Evidence for cryptic speciation in directly transmitted Gyrodactylid parasites of Trinidadian guppies

Cryptic species complexes are common among parasites, which tend to have large populations and are subject to rapid evolution. Such complexes may arise through host-parasite co-evolution and/or host switching. For parasites that reproduce directly on their host, there might be increased opportunities for sympatric speciation, either by exploiting different hosts or different micro-habitats within the same host. The genus Gyrodactylus is a specious group of viviparous monogeneans. These ectoparasites transfer between teleosts during social contact and cause significant host mortality. Their impact on the guppy (Poecilia reticulata), an iconic evolutionary and ecological model species, is well established and yet the population genetics and phylogenetics of these parasites remains understudied. Using mtDNA sequencing of the host and its parasites, we provide evidence of cryptic speciation in Gyrodactylus bullatarudis, G. poeciliae and G. turnbulli. For the COII gene, genetic divergence of lineages within each parasite species ranged between 5.7 and 17.2%, which is typical of the divergence observed between described species in this genus. Different lineages of G. turnbulli and G. poeciliae appear geographically isolated, which could imply allopatric speciation. In addition, for G. poeciliae, co-evolution with a different host species cannot be discarded due to its host range. This parasite was originally described on P. caucana, but for the first time here it is also recorded on the guppy. The two cryptic lineages of G. bullatarudis showed considerable geographic overlap. G. bullatarudis has a known wide host range and it can also utilize a killifish (Anablepsoides hartii) as a temporary host. This killifish is capable of migrating overland and it could act as a transmission vector between otherwise isolated populations. Additional genetic markers are needed to confirm the presence of these cryptic Gyrodactylus species complexes, potentially leading to more in-depth genetic, ecological and evolutionary analyses on this multi-host-parasite system

Gyrodactylus orecchiae sp. n. (Monogenea: Gyrodactylidae) from farmed populations of gilthead seabream (Sparus aurata) in the Adriatic Sea

Gyrodactylus orecchiae sp. n. (Monogenea, Gyrodactylidae) is described from the skin, fins, eyes and gills of juvenile Sparus aurata L. (gilthead seabream) following two outbreaks of gyrodactylosis amongst stocks held in inshore floating cages on the Adriatic coast of Albania and Croatia. Fish were heavily infected (1000+ gyrodactylids/fish) with G. orecchiae which reportedly resulted in ~2–10% mortality amongst the infected stock. Morphologically, the haptoral hooks of G. orecchiae most closely resemble those of Gyrodactylus arcuatus Bychowsky, 1933 in the approximate shape of the ventral bar with its pronounced ventral bar processes and marginal hook sickles which possess a square line to the inner edge of the sickle blade and large rounded heels. The marginal hooks are also morphologically similar to those of Gyrodactylus quadratidigitus Longshaw, Pursglove et Shinn, 2003 and Gyrodactylus colemanensis Mizelle et Kritsky, 1967, but G. orecchiae can be readily discriminated from all three species by the characteristic infolding of the hamuli roots and the shape of the marginal hook sickle. Molecular sequencing of the ITS1, 5.8S, ITS2 regions (513+157+404 bp, respectively) of G. orecchiae and alignment with other gyrodactylids for which these same genomic regions have been determined, suggests that this is a new species. No similarities were found when the ITS1 region of G. orecchiae was compared with 84 species of Gyrodactylus available on GenBank

HER3 and downstream pathways are involved in colonization of brain metastases from breast cancer

