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1.  Regional areas and widths of the midsagittal corpus callosum among HIV-infected patients on stable antiretroviral therapies 
Journal of neurovirology  2011;17(4):368-379.
Recent reports suggest that a growing number of human immunodeficiency virus (HIV)-infected persons show signs of persistent cognitive impairment even in the context of combination antiretroviral therapies (cART). The basis for this finding remains poorly understood as there are only a limited number of studies examining the relationship between CNS injury, measures of disease severity, and cognitive function in the setting of stable disease. This study examined the effects of HIV infection on cerebral white matter using quantitative morphometry of the midsagittal corpus callosum (CC) in 216 chronically infected participants from the multisite HIV Neuroimaging Consortium study currently receiving cART and 139 controls. All participants underwent MRI assessment, and HIV-infected subjects also underwent measures of cognitive function and disease severity. The midsagittal slice of the CC was quantified using two semi-automated procedures. Group comparisons were accomplished using ANOVA, and the relationship between CC morphometry and clinical covariates (current CD4, nadir CD4, plasma and CSF HIV RNA, duration of HIV infection, age, and ADC stage) was assessed using linear regression models. HIV-infected patients showed significant reductions in both the area and linear widths for several regions of the CC. Significant relationships were found with ADC stage and nadir CD4 cell count, but no other clinical variables. Despite effective treatment, significant and possibly irreversible structural loss of the white matter persists in the setting of chronic HIV disease. A history of advanced immune suppression is a strong predictor of this complication and suggests that antiretroviral intervention at earlier stages of infection may be warranted.
PMCID: PMC4309645  PMID: 21556960
HIV; Corpus callosum; Nadir CD4; White matter; CART
2.  Engulfment of Activated Apoptotic Cells Abolishes TGF-β–Mediated Immunoregulation via the Induction of IL-6 
Phagocytosis of apoptotic cells (ACs) is usually a potent immunoregulatory signal but can also promote inflammation. In this article, we show that administration of apoptotic dendritic cells (DCs) inhibited inflammation in vivo through increasing production of TGF-β from intrinsic DCs and B cells. However, ACs derived from LPS-activated DCs failed to restrain inflammation because of a short-lived but marked IL-6 response, which abolished the increase in TGF-β. Inhibition of IL-6 restored the protective anti-inflammatory properties of aACs and the TGF-β response. DCs isolated from mice that had received resting but not activated ACs could transfer the suppression of inflammation to recipient mice. These transferred DCs stimulated B cell TGF-β production and relied on an intact B cell compartment to limit inflammation. These results highlight how the activation state of AC governs their ability to control inflammation through reciprocal regulation of IL-6 and TGF-β.
PMCID: PMC4319310  PMID: 25601923
3.  Hitch-hiker taken for a ride: an unusual cause of myocarditis, septic shock and adult respiratory distress syndrome 
BMJ Case Reports  2013;2013:bcr2012007155.
Rocky Mountain spotted fever (RMSF) is a serious tick-borne illness caused by Rickettsia rickettsii that is endemic in southeastern USA. Although RMSF has been described as causing the classic clinical triad of fever, headache and a characteristic rash, serious and potentially life-threatening manifestations can occur. Cardiopulmonary involvement, although infrequent, may occur with severe cases of RMSF. Rickettsial myocarditis is an uncommon occurrence. We present a case of a previously healthy 26-year-old man, who was hitch-hiking across the southeastern USA, with serologically proven RMSF causing adult respiratory distress syndrome, septic shock and myocarditis manifested by elevated cardiac enzymes and decrease in myocardial function. After treatment with antibiotics, the myocarditis resolved. Therefore, although unusual, clinicians should be aware of possible myocardial involvement in patients with appropriate tick-exposure histories or other clinical signs of RMSF.
PMCID: PMC3603717  PMID: 23314875
4.  Ovary ecdysteroidogenic hormone functions independently of the insulin receptor in the yellow fever mosquito, Aedes aegypti 
Insect biochemistry and molecular biology  2013;43(12):10.1016/j.ibmb.2013.09.004.
