Impaired cerebral vasoreactivity in type 2 diabetes mellitus

The aim of our study was to assess cerebral vasoreactivity (CVR) in type 2 diabetes mellitus (DM2) and factors which may influence on it. According to previous studies, evaluating CVR in DM2 on the similar way, the results were dubious. For the evaluation CVR we used breath holding index (BHI) and transcranial Doppler ultrasound (TCD) in 50 patients with DM2 and 50 sex- and age-matched healthy controls. We observed epidemiologic and clinic data, other vascular risk factors and laboratory parameters. We found statistically significant difference in BHI between patients with DM2 (BHI = 0.69 +/- 0.31) and age- and sex-matched healthy controls (BHI = 1.33+/-0.28) (p < 0.05 ). Because of a significant correlation between BHI and age (p < 0.001) in healthy controls we made an adjustment of BHI for age before further analyses (BHIadj). In DM2 group we found a significant correlation between BHIadj and age (p = 0.0004), fasting glycemia (p = 0.04), and albuminuria (p = 0.04) (creatinine clearance in multivariate analysis (p = 0.007)). Our study has shown that CVR is impaired in DM2 patients and that it's severity was associated with age, fasting glycemia and renal function. Functional TCD is a very good screening method for detection and monitoring of cerebral microangiopathic changes in DM2 patients.     

A single-cell sequencing approach to the classification of large, vacuolated sulfur bacteria

The colorless, large sulfur bacteria are well known because of their intriguing appearance, size and abundance in sulfidic settings. Since their discovery in 1803 these bacteria have been classified according to their conspicuous morphology. However, in microbiology the use of morphological criteria alone to predict phylogenetic relatedness has frequently proven to be misleading. Recent sequencing of a number of 16S rRNA genes of large sulfur bacteria revealed frequent inconsistencies between the morphologically determined taxonomy of genera and the genetically derived classification. Nevertheless, newly described bacteria were classified based on their morphological properties, leading to polyphyletic taxa. We performed sequencing of 16S rRNA genes and internal transcribed spacer (ITS) regions, together with detailed morphological analysis of hand-picked individuals of novel non-filamentous as well as known filamentous large sulfur bacteria, including the hitherto only partially sequenced species Thiomargarita namibiensis, Thioploca araucae and Thioploca chileae. Based on 128 nearly full-length 16S rRNA-ITS sequences, we propose the retention of the family Beggiatoaceae for the genera closely related to Beggiatoa, as opposed to the recently suggested fusion of all colorless sulfur bacteria into one family, the Thiotrichaceae. Furthermore, we propose the addition of nine Candidatus species along with seven new Candidatus genera to the family Beggiatoaceae. The extended family Beggiatoaceae thus remains monophyletic and is phylogenetically clearly separated from other related families.     

Production of pro- and anti-inflammatory cytokines by monocytes from patients with paracoccidioidomycosis

Monocytes and macrophages can produce a large repertoire of cytokines and participate in the pathogenesis of granulomatous diseases. We investigated the production of pro- and anti-inflammatory cytokines by monocytes from patients with active paracoccidioidomycosis. Peripheral blood monocytes from 37 patients and 29 healthy controls were cultivated with or without 10 microg/ml of lipopolysaccharide (LPS) for 18 h at 37 degrees C, and the cytokine levels were determined in the culture supernatants by enzyme immunoassay. The results showed that the endogenous levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8, IL-10 and transforming growth factor beta detected in the supernatant of patient monocytes cultivated without stimulus were significantly higher than those produced by healthy controls. These data demonstrated that monocytes from patients with active paracoccidioidomycosis produce high levels of cytokines with both inflammatory and anti-inflammatory activities. However, patient monocytes produced significantly lower TNF-alpha and IL-6 levels in response to LPS when compared to normal subjects, suggesting an impairment in their capacity to produce these cytokines after LPS stimulation. Concentrations of IL-1beta, IL-8 and IL-10 in cultures stimulated with LPS were higher in patients than in controls. These results suggest that an imbalance in the production of pro- and anti-inflammatory cytokines might be associated with the pathogenesis of paracoccidioidomycosis.     

The role of vision and proprioception in the aversion of rats to the open arms of an elevated plus-maze

The elevated plus-maze test is usually run with a short edge surrounding the open arms in order to prevent the rats from falling. The present experiment investigated the role of transparent edges differing in heights: 1 (used as control), 5, 10, 20 and 40 cm, the latter the same height as the closed arm walls. Additionally, this 40-cm high transparent edge was also studied covered by white translucent or black opaque paper. The data show that the time spent in the open arms was significantly greater when the edge height was 5, 10 or 40 cm covered by the white or black paper. However, there were no differences from the 1-cm control edge when the height was 40 cm transparent. A similar effect was observed when entries in the open arms and total entries were analyzed. The facts that there were no differences when the open arms were surrounded by 1- or 40-cm transparent edges (which allow thigmotaxis) and that the same 40-cm edge caused increases in exploratory behavior when covered by papers indicate that vision triggers aversion to open spaces.     

