Divergent calcium signaling in RBCs from Tropidurus torquatus (Squamata – Tropiduridae) strengthen classification in lizard evolution

Abstract\ud \ud \ud \ud Background\ud \ud We have previously reported that a Teiid lizard red blood cells (RBCs) such as Ameiva ameiva and Tupinambis merianae controls intracellular calcium levels by displaying multiple mechanisms. In these cells, calcium stores could be discharged not only by: thapsigargin, but also by the Na+/H+ ionophore monensin, K+/H+ ionophore nigericin and the H+ pump inhibitor bafilomycin as well as ionomycin. Moreover, these lizards possess a P2Y-type purinoceptors that mobilize Ca2+ from intracellular stores upon ATP addition.\ud \ud \ud \ud Results\ud \ud Here we report, that RBCs from the tropidurid lizard Tropidurus torquatus store Ca2+ in endoplasmic reticulum (ER) pool but unlike in the referred Teiidae, these cells do not store calcium in monensin-nigericin sensitive pools. Moreover, mitochondria from T. torquatus RBCs accumulate Ca2+. Addition of ATP to a calcium-free medium does not increase the [Ca2+]c levels, however in a calcium medium we observe an increase in cytosolic calcium. This is an indication that purinergic receptors in these cells are P2X-like.\ud \ud \ud \ud Conclusion\ud \ud T. torquatus RBCs present different mechanisms from Teiid lizard red blood cells (RBCs), for controlling its intracellular calcium levels. At T. torquatus the ion is only stored at endoplasmic reticulum and mitochondria. Moreover activation of purinergic receptor, P2X type, was able to induce an influx of calcium from extracelullar medium. These studies contribute to the understanding of the evolution of calcium homeostasis and signaling in nucleated RBCs.We thank Fundação de Amparo à Pesquisa de São Paulo (FAPESP) for funding CRSG. FHB received fellowship from FAPESP. We thank Robson Sartorello and Miguel T. Rodrigues for collecting the lizards.We thank Fundação de Amparo à Pesquisa de São Paulo (FAPESP) for funding CRSG. FHB received fellowship from FAPESP. We thank Robson Sartorello and Miguel T. Rodrigues for collecting the lizards

(2E)-2-[(3E)-4-Phenyl­but-3-en-2-yl­idene]hydrazinecarboxamide

In the title compound, C11H13N3O, the phenyl ring is disordered over two sites, with occupancy factors in a 0.520 (17):0.480 (17) ratio. The dihedral angle between the ring planes of the major and minor components of the disordered ring is 12.9 (2)°. In the crystal, mol­ecules are linked by N—H⋯O hydrogen bonds, forming R 2 2(8) ring motifs. C—H⋯O, C—H⋯N and C—H⋯π inter­actions also occur

Cyclic AMP and calcium interplay as second messengers in melatonin-dependent regulation of Plasmodium falciparum cell cycle

The host hormone melatonin increases cytoplasmic Ca2+ concentration and synchronizes Plasmodium cell cycle (Hotta, C.T., M.L. Gazarini, F.H. Beraldo, F.P. Varotti, C. Lopes, R.P. Markus, T. Pozzan, and C.R. Garcia. 2000. Nat. Cell Biol. 2:466–468). Here we show that in Plasmodium falciparum melatonin induces an increase in cyclic AMP (cAMP) levels and cAMP-dependent protein kinase (PKA) activity (40 and 50%, respectively)

Domains of STIP1 responsible for regulating PrPC-dependent amyloid-β oligomer toxicity.

Soluble oligomers of amyloid-beta peptide (AβO) transmit neurotoxic signals through the cellular prion protein (PrP(C)) in Alzheimer\u27s disease (AD). Secreted stress-inducible phosphoprotein 1 (STIP1), an Hsp70 and Hsp90 cochaperone, inhibits AβO binding to PrP(C) and protects neurons from AβO-induced cell death. Here, we investigated the molecular interactions between AβO and STIP1 binding to PrP(C) and their effect on neuronal cell death. We showed that residues located in a short region of PrP (90-110) mediate AβO binding and we narrowed the major interaction in this site to amino acids 91-100. In contrast, multiple binding sites on STIP1 (DP1, TPR1 and TPR2A) contribute to PrP binding. DP1 bound the N-terminal of PrP (residues 23-95), whereas TPR1 and TPR2A showed binding to the C-terminal of PrP (residues 90-231). Importantly, only TPR1 and TPR2A directly inhibit both AβO binding to PrP and cell death. Furthermore, our structural studies reveal that TPR1 and TPR2A bind to PrP through distinct regions. The TPR2A interface was shown to be much more extensive and to partially overlap with the Hsp90 binding site. Our data show the possibility of a PrP, STIP1 and Hsp90 ternary complex, which may influence AβO-mediated cell death

Estudo da infestação por Haematobia irritans e por larvas de Dermatobia hominis em bovinos de corte.