Most mosquito species must feed on the blood of a vertebrate host to produce eggs. In the yellow fever mosquito, Aedes aegypti, blood feeding triggers medial neurosecretory cells in the brain to release insulin-like peptides (ILPs) and ovary ecdysteroidogenic hormone (OEH). Theses hormones thereafter directly induce the ovaries to produce ecdysteroid hormone (ECD), which activates the synthesis of yolk proteins in the fat body for uptake by oocytes. ILP3 stimulates ECD production by binding to the mosquito insulin receptor (MIR). In contrast, little is known about the mode of action of OEH, which is a member of a neuropeptide family called neuroparsin. Here we report that OEH is the only neuroparsin family member present in the Ae. aegypti genome and that other mosquitoes also encode only one neuroparsin gene. Immunoblotting experiments suggested that the full-length form of the peptide, which we call long OEH (lOEH), is processed into short OEH (sOEH). The importance of processing, however, remained unclear because a recombinant form of lOEH (rlOEH) and synthetic sOEH exhibited very similar biological activity. A series of experiments indicated that neither rlOEH nor sOEH bound to ILP3 or the MIR. Signaling studies further showed that ILP3 activated the MIR but rlOEH did not, yet both neuropeptides activated Akt, which is a marker for insulin pathway signaling. Our results also indicated that activation of TOR signaling in the ovaries required co-stimulation by amino acids and either ILP3 or rlOEH. Overall, we conclude that OEH activates the insulin signaling pathway independently of the MIR, and that insulin and TOR signaling in the ovaries is coupled.
PMCID: PMC3885182  PMID: 24076067
5.  Parasites and genetic diversity in an invasive bumblebee 
The Journal of Animal Ecology  2014;83(6):1428-1440.
Biological invasions are facilitated by the global transportation of species and climate change. Given that invasions may cause ecological and economic damage and pose a major threat to biodiversity, understanding the mechanisms behind invasion success is essential.Both the release of non-native populations from natural enemies, such as parasites, and the genetic diversity of these populations may play key roles in their invasion success.We investigated the roles of parasite communities, through enemy release and parasite acquisition, and genetic diversity in the invasion success of the non-native bumblebee, Bombus hypnorum, in the United Kingdom.The invasive B. hypnorum had higher parasite prevalence than most, or all native congeners for two high-impact parasites, probably due to higher susceptibility and parasite acquisition. Consequently parasites had a higher impact on B. hypnorum queens’ survival and colony-founding success than on native species. Bombus hypnorum also had lower functional genetic diversity at the sex-determining locus than native species. Higher parasite prevalence and lower genetic diversity have not prevented the rapid invasion of the United Kingdom by B. hypnorum. These data may inform our understanding of similar invasions by commercial bumblebees around the world.This study suggests that concerns about parasite impacts on the small founding populations common to re-introduction and translocation programs may be less important than currently believed.
PMCID: PMC4235342  PMID: 24749545
Apicystis; biological invasion; Bombus hypnorum; enemy release; parasite acquisition; Sphaerularia
6.  Individual Differences in the Balance of GABA to Glutamate in pFC Predict the Ability to Select among Competing Options 
Journal of cognitive neuroscience  2014;26(11):2490-2502.
Individuals vary greatly in their ability to select one item or response when presented with a multitude of options. Here we investigate the neural underpinnings of these individual differences. Using magnetic resonance spectroscopy, we found that the balance of inhibitory versus excitatory neurotransmitters in pFC predicts the ability to select among task-relevant options in two language production tasks. The greater an individual’s concentration of GABA relative to glutamate in the lateral pFC, the more quickly he or she could select a relevant word from among competing options. This outcome is consistent with our computational modeling of this task [Snyder, H. R., Hutchison, N., Nyhus, E., Curran, T., Banich, M. T., O’Reilly, R. C., et al. Neural inhibition enables selection during language processing. Proceedings of the National Academy of Sciences, U.S.A., 107, 16483–16488, 2010], which predicts that greater net inhibition in pFC increases the efficiency of resolving competition among task-relevant options. Moreover, the association with the GABA/glutamate ratio was specific to selection and was not observed for executive function ability in general. These findings are the first to link the balance of excitatory and inhibitory neural transmission in pFC to specific aspects of executive function.
PMCID: PMC4182145  PMID: 24742191
7.  Metagenomic insights into strategies of carbon conservation and unusual sulfur biogeochemistry in a hypersaline Antarctic lake 
The ISME Journal  2013;7(10):1944-1961.
