principle methodology in OPSCC.
For decades, southern China has been considered to be an important source for emerging influenza viruses since key hosts live together in high densities in areas with intensive agriculture. However, the underlying conditions of emergence and spread of avian influenza viruses (AIV) have not been studied in detail, particularly the complex spatiotemporal interplay of viral transmission between wild and domestic ducks, two major actors of AIV epidemiology. In this synthesis, we examine the risks of avian influenza spread in Poyang Lake, an area of intensive free-ranging duck production and large numbers of wild waterfowl. Our synthesis shows that farming of free-grazing domestic ducks is intensive in this area and synchronized with wild duck migration. The presence of juvenile domestic ducks in harvested paddy fields prior to the arrival and departure of migrant ducks in the same fields may amplify the risk of AIV circulation and facilitate the transmission between wild and domestic populations. We provide evidence associating wild ducks migration with the spread of H5N1 in the spring of 2008 from southern China to South Korea, Russia, and Japan, supported by documented wild duck movements and phylogenetic analyses of highly pathogenic avian influenza H5N1 sequences. We suggest that prevention measures based on a modification of agricultural practices may be implemented in these areas to reduce the intensity of AIV transmission between wild and domestic ducks. This would require involving all local stakeholders to discuss feasible and acceptable solutions.
We present a pipeline to perform integrative analysis of mate-pair (MP) and paired-end (PE) genomic DNA sequencing data. Our pipeline detects structural variations (SVs) by taking aligned sequencing read pairs as input and classifying these reads into properly paired and discordantly paired categories based on their orientation and inferred insert sizes. Recurrent SV was identified from the discordant read pairs. Our pipeline takes into account genomic annotation and genome repetitive element information to increase detection specificity. Application of our pipeline to whole-genome MP and PE sequencing data from three multiple myeloma cell lines (KMS11, MM.1S, and RPMI8226) recovered known SVs, such as heterozygous TRAF3 deletion, as well as a novel experimentally validated SPI1 - ZNF287 inter-chromosomal rearrangement in the RPMI8226 cell line.
Inverted duplications are a common type of copy number variation (CNV) in germline and somatic genomes. Large duplications that include many genes can lead to both neurodevelopmental phenotypes in children and gene amplifications in tumors. There are several models for inverted duplication formation, most of which include a dicentric chromosome intermediate followed by breakage-fusion-bridge (BFB) cycles, but the mechanisms that give rise to the inverted dicentric chromosome in most inverted duplications remain unknown. Here we have combined high-resolution array CGH, custom sequence capture, next-generation sequencing, and long-range PCR to analyze the breakpoints of 50 nonrecurrent inverted duplications in patients with intellectual disability, autism, and congenital anomalies. For half of the rearrangements in our study, we sequenced at least one breakpoint junction. Sequence analysis of breakpoint junctions reveals a normal-copy disomic spacer between inverted and non-inverted copies of the duplication. Further, short inverted sequences are present at the boundary of the disomic spacer and the inverted duplication. These data support a mechanism of inverted duplication formation whereby a chromosome with a double-strand break intrastrand pairs with itself to form a "fold-back" intermediate that, after DNA replication, produces a dicentric inverted chromosome with a disomic spacer corresponding to the site of the fold-back loop. This process can lead to inverted duplications adjacent to terminal deletions, inverted duplications juxtaposed to translocations, and inverted duplication ring chromosomes.
Highly pathogenic avian influenza H5N1 remains a serious concern for both poultry and human health. Wild waterfowl are considered to be the reservoir for low pathogenic avian influenza viruses; however, relatively little is known about their movement ecology in regions where HPAI H5N1 outbreaks regularly occur. We studied movements of the ruddy shelduck (Tadorna ferruginea), a wild migratory waterfowl species that was infected in the 2005 Qinghai Lake outbreak. We defined their migration with Brownian Bridge utilization distribution models and their breeding and wintering grounds with fixed kernel home ranges. We correlated their movements with HPAI H5N1 outbreaks, poultry density, land cover, and latitude in the Central Asian Flyway. Our Akaike Information Criterion analysis indicated that outbreaks were correlated with land cover, latitude, and poultry density. Although shelduck movements were included in the top two models, they were not a top parameter selected in AICc stepwise regression results. However, timing of outbreaks suggested that outbreaks in the flyway began during the winter in poultry with spillover to wild birds during the spring migration. Thus, studies of the movement ecology of wild birds in areas with persistent HPAI H5N1 outbreaks may contribute to understanding their role in transmission of this disease.