Diversity of honey stores and their impact on pathogenic bacteria of the honeybee,Apis mellifera

Honeybee colonies offer an excellent environment for microbial pathogen development. The highest virulent, colony killing, bacterial agents are Paenibacillus larvae causing American foulbrood (AFB), and European foulbrood (EFB) associated bacteria. Besides the innate immune defense, honeybees evolved behavioral defenses to combat infections. Foraging of antimicrobial plant compounds plays a key role for this “social immunity” behavior. Secondary plant metabolites in floral nectar are known for their antimicrobial effects. Yet, these compounds are highly plant specific, and the effects on bee health will depend on the floral origin of the honey produced. As worker bees not only feed themselves, but also the larvae and other colony members, honey is a prime candidate acting as self‐medication agent in honeybee colonies to prevent or decrease infections. Here, we test eight AFB and EFB bacterial strains and the growth inhibitory activity of three honey types. Using a high‐throughput cell growth assay, we show that all honeys have high growth inhibitory activity and the two monofloral honeys appeared to be strain specific. The specificity of the monofloral honeys and the strong antimicrobial potential of the polyfloral honey suggest that the diversity of honeys in the honey stores of a colony may be highly adaptive for its “social immunity” against the highly diverse suite of pathogens encountered in nature. This ecological diversity may therefore operate similar to the well‐known effects of host genetic variance in the arms race between host and parasite.     

Early steps of clathrin-mediated endocytosis involved in phagosomal escape of Fcgamma receptor-targeted adenovirus

Adenovirus type 2 (Ad2) and Ad5 enter epithelial cells via the coxsackievirus B Ad receptor (CAR) and alpha(v) integrin coreceptors. In the absence of CAR, they can be directed to the Fcgamma receptor 1 of hematopoietic cells by an adaptor comprising the extracellular CAR domain and the Fc portion of a human immunoglobulin G (CARex-Fc). This gives rise to Ad aggregates and single particles which together enhance gene delivery up to 250-fold compared to adaptor-less viruses. A small interfering RNA knockdown of the clathrin heavy chain and quantitative electron microscopy of hematopoietic leukemia cells showed that the majority of Ads were phagocytosed as clusters of 1 to 3 microm in diameter and that about 10% of the particles entered cells by clathrin-mediated endocytosis. The clathrin knockdown did not affect phagocytosis but, surprisingly, inhibited viral escape from phagosomes. Similarly, blocking an early stage of clathrin-coated pit assembly inhibited phagosomal escape and infection but not aggregate uptake, unlike blocking of a late stage of clathrin-coated pit formation. We propose a cooperative interaction of clathrin-mediated endocytosis and phagocytosis triggering phagosomal lysis and infection.     

Clinical Evaluation of Adriamycin,a New Antitumour Antibiotic

Adriamycin, a new antitumour antibiotic of the anthracycline group with a structural formula very similar to daunorubicin, has proved to have potent tumour-growth-inhibiting properties, and to be particularly effective in childhood malignancies. Though adriamycin produces a higher percentage of side-effects than daunorubicin—namely, stomatitis and alopecia—a lower dosage may be used for therapy.     

A Genome-wide RNAi Screen Reveals a Trio-Regulated Rho GTPase Circuitry Transducing Mitogenic Signals Initiated by G Protein-Coupled Receptors

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Highlights? Human cancers harbor frequent mutations in Gq-linked GPCRs and Gα_q subunits ? A genome-wide RNAi screen revealed that Trio is essential for activating AP-1 via Gα_q ? A network of Trio-regulated Rho GTPases and MAPKs links Gq to the nucleus ? A hard-wired Gq-Trio signaling axis promotes the growth of many human malignancies     

L'accrescimento dell' embrione dei Cefalopodi

Zusammenfassung Das Wachstum des Embryos vonSepia officinalis geschieht durch Wasseraufnahme von seiten des Embryos (im engeren Sinne); der Dottersack zeigt zwar im Beginn der Entwicklung eine schwache Wasseraufnahme, der Wassergehalt bleibt aber dann etwa konstant; erst in den letzten Stadien der Entwicklung tritt wieder eine geringfügige Wasseraufnahme ein.Der Wassergehalt des Embryos überschreitet, im Momente des Ausschlüpfens, das Doppelte desjenigen des soeben abgelegten Eies.DasSepia-Ei nimmt im Laufe der Entwicklung mineralische Bestandteile auf. Der Aschengehalt ist im Stadium des Ausschlüpfens etwa viermal so groß wie bei dem eben abgelegten Ei.Von den organischen Bestandteilen des Eies sind 19,1% nicht am Aufbau des Embryos beteiligt; sie werden im Stoffwechsel des Embryos verbraucht oder bilden die perivitelline Flüssigkeit.Die Eihüllen werden im Laufe der Entwicklung reicher an Wasser und mineralischen Bestandteilen, die aus dem Medium stammen.Das Wasser und die mineralischen Bestandteile, die im Laufe der Entwicklung im Embryo angereichert werden, stammen letzten Endes aus dem umgebenden Medium.