Introduction: Metastases to the brain from breast cancer have a high mortality, and basal-like breast cancers have a propensity for brain metastases. However, the mechanisms that allow cells to colonize the brain are unclear.Methods: We used morphology, immunohistochemistry, gene expression and somatic mutation profiling to analyze 39 matched pairs of primary breast cancers and brain metastases, 22 unmatched brain metastases of breast cancer, 11 non-breast brain metastases and 6 autopsy cases of patients with breast cancer metastases to multiple sites, including the brain.Results: Most brain metastases were triple negative and basal-like. the brain metastases over-expressed one or more members of the HER family and in particular HER3 was significantly over-expressed relative to matched primary tumors. Brain metastases from breast and other primary sites, and metastases to multiple organs in the autopsied cases, also contained somatic mutations in EGFR, HRAS, KRAS, NRAS or PIK3CA. This paralleled the frequent activation of AKT and MAPK pathways. in particular, activation of the MAPK pathway was increased in the brain metastases compared to the primary tumors.Conclusions: Deregulated HER family receptors, particularly HER3, and their downstream pathways are implicated in colonization of brain metastasis. the need for HER family receptors to dimerize for activation suggests that tumors may be susceptible to combinations of anti-HER family inhibitors, and may even be effective in the absence of HER2 amplification (that is, in triple negative/basal cancers). However, the presence of activating mutations in PIK3CA, HRAS, KRAS and NRAS suggests the necessity for also specifically targeting downstream molecules.Ludwig Institute of Cancer ResearchNational Breast Cancer FoundationUniv Queensland, Clin Res Ctr, Brisbane, Qld 4029, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, AustraliaUniversidade Federal de São Paulo, EPM, Dept Anat Patol, BR-04024000 São Paulo, BrazilGriffith Univ, Brisbane, Qld 4011, AustraliaUniv Queensland, Ctr Magnet Resonance, Brisbane, Qld 4072, AustraliaEijkman Inst, Jakarta 10430, IndonesiaInst Nacl Canc, Dept Patol, BR-20230130 Rio de Janeiro, BrazilLab Salomao & Zoppi, Dept Patol, BR-04104000 São Paulo, BrazilCharles Univ Prague, Fac Med, Dept Pathol, Plzen 30605, Czech RepublicUniv Sydney, Inst Clin Pathol & Med Res, Sydney W Area Hlth Serv, Sydney, NSW 2145, AustraliaUniv Sydney, Westmead Millennium Inst, Sydney W Area Hlth Serv, Sydney, NSW 2145, AustraliaPeter MacCallum Canc Ctr, Dept Pathol, Melbourne, Vic 3002, AustraliaUniv Queensland, Queensland Brain Inst, Brisbane, Qld 4072, AustraliaRoyal Brisbane & Womens Hosp, Brisbane, Qld 4029, AustraliaUniversidade Federal de São Paulo, EPM, Dept Anat Patol, BR-04024000 São Paulo, BrazilWeb of Scienc

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Developmental and evolutionary assumptions in a study about the impact of premature birth and low income on mother–infant interaction

In order to study the impact of premature birth and low income on mother–infant interaction, four Portuguese samples were gathered: full-term, middle-class (n=99); premature, middle-class (n=63); full-term, low income (n=22); and premature, low income (n=21). Infants were filmed in a free play situation with their mothers, and the results were scored using the CARE Index. By means of multinomial regression analysis, social economic status (SES) was found to be the best predictor of maternal sensitivity and infant cooperative behavior within a set of medical and social factors. Contrary to the expectations of the cumulative risk perspective, two factors of risk (premature birth together with low SES) were as negative for mother–infant interaction as low SES solely. In this study, as previous studies have shown, maternal sensitivity and infant cooperative behavior were highly correlated, as was maternal control with infant compliance. Our results further indicate that, when maternal lack of responsiveness is high, the infant displays passive behavior, whereas when the maternal lack of responsiveness is medium, the infant displays difficult behavior. Indeed, our findings suggest that, in these cases, the link between types of maternal and infant interactive behavior is more dependent on the degree of maternal lack of responsiveness than it is on birth status or SES. The results will be discussed under a developmental and evolutionary reasonin

Cognitive Dysfunction Is Sustained after Rescue Therapy in Experimental Cerebral Malaria, and Is Reduced by Additive Antioxidant Therapy