Species of Old World fruit-bats (family Pteropodidae) have been identified as the natural hosts of a number of novel and highly pathogenic viruses threatening livestock and human health. We used GPS data loggers to record the nocturnal foraging movements of Acerodon jubatus, the Golden-crowned flying fox in the Philippines to better understand the landscape utilisation of this iconic species, with the dual objectives of pre-empting disease emergence and supporting conservation management. Data loggers were deployed on eight of 54 A. jubatus (two males and six females) captured near Subic Bay on the Philippine island of Luzon between 22 November and 2 December 2010. Bodyweight ranged from 730 g to 1002 g, translating to a weight burden of 3-4% of bodyweight. Six of the eight loggers yielded useful data over 2-10 days, showing variability in the nature and range of individual bat movements. The majority of foraging locations were in closed forest and most were remote from evident human activity. Forty-six discrete foraging locations and five previously unrecorded roost locations were identified. Our findings indicate that foraging is not a random event, with the majority of bats exhibiting repetitious foraging movements night-to-night, that apparently intact forest provides the primary foraging resource, and that known roost locations substantially underestimate the true number (and location) of roosts. Our initial findings support policy and decision-making across perspectives including landscape management, species conservation, and potentially disease emergence.
Many tumors have highly rearranged genomes, but a major unknown is the relative importance and timing of genome rearrangements compared to sequence-level mutation. Chromosome instability might arise early, be a late event contributing little to cancer development, or happen as a single catastrophic event. Another unknown is which of the point mutations and rearrangements are selected. To address these questions we show, using the breast cancer cell line HCC1187 as a model, that we can reconstruct the likely history of a breast cancer genome. We assembled probably the most complete map to date of a cancer genome, by combining molecular cytogenetic analysis with sequence data. In particular, we assigned most sequence-level mutations to individual chromosomes by sequencing of flow sorted chromosomes. The parent of origin of each chromosome was assigned from SNP arrays. We were then able to classify most of the mutations as earlier or later according to whether they occurred before or after a landmark event in the evolution of the genome, endoreduplication (duplication of its entire genome). Genome rearrangements and sequence-level mutations were fairly evenly divided earlier and later, suggesting that genetic instability was relatively constant throughout the life of this tumor, and chromosome instability was not a late event. Mutations that caused chromosome instability would be in the earlier set. Strikingly, the great majority of inactivating mutations and in-frame gene fusions happened earlier. The non-random timing of some of the mutations may be evidence that they were selected.
Cancer genomes are complex, carrying thousands of somatic mutations including base substitutions, insertions and deletions, rearrangements, and copy number changes that have been acquired over decades. Recently, technologies have been introduced that allow generation of high-resolution, comprehensive catalogs of somatic alterations in cancer genomes. However, analyses of these data sets generally do not indicate the order in which mutations have occurred, or the resulting karyotype. Here, we introduce a mathematical framework that begins to address this problem. By using samples with accurate data sets, we can reconstruct relatively complex temporal sequences of rearrangements and provide an assembly of genomic segments into digital karyotypes. For cancer genes mutated in rearranged regions, this information can provide a chronological examination of the selective events that have taken place.
Characterizing the interface between wild and domestic animal populations is increasingly recognized as essential in the context of emerging infectious diseases (EIDs) that are transmitted by wildlife. More specifically, the spatial and temporal distribution of contact rates between wild and domestic hosts is a key parameter for modeling EIDs transmission dynamics. We integrated satellite telemetry, remote sensing and ground-based surveys to evaluate the spatio-temporal dynamics of indirect contacts between wild and domestic birds to estimate the risk that avian pathogens such as avian influenza and Newcastle viruses will be transmitted between wildlife to poultry. We monitored comb ducks (Sarkidiornis melanotos melanotos) with satellite transmitters for seven months in an extensive Afro-tropical wetland (the Inner Niger Delta) in Mali and characterise the spatial distribution of backyard poultry in villages. We modelled the spatial distribution of wild ducks using 250-meter spatial resolution and 8-days temporal resolution remotely-sensed environmental indicators based on a Maxent niche modelling method.