Organic Lake is a shallow, marine-derived hypersaline lake in the Vestfold Hills, Antarctica that has the highest reported concentration of dimethylsulfide (DMS) in a natural body of water. To determine the composition and functional potential of the microbial community and learn about the unusual sulfur chemistry in Organic Lake, shotgun metagenomics was performed on size-fractionated samples collected along a depth profile. Eucaryal phytoflagellates were the main photosynthetic organisms. Bacteria were dominated by the globally distributed heterotrophic taxa Marinobacter, Roseovarius and Psychroflexus. The dominance of heterotrophic degradation, coupled with low fixation potential, indicates possible net carbon loss. However, abundant marker genes for aerobic anoxygenic phototrophy, sulfur oxidation, rhodopsins and CO oxidation were also linked to the dominant heterotrophic bacteria, and indicate the use of photo- and lithoheterotrophy as mechanisms for conserving organic carbon. Similarly, a high genetic potential for the recycling of nitrogen compounds likely functions to retain fixed nitrogen in the lake. Dimethylsulfoniopropionate (DMSP) lyase genes were abundant, indicating that DMSP is a significant carbon and energy source. Unlike marine environments, DMSP demethylases were less abundant, indicating that DMSP cleavage is the likely source of high DMS concentration. DMSP cleavage, carbon mixotrophy (photoheterotrophy and lithoheterotrophy) and nitrogen remineralization by dominant Organic Lake bacteria are potentially important adaptations to nutrient constraints. In particular, carbon mixotrophy relieves the extent of carbon oxidation for energy production, allowing more carbon to be used for biosynthetic processes. The study sheds light on how the microbial community has adapted to this unique Antarctic lake environment.
PMCID: PMC3965305  PMID: 23619305
metagenomics; Organic Lake; Antarctic microbial ecology; nutrient cycles; dimethylsulfide
8.  The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study Protocol 
Stroke; a journal of cerebral circulation  2013;44(10):10.1161/STROKEAHA.113.002332.
Background and Purpose
Epidemiologic studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, age at presentation, and outcomes among non-Hispanic white, black, and Hispanic populations. We report here the design and methods for this large, prospective, multi-center case-control study of ICH.
The ERICH study is a multi-center, prospective case-control study of ICH. Cases are identified by hot-pursuit and enrolled using standard phenotype and risk factor information and include neuroimaging and blood sample collection. Controls are centrally identified by random digit dialing to match cases by age (+/−5 years), race, ethnicity, gender and metropolitan region.
As of March 22, 2013, 1,655 cases of ICH had been recruited into the study which is 101.5% of the target for that date and 851 controls had been recruited which is 67.2% of the target for that date (1,267 controls) for a total of 2,506 subjects which is 86.5% of the target for that date (2,897 subjects). Of the 1,655 cases enrolled, 1,640 cases had the case interview entered into the database of which 628 (38%) were non-Hispanic black, 458 (28%) were non-Hispanic white and 554 (34%) were Hispanic. Of the 1,197 cases with imaging submitted, 876 (73.2%) had a 24 hour follow-up CT available In addition to CT imaging, 607 cases have had MRI evaluation.
The ERICH study is a large, case-control study of ICH with particular emphasis on recruitment of minority populations for the identification of genetic and epidemiologic risk factors for ICH and outcomes after ICH.
PMCID: PMC3873723  PMID: 24021679
Stroke; Intracerebral Hemorrhage; Risk Factors; Hypertension; Minorities; Genetics; Genomics
10.  Deep sequencing of non-ribosomal peptide synthetases and polyketide synthases from the microbiomes of Australian marine sponges 
The ISME Journal  2013;7(9):1842-1851.
The biosynthesis of non-ribosomal peptide and polyketide natural products is facilitated by multimodular enzymes that contain domains responsible for the sequential condensation of amino and carboxylic subunits. These conserved domains provide molecular targets for the discovery of natural products from microbial metagenomes. This study demonstrates the application of tag-encoded FLX amplicon pyrosequencing (TEFAP) targeting non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) genes as a method for determining the identity and diversity of natural product biosynthesis genes. To validate this approach, we assessed the diversity of NRPS and PKS genes within the microbiomes of six Australian marine sponge species using both TEFAP and metagenomic whole-genome shotgun sequencing approaches. The TEFAP approach identified 100 novel ketosynthase (KS) domain sequences and 400 novel condensation domain sequences within the microbiomes of the six sponges. The diversity of KS domains within the microbiome of a single sponge species Scopalina sp. exceeded that of any previously surveyed marine sponge. Furthermore, this study represented the first to target the condensation domain from NRPS biosynthesis and resulted in the identification of a novel condensation domain lineage. This study highlights the untapped potential of Australian marine sponges for the isolation of novel bioactive natural products. Furthermore, this study demonstrates that TEFAP approaches can be applied to functional genes, involved in natural product biosynthesis, as a tool to aid natural product discovery. It is envisaged that this approach will be used across multiple environments, offering an insight into the biological processes that influence the production of secondary metabolites.