Neurological impairments are frequently detected in children surviving cerebral malaria (CM), the most severe neurological complication of infection with Plasmodium falciparum. The pathophysiology and therapy of long lasting cognitive deficits in malaria patients after treatment of the parasitic disease is a critical area of investigation. In the present study we used several models of experimental malaria with differential features to investigate persistent cognitive damage after rescue treatment. Infection of C57BL/6 and Swiss (SW) mice with Plasmodium berghei ANKA (PbA) or a lethal strain of Plasmodium yoelii XL (PyXL), respectively, resulted in documented CM and sustained persistent cognitive damage detected by a battery of behavioral tests after cure of the acute parasitic disease with chloroquine therapy. Strikingly, cognitive impairment was still present 30 days after the initial infection. In contrast, BALB/c mice infected with PbA, C57BL6 infected with Plasmodium chabaudi chabaudi and SW infected with non lethal Plasmodium yoelii NXL (PyNXL) did not develop signs of CM, were cured of the acute parasitic infection by chloroquine, and showed no persistent cognitive impairment. Reactive oxygen species have been reported to mediate neurological injury in CM. Increased production of malondialdehyde (MDA) and conjugated dienes was detected in the brains of PbA-infected C57BL/6 mice with CM, indicating high oxidative stress. Treatment of PbA-infected C57BL/6 mice with additive antioxidants together with chloroquine at the first signs of CM prevented the development of persistent cognitive damage. These studies provide new insights into the natural history of cognitive dysfunction after rescue therapy for CM that may have clinical relevance, and may also be relevant to cerebral sequelae of sepsis and other disorders

BluePort: A Platform to Study the Eosinophilic Response of Mice to the Bite of a Vector of Leishmania Parasites, Lutzomyia longipalpis Sand Flies

transmission in residents of endemic areas has been attributed to the acquisition of immunity to sand fly salivary proteins. One theoretical way to accelerate the acquisition of this immunity is to increase the density of antigen-presenting cells at the sand fly bite site. Here we describe a novel tissue platform that can be used for this purpose. sand flies. Results presented indicate that a shift in the inflammatory response, from neutrophilic to eosinophilic, is the main histopathological feature associated with the immunity acquired through repeated exposure to the bite of sand flies, and that the BluePort tissue compartment could be used to accelerate this process. In addition, changes observed inside the BluePort parenchyma indicate that it could be used to study complex immunobiological processes, and to develop ectopic secondary lymphoid structures.Understanding the characteristics of the dermal response to the bite of sand flies is a critical element of strategies to control leishmaniasis using vaccines that target salivary proteins. Finding that dermal eosinophilia is such a prominent component of the anti-salivary immunity induced by repeated exposure to sand fly bites raises one important consideration: how to avoid the immunological conflict derived from a protective Th2-driven immunity directed to sand fly saliva with a protective Th1-driven immunity directed to the parasite. The BluePort platform is an ideal tool to address experimentally this conundrum

Cultivation-Independent Methods Reveal Differences among Bacterial Gut Microbiota in Triatomine Vectors of Chagas Disease

Chagas disease is one of the most important endemic diseases of South and Central America. Its causative agent is the protozoan Trypanosoma cruzi, which is transmitted to humans by blood-feeding insects known as triatomine bugs. These vectors mainly belong to Rhodnius, Triatoma and Panstrongylus genera of Reduviidae. The bacterial communities in the guts of these vectors may have important effects on the biology of T. cruzi. For this reason, we analyzed the bacterial diversity hosted in the gut of different species of triatomines using cultivation-independent methods. Among Rhodnius sp., we observed similar bacterial communities from specimens obtained from insectaries or sylvatic conditions. Endosymbionts of the Arsenophonus genus were preferentially associated with insects of the Panstrongylus and Triatoma genera, whereas the bacterial genus Serratia and Candidatus Rohrkolberia were typical of Rhodnius and Dipetalogaster, respectively. The diversity of the microbiota tended to be the largest in the Triatoma genus, with species of both Arsenophonus and Serratia being detected in T. infestans