Anti-Trypanosoma cruzi and cytotoxic activities of Eugenia uniflora L

Chagas disease is caused by Trypanosoma cruzi, being considered a public health problem. An alternative to combat this pathogen is the use of natural products isolated from fruits such as Eugenia uniflora, a plant used by traditional communities as food and medicine due to its antimicrobial and biological activities. Ethanolic extract from E. uniflora was used to evaluate in vitro anti-epimastigote and cytotoxic activity. This is the first record of anti-Trypanosoma activity of E. uniflora, demonstrating that a concentration presenting 50% of activity (EC(50)) was 62.76 μg/mL. Minimum inhibitory concentration (MIC) was ≤ 1024 μg/mL. Our results indicate that E. uniflora could be a source of plant-derived natural products with anti-epimastigote activity with low toxicity.     

Protein kinase A modulates the activity of a major human isoform of ABCG1

ABCG1 is an ABC half-transporter that exports cholesterol from cells to HDL. This study set out to investigate differences in posttranslational processing of two human ABCG1 protein isoforms, termed ABCG1(+12) and ABCG1(- 12), that differ by the presence or absence of a 12 amino acid peptide. ABCG1(+12) is expressed in human cells and tissues, but not in mice. We identified two protein kinase A (PKA) consensus sites in ABCG1(+12), absent from ABCG1(- 12). Inhibition of PKA with either of two structurally unrelated inhibitors resulted in a dose-dependent increase in cholesterol export from cells expressing ABCG1(+12), whereas ABCG1(- 12)-expressing cells were unaffected. This was associated with stabilization of the ABCG1(+12) protein, and ABCG1(+12)-S389 was necessary to mediate these effects. Mutation of this serine to aspartic acid, simulating a constitutively phosphorylated state, resulted in accelerated degradation of ABCG1(+12) and reduced cholesterol export. Engineering an equivalent PKA site into ABCG1(- 12) rendered this isoform responsive to PKA inhibition, confirming the relevance of this sequence. Together, these results demonstrate an additional level of complexity to the posttranslational control of this human ABCG1 isoform that is absent from ABCG1(- 12) and the murine ABCG1 homolog.     

The role of evolutionary intermediates in the host adaptation of canine parvovirus

The adaptation of viruses to new hosts is a poorly understood process likely involving a variety of viral structures and functions that allow efficient replication and spread. Canine parvovirus (CPV) emerged in the late 1970s as a host-range variant of a virus related to feline panleukopenia virus (FPV). Within a few years of its emergence in dogs, there was a worldwide replacement of the initial virus strain (CPV type 2) by a variant (CPV type 2a) characterized by four amino acid differences in the capsid protein. However, the evolutionary processes that underlie the acquisition of these four mutations, as well as their effects on viral fitness, both singly and in combination, are still uncertain. Using a comprehensive experimental analysis of multiple intermediate mutational combinations, we show that these four capsid mutations act in concert to alter antigenicity, cell receptor binding, and relative in vitro growth in feline cells. Hence, host adaptation involved complex interactions among both surface-exposed and buried capsid mutations that together altered cell infection and immune escape properties of the viruses. Notably, most intermediate viral genotypes containing different combinations of the four key amino acids possessed markedly lower fitness than the wild-type viruses.     

Ticks (Acari: Ixodidae) associated with small terrestrial mammals in the state of Minas Gerais, southeastern Brazil

From June 2005 to November 2010, 43 small mammals encompassing 6 species of Didelphimorphia, 8 species of Rodentia, and 1 species of Lagomorpha were found parasitized by ticks in the state of Minas Gerais, southeastern Brazil. Nine tick species, in total 186 specimens, were identified as follows: Amblyomma cajennense (larvae and nymphs) on opossums and rodents; Amblyomma ovale (nymphs) on rodents; Amblyomma parvum (nymphs) on rodents; Amblyomma coelebs (nymphs) on opossums; Amblyomma dubitatum (nymph) on opossums; Ixodes amarali (females, nymphs, and larvae) on opossums and rodents; Ixodes loricatus (male, females, nymph) on opossums; Ixodes schulzei (female) on rodents; and Haemaphysalis leporispalustris (female) on rabbits. Most of the tick-host associations found in the present study have never been recorded in the literature; those include three new host records for I. amarali, four for A. cajennense, one for A. dubitatum, two for A. ovale, and one for A. coelebs. In addition, we provide the first record of A. coelebs in the state of Minas Gerais.     