PMCID: PMC3749504  PMID: 23598791
sponges; NRPS/PKS; symbionts; pyrosequencing
11.  Progressive Cerebral Injury in the Setting of Chronic HIV Infection and Antiretroviral Therapy 
Journal of neurovirology  2013;19(3):209-218.
Emerging evidence suggests that CNS injury and neurocognitive impairment persist in the setting of chronic HIV infection and combination antiretroviral therapy (CART). Yet whether neurological injury can progress in this setting remains uncertain.
Magnetic resonance spectroscopy, neurocognitive and clinical assessments were performed over two years in 226 HIV-infected individuals on stable CART, including 138 individuals who were neurocognitively asymptomatic (NA). Concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myoinositol (MI), and glutamate/glutamine (Glx) were measured in the midfrontal cortex (MFC), frontal white matter (FWM) and basal ganglia (BG). Longitudinal changes in metabolite levels were determined using linear mixed effect models, as were metabolite changes in relation to global neurocognitive function.
HIV-infected subjects showed significant annual decreases in brain metabolite levels in all regions examined, including NAA (2.95%), Cho (2.61%) in the FWM; NAA (1.89%), Cr (1.84%), Cho (2.19%) and Glx (6.05%) in the MFC; and Glx (2.80%) in the BG. Similar metabolite decreases were observed in the NA and subclinically impaired subgroups, including subjects with virologic suppression in plasma and CSF. Neurocognitive decline was associated with longitudinal decreases in Glx in the FWM and the BG, and in NAA in the BG.
Widespread progressive changes in the brain, including neuronal injury, occur in chronically HIV-infected persons despite stable antiretroviral treatment and virologic suppression and can lead to neurocognitive declines. The basis for these findings is poorly understood and warrants further study.
PMCID: PMC3740160  PMID: 23613008
12.  White Matter Abnormalities and Working Memory Impairment in Systemic Lupus Erythematosus 
Many patients with systemic lupus erythematosus (SLE) have working memory deficits. Few studies have evaluated working memory performance and neurometabolite profile using magnetic resonance spectroscopy (MRS) in SLE.
We gave the Paced Auditory Serial Addition Test (PASAT), a measure of working memory, to 73 patients with SLE. We calculated total score, dyads, chunking, and cognitive fatigue. Using MRS, we determined the ratio of choline to creatine (Ch/Cr) in normal-looking right and left frontal lobe white matter.
Twenty-nine percent of patients showed impaired working memory on the PASAT. Total PASAT score inversely correlated with right and left frontal white matter Ch/Cr. Left frontal white matter Ch/Cr correlated with percent chunking and inversely correlated with total and percent of dyads. Right frontal white matter Ch/Cr correlated with percent chunking and inversely correlated with total and percent dyads. There was no relationship between cognitive fatigue and either left or right frontal white matter Ch/Cr. Longer disease duration was associated with higher left frontal white matter Ch/Cr. Correlations remained significant between left frontal white matter Ch/Cr and total PASAT score and total dyads when disease duration was considered.
Patients with SLE were impaired on the PASAT. Lower total PASAT score and fewer dyads correlated with higher left frontal microstructural white matter damage, while cognitive fatigue did not. This pattern suggests that early white matter damage interferes with working memory in SLE and provides further insight into the neurobiological basis of mild cognitive dysfunction related to microstructural white matter injury.
PMCID: PMC3768147  PMID: 23812169
systemic lupus erythematosus (SLE); working memory; Paced Auditory Serial Addition Test (PASAT); MRS; white matter
13.  Influence of Depth of Interaction upon the Performance of Scintillator Detectors 
PLoS ONE  2014;9(5):e98177.
The uncertainty in time of particle detection within a scintillator detector, characterised by the coinci- dence time resolution (CTR), is explored with respect to the interaction position within the scintillator crystal itself. Electronic collimation between two scintillator detectors is utilised to determine the CTR with depth of interaction (DOI) for different materials, geometries and wrappings. Significantly, no rela- tionship between the CTR and DOI is observed within experimental error. Confinement of the interaction position is seen to degrade the CTR in long scintillator crystals by 10%.
PMCID: PMC4038557  PMID: 24875832
14.  Intrahepatic Fat is Increased in Neonatal Offspring of Obese Women with Gestational Diabetes 
The Journal of pediatrics  2012;162(5):930-936.e1.
