Bird ticks in an area of the Cerrado of Minas Gerais State, southeast Brazil

In the present study the tick prevalence, mean intensity of infestation and species were recorded on birds captured between January 2009 and December 2010 in the Ecological Station Pirapitinga-ESEC from Minas Gerais State, Brazil. A total of 967 birds, from 15 families and 40 species were captured and 165 (17.1 %) individuals were parasitized by ticks. Of these 160 (97 %) belonged to the order Passeriformes. Five tick species were identified: Amblyomma longirostre (n = 274) was the most common species followed by Amblyomma parvum (n = 43), Amblyomma nodosum (n = 39), Amblyomma ovale (n = 24) and Riphicephalus sanguineus (n = 7). None of 61 unengorged larvae molted to nymph. The mean intensity of infestation was 2.7 ± 2.4 ticks per bird (448 ticks/165 birds) ranging from 1 to 10. Only 19 (11.4 %) birds were infested with one species of tick. The remaining birds were infested by two, three or four species of ticks. Also new hosts for all five ticks were recorded. Only nymphs were recorded throughout the year with two similar peaks during autumn and winter 2009 and 2010.     

PPP4R2 regulates neuronal cell differentiation and survival, functionally cooperating with SMN

Spinal muscular atrophy (SMA) is a human disease caused by reduced levels of the Survival of Motor Neuron (SMN) protein, leading to progressive loss of motor neurons and muscular paralysis. However, it is still not very clear why these cells are specifically sensitive to SMN levels. Therefore, understanding which proteins may functionally interact with SMN in a neuronal context is a very important issue. PPP4R2, a regulatory subunit of the protein phosphatase 4 (PPP4C), was previously identified as a functional interactor of the SMN complex, but has never been studied in neuronal cells. In this report, we show that PPP4R2 displays a very dynamic intracellular localization in mouse and rat neuronal cell lines and in rat primary hippocampal neurons, strongly correlating with differentiation. More importantly, we found that PPP4R2 loss of function impairs the differentiation of the mouse motor-neuronal cell line NSC-34, an effect that can be counteracted by SMN overexpression. In addition, we show that PPP4R2 may specifically protect NSC-34 cells from DNA damage-induced apoptosis and that it is capable to functionally cooperate with SMN in this activity. Our data indicate that PPP4R2 is a SMN partner that may modulate the differentiation and survival of neuronal cells.     

Coccidial dispersion across New World marsupials: Klossiella tejerai Scorza,Torrealba & Dagert, 1957 (Apicomplexa: Adeleorina) from the Brazilian common opossum Didelphis aurita (Wied-Neuwied) (Mammalia: Didelphimorphia)

Klossiella tejerai Scorza, Torrealba & Dagert, 1957 is a primitive coccidian parasite reported from the New World marsupials Didelphis marsupialis (Linnaeus) and Marmosa demerarae (Thomas). The current work describes K. tejerai from the Brazilian common opossum Didelphis aurita (Wied-Neuwied) in Southeastern Brazil, evidencing the coccidial dispersion across opossums of the same family. The sporocysts recovered from urine samples were ellipsoidal, 20.4 × 12.7 µm, with sporocyst residuum composed of scattered spherules and c.13 sporozoites per sporocyst, with refractile bodies and nucleus. Macrogametes, microgametes, sporonts, sporoblasts/sporocysts were identified within parasitophorous vacuoles of epithelial cells located near the renal corticomedullary junction. Didelphis marsupialis should not have transmitted K. tejerai to D. aurita because they are not sympatric; however M. demerarae is sympatric with D. marsupialis and D. aurita. Therefore, D. aurita becomes the third host species for K. tejerai in South America.     

Interaction of copper(II) with imidazole pyridine nitrogen-containing ligands in aqueous medium: a spectroscopic study.

