A MORC protein complex modulates epigenetic control of gene expression through interaction with heterochromatin.

Dynamic control of gene expression is critical for blood stage development of malaria parasites. Here, we used multi-omic analyses to investigate transcriptional regulation by the chromatin-associated microrchidia protein, MORC, during asexual blood stage development of the human malaria parasite . We show that MORC (PF3D7_1468100) interacts with a suite of nuclear proteins, including APETALA2 (ApiAP2) transcription factors (AP2-G5, AP2-O5, AP2-I, PF3D7_0420300, PF3D7_0613800, PF3D7_1107800, and PF3D7_1239200), a DNA helicase DS60 (PF3D7_1227100), and other chromatin remodelers (CHD1 and EELM2).

Bradykinin promotes murine melanoma cell migration and invasion through endogenous production of superoxide and nitric oxide.

Spatial confinement and temporal regulation of signaling by nitric oxide (NO) and reactive oxygen species (ROS) occurs in cancer cells. Signaling mediated by NO and ROS was investigated in two sub clones of the murine melanoma B16F10-Nex2 cell line, Nex10C and Nex8H treated or not with bradykinin (BK). The sub clone Nex10C, similar to primary site cells, has a low capacity for colonizing the lungs, whereas the sub clone Nex8H, similar to metastatic cells, corresponds to a highly invasive melanoma.

Src kinase activation by nitric oxide promotes resistance to anoikis in tumour cell lines.

Tumour progression involves the establishment of tumour metastases at distant sites. Resistance to anoikis, a form of cell death that occurs when cells lose contact with the extracellular matrix and with neighbouring cells, is essential for metastases. NO has been associated with anoikis.

Plasmodium falciparum GPCR-like receptor SR25 mediates extracellular K sensing coupled to Ca signaling and stress survival.

The malaria parasite Plasmodium falciparum is exposed, during its development, to major changes of ionic composition in its surrounding medium. We demonstrate that the P. falciparum serpentine-like receptor PfSR25 is a monovalent cation sensor capable of modulating Ca signaling in the parasites.

Signaling transcript profile of the asexual intraerythrocytic development cycle of induced by melatonin and cAMP.

According to the World Health Organization (WHO), is the deadliest parasite among all species. This parasite possesses the ability to sense molecules, including melatonin (MEL) and cAMP, and modulate its cell cycle accordingly. MEL synchronizes the development of this malaria parasite by activating several cascades, including the generation of the second messenger cAMP.

Combination of Bioactive Polymeric Membranes and Stem Cells for Periodontal Regeneration: In Vitro and In Vivo Analyses.

Regeneration of periodontal tissues requires a concerted effort to obtain consistent and predictable results in vivo. The aim of the present study was to test a new family of bioactive polymeric membranes in combination with stem cell therapy for periodontal regeneration. In particular, the novel polyester poly(isosorbide succinate-co-L-lactide) (PisPLLA) was compared with poly(L-lactide) (PLLA).

Ras, Rac1, and phosphatidylinositol-3-kinase (PI3K) signaling in nitric oxide induced endothelial cell migration.

The small GTP-binding proteins Ras and Rac1 are molecular switches exchanging GDP for GTP and converting external signals in response to a variety of stimuli. Ras and Rac1 play an important role in cell proliferation, cell differentiation, and cell migration. Rac1 is directly involved in the reorganization and changes in the cytoskeleton during cell motility.

Investigation of antimalarial activity, cytotoxicity and action mechanism of piperazine derivatives of betulinic acid.

Objectives: To semisynthesise piperazine derivatives of betulinic acid to evaluate antimalarial activity, cytotoxicity and action mechanism.

Methods: The new derivatives were evaluated against the CQ-sensitive Plasmodium falciparum 3D7 strain by flow cytometry (FC) using YOYO-1 as stain. Cytotoxicity of 4a and 4b was performed with HEK293T cells for 24 and 48 h by MTT assay.

Endothelium-derived nitric oxide (NO) activates the NO-epidermal growth factor receptor-mediated signaling pathway in bradykinin-stimulated angiogenesis.

Nitric oxide (NO) is involved in angiogenesis and stimulates the EGF-R signaling pathway. Stimulation of different endothelial cell lines with bradykinin (BK) activates the endothelial NO synthase (eNOS) and promotes EGF-R tyrosine phosphorylation. Increase in NO production correlated with enhanced phosphorylation of tyrosine residues and S-nitrosylation of the EGF-R.

Biological evaluation of hydroxynaphthoquinones as anti-malarials.

Background: The hydroxynaphthoquinones have been extensively investigated over the past 50 years for their anti-malarial activity. One member of this class, atovaquone, is combined with proguanil in Malarone®, an important drug for the treatment and prevention of malaria.