To assess the precision magnetic resonance imaging (MRI) in the neonate and determine if there is an early maternal influence on the pattern of neonatal fat deposition in the offspring of mothers with gestational diabetes (GDM) and obesity compared with the offspring of normal weight women.
Study design
25 neonates, born to normal weight mothers (n=13) and to obese mothers with GDM (n=12), underwent MRI for measurement of subcutaneous and intra-abdominal fat and magnetic resonance spectroscopy for the measurement of intrahepatocellular (IHCL) fat at 1-3 weeks of age.
Infants born to obese/GDM mothers had a mean 68% increase in IHCL compared with infants born to normal weight mothers. For all infants, IHCL correlated with maternal pre-pregnancy BMI but not with subcutaneous adiposity.
Deposition of liver fat in the neonate correlates highly with maternal BMI. This finding may have implications for understanding the developmental origins of childhood NAFLD.
PMCID: PMC3610780  PMID: 23260099
Non Alcoholic Fatty Liver Disease; Fetal programming; maternal obesity; gestational diabetes mellitus; abdominal fat; magnetic resonance imaging; magnetic resonance spectroscopy
15.  Neonatal Abstinence Syndrome: Treatment and Pediatric Outcomes 
Recent rise in rates of opiate replacement therapy among pregnant women have resulted in increasing number of infants requiring treatment for neonatal abstinence syndrome. Short- and long-term developmental outcomes associated with prenatal opiate exposure are discussed, including symptoms and severity of neonatal abstinence syndrome (NAS), and early cognitive and motor delays. Maternal and infant risk factors are discussed, and include patterns of maternal substance use during pregnancy, genetic risk, polysubstance exposure pharmacologic treatment for NAS and breastfeeding. The importance of characterizing corollary environmental risk factors is also considered.
PMCID: PMC3589586  PMID: 23314720
Neonatal Abstinence Syndrome; maternal opiate dependence; pharmacological treatment for opiate addiction; neonatal and long-term developmental outcomes
16.  Can we protect the kidneys after hypertensive pregnancy? 
PMCID: PMC3576435  PMID: 23339153
17.  The Ecological and Geographic Context of Morphological and Genetic Divergence in an Understorey-Dwelling Bird 
PLoS ONE  2014;9(2):e85903.
Advances in understanding the process of species formation require an integrated perspective that includes the evaluation of spatial, ecological and genetic components. One approach is to focus on multiple stages of divergence within the same species. Species that comprise phenotypically different populations segregated in apparently distinct habitats, in which range is presently continuous but was putatively geographically isolated provide an interesting system to study the mechanisms of population divergence. Here, we attempt to elucidate the role of ecology and geography in explaining observed morphological and genetic variation in an understorey-dwelling bird endemic to southeastern Africa, where two subspecies are recognized according to phenotype and habitat affinity. We carried out a range-wide analysis of climatic requirements, morphological and genetic variation across southeast Africa to test the hypothesis that the extent of gene flow among populations of the brown scrub-robin are influenced by their distinct climatic niches. We recovered two distinct trends depending on whether our analyses were hierarchically structured at the subspecies or at the within subspecies level. Between subspecies we found pronounced morphological differentiation associated with strong reproductive isolation (no gene flow) between populations occupying divergent climatic niches characterized by changes in the temperature of the warmest and wettest month. In contrast, within subspecies, we recovered continuous morphological variation with extensive gene flow among populations inhabiting the temperate and sub-tropical forests of southern Africa, despite divergence along the climate axis that is mainly determined by minimum temperature and precipitation of the coldest months. Our results highlight the role of niche divergence as a diversifying force that can promote reproductive isolation in vertebrates.
PMCID: PMC3917827  PMID: 24516521
18.  Increased glutamate concentration in the auditory cortex of persons with autism and first-degree relatives: A 1H-MRS study 
Lay Abstract
We investigated brain chemistry of the primary region of the brain involved in auditory processing in adults with autism spectrum disorder (ASD). Due to the highly heritable nature of ASD and the lack of prior brain chemistry data on unaffected first-degree relatives, we also enrolled parents of children with ASD (pASD), comparing both groups to a healthy adult control group. The technique used to quantify chemical signals was magnetic resonance spectroscopy (MRS), which we used to assess the concentration of auditory glutamate, the primary excitatory brain neurotransmitter, as well as other metabolites that assess neuronal integrity and metabolism. We found significantly higher levels of auditory glutamate in persons with ASD. In addition, increases in two other metabolites, n-acetyl-aspartate (NAA), and creatine (Cr), were observed in the ASD group. No differences were observed in the pASD group in any MRS measurement. We interpret the glutamate finding as suggestive of an increase in brain excitability, and the NAA and Cr findings as indicative of a change in brain energy metabolism in ASD.