The acquisition of resistance to protein kinase inhibitors is a growing problem in cancer treatment. We modeled acquired resistance to the MEK1/2 (mitogen-activated or extracellular signal–regulated protein kinase kinases 1 and 2) inhibitor selumetinib (AZD6244) in colorectal cancer cell lines harboring mutations in BRAF (COLO205 and HT29 lines) or KRAS (HCT116 and LoVo lines). AZD6244-resistant derivatives were refractory to AZD6244-induced cell cycle arrest and death and exhibited a marked increase in ERK1/2 (extracellular signal–regulated kinases 1 and 2) pathway signaling and cyclin D1 abundance when assessed in the absence of inhibitor. Genomic sequencing revealed no acquired mutations in MEK1 or MEK2, the primary target of AZD6244. Rather, resistant lines showed a marked up-regulation of their respective driving oncogenes, BRAF600E or KRAS13D, due to intrachromosomal amplification. Inhibition of BRAF reversed resistance to AZD6244 in COLO205 cells, which suggested that combined inhibition of MEK1/2 and BRAF may reduce the likelihood of acquired resistance in tumors with BRAF600E. Knockdown of KRAS reversed AZD6244 resistance in HCT116 cells as well as reduced the activation of ERK1/2 and protein kinase B; however, the combined inhibition of ERK1/2 and phosphatidylinositol 3-kinase signaling had little effect on AZD6244 resistance, suggesting that additional KRAS effector pathways contribute to this process. Microarray analysis identified increased expression of an 18-gene signature previously identified as reflecting MEK1/2 pathway output in resistant cells. Thus, amplification of the driving oncogene (BRAF600E or KRAS13D) can drive acquired resistance to MEK1/2 inhibitors by increasing signaling through the ERK1/2 pathway. However, up-regulation of KRAS13D leads to activation of multiple KRAS effector pathways, underlining the therapeutic challenge posed by KRAS mutations. These results may have implications for the use of combination therapies.
Birds that fly over mountain barriers must be capable of meeting the increased energetic cost of climbing in low-density air, even though less oxygen may be available to support their metabolism. This challenge is magnified by the reduction in maximum sustained climbing rates in large birds. Bar-headed geese (Anser indicus) make one of the highest and most iconic transmountain migrations in the world. We show that those populations of geese that winter at sea level in India are capable of passing over the Himalayas in 1 d, typically climbing between 4,000 and 6,000 m in 7-8 h. Surprisingly, these birds do not rely on the assistance of upslope tailwinds that usually occur during the day and can support minimum climb rates of 0.8-2.2 km·h(-1), even in the relative stillness of the night. They appear to strategically avoid higher speed winds during the afternoon, thus maximizing safety and control during flight. It would seem, therefore, that bar-headed geese are capable of sustained climbing flight over the passes of the Himalaya under their own aerobic power.
Rearrangements of the genome can be detected by microarray methods and massively parallel sequencing, which identify copy-number alterations and breakpoint junctions, but these techniques are poorly suited to reconstructing the long-range organization of rearranged chromosomes, for example, to distinguish between translocations and insertions. The single-DNA-molecule technique HAPPY mapping is a method for mapping normal genomes that should be able to analyse genome rearrangements, i.e. deviations from a known genome map, to assemble rearrangements into a long-range map. We applied HAPPY mapping to cancer cell lines to show that it could identify rearrangement of genomic segments, even in the presence of normal copies of the genome. We could distinguish a simple interstitial deletion from a copy-number loss at an inversion junction, and detect a known translocation. We could determine whether junctions detected by sequencing were on the same chromosome, by measuring their linkage to each other, and hence map the rearrangement. Finally, we mapped an uncharacterized reciprocal translocation in the T-47D breast cancer cell line to about 2?kb and hence cloned the translocation junctions. We conclude that HAPPY mapping is a versatile tool for determining the structure of rearrangements in the human genome.
