The serine peptidase inhibitor N-ρ-tosyl-l-phenylalanine chloromethyl ketone (TPCK) affects the cell biology of Candida haemulonii species complex

Candida haemulonii species complex (C. haemulonii, C. haemulonii var. vulnera and Candida duobushaemulonii) is composed by emerging and multidrug-resistant (MDR) yeasts. Candidiasis, the disease caused by these species, is difficult to treat and culminates in clinical failures and patient death. It is well-known that Candida peptidases play important roles in the fungus–host interactions, and hence these enzymes are promising targets for developing new antifungal drugs. Recently, serine-type peptidases were described in clinical isolates of C. haemulonii complex with the ability to cleave relevant key host proteins. Herein, the effects of serine peptidase inhibitors (SPIs) on the cell biology of this fungal complex were evaluated. Initially, eight distinct SPIs (phenylmethylsulfonyl fluoride – PMSF, 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride – AEBSF, N-α-tosyl-l-lysine chloromethyl ketone hydrochloride – TLCK, N-p-tosyl-l-phenylalanine chloromethyl ketone – TPCK, simeprevir, boceprevir, danoprevir and telaprevir) were tested on the fungal growth. TPCK showed the best efficacy in controlling cell proliferation, being selected for the following experiments. This SPI induced changes in the architecture of yeast cells, as observed by scanning electron microscopy, besides injuries at the plasma membrane and reduction in the ergosterol content. TPCK also diminished the ability of yeasts to adhere to abiotic (polystyrene and glass) and biotic (murine macrophages) surfaces in a typically concentration-dependent manner. In addition, the 24 h-treatment of the mature biofilm promoted a decrease in biomass, viability and extracellular matrix. Altogether, our results highlight that SPIs may be promising new therapeutic agents in the treatment of candidiasis caused by emergent, opportunistic and MDR species forming the C. haemulonii complex.     

The role of calcium channel blockers and resveratrol in the prevention of paraquat-induced parkinsonism in Drosophila melanogaster: a locomotor analysis

Studies have suggested that neuronal loss in Parkinson's disease (PD) could be related to the pacemaker activity of the substantia nigra pars compacta generated by L-type Ca(v) 1.3 calcium channels, which progressively substitute voltage-dependent sodium channels in this region during aging. Besides this mechanism, which leads to increases in intracellular calcium, other factors are also known to play a role in dopaminergic cell death due to overproduction of reactive oxygen species. Thus, dihydropyridines, a class of calcium channel blockers, and resveratrol, a polyphenol that presents antioxidant properties, may represent therapeutic alternatives for the prevention of PD. In the present study, we tested the effects of the dihydropyridines, isradipine, nifedipine, and nimodipine and of resveratrol upon locomotor behavior in Drosophila melanogaster. As previously described, paraquat induced parkinsonian-like motor deficits. Moreover, none of the drugs tested were able to prevent the motor deficits produced by paraquat. Additionally, isradipine, nifedipine, resveratrol, and ethanol (vehicle), when used in isolation, induced motor deficits in flies. This study is the first demonstration that dyhidropyridines and resveratrol are unable to reverse the locomotor impairments induced by paraquat in Drosophila melanogaster.     

Critically endangered blonde capuchins fish for termites and use new techniques to accomplish the task

We report the spontaneous modification and use of sticks to fish for termites, above the ground, in wild blonde capuchins (Cebus flavius). These critically endangered Neotropical primates inhabit remnants of the Atlantic Forest. They used two previously undescribed techniques to enhance their termite capture success: nest tapping and stick rotation. The current ecologically based explanation for tool use in wild capuchins (i.e. terrestrial habits and bipedalism) must be viewed cautiously. Instead, remarkable manual skills linked to a varied diet seem important in promoting tool use in different contexts. The repertoire of tool-using techniques employed by wild capuchins has been expanded, highlighting the behavioural versatility in this genus.     

Iron Status and Helicobacter pylori Infection in Symptomatic Children: An International Multi-Centered Study

Objective

Iron deficiency (ID) and iron deficiency anaemia (IDA) are global major public health problems, particularly in developing countries. Whilst an association between H. pylori infection and ID/IDA has been proposed in the literature, currently there is no consensus. We studied the effects of H. pylori infection on ID/IDA in a cohort of children undergoing upper gastrointestinal endoscopy for upper abdominal pain in two developing and one developed country.

Methods

In total 311 children (mean age 10.7±3.2 years) from Latin America - Belo Horizonte/Brazil (n = 125), Santiago/Chile (n = 105) - and London/UK (n = 81), were studied. Gastric and duodenal biopsies were obtained for evaluation of histology and H. pylori status and blood samples for parameters of ID/IDA.

Results

The prevalence of H. pylori infection was 27.7% being significantly higher (p<0.001) in Latin America (35%) than in UK (7%). Multiple linear regression models revealed H. pylori infection as a significant predictor of low ferritin and haemoglobin concentrations in children from Latin-America. A negative correlation was observed between MCV (r = −0.26; p = 0.01) and MCH (r = −0.27; p = 0.01) values and the degree of antral chronic inflammation, and between MCH and the degree of corpus chronic (r = −0.29, p = 0.008) and active (r = −0.27, p = 0.002) inflammation.