Scientific Abstract
Increased glutamate levels have been reported in the hippocampal and frontal regions of persons with autism using proton magnetic resonance spectroscopy (1H-MRS). Although autism spectrum disorders (ASD) are highly heritable, MRS studies have not included relatives of persons with ASD. We therefore conducted a study to determine if glutamate levels are elevated in people with autism and parents of children with autism.
Single-voxel, point resolved spectroscopy (PRESS) data were acquired at 3T for left and right hemisphere auditory cortical voxels in 13 adults with autism, 15 parents of children with autism, and 15 adult control subjects. The primary measure was Glx. Additional measures included n-acetyl-aspartate (NAA), choline (Cho), myoinositol (mI) and creatine (Cr).
The autism group had significantly higher Glx, NAA and Cr concentrations than the control subjects. Parents did not differ from control subjects on any measures. No significant differences in Cho or mI levels were seen among groups. No reliable correlations between autism symptom measures and MRS variables were seen after Bonferroni correction for multiple comparisons.
The elevation in Glx in autism is consistent with prior MRS data in the hippocampus and frontal lobe and may suggest increased cortical excitability. Increased NAA and Cr may indicate brain metabolism disturbances in autism. In the current study, we found no reliable evidence of a familial effect for any spectroscopy measure. This may indicate that these metabolites have no heritable component in autism, the presence of a compensatory factor in parents, or sample specific limitations such the participation of singleton families.
PMCID: PMC3580156  PMID: 23166003
glutamate; n-acetyl-aspartate; creatine; spectroscopy; auditory cortex
19.  Effects of the Botanical Insecticide, Toosendanin, on Blood Digestion and Egg Production by Female Aedes aegypti (Diptera: Culicidae): Topical Application and Ingestion 
Journal of medical entomology  2013;50(1):112-121.
Botanical insecticides offer novel chemistries and actions that may provide effective mosquito control. Toosendanin (TSN, 95% purity) is one such insecticide used to control crop pests in China, and in this study, it was evaluated for lethal and sublethal effects on larvae and females of the yellowfever mosquito, Aedes aegypti (L.). TSN was very toxic to first instar larvae after a 24 h exposure (LC50 = 60.8 μg/ml) and to adult females up to 96 h after topical treatment (LD50 = 4.3 μg/female) or ingestion in a sugar bait (LC50 = 1.02 μg/μl). Treatment of first instars for 24 h with a range of sublethal doses (6.3–25 μg/ml) delayed development to pupae by 1 to 2 d. Egg production and larval hatching from eggs were dose dependently reduced (>45%) by TSN doses (1.25–10.0 μg) topically applied to females 24 h before or 1 h after a bloodmeal. Ingestion of TSN (0.031–0.25 μg/μl of sugar bait) by females 24 h before a bloodmeal also greatly reduced egg production and larval hatch; no eggs were oviposited by females ingesting the highest dose. Further studies revealed that topical or ingested TSN dose-dependently disrupted yolk deposition in oocytes, blood ingestion and digestion, and ovary ecdysteroid production in blood-fed females. Overall, our results indicate that TSN is an effective insecticide for Ae. aegypti larvae and adults, because of its overt toxicity at high doses and disruption of development and reproduction at sublethal doses.
PMCID: PMC3893133  PMID: 23427659
mosquito; reproduction; toxicity
20.  Influence of Age and Nutritional Status on Flight Performance of the Asian Tiger Mosquito Aedes albopictus (Diptera: Culicidae) 
Insects  2013;4(3):404-412.