The acquisition of resistance to protein kinase inhibitors is a growing problem in cancer treatment. We modeled acquired resistance to the MEK1/2 (mitogen-activated or extracellular signal-regulated protein kinase kinases 1 and 2) inhibitor selumetinib (AZD6244) in colorectal cancer cell lines harboring mutations in BRAF (COLO205 and HT29 lines) or KRAS (HCT116 and LoVo lines). AZD6244-resistant derivatives were refractory to AZD6244-induced cell cycle arrest and death and exhibited a marked increase in ERK1/2 (extracellular signal-regulated kinases 1 and 2) pathway signaling and cyclin D1 abundance when assessed in the absence of inhibitor. Genomic sequencing revealed no acquired mutations in MEK1 or MEK2, the primary target of AZD6244. Rather, resistant lines showed a marked up-regulation of their respective driving oncogenes, BRAF(600E) or KRAS(13D), due to intrachromosomal amplification. Inhibition of BRAF reversed resistance to AZD6244 in COLO205 cells, which suggested that combined inhibition of MEK1/2 and BRAF may reduce the likelihood of acquired resistance in tumors with BRAF(600E). Knockdown of KRAS reversed AZD6244 resistance in HCT116 cells as well as reduced the activation of ERK1/2 and protein kinase B; however, the combined inhibition of ERK1/2 and phosphatidylinositol 3-kinase signaling had little effect on AZD6244 resistance, suggesting that additional KRAS effector pathways contribute to this process. Microarray analysis identified increased expression of an 18-gene signature previously identified as reflecting MEK1/2 pathway output in resistant cells. Thus, amplification of the driving oncogene (BRAF(600E) or KRAS(13D)) can drive acquired resistance to MEK1/2 inhibitors by increasing signaling through the ERK1/2 pathway. However, up-regulation of KRAS(13D) leads to activation of multiple KRAS effector pathways, underlining the therapeutic challenge posed by KRAS mutations. These results may have implications for the use of combination therapies.
Qinghai Lake in central China has been at the center of debate on whether wild birds play a role in circulation of highly pathogenic avian influenza virus H5N1. In 2005, an unprecedented epizootic at Qinghai Lake killed more than 6000 migratory birds including over 3000 bar-headed geese (Anser indicus). H5N1 subsequently spread to Europe and Africa, and in following years has re-emerged in wild birds along the Central Asia flyway several times.
Reciprocal chromosome translocations are often not exactly reciprocal. Most familiar are deletions at the breakpoints, up to megabases in extent. We describe here the opposite phenomenon-duplication of tens or hundreds of kilobases at the breakpoint junction, so that the same sequence is present on both products of a translocation. When the products of the translocation are mapped on the genome, they overlap. We report several of these "overlapping-breakpoint" duplications in breast cancer cell lines HCC1187, HCC1806, and DU4475. These lines also had deletions and essentially balanced translocations. In HCC1187 and HCC1806, we identified five cases of duplication ranging between 46 kb and 200 kb, with the partner chromosome showing deletions between 29 bp and 31 Mb. DU4475 had a duplication of at least 200 kb. Breakpoints were mapped using array painting, i.e., hybridization of chromosomes isolated by flow cytometry to custom oligonucleotide microarrays. Duplications were verified by fluorescent in situ hybridization (FISH), PCR on isolated chromosomes, and cloning of breakpoints. We propose that these duplications are the counterpart of deletions and that they are produced at a replication bubble, comprising two replication forks with the duplicated sequence in between. Both copies of the duplicated sequence would go to one daughter cell, on different products of the translocation, while the other daughter cell would show deletion. These duplications may have been overlooked because they may be missed by FISH and array-CGH and may be interpreted as insertions by paired-end sequencing. Such duplications may therefore be quite frequent.
In somatic cells, Holliday junctions can be formed between sister chromatids during the recombinational repair of DNA breaks or after replication fork demise. A variety of processes act upon Holliday junctions to remove them from DNA, in events that are critical for proper chromosome segregation. In human cells, the BLM protein, inactivated in individuals with Blooms syndrome, acts in combination with topoisomerase III?, RMI1 and RMI2 (BTR complex) to promote the dissolution of double Holliday junctions. Cells defective for BLM exhibit elevated levels of sister chromatid exchanges (SCEs) and patients with Blooms syndrome develop a broad spectrum of early-onset cancers caused by chromosome instability. MUS81-EME1 (refs 4-7), SLX1-SLX4 (refs 8-11) and GEN1 (refs 12, 13) also process Holliday junctions but, in contrast to the BTR complex, do so by endonucleolytic cleavage. Here we deplete these nucleases from Blooms syndrome cells to analyse human cells compromised for the known Holliday junction dissolution/resolution pathways. We show that depletion of MUS81 and GEN1, or SLX4 and GEN1, from Blooms syndrome cells results in severe chromosome abnormalities, such that sister chromatids remain interlinked in a side-by-side arrangement and the chromosomes are elongated and segmented. Our results indicate that normally replicating human cells require Holliday junction processing activities to prevent sister chromatid entanglements and thereby ensure accurate chromosome condensation. This phenotype was not apparent when both MUS81 and SLX4 were depleted from Blooms syndrome cells, suggesting that GEN1 can compensate for their absence. Additionally, we show that depletion of MUS81 or SLX4 reduces the high frequency of SCEs in Blooms syndrome cells, indicating that MUS81 and SLX4 promote SCE formation, in events that may ultimately drive the chromosome instabilities that underpin early-onset cancers associated with Blooms syndrome.