Activity-dependent phosphorylation of GABAA receptors regulates receptor insertion and tonic current

The expression of GABA(A) receptors and the efficacy of GABAergic neurotransmission are subject to adaptive compensatory regulation as a result of changes in neuronal activity. Here, we show that activation of L-type voltage-gated Ca(2+) channels (VGCCs) leads to Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) phosphorylation of S383 within the β3 subunit of the GABA(A) receptor. Consequently, this results in rapid insertion of GABA(A) receptors at the cell surface and enhanced tonic current. Furthermore, we demonstrate that acute changes in neuronal activity leads to the rapid modulation of cell surface numbers of GABA(A) receptors and tonic current, which are critically dependent on Ca(2+) influx through L-type VGCCs and CaMKII phosphorylation of β3S383. These data provide a mechanistic link between activity-dependent changes in Ca(2+) influx through L-type channels and the rapid modulation of GABA(A) receptor cell surface numbers and tonic current, suggesting a homeostatic pathway involved in regulating neuronal intrinsic excitability in response to changes in activity.     

Effect of vertical sleeve gastrectomy in melanocortin receptor 4-deficient rats

Bariatric surgery is currently the most effective treatment for obesity. Vertical sleeve gastrectomy (VSG), a commonly applied bariatric procedure, involves surgically incising most of the volume of the stomach. In humans, partial loss of melanocortin receptor-4 (MC4R) activity is the most common monogenic correlate of obesity regardless of lifestyle. At present it is unclear whether genetic alteration of MC4R signaling modulates the beneficial effects of VSG. Following VSG, we analyzed body weight, food intake, glucose sensitivity, and macronutrient preference of wild-type and MC4R-deficient (Mc4r(+/-) and Mc4r(-/-)) rats compared with sham-operated controls. VSG reduced body weight and fat mass and improved glucose metabolism and also shifted preference toward carbohydrates and away from fat. All of this occurred independently of MC4R activity. In addition, MC4R was resequenced in 46 human subjects who underwent VSG. We observed common genetic variations in the coding sequence of MC4R in five subjects. However, none of those variations appeared to affect the outcome of VSG. Taken together, these data suggest that the beneficial effect of VSG on body weight and glucose metabolism is not mediated by alterations in MC4R activity.     

Enzymatic modification of chitosan with quercetin and its application as antioxidant edible films

Quercetin, rutin, naringin, hesperidin and chrysin were tested as substrates for cloroperoxidase to produce reactive quinones to graft onto chitosan. Quercetin and rutin quinones were successfully chemically attached to low molecular weight chitosan. The quercetin-modified chitosan showed an enhancement of plastic, antioxidant and antimicrobial properties as well as of thermal degradability. Finally, chitosan-quercetin films visibly decreased enzymatic oxidation when applied to Opuntia ficus indica cladodes.     

Range‐wide patterns of migratory connectivity in the western sandpiper Calidris mauri

Understanding the population dynamics of migratory animals and predicting the consequences of environmental change requires knowing how populations are spatially connected between different periods of the annual cycle. We used stable isotopes to examine patterns of migratory connectivity across the range of the western sandpiper Calidris mauri. First, we developed a winter isotope basemap from stable‐hydrogen (δD), ‐carbon (δ¹³C), and ‐nitrogen (δ¹⁵N) isotopes of feathers grown in wintering areas. δD and δ¹⁵N values from wintering individuals varied with the latitude and longitude of capture location, while δ¹³C varied with longitude only. We then tested the ability of the basemap to assign known‐origin individuals. Sixty percent of wintering individuals were correctly assigned to their region of origin out of seven possible regions. Finally, we estimated the winter origins of breeding and migrant individuals and compared the resulting empirical distribution against the distribution that would be expected based on patterns of winter relative abundance. For breeding birds, the distribution of winter origins differed from expected only among males in the Yukon‐Kuskokwim (Y‐K) Delta and Nome, Alaska. Males in the Y‐K Delta originated overwhelmingly from western Mexico, while in Nome, there were fewer males from western North America and more from the Baja Peninsula than expected. An unexpectedly high proportion of migrants captured at a stopover site in the interior United States originated from eastern and southern wintering areas, while none originated from western North America. In general, we document substantial mixing between the breeding and wintering populations of both sexes, which will buffer the global population of western sandpipers from the effects of local habitat loss on both breeding and wintering grounds.     

Hoiamide D, a marine cyanobacteria-derived inhibitor of p53/MDM2 interaction

Bioassay-guided fractionation of two cyanobacterial extracts from Papua New Guinea has yielded hoiamide D in both its carboxylic acid and conjugate base forms. Hoiamide D is a polyketide synthase (PKS)/non-ribosomal peptide synthetase (NRPS)-derived natural product that features two consecutive thiazolines and a thiazole, as well as a modified isoleucine residue. Hoiamide D displayed inhibitory activity against p53/MDM2 interaction (EC(50)=4.5 μM), an attractive target for anticancer drug development.