The Asian tiger mosquito, Aedes albopictus, is a competent vector for arboviruses and recently was implicated as the vector of the first autochthonous cases of dengue and chikungunya in southern Europe. The objective of this study was to analyze the flight performance of female Ae. albopictus of different ages that were starved, sugar-fed, or sugar-fed and blood-fed, using flight mills. After three days of starvation post emergence, females flew an average distance of 0.7 ± 0.5 km in 1.9 ± 1.5 h during a 16 h trial period, whereas sugar- or sugar- and blood-fed females of this age covered a significantly higher distance of around 3 km with a mean total flight time of around 6 h. The age of females (up to four weeks) had no effect on performance. The average of maximal continuous flight segments of sugar-fed (2.14 ± 0.69 h) and blood-fed (3.17 ± 0.82 h) females was distinctly higher than of starved females (0.38 ± 0.15 h) of which most flyers (83%) performed maximal flight segments that lasted no longer than 0.5 h. Overall, the results for the laboratory monitored flight performance of Ae. albopictus confirm their ability to disperse a few kilometres between breeding site and host.
PMCID: PMC3882092  PMID: 24404384
Aedes albopictus; flight potential; distance; vector; mosquito
21.  The Gut Bacterial Community of Mammals from Marine and Terrestrial Habitats 
PLoS ONE  2013;8(12):e83655.
After birth, mammals acquire a community of bacteria in their gastro-intestinal tract, which harvests energy and provides nutrients for the host. Comparative studies of numerous terrestrial mammal hosts have identified host phylogeny, diet and gut morphology as primary drivers of the gut bacterial community composition. To date, marine mammals have been excluded from these comparative studies, yet they represent distinct examples of evolutionary history, diet and lifestyle traits. To provide an updated understanding of the gut bacterial community of mammals, we compared bacterial 16S rRNA gene sequence data generated from faecal material of 151 marine and terrestrial mammal hosts. This included 42 hosts from a marine habitat. When compared to terrestrial mammals, marine mammals clustered separately and displayed a significantly greater average relative abundance of the phylum Fusobacteria. The marine carnivores (Antarctic and Arctic seals) and the marine herbivore (dugong) possessed significantly richer gut bacterial community than terrestrial carnivores and terrestrial herbivores, respectively. This suggests that evolutionary history and dietary items specific to the marine environment may have resulted in a gut bacterial community distinct to that identified in terrestrial mammals. Finally we hypothesize that reduced marine trophic webs, whereby marine carnivores (and herbivores) feed directly on lower trophic levels, may expose this group to high levels of secondary metabolites and influence gut microbial community richness.
PMCID: PMC3875473  PMID: 24386245
22.  Genetic Variability of the Neogregarine Apicystis bombi, an Etiological Agent of an Emergent Bumblebee Disease 
PLoS ONE  2013;8(12):e81475.
The worldwide spread of diseases is considered a major threat to biodiversity and a possible driver of the decline of pollinator populations, particularly when novel species or strains of parasites emerge. Previous studies have suggested that populations of introduced European honeybee (Apis mellifera) and bumblebee species (Bombus terrestris and Bombus ruderatus) in Argentina share the neogregarine parasite Apicystis bombi with the native bumblebee (Bombus dahlbomii). In this study we investigated whether A. bombi is acting as an emergent parasite in the non-native populations. Specifically, we asked whether A. bombi, recently identified in Argentina, was introduced by European, non-native bees. Using ITS1 and ITS2 to assess the parasite’s intraspecific genetic variation in bees from Argentina and Europe, we found a largely unstructured parasite population, with only 15% of the genetic variation being explained by geographic location. The most abundant haplotype in Argentina (found in all 9 specimens of non-native species) was identical to the most abundant haplotype in Europe (found in 6 out of 8 specimens). Similarly, there was no evidence of structuring by host species, with this factor explaining only 17% of the genetic variation. Interestingly, parasites in native Bombus ephippiatus from Mexico were genetically distant from the Argentine and European samples, suggesting that sufficient variability does exist in the ITS region to identify continent-level genetic structure in the parasite. Thus, the data suggest that A. bombi from Argentina and Europe share a common, relatively recent origin. Although our data did not provide information on the direction of transfer, the absence of genetic structure across space and host species suggests that A. bombi may be acting as an emergent infectious disease across bee taxa and continents.
PMCID: PMC3855659  PMID: 24324696
23.  Pathological and Evolutionary Implications of Retroviruses as Mobile Genetic Elements 
Genes  2013;4(4):573-582.
Retroviruses, a form of mobile genetic elements, have important roles in disease and primate evolution. Exogenous retroviruses, such as human immunodeficiency virus (HIV), have significant pathological implications that have created a massive public health challenge in recent years. Endogenous retroviruses (ERVs), which are the primary focus of this review, can also be pathogenic, as well as being beneficial to a host in some cases. Furthermore, retroviruses may have played a key role in primate evolution that resulted in the incorporation of these elements into the human genome. Retroviruses are mobile genetic elements that have important roles in disease and primate evolution. We will further discuss the pathogenic potential of retroviruses, including their role in cancer biology, and will briefly summarize their evolutionary implications.