Highly pathogenic avian influenza (HPAI) H5N1 virus persists in Asia, posing a threat to poultry, wild birds, and humans. Previous work in Southeast Asia demonstrated that HPAI H5N1 risk is related to domestic ducks and people. Other studies discussed the role of migratory birds in the long distance spread of HPAI H5N1. However, the interplay between local persistence and long-distance dispersal has never been studied. We expand previous geospatial risk analysis to include South and Southeast Asia, and integrate the analysis with migration data of satellite-tracked wild waterfowl along the Central Asia flyway. We find that the population of domestic duck is the main factor delineating areas at risk of HPAI H5N1 spread in domestic poultry in South Asia, and that other risk factors, such as human population and chicken density, are associated with HPAI H5N1 risk within those areas. We also find that satellite tracked birds (Ruddy Shelduck and two Bar-headed Geese) reveal a direct spatio-temporal link between the HPAI H5N1 hot-spots identified in India and Bangladesh through our risk model, and the wild bird outbreaks in May-June-July 2009 in China (Qinghai Lake), Mongolia, and Russia. This suggests that the continental-scale dynamics of HPAI H5N1 are structured as a number of persistence areas delineated by domestic ducks, connected by rare transmission through migratory waterfowl.
Poyang Lake is situated within the East Asian Flyway, a migratory corridor for waterfowl that also encompasses Guangdong Province, China, the epicenter of highly pathogenic avian influenza (HPAI) H5N1. The lake is the largest freshwater body in China and a significant congregation site for waterfowl; however, surrounding rice fields and poultry grazing have created an overlap with wild waterbirds, a situation conducive to avian influenza transmission. Reports of HPAI H5N1 in healthy wild ducks at Poyang Lake have raised concerns about the potential of resilient free-ranging birds to disseminate the virus. Yet the role wild ducks play in connecting regions of HPAI H5N1 outbreak in Asia is hindered by a lack of information about their migratory ecology. During 2007-08 we marked wild ducks at Poyang Lake with satellite transmitters to examine the location and timing of spring migration and identify any spatiotemporal relationship with HPAI H5N1 outbreaks. Species included the Eurasian wigeon (Anas penelope), northern pintail (Anas acuta), common teal (Anas crecca), falcated teal (Anas falcata), Baikal teal (Anas formosa), mallard (Anas platyrhynchos), garganey (Anas querquedula), and Chinese spotbill (Anas poecilohyncha). These wild ducks (excluding the resident mallard and Chinese spotbill ducks) followed the East Asian Flyway along the coast to breeding areas in northern China, eastern Mongolia, and eastern Russia. None migrated west toward Qinghai Lake (site of the largest wild bird epizootic), thus failing to demonstrate any migratory connection to the Central Asian Flyway. A newly developed Brownian bridge spatial analysis indicated that HPAI H5N1 outbreaks reported in the flyway were related to latitude and poultry density but not to the core migration corridor or to wetland habitats. Also, we found a temporal mismatch between timing of outbreaks and wild duck movements. These analyses depend on complete or representative reporting of outbreaks, but by documenting movements of wild waterfowl, we present ecological knowledge that better informs epidemiological investigations seeking to explain and predict the spread of avian influenza viruses.