Methods: Anti-malarial activity was assessed in vitro for a series of 3-alkyl-2-hydroxy-1,4-naphthoquinones (N1-N5) evaluating the parasitaemia after 48 hours of incubation.

Two series of new semisynthetic triterpene derivatives: differences in anti-malarial activity, cytotoxicity and mechanism of action.

Background: The discovery and development of anti-malarial compounds of plant origin and semisynthetic derivatives thereof, such as quinine (QN) and chloroquine (CQ), has highlighted the importance of these compounds in the treatment of malaria. Ursolic acid analogues bearing an acetyl group at C-3 have demonstrated significant anti-malarial activity. With this in mind, two new series of betulinic acid (BA) and ursolic acid (UA) derivatives with ester groups at C-3 were synthesized in an attempt to improve anti-malarial activity, reduce cytotoxicity, and search for new targets.

Pain in popular singers.

Purpose: To identify and characterize the presence of body pains in popular singers, to observe the differences in the reported pains according to gender, and to relate with data regarding vocal behavior and usage in this population.

Methods: A self-explanatory questionnaire was applied to 100 popular singers (50 men and 50 women), in order to collect information about personal identification, voice use and presence of pains. Pains were divided into two groups: proximal pains (TMA, tongue, throat, nape, shoulders, neck, and pain during speech), and distal pains (arms, back/column, chest, hands, ear, and headache).

Synthesis and antiplasmodial activity of betulinic acid and ursolic acid analogues.

More than 40% of the World population is at risk of contracting malaria, which affects primarily poor populations in tropical and subtropical areas. Antimalarial pharmacotherapy has utilised plant-derived products such as quinine and artemisinin as well as their derivatives. However, worldwide use of these antimalarials has caused the spread of resistant parasites, resulting in increased malaria morbidity and mortality.

S-nitrosoglutathione and endothelial nitric oxide synthase-derived nitric oxide regulate compartmentalized ras S-nitrosylation and stimulate cell proliferation.

Aims: S-nitrosylation of Cys118 is a redox-based mechanism for Ras activation mediated by nitric oxide (NO) at the plasma membrane.

Results: Ras signaling pathway stimulation by 50 and/or 100 μM of S-nitrosoglutathione (GSNO) causes proliferation of HeLa cells. Proliferation was not observed in HeLa cells overexpressing non-nitrosatable H-Ras(C118S).

The PfNF-YB transcription factor is a downstream target of melatonin and cAMP signalling in the human malaria parasite Plasmodium falciparum.

Plasmodium falciparum causes the most severe form of malaria and is responsible for the majority of deaths worldwide. The mechanism of cell cycle control within intra-erythrocytic stages has been examined as a potential means of a promising way to identifying how to stop parasite development in red blood cells. Our group determined that melatonin increases parasitemia in P.

Comparison of clinical characteristics of patients with adductor laryngeal dystonia in the focal and segmental types.

Unlabelled: Dystonia is a central motor processing neurological disorder characterized by abnormal, often action-induced, involuntary movements or uncontrolled spasms.

Aim: To compare patients with the diagnoses of focal and segmental adductor laryngeal dystonia at the Neurolarynx Outpatient Clinic of the Federal University of São Paulo.

Materials And Methods: A clinical retrospective study of data collected from patient registries from 2003 to 2009.

Protein tyrosine phosphatase alpha regulates cell detachment and cell death profiles induced by nitric oxide donors in the A431 human carcinoma cell line.

We investigated the role of protein tyrosine phosphatase-alpha (PTPα) expression in the cell death profile of the A431 human carcinoma cell line that was induced by cytotoxic concentrations of the nitric oxide (NO) donors sodium nitroprusside (SNP) and 3,3-bis-(aminoethyl)-1-hydroxy-2-oxo-1-triazene (NOC-18). Both NO donors promoted extensive cell detachment in A431 parental cells as compared to the detachment observed for A431 cells that ectopically expressed PTPα (A431 (A27B(PTPα)) cells). The NO-induced cell death characteristics for both cell lines were examined.

Regulatory effects of nitric oxide on Src kinase, FAK, p130Cas, and receptor protein tyrosine phosphatase alpha (PTP-alpha): a role for the cellular redox environment.

The role of NO in regulating the focal adhesion proteins, Src, FAK, p130 Cas, and PTP-alpha, was investigated. Fibroblasts expressing PTP-alpha (PTP-alpha(WT) cells), fibroblasts "knockout" for PTP-alpha (PTP-alpha(-/-) cells), and "rescued" "knockout" fibroblasts (PTP-alpha A5/3 cells) were stimulated with either S-nitroso-N-acetylpenicillamine (SNAP) or fetal bovine serum (FBS). FBS increased inducible NO synthase in both cell lines.

Dysphonia severity degree and phonation onset