Conclusions

This study demonstrates that H. pylori infection in children influences the serum ferritin and haemoglobin concentrations, markers of early depletion of iron stores and anaemia respectively.     

Synthesis and antibacterial activity of conjugates between norfloxacin and analogues of the siderophore vanchrobactin

From synthetic functionalized analogues of vanchrobactin, a siderophore produced by the fish pathogenic bacteria Vibrio anguillarum serotype O2, several vanchrobactin analogues–norfloxacin conjugates were obtained and their antimicrobial activities against the wild-type and mutant strains of Vibrio anguillarum serotype O2 have been determined.     

Disproportionation of rosin on an industrial Pd/C catalyst: reaction pathway and kinetic model discrimination

In this work, a phenomenological study of the isomerisation and disproportionation of rosin acids using an industrial 5% Pd on charcoal catalyst from 200 to 240°C is carried out. Medium composition is determined by elemental microanalysis, GC-MS and GC-FID. Dehydrogenated and hydrogenated acid species molar amounts in the final product show that dehydrogenation is the main reaction. Moreover, both hydrogen and non-hydrogen concentration considering kinetic models are fitted to experimental data using a multivariable non-linear technique. Statistical discrimination among the proposed kinetic models lead to the conclusion hydrogen considering models fit much better to experimental results. The final kinetic model involves first-order isomerisation reactions of neoabietic and palustric acids to abietic acid, first-order dehydrogenation and hydrogenation of this latter acid, and hydrogenation of pimaric acids. Hydrogenation reactions are partial first-order regarding the acid and hydrogen.     

Benthic macroinfaunal assemblages associated with Amazonian saltmarshes

The composition and abundance of the poorly known benthic macroinfauna associated with northern Brazilian saltmarshes, were described from eight sites (between 0°42′2.5″S, 47°52′44.1″W and 0°50′17.3″S, 46°36′13.3″W) along the Pará coast, Brazil. Sampling was carried out in November of 2007. Univariate and multivariate analyses were used to test for differences in sediment, vegetation and macroinfaunal variables among sites. No vertical zonation of the macroinfauna was detected. Macroinfaunal structure differed greatly among sites with different sediment and vegetation characteristics. Number of individuals and taxa were low in sites with sandy sediments and short, sparse vegetation and high in those with silty sediments with high organic matter and water contents, and tall, dense vegetation. Increasing number of individuals and taxa were associated with a geographical gradient in pore water salinity, which increases from west to east, coinciding with patterns of rainfall described for the Pará coast.     

Marine sediments from southeastern Brazilian continental shelf: A 1200 year record of upwelling productivity

A sediment core from the Cabo Frio coastal shelf (?23.19 S, ?41.8 W; 117 m depth), was analyzed for TOC, C/N ratio, organic petrography and planktonic foraminiferal content to evaluate variations in local productivity caused by changes in upwelling intensity and its relation to regional and global climatic variations during the last millennium. The Cabo Frio core recorded the last 1200 years of sedimentation, with rates varying from 0.11 to 0.32 mm yr^?1. Foraminiferal and organic geochemical analyses indicate the occurrence of three distinct periods of productivity. From 850 AD until 1070 AD, foraminifera fluxes consisting primarily of Turborotalita quinqueloba indicate stronger South Atlantic Central Water (SACW) transport onto the shelf, which induced high biological productivity that was also recorded by high TOC and marine palynomorphs content and a low C/N atomic ratio. This period coincided with a northward displacement of the atmospheric Intertropical Convergence Zone (ITCZ) and South Atlantic High (SAH) systems driven by positive temperature anomalies in the North Atlantic Ocean during the Medieval Climate Anomaly (MCA). From 1070 until 1500 AD, low TOC flux and planktonic foraminifera fluxes and high C/N atomic ratios suggest a reduction in marine productivity, probably driven by reduced transport of SACW associated with the southward displacement of the SAH and weakening of northeasterly winds. The period between 1500 and 1830 AD, which corresponds to the Little Ice Age, is marked by increased fluxes of planktonic foraminifera, principally of Globigerina bulloides and Globigerinita glutinata. These species mark an increase in productivity linked to SACW upwelling, supported by the enhancement of northeasterly winds and southward displacement of the ITCZ and SAH.     

Cellular spelunking: exploring adipocyte caveolae

It has been known for decades that the adipocyte cell surface is particularly rich in small invaginations we now know to be caveolae. These structures are common to many cell types but are not ubiquitous. They have generated considerable curiosity, as manifested by the numerous publications on the topic that describe various, sometimes contradictory, caveolae functions. Here, we review the field from an "adipocentric" point of view and suggest that caveolae may have a function of particular use for the fat cell, namely the modulation of fatty acid flux across the plasma membrane. Other functions for adipocyte caveolae that have been postulated include participation in signal transduction and membrane trafficking pathways, and it will require further experimental scrutiny to resolve controversies surrounding these possible activities.