UV (300-400 nm) and FT/IR (4000-850 cm(-1)) spectra were considered for a structural discussion of the copper(II) complexes formed with a series of imidazole-containing ligands (namely L-histidine, N-acetyl-L-histidine, histamine, L-histidine methyl ester and carnosine) in aqueous solution (T=25 degrees C, I=0.1 M). A shoulder at 330 nm was recorded for the main copper(II) complexes with all the ligands considered with the exception of carnosine: this singularity is discussed and a spectrum-structure correlation is proposed. epsilon(330) values were evaluated for CuL (59 M(-1) cm(-1)) and Cu(2)L(2)H(-2) (577 M(-1) cm(-1)) complexes with histamine and for CuL(2) (49 M(-1) cm(-1)) and CuL(3) (163 M(-1) cm(-1)) with N-acetyl-L-histidine, thus indicating the usefulness of UV spectra in the explored region for the purpose of structural definition. FT/IR spectra (recorded both in aqueous solution and on the residue of evaporated solutions of carnosine and N-acetyl-L-histidine only) help to reveal a significant conformational rearrangement of the ligand, corresponding to complex formation in solution: in fact, modifications in the fingerprint region of the FT/IR spectrum for the dimer of carnosine are observed. Indications of a copper(II)-imidazole nitrogen interaction are also obtained from FT/IR data in the 1000-1100 cm(-1) range.     

Palaeoenvironment and palaeoclimate in the western Liguria region (northwestern Italy) during the Last Glacial. The small mammal sequence of Riparo Mochi (Balzi Rossi,Ventimiglia)

Riparo Mochi is considered a key site for the Middle–Upper Palaeolithic chrono-cultural sequence in the Mediterranean area. Climatic and environmental conditions have been reconstructed after the study of the small mammal assemblage by means of linear regression method and the Habitat Weighting method. The climate proxies for the late Mousterian and Proto-Aurignacian (cultural units I to G) indicate an environment with a relative high percentage of forest component during two cold and one relative warm oscillations. Open environments with low temperatures are registered for the Gravettian (cultural Unit D) allowing a possible relation to the Heinrich 3 Event. The final Gravettian (cultural Unit C) shows a relative warm peak, tentatively related to Greenland Interstadial 2. The late Epigravettian (cultural Unit A) is characterized by a high percentage of forest-related environment suggesting that this horizon formed during the Bølling–Allerød Interstadial. Finally, the Riparo Mochi sequence contributes to reconstruct the processes of faunal changes along the northern Tyrrhenian coast in a period of climatic instability, especially during the end of Marine Isotope Stage 3 when foraging groups adopted different mobility strategies between southern France and the Italian peninsula.     

Synthesis and biological validation of novel pyrazole derivatives with anticancer activity guided by 3D-QSAR analysis

Using literature data on anticancer activity of pyrazole derivatives, 3D-QSAR models were developed and 3D-QSAR analysis was performed. The 3D-QSAR analysis enabled identification of molecular properties that have the highest impact on antitumor activity against lung cancer cells. The results of 3D-QSAR analysis were taken into account while new compounds were designed. Obtained 3D-QSAR models were used for prediction of activity of new compounds. In this way, design of new compounds was guided by 3D-QSAR analysis which was performed on literature data. Ten new pyrazole derivatives were synthesised and their antitumor activities against A549 and NCIH23 lung cancer cells were validated. In order to obtain full profile of anticancer activity, cells viability (MTS) assays were combined with cell proliferation (BrdU) assays which measure actively dividing cells in treated sample. Experimental measurements showed good agreement between predicted and measured activities for majority of compounds. Also, anticancer activities of new pyrazole derivatives pointed to the chemical groups that can be useful in designing antitumor molecules. Substitution of hydrazine linker with rigid, 1,2,4-oxadiazole moiety resulted in compound 10, which has low (if any) cytotoxic activity and high potential cytostatic activity. Therefore, compound 10 presents a good starting point for design of new, more potent and safer anticancer therapeutics.     