PMCID: PMC3927575  PMID: 24705263
transposon; mobile genetic element; virology
24.  Cultivation and Complete Genome Sequencing of Gloeobacter kilaueensis sp. nov., from a Lava Cave in Kīlauea Caldera, Hawai'i 
PLoS ONE  2013;8(10):e76376.
The ancestor of Gloeobacter violaceus PCC 7421T is believed to have diverged from that of all known cyanobacteria before the evolution of thylakoid membranes and plant plastids. The long and largely independent evolutionary history of G. violaceus presents an organism retaining ancestral features of early oxygenic photoautotrophs, and in whom cyanobacteria evolution can be investigated. No other Gloeobacter species has been described since the genus was established in 1974 (Rippka et al., Arch Microbiol 100:435). Gloeobacter affiliated ribosomal gene sequences have been reported in environmental DNA libraries, but only the type strain's genome has been sequenced. However, we report here the cultivation of a new Gloeobacter species, G. kilaueensis JS1T, from an epilithic biofilm in a lava cave in Kīlauea Caldera, Hawai'i. The strain's genome was sequenced from an enriched culture resembling a low-complexity metagenomic sample, using 9 kb paired-end 454 pyrosequences and 400 bp paired-end Illumina reads. The JS1T and G. violaceus PCC 7421T genomes have little gene synteny despite sharing 2842 orthologous genes; comparing the genomes shows they do not belong to the same species. Our results support establishing a new species to accommodate JS1T, for which we propose the name Gloeobacter kilaueensis sp. nov. Strain JS1T has been deposited in the American Type Culture Collection (BAA-2537), the Scottish Marine Institute's Culture Collection of Algae and Protozoa (CCAP 1431/1), and the Belgian Coordinated Collections of Microorganisms (ULC0316). The G. kilaueensis holotype has been deposited in the Algal Collection of the US National Herbarium (US# 217948). The JS1T genome sequence has been deposited in GenBank under accession number CP003587. The G+C content of the genome is 60.54 mol%. The complete genome sequence of G. kilaueensis JS1T may further understanding of cyanobacteria evolution, and the shift from anoxygenic to oxygenic photosynthesis.
PMCID: PMC3806779  PMID: 24194836
25.  Early detection of neuropathophysiology using diffusion-weighted magnetic resonance imaging in asymptomatic cats with feline immunodeficiency viral infection 
Journal of neurovirology  2011;17(4):341-352.
HIV infection results in a highly prevalent syndrome of cognitive and motor disorders designated as HIV-associated dementia (HAD). Neurologic dysfunction resembling HAD has been documented in cats infected with strain PPR of the feline immunodeficiency virus (FIV), whereas another highly pathogenic strain (C36) has not been known to cause neurologic signs. Animals experimentally infected with equivalent doses of FIV-C36 or FIV-PPR, and uninfected controls were evaluated by magnetic resonance diffusion-weighted imaging (DW-MRI) and spectroscopy (MRS) at 17.5 – 18 weeks post-infection, as part of a study of viral clade pathogenesis in FIV infected cats. Goals of the MR imaging portion of the project were to determine whether this methodology was capable of detecting early neuropathophysiology in the absence of outward manifestation of neurological signs, and to compare MR imaging results for the two viral strains expected to have differing degrees of neurologic effects. We hypothesized that there would be increased diffusion, evidenced by the apparent diffusion coefficient as measured by DW-MRI, and altered metabolite ratios measured by MRS, in the brains of FIV-PPR infected cats relative to C36-infected cats and uninfected controls. Increased apparent diffusion coefficients were seen in the white matter, gray matter, and basal ganglia of both the PPR and C36 infected (asymptomatic) cats. Thalamic MRS metabolite ratios did not differ between groups. The equivalently increased diffusion by DW-MRI suggests similar indirect neurotoxicity mechanisms for the two viral genotypes. DW-MRI is a sensitive tool to detect neuropathophysiological changes in vivo that could be useful during longitudinal studies of FIV.
PMCID: PMC3749835  PMID: 21786078
Lentiviral neuropathology; HIV-associated dementia (HAD); Magnetic Resonance Spectroscopy (MRS); Diffusion-Weighted Imaging (DW-MRI); Apparent Diffusion Coefficient (ADC); FIV-PPR; FIV-C36

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