Comparative Meiotic Studies in Triatoma sordida (Stål) and T. guasayana Wygodzinsky & Abalos (Reduviidae, Heteroptera)

Triatoma sordida and T. guasayana are competent Trypanosoma cruzi vectors, with overlapping distribution areas in Argentina. Both species are morphologically similar, and their immature stages are hard to discriminate. Cytogenetic studies in the genus Triatoma reveal scarce karyotypic variations, being 2n= 20 + XY the most frequent diploid number in males. In the present work the meiotic behaviour of different Argentinian populations of T. sordida and T. guasayana has been analyzed; the meiotic karyotype of both species has also been compared. The species differ in total chromosome area and in the relative area of the sex chromosomes. These meiotic karyotypic differences constitute an additional tool for the taxonomic characterization of T. sordida and T. guasayana. The analysis of an interpopulation hybrid of T. sordida (Brazil x Argentina) reveals a regular meiotic behaviour, despite the presence of heteromorphic bivalents. Our observations support the hypothesis that karyotype variations through the gain or loss of heterochromatin can not be considered as a primary mechanism of reproductive isolation in Triatoma.

The degradation of HFR1, a putative bHLH class transcription factor involved in light signaling, is regulated by phosphorylation and requires COP1.

All developmental transitions throughout the life cycle of a plant are influenced by light. In Arabidopsis, multiple photoreceptors including the UV-A/blue-sensing cryptochromes (cry1-2) and the red/far-red responsive phytochromes (phyA-E) monitor the ambient light conditions. Light-regulated protein stability is a major control point of photomorphogenesis. The ubiquitin E3 ligase COP1 (constitutively photomorphogenic 1) regulates the stability of several light-signaling components. HFR1 (long hypocotyl in far-red light) is a putative transcription factor with a bHLH domain acting downstream of both phyA and the cryptochromes. HFR1 is closely related to PIF1, PIF3, and PIF4 (phytochrome interacting factor 1, 3 and 4), but in contrast to the latter three, there is no evidence for a direct interaction between HFR1 and the phytochromes. Here, we show that the protein abundance of HFR1 is tightly controlled by light. HFR1 is an unstable phosphoprotein, particularly in the dark. The proteasome and COP1 are required in vivo to degrade phosphorylated HFR1. In addition, HFR1 can interact with COP1, consistent with the idea of COP1 directly mediating HFR1 degradation. We identify a domain, conserved among several bHLH class proteins involved in light signaling , as a determinant of HFR1 stability. Our physiological experiments indicate that the control of HFR1 protein abundance is important for a normal de-etiolation response.

Swallowing difficulties with oral drugs among polypharmacy patients attending community pharmacies.

Background Swallowing difficulties are common and can affect patients' ability to take solid oral dosage forms, thus compromising medication adherence. Strategies developed by patients to overcome such difficulties while taking medicines have seldom been described. Objective To determine prevalence and characteristics of swallowing difficulties among primary care patients attending their community pharmacies; to explore strategies developed by patients to overcome their difficulties, and health professionals' awareness of these problems. Setting Prospective study with a semi-structured questionnaire in random community pharmacies located in two Swiss regions. Method In each pharmacy, an interviewer asked 16 questions to each consecutive patient (18 years and older) with a prescription for at least 3 different solid oral forms. Main outcome measure Quantification of number of patients with swallowing difficulties and detailed description of difficulties. Results Among 122 pharmacies, 59 (48 %) accepted to join the study and 410 patients were enrolled. Thirty-seven patients (9.0 %) reported ongoing swallowing difficulties, while 55 patients (13.4 %) reported past difficulties. For the majority of patients, difficulties occurred at each single dose (83.7 %), with a single medication (59.8 %) and lasted for less than 12 months (53.8 %). Number of tablets was not the main trigger. Swallowing difficulties impaired extremely daily life in 12 % of the patients. Intentional non adherence (23 % of patients) and altering the oral dose formulation were the most common and potentially harmful strategies used by patients to overcome their swallowing difficulties. According to the patients, pharmacists and physicians rarely inquired about their swallowing difficulties. Conclusion We report a fairly high prevalence of swallowing difficulties in polypharmacy patients attending their community pharmacies. Pharmacists have to interview patients on their swallowing difficulties in a more systematic way, support patients in finding solutions and refer them to their physician if necessary to ensure continuity in care.