As miíases provocadas por larvas de conhecidas como berne e o parasitismo pela mosca-dos-chifres, causam graves prejuízos aos pecuaristas no Brasil. Como têm sido observadas diferenças nas infestações entre animais de diferentes grupos genéticos, o presente estudo teve por objetivo verificar se existe diferença na suscetibilidade/resistência às infestações por bernes e mosca-dos-chifres, em bovinos de dois grupos genéticos diferentes. Foram utilizados bovinos machos e fêmeas, nascidos de outubro a dezembro de 2008 puros , da raça Nelore (n=28) e animais com maior grau de sangue , filhos de vacas ½ Canchim + ½ Nelore inseminadas com Angus (TC, n=17). Estes animais foram mantidos sem qualquer tratamento químico para controle de parasitas, em piquetes rotacionados de capim tanzânia ( ), na fazenda experimental da Embrapa Pecuária Sudeste e receberam suplementação somente no inverno. Mensalmente foram feitas avaliações por meio de inspeções visuais e táteis para contagem dos nódulos de bernes presentes em todo o corpo dos animais. As contagens das moscas-dos-chifres foram feitas simultaneamente às contagens de bernes, por meio da análise em computador de fotografias da região lombar de cada animal. Até o momento foram realizadas 10 contagens, totalizando 450 observações (de agosto de 2009 a maio de 2010). Todos os dados obtidos foram transformados em log (n+1) e analisados por meio do procedimento MIXED do SAS (2002/2003), de acordo com um modelo que incluiu os efeitos de grupo genético (GG), sexo (SX), contagem (CO) e interações, além do resíduo. Os resultados obtidos até o momento mostraram que os animais ?Nelore intensivo? (NI) apresentaram menores infestações pelos ectoparasitas estudados, que os animais ?Tricross? (TC). As maiores diferenças entre os grupos genéticos foram observadas para as infestações por bernes, sendo que as médias erro padrão foram de 0,10 0,04 e 0,58 0,05, para os animais NI e TC, respectivamente. As maiores infestações por bernes ocorreram durante os meses mais quentes e úmidos (dezembro/janeiro ). Para a mosca-dos-chifres as médias erro padrão foram de 1,01 0,05 para os animais NI e 1,41 0,064 para os animais TC e os machos apresentaram infestações superiores àquelas observadas para as fêmeas

Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1)

Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a cochaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against certain brain proteins, including antibodies against STIP1. Maternal antibodies can cross the fetus blood-brain barrier during pregnancy, suggesting the possibility that they can interfere with STIP1 levels and, presumably, functions. However, it is currently unknown whether abnormal levels of STIP1 have any impact in ASD-related behavior. Here, we used mice with reduced (50%) or increased STIP1 levels (fivefold) to test for potential ASD-like phenotypes. We found that increased STIP1 regulates the abundance of Hsp70 and Hsp90, whereas reduced STIP1 does not affect Hsp70, Hsp90 or the prion protein. Interestingly, BAC transgenic mice presenting fivefold more STIP1 show no major phenotype when examined in a series of behavioral tasks, including locomotor activity, elevated plus maze, Morris water maze and five-choice serial reaction time task (5-CSRTT). In contrast, mice with reduced STIP1 levels are hyperactive and have attentional deficits on the 5-CSRTT, but exhibit normal performance for the other tasks. We conclude that reduced STIP1 levels can contribute to phenotypes related to ASD. However, future experiments are needed to define whether it is decreased chaperone capacity or impaired prion protein signaling that contributes to these phenotypes

Efeito da suplementação com a zeólita natural estilbita sobre a infecção por nematódeos gastrintestinais em ovinos no estado de São Paulo

bitstream/item/57229/1/Boletim29.pd

The Transient Receptor Potential Melastatin 2 (TRPM2) Channel Contributes to beta-Amyloid Oligomer-Related Neurotoxicity and Memory Impairment

In Alzheimer\u27s disease, accumulation of soluble oligomers of beta-amyloid peptide is known to be highly toxic, causing disturbances in synaptic activity and neuronal death. Multiple studies relate these effects to increased oxidative stress and aberrant activity of calcium-permeable cation channels leading to calcium imbalance. The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+-permeable nonselective cation channel activated by oxidative stress, has been implicated in neurodegenerative diseases, and more recently in amyloid-induced toxicity. Here we show that the function of TRPM2 is augmented by treatment of cultured neurons with beta-amyloid oligomers. Aged APP/PS1 Alzheimer\u27s mouse model showed increased levels of endoplasmic reticulum stress markers, protein disulfide isomerase and phosphorylated eukaryotic initiation factor 2 alpha, as well as decreased levels of the presynaptic marker synaptophysin. Elimination of TRPM2 in APP/PS1 mice corrected these abnormal responses without affecting plaque burden. These effects of TRPM2 seem to be selective for beta-amyloid toxicity, as ER stress responses to thapsigargin or tunicamycin in TRPM2(-/-) neurons was identical to that of wild-type neurons. Moreover, reduced microglial activation was observed in TRPM2(-/-)/APP/PS1 hippocampus compared with APP/PS1 mice. In addition, age-dependent spatial memory deficits in APP/PS1 mice were reversed in TRPM2(-/-)/APP/PS1 mice. These results reveal the importance of TRPM2 for beta-amyloid neuronal toxicity, suggesting that TRPM2 activity could be potentially targeted to improve outcomes in Alzheimer\u27s disease