Ongoing meat and food industry consolidation has resulted in the creation of larger and more complex, vertically integrated and/or coordinated food production systems. These systems have also been focused on development of differentiated Value Chains as a departure from the traditional commodity oriented Supply Chains. The main goal of value chains is to achieve sustainable competitiveness through focusing resources on efficiently producing goods that offer superior consumer-recognized value. A closely-aligned value chain often contains vertically and horizontally linked players such as genetics and genetic improvement program(s), farmer(s), processor(s), distributor(s), and retailer(s). In this paper we postulate that the underlying foundation of the success of meat value chain accomplishments has been through substantial development of animal genetic technologies enabling sustainable production of animal protein-based consumer products of desirable quantity and quality. It is plausible to assume that further advancement in genomic selection and eventually proteomics will enable implementation of more complex genetic improvement programs leading to further development of differentiated meat value chains focused on ever changing consumer needs.
Determining if outbreak data collected by regional or international organizations can reflect patterns observed in more detailed data collected by national veterinary services is a necessary first step if global databases are to be used for making inference about determinants of disease maintenance and spread and for emergency planning and response. We compared two data sources that capture spatial and temporal information about H5N1 highly pathogenic avian influenza outbreaks reported since 2004 in four countries: Bangladesh, Egypt, Turkey, and Vietnam. One data source consisted of reports collected as part of each countrys national veterinary services surveillance program, while the other data source included reports collected using the Emergency Prevention System for Priority Animal and Plant Pests and Diseases (EMPRES-i) global animal health information system. We computed Spearman rank-order correlation statistics to compare spatial and temporal outbreak distributions, and applied a space-time permutation test to check for consistency between the two data sources. Although EMPRES-i typically captured fewer outbreaks than detailed national reporting data, the overall similarity in space and time, particularly after 2006, reflect the ability of the EMPRES-i system to portray disease patterns comparable to those observed in national data sets. Specifically, we show that the two datasets exhibit higher positive correlations in outbreak timing and reported locations after 2006 when compared to December 2003 through 2006. Strengthening the capacity of global systems to acquire data from national and regional databases will improve global analysis efforts and increase the ability of such systems to rapidly alert countries and the international community of potential disease threats.
Genes that are broken or fused by structural changes to the genome are an important class of mutation in the leukemias and sarcomas but have been largely overlooked in the common epithelial cancers. Large-scale sequencing is changing our perceptions of the cancer genome, and it is now being applied to structural changes, using the paired end strategy. This reveals more clearly than before the extent to which many cancer genomes are rearranged and how much these rearrangements contribute to the mutational burden of epithelial tumors. In particular, there are probably many fusion genes, analogous to those found in leukemias, to be found in common cancers, such as breast carcinoma, and some of these will prove to be important in cancer diagnosis and treatment.
Virological, molecular and serological studies were carried out to determine the status of infections with avian influenza viruses (AIV) in different species of wild waterbirds in Iran during 2003-2007. Samples were collected from 1146 birds representing 45 different species with the majority of samples originating from ducks, coots and shorebirds. Samples originated from 6 different provinces representative for the 15 most important wintering sites of migratory waterbirds in Iran.
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) approximately 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.
The dispersal of individuals among fragmented populations is generally thought to prevent genetic and demographic isolation, and ultimately reduce extinction risk. In this study, we show that a century of reduction in coastal old-growth forests, as well as a number of other environmental factors, has probably resulted in the genetic divergence of marbled murrelets (Brachyramphus marmoratus) in central California, despite the fact that 7 per cent of modern-sampled murrelets in this population were classified as migrants using genetic assignment tests. Genetic differentiation appears to persist because individuals dispersing from northern populations contributed relatively few young to the central California population, as indicated by the fact that migrants were much less likely to be members of parent-offspring pairs than residents (10.5% versus 45.4%). Moreover, a recent 1.4 per cent annual increase in the proportion of migrants in central California, without appreciable reproduction, may have masked an underlying decline in the resident population without resulting in demographic rescue. Our results emphasize the need to understand the behaviour of migrants and the extent to which they contribute offspring in order to determine whether dispersal results in gene flow and prevents declines in resident populations.