Epidemiology of Chagas disease in Ecuador. A brief review

Chagas disease is a complex public health problem that has been underestimated in Ecuador. Here we review the relevant published information, and present unpublished and new data that help to understand the current Chagas disease epidemiological situation and its evolution in the country. Three main characteristics have been identified: (i) persistence of Trypanosoma cruzi transmission in already known foci; (ii) a marked endemicity in some urban areas of Guayaquil; and (iii) the transformation of new Amazon foci into truly endemic areas. The situation in other suspect areas remains uncertain. Five Triatominae species have been implicated in the transmission of T. cruzi to people in Ecuador (Triatoma dimidiata, Rhodnius ecuadoriensis, R. pictipes, R. robustus and Panstrongylus geniculatus), but some others may also play a role in some areas (P. rufotuberculatus, P. howardi, T. carrioni and P. chinai). Other Triatominae reported seem to have little or no epidemiological relevance (T. venosa, T. dispar, Eratyrus mucronatus, E. cuspidatus, P. lignarius and Cavernicola pilosa). High frequency of acute cases and severe chronic disease has been observed. Although cardiomyopathy is more frequent, serious digestive disease is also present. It is estimated that around 120,000-200,000 people may be infected. 2.2 to 3.8 million people are estimated to live under transmission risk conditions.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Narrative Diagrammatik. Mit einer Modellanalyse: Die Diagrammatik des "Decameron"

Taking as a starting point the seeming inconsistency of late-medieval romances notoriously 'run wild' (verwildert), this article is concerned with the description of an abstract form of narrative coherence that is based on the notion of the diagrammatic. In a first section, this concept is illustrated in a simplified manner by an analysis of Boccaccio's Decameron based on two levels of spatial structure: that of the autograph Berlin manuscript (Codex Hamilton 90) and that of the recipient's mental visualisation of the relations between the frame and the tales of the work. It is argued that the connectivity of the work as a whole depends on the perception of those two spatial representations of the plot. A second section develops this concept in a more theoretical fashion, drawing on Charles Sanders Peirce's notion of diagrammatic reasoning as a way of perceiving relations through mental and material topological representations. Correspondingly, a view of narrative is proposed that does not depend on the traditional perspective of temporal sequence but emphasizes the spatial structure of literary narrative. It is argued that these conditions form the primary ontological mode of narrative, whereas the temporal development of a story is an aesthetic illusion that has been specifically stimulated by the narrative conventions of approximately the past three centuries and must thus be considered a secondary effect. To conclude, an interpretation in miniature of an aspect of Heinrich von Neustadt's Apollonius von Tyrland that seems to have 'run wild' is undertaken from a diagrammatic perspective.

Atomic force and electron microscopic-based study of sarcolemmal surface of living cardiomyocytes unveils unexpected mitochondrial shift in heart failure.

Loss of T-tubules (TT), sarcolemmal invaginations of cardiomyocytes (CMs), was recently identified as a general heart failure (HF) hallmark. However, whether TT per se or the overall sarcolemma is altered during HF process is still unknown. In this study, we directly examined sarcolemmal surface topography and physical properties using Atomic Force Microscopy (AFM) in living CMs from healthy and failing mice hearts. We confirmed the presence of highly organized crests and hollows along myofilaments in isolated healthy CMs. Sarcolemma topography was tightly correlated with elasticity, with crests stiffer than hollows and related to the presence of few packed subsarcolemmal mitochondria (SSM) as evidenced by electron microscopy. Three days after myocardial infarction (MI), CMs already exhibit an overall sarcolemma disorganization with general loss of crests topography thus becoming smooth and correlating with a decreased elasticity while interfibrillar mitochondria (IFM), myofilaments alignment and TT network were unaltered. End-stage post-ischemic condition (15days post-MI) exacerbates overall sarcolemma disorganization with, in addition to general loss of crest/hollow periodicity, a significant increase of cell surface stiffness. Strikingly, electron microscopy revealed the total depletion of SSM while some IFM heaps could be visualized beneath the membrane. Accordingly, mitochondrial Ca(2+) studies showed a heterogeneous pattern between SSM and IFM in healthy CMs which disappeared in HF. In vitro, formamide-induced sarcolemmal stress on healthy CMs phenocopied post-ischemic kinetics abnormalities and revealed initial SSM death and crest/hollow disorganization followed by IFM later disarray which moved toward the cell surface and structured heaps correlating with TT loss. This study demonstrates that the loss of crest/hollow organization of CM surface in HF occurs early and precedes disruption of the TT network. It also highlights a general stiffness increased of the CM surface most likely related to atypical IFM heaps while SSM died during HF process. Overall, these results indicate that initial sarcolemmal stress leading to SSM death could underlie subsequent TT disarray and HF setting.

Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways.