A comparative analysis of structure and spatial distribution of decorin in human leiomyoma and normal myometrium

Leiomyoma is a benign smooth muscle tumor of the uterus that affects many women in active reproductive life. It is composed by bundles of smooth muscle cells surrounded by extracellular matrix. We have recently shown that the glycosylation of extracellular matrix proteoglycans is modified in leiomyoma: increased amounts of galactosaminoglycans with structural modifications are present. The data here presented show that decorin is present in both normal myometrium and leiomyoma but tumoral decorin is glycosylated with longer galactosaminoglycan side chains. Furthermore, these chains contain a higher ratio D-glucuronate/L-iduronate, as compared to normal tissue. To determine if these changes in proteoglycan glycosylation correlates with modifications in the extracellular matrix organization, we compared the general structural architecture of leiomyoma to normal myometrium. By histochemical and immunofluorescence methods, we found a reorganization of muscle fibers and extracellular matrix, with changes in the distribution of glycoproteins, proteoglycans, and collagen. Thin reticular fibers, possibly composed by types I and III collagen, were replaced by thick fibers, possibly richer in type I collagen. Type I collagen colocalized with decorin both in leiomyoma and normal myometrium, in contrast to type IV collagen that did not. The relative amount of decorin was increased and the distribution of decorin and collagen was totally modified in the tumor, as compared to the normal myometrium. These findings reveal that not only decorin structure is modified in leiomyoma but also the tissue architecture changed, especially concerning extracellular matrix.     

Tau localises within mitochondrial sub-compartments and its caspase cleavage affects ER-mitochondria interactions and cellular Ca2+ handling

Intracellular neurofibrillary tangles (NFT) composed by tau and extracellular amyloid beta (Aβ) plaques accumulate in Alzheimer's disease (AD) and contribute to neuronal dysfunction. Mitochondrial dysfunction and neurodegeneration are increasingly considered two faces of the same coin and an early pathological event in AD. Compelling evidence indicates that tau and mitochondria are closely linked and suggests that tau-dependent modulation of mitochondrial functions might be a trigger for the neurodegeneration process; however, whether this occurs either directly or indirectly is not clear. Furthermore, whether tau influences cellular Ca²⁺ handling and ER-mitochondria cross-talk is yet to be explored. Here, by focusing on wt tau, either full-length (2N4R) or the caspase 3-cleaved form truncated at the C-terminus (2N4RΔC₂₀), we examined the above-mentioned aspects. Using new genetically encoded split-GFP-based tools and organelle-targeted aequorin probes, we assessed: i) tau distribution within the mitochondrial sub-compartments; ii) the effect of tau on the short- (8–10?nm) and the long- (40–50?nm) range ER-mitochondria interactions; and iii) the effect of tau on cytosolic, ER and mitochondrial Ca²⁺ homeostasis. Our results indicate that a fraction of tau is found at the outer mitochondrial membrane (OMM) and within the inner mitochondrial space (IMS), suggesting a potential tau-dependent regulation of mitochondrial functions. The ER Ca²⁺ content and the short-range ER-mitochondria interactions were selectively affected by the expression of the caspase 3-cleaved 2N4RΔC₂₀ tau, indicating that Ca²⁺ mis-handling and defects in the ER-mitochondria communications might be an important pathological event in tau-related dysfunction and thereby contributing to neurodegeneration. Finally, our data provide new insights into the molecular mechanisms underlying tauopathies.     

Expression of CD64 on Circulating Neutrophils Favoring Systemic Inflammatory Status in Erythema Nodosum Leprosum

Erythema Nodosum Leprosum (ENL) is an immune reaction in leprosy that aggravates the patient´s clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-γ and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1) Lepromatous leprosy, (2) Borderline leprosy, (3) Reversal reaction, (4) ENL, and (5) ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates—a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64, presumably contributing to the immunopathogenesis of the disease.     

Production and purification of a novel extracellular lipase from Alternaria brassicicola

Alternaria brassicicola produced higher quantities (3.2 U/ml) of an inducible extracellular lipase (EC 3.1.1.3) in shaken synthetic medium supplemented with 20 mM methyloleate. After purification, the M r of the lipase was determined as 80 kDa by SDS-PAGE and estimated at 85 kDa using gel filtration, which suggest that the enzyme may be a monomer. The optimum pH and temperature for activity of the enzyme were 9.0 and 25ºC, respectively. Using umbelliferone esters, the lipase was shown highly specific towards a synthetic substrate with long-chain unsaturated fatty acid.