Evaluating the potential involvement of wild avifauna in the emergence of highly pathogenic avian influenza H5N1 (hereafter H5N1) requires detailed analyses of temporal and spatial relationships between wild bird movements and disease emergence. The death of wild swans (Cygnus spp.) has been the first indicator of the presence of H5N1 in various Asian and European countries; however their role in the geographic spread of the disease remains poorly understood. We marked 10 whooper swans (Cygnus cygnus) with GPS transmitters in northeastern Mongolia during autumn 2006 and tracked their migratory movements in relation to H5N1 outbreaks. The prevalence of H5N1 outbreaks among poultry in eastern Asia during 2003-2007 peaked during winter, concurrent with whooper swan movements into regions of high poultry density. However outbreaks involving poultry were detected year round, indicating disease perpetuation independent of migratory waterbird presence. In contrast, H5N1 outbreaks involving whooper swans, as well as other migratory waterbirds that succumbed to the disease in eastern Asia, tended to occur during seasons (late spring and summer) and in habitats (areas of natural vegetation) where their potential for contact with poultry is very low to nonexistent. Given what is known about the susceptibility of swans to H5N1, and on the basis of the chronology and rates of whooper swan migration movements, we conclude that although there is broad spatial overlap between whooper swan distributions and H5N1 outbreak locations in eastern Asia, the likelihood of direct transmission between these groups is extremely low. Thus, our data support the hypothesis that swans are best viewed as sentinel species, and moreover, that in eastern Asia, it is most likely that their infections occurred through contact with asymptomatic migratory hosts (e.g., wild ducks) at or near their breeding grounds.
A Fourier-Bessel (FB) basis is used to solve two-dimensional (2D) cylindrical Maxwells equations for localized states within dielectric structures that possess rotational symmetry. The technique is used to determine the wavelengths and profiles of the stationary states supported by the structure and identify the bandgaps. 12-fold quasi-crystals for the TE and TM polarizations are analyzed. Since the FB approach with 2D photonic crystals in this fashion is new, the accuracy of the results is confirmed using finite-difference time-domain simulations.
The highly pathogenic avian influenza (H5N1 subtype) recurred in Nigeria after 9 months period of no reported case. A critical look at possible sources of the re-occurrence was desirable. The objective of this study was to determine whether avian influenza viruses were present at reasonably detectable levels (0.5%) in possible "bridge" species of wild and domestic birds. The study was conducted in 8 Nigerian states. A total of 403 birds from 40 species were sampled. Virus isolation was done in embryonated chicken eggs according to standard protocols. The test results were all negative for avian influenza viruses. The overall confidence interval (CI) calculated in R using the exact binomial confidence interval function was 0-0.007406. Tawny Eagle (Aquila rapax) was the lowest sampled 0.3% (1/403) and Red-billed Firefinch (Lagonosticta senegala) the highest 11.7% (47/403). The limitations of the sample size and possibly designing effects on the study, as to make concrete conclusions were acknowledged. Species of wild birds, so identified in the study could be useful in future surveys. Furthermore, multidisciplinary and community oriented approach, blending targeted and passive surveillances was suggested. This approach was envisaged to bring about wider coverage of "bridge" species and clearer insight of their possible roles in avian influenza re-occurrences and spread in Nigeria.
Heterogeneity in the transmission rates of pathogens across hosts or environments may produce disease hotspots, which are defined as specific sites, times or species associations in which the infection rate is consistently elevated. Hotspots for avian influenza virus (AIV) in wild birds are largely unstudied and poorly understood. A striking feature is the existence of a unique but consistent AIV hotspot in shorebirds (Charadriiformes) associated with a single species at a specific location and time (ruddy turnstone Arenaria interpres at Delaware Bay, USA, in May). This unique case, though a valuable reference, limits our capacity to explore and understand the general properties of AIV hotspots in shorebirds. Unfortunately, relatively few shorebirds have been sampled outside Delaware Bay and they belong to only a few shorebird families; there also has been a lack of consistent oropharyngeal sampling as a complement to cloacal sampling. In this study we looked for AIV hotspots associated with other shorebird species and/or with some of the larger congregation sites of shorebirds in the old world. We assembled and analysed a regionally extensive dataset of AIV prevalence from 69 shorebird species sampled in 25 countries across Africa and Western Eurasia. Despite this diverse and extensive coverage we did not detect any new shorebird AIV hotspots. Neither large shorebird congregation sites nor the ruddy turnstone were consistently associated with AIV hotspots. We did, however, find a low but widespread circulation of AIV in shorebirds that contrast with the absence of AIV previously reported in shorebirds in Europe. A very high AIV antibody prevalence coupled to a low infection rate was found in both first-year and adult birds of two migratory sandpiper species, suggesting the potential existence of an AIV hotspot along their migratory flyway that is yet to be discovered.