BACKGROUND: Activation of coagulation and fibrinolysis play a role in the pathophysiology of experimental arthritis. Objective: To determine the extent of activation of the coagulation and fibrinolytic pathways in different joint diseases in humans and to ascertain the factors that may influence fibrin deposition within the joint. METHODS: Plasma from normal subjects (controls, n= 21) and plasma and synovial fluid samples from patients with rheumatoid arthritis (RA; n = 64), osteoarthritis (OA; n = 29), spondyloarthropathy (SpA; n = 22) and crystal arthritis (CA; n = 25) were analyzed for the levels of TF (tissue factor) and tissue factor pathway inhibitor (TFPI) activities, thrombin-antithrombin III (TAT) complexes, and F1 + 2 (thrombin fragment), fibrin d-dimer and thrombin-activated fibrinolysis inhibitor (TAFI) antigenic levels. The measurements were analyzed by pairwise correlation with each other as well as with standard parameters of inflammation [C-reactive protein (CRP), joint leukocyte count]. Inter-group comparisons were performed to look for disease-specific differences. RESULTS: Compared with healthy controls, patients with joint diseases had higher levels of TAT, F1 + 2 and d-dimers in their plasma. In the synovial fluid, TF activity, TAT, d-dimers, and TAFI were significantly higher in inflammatory arthritides than in OA. The levels were highest in RA patients. In the plasma, TF activity was correlated with TAT and d-dimer levels with CRP, TFPI, and TAT. In the synovial fluid, TF activity correlated with plasma CRP levels, synovial fluid leukocyte count, and synovial TAT and TAFI levels. In addition, synovial d-dimers correlated with CRP, and synovial TAFI levels were correlated with synovial F1 + 2 and TAT. CONCLUSIONS: Activation of the coagulation and fibrinolytic cascades in the joint and in the circulation is evident in both inflammatory and degenerative joint diseases. Within the joint, inflammatory mechanisms leading to TF-mediated activation of the coagulation pathway and subsequent fibrin deposition is the most likely explanation for the observed findings. In the plasma, the link between inflammation (CRP increase) and TF activation is weak, and a non-TF-mediated mechanism of coagulation activation could explain these findings. RA is characterized by significantly higher levels of TAT in the synovial fluid and plasma than other arthritides. Although fibrinolytic activity is linked to inflammation, the increased amounts of TAFI in the joint, particularly in RA, may explain why fibrin formation is so prominent in this condition compared with other joint diseases.

Observations on the Domestic Ecology of Rhodnius ecuadoriensis (Triatominae)

Rhodnius ecuadoriensis infests peridomiciles and colonises houses in rural southern Ecuador. Six out of 84 dwellings (7%) surveyed in a rural village were infested (78 bugs/infested domicile; 279 bugs were collected in a single dwelling). Precipitin tests revealed R. ecuadoriensis fed on birds (65%), rodents (31%), marsupials (8%), and humans (15%) - mixed bloodmeals detected in 37.5% of individual samples. Trypanosoma cruzi from opossums and rodents may thus be introduced into the domestic cycle. Wasp parasitoidism was detected in 6.5% of 995 R. ecuadoriensis eggs (only in peridomestic habitats). Control strategies should integrate insecticide spraying (indoors and peridomestic), better management of poultry, and housing improvements. A possible inefficacy of Malathion is reported.

Juli Cèsar, tirà i visionari? : l'esfondrament de la República romana

Aquest treball emmarca la vida de Juli Cèsar en el procés d'esfondrament de la República romana i la guerra civil. La seva vida n'és el fil conductor. També hi ha anàlisis descontextualitzades d'aquesta vida (la lluita entre optimates i populares, els mandats extraordinaris, la figura dels tribuns de la plebs i l'imperialisme romà), necessaris per a entendre aquest pas de República a Principat.

Expression and developmental regulation of Ehk-1, a neuronal Elk-like receptor tyrosine kinase in brain.

Protein tyrosine kinases are pivotal in central nervous tissue development and maintenance. Here we focus on the expression of Ehk-1, a novel Elk-related receptor tyrosine kinase. Ehk-1 gene expression is observed in the developing and adult central nervous system and is highly regulated throughout development at both the messenger RNA and protein levels. Three messenger RNA transcripts of 8.5, 5.9 and 5.1 kb are detectable in the rat brain and a variety of splice possibilities have been identified. However, a major protein species of around M(r) 120,000 predominates throughout development. Ehk-1 messenger RNA and protein levels are highest in the first postnatal week. By in situ messenger RNA hybridization the gene is expressed by all neurons of the adult brain, but mostly in the hippocampus, cerebral cortex and large neurons of the deep cerebellar nuclei, as well as the Purkinje and granular cells of the cerebellum. At earlier stages of development, transcripts are most prominent in the periventricular germinal layers of the brain. Immunohistochemistry reveals a pronounced membrane associated protein expression in immature neurons. In the adult animal, peak reactivity was found in the neuropil with sparing of most perikarya. The spatial and temporal pattern of ehk-1 gene expression suggests a role in both the development and maintenance of differentiated neurons of the central nervous system.

Evaluation of Mesocyclops annulatus (Copepoda: Cyclopoidea) as a control agent of Aedes aegypti (Diptera: Culicidae) in Argentina

We evaluated the potential of Mesocyclops annulatus as a control agent of Aedes aegypti in La Plata city (Argentina). Mosquito larval survivorship due to predation by these copepods was estimated at weekly intervals during the oviposition period of A. aegypti. Mean weekly A. aegypti larval survivorship in cylindrical plastic containers (12 cm height and 11 cm diameter) with copepods was significantly lower than in control containers. Furthermore, weekly larval survival was negatively correlated with M. annulatus adult density, and approximately 23 adult copepods/container would be a threshold density over which the weekly mosquito larval survivorship approached zero. The copepods were able to persist in all containers during approximately 100 days (in three of them until the end of the experiment: 155 days) without the resource represented by A. aegypti larvae. The predation and persistence observed suggest that M. annulatus is a potential control agent to be considered in biological control programs.