Genetic and behavioral differences between above and below ground Culex pipiens bioforms.

Efficiency of mosquito-borne disease transmission is dependent upon both the preference and fidelity of mosquitoes as they seek the blood of vertebrate hosts. While mosquitoes select their blood hosts through multi-modal integration of sensory cues, host-seeking is primarily an odor-guided behavior. Differences in mosquito responses to hosts and their odors have been demonstrated to have a genetic component, but the underlying genomic architecture of these responses has yet to be fully resolved. Here, we provide the first characterization of the genomic architecture of host preference in the polymorphic mosquito species, Culex pipiens. The species exists as two morphologically identical bioforms, each with distinct avian and mammalian host preferences. Cx. pipiens females with empirically measured host responses were prepared into reduced representation DNA libraries and sequenced to identify genomic regions associated with host preference. Multiple genomic regions associated with host preference were identified on all 3 Culex chromosomes, and these genomic regions contained clusters of chemosensory genes, as expected based on work in Anopheles gambiae complex mosquitoes and in Aedes aegypti. One odorant receptor and one odorant binding protein gene showed one-to-one orthologous relationships to differentially expressed genes in A. gambiae complex members with divergent host preferences. Overall, our work identifies a distinct set of odorant receptors and odorant binding proteins that may enable Cx. pipiens females to distinguish between their vertebrate blood host species, and opens avenues for future functional studies that could measure the unique contributions of each gene to host preference phenotypes.

Characteristics of cardiomyopathy in Alström syndrome: Prospective single-center data on 38 patients.

BACKGROUND: Alström syndrome (AS) is a rare monogenetic disorder with multi-organ involvement. Complex metabolic disturbances are common and cardiomyopathy is a well-recognized feature in infants as well as in older children and adults. Although the mechanism of cardiomyopathy is not known, previous reports suggest that individuals with infantile-onset cardiac disease recover completely. METHODS: In this single center prospective series of 38 children and adults (age range 1.7 to 37.9years; 20 females) with AS, we evaluated cardiac manifestations in detail, in the context of specific ALMS1 mutations and multisystem involvement. All patients underwent ALMS1 sequencing, biochemical testing, electrocardiogram, and echocardiographic imaging with speckle tracking to evaluate systolic strain; 21 patients underwent cardiac magnetic resonance imaging with T1 mapping. RESULTS: Approximately half of patients (17/38) had a previous diagnosis of cardiomyopathy. Global longitudinal strain, a measure of systolic contractile function, was abnormal in 94% of patients and correlated with body mass index (r=0.602, p=0.002) and C-reactive protein level (r=0.56, p=0.004), but only in children. Electrocardiographic abnormalities were seen in two-thirds of patients, and left ventricular dilatation and/or dysfunction was present in 4 adults and 4 children. CONCLUSION: AS patients with a history of resolved infantile cardiomyopathy continue to have residual impairment in cardiac function. For patients with a normal ejection fraction and no prior cardiac history, strain can be abnormal, suggesting subclinical cardiac involvement. Close cardiac screening and aggressive modification of other manifestations of AS that are risk factors for cardiac disease, including obesity, inflammation, diabetes and dyslipidemia, are essential in caring for patients with AS.

Differential Gene Expression in the Heads of Behaviorally Divergent Culex pipiens Mosquitoes.

Host preferences of Cx. pipiens, a bridge vector for West Nile virus to humans, have the potential to drive pathogen transmission dynamics. Yet much remains unknown about the extent of variation in these preferences and their molecular basis. We conducted host choice assays in a laboratory setting to quantify multi-day human and avian landing rates for Cx. pipiens females. Assayed populations originated from five above-ground and three below-ground breeding and overwintering habitats. All three below-ground populations were biased toward human landings, with rates of human landing ranging from 69-85%. Of the five above-ground populations, four had avian landing rates of >80%, while one landed on the avian host only 44% of the time. Overall response rates and willingness to alternate landing on the human and avian hosts across multiple days of testing also varied by population. For one human- and one avian-preferring population, we examined patterns of differential expression and splice site variation at genes expressed in female heads. We also compared gene expression and splice site variation within human-seeking females in either gravid or host-seeking physiological states to identify genes that may regulate blood feeding behaviors. Overall, we identified genes with metabolic and regulatory function that were differentially expressed in our comparison of gravid and host-seeking females. Differentially expressed genes in our comparison of avian- and human-seeking females were enriched for those involved in sensory perception. We conclude with a discussion of specific sensory genes and their potential influence on the divergent behaviors of avian- and human-seeking Cx. pipiens.

Reversal of a rheologic cardiomyopathy following hematopoietic stem cell transplantation for sickle cell disease.

Cardiac complications have been well-described in sickle cell disease; however, it has been rare to see improvements in cardiac abnormalities following any interventions. Previous work has shown no significant structural changes after treatment with hydroxyurea. The cardiac effects of red blood cell exchange transfusion (RBCx) and hematopoietic stem cell transplantation (HSCT) have not been well described. We studied 56 patients undergoing HSCT (41 HLA-matched, 15 haploidentical), of whom 32 had RBCx within 3 months before HSCT. Echocardiograms and laboratory parameters were obtained at baseline, and at 3, 6, and 12 months following HSCT. Although hemolytic parameters and anemia improved following RBCx, there was a small increase in left ventricular volume index. Following successful HSCT, however, there were significant improvements in cardiac size, function, and diastolic filling parameters at 3 months followed by continued smaller improvements up to 1 year. There was a significant improvement in N-terminal pro B-type natriuretic peptide levels and a trend toward improvement in 6-minute walk time 1 year after HSCT. The magnitude of cardiac improvement seen following HSCT was comparable to that observed following correction of a volume overload state as seen in pregnancy or after repair of chronic valvular regurgitation. Further studies in sickle cell disease patients will help delineate which cardiac complications and what level of severity should be considered indications for HSCT.