To assess West Nile virus (WNV) infection in wild resident and migratory birds, we tested 3887 samples from 1784 birds belonging to 119 identified species within 30 families collected during 2008-10 from 13 states in India. The serum samples were tested for WNV antibodies initially by a competition ELISA and subsequently by a micro-plaque reduction neutralization test (Micro-PRNT), whereas tracheal and cloacal swabs were subjected to real-time RT-PCR for the detection of the WNV RNA. Twenty six birds (2.46%) out of 1058 tested showed evidence of flavivirus antibodies by ELISA. End point neutralization antibody determinations for WNV and Japanese encephalitis virus (JEV) showed that of the 22 ELISA positive sera, WNV-specific neutralizing antibodies were detected in 17 samples representing nine species of wild birds (residents: Purple swamphen, Little cormorant, Little egret, Black ibis and Spot-billed duck; residents with winter influx: Common coot and Mallard; migratory birds: Ruff and Purple heron), and two samples were positive for both WNV and JEV antibodies. The WNV-specific antibodies were most commonly detected in Mallards and Common coots. WNV genomic RNA was not detected by real-time RT-PCR. The results in this study suggest that wild resident birds are infected occasionally and wild migratory birds rarely with WNV. Additionally, our study provides evidence of WNV infection in eastern and northern India for the first time.
The expansion of repressive epigenetic marks has been implicated in heterochromatin formation during embryonic development, but the general applicability of this mechanism is unclear. Here we show that nuclear rearrangement of repressive histone marks H3K9me3 and H3K27me3 into nonoverlapping structural layers characterizes senescence-associated heterochromatic foci (SAHF) formation in human fibroblasts. However, the global landscape of these repressive marks remains unchanged upon SAHF formation, suggesting that in somatic cells, heterochromatin can be formed through the spatial repositioning of pre-existing repressively marked histones. This model is reinforced by the correlation of presenescent replication timing with both the subsequent layered structure of SAHFs and the global landscape of the repressive marks, allowing us to integrate microscopic and genomic information. Furthermore, modulation of SAHF structure does not affect the occupancy of these repressive marks, nor vice versa. These experiments reveal that high-order heterochromatin formation and epigenetic remodeling of the genome can be discrete events.
The effect of adding a thin high index dielectric overlay layer onto a 3-layer slab waveguide demonstrates several interesting features that can be exploited in integrated optical device configurations. A simple modal analysis is employed to examine the behavior of guided light launched from a 3-layer waveguide structure then coupled and propagated in the 4-layer overlay region. Modal properties typically overlooked in conventional slab waveguides are made use of in the design and theoretical analysis of an MMI device and optical index of refraction sensor. The optical structure presented here can form the backdrop waveguide design for more complex and active devices.
A unique pattern of highly pathogenic avian influenza (HPAI) H5N1 outbreaks has emerged along the Central Asia Flyway, where infection of wild birds has been reported with steady frequency since 2005. We assessed the potential for two hosts of HPAI H5N1, the bar-headed goose (Anser indicus) and ruddy shelduck (Tadorna tadorna), to act as agents for virus dispersal along this thoroughfare. We used an eco-virological approach to compare the migration of 141 birds marked with GPS satellite transmitters during 2005-2010 with: 1) the spatio-temporal patterns of poultry and wild bird outbreaks of HPAI H5N1, and 2) the trajectory of the virus in the outbreak region based on phylogeographic mapping. We found that biweekly utilization distributions (UDs) for 19.2% of bar-headed geese and 46.2% of ruddy shelduck were significantly associated with outbreaks. Ruddy shelduck showed highest correlation with poultry outbreaks owing to their wintering distribution in South Asia, where there is considerable opportunity for HPAI H5N1 spillover from poultry. Both species showed correlation with wild bird outbreaks during the spring migration, suggesting they may be involved in the northward movement of the virus. However, phylogeographic mapping of HPAI H5N1 clades 2.2 and 2.3 did not support dissemination of the virus in a northern direction along the migration corridor. In particular, two subclades (2.2.1 and 2.3.2) moved in a strictly southern direction in contrast to our spatio-temporal analysis of bird migration. Our attempt to reconcile the disciplines of wild bird ecology and HPAI H5N1 virology highlights prospects offered by both approaches as well as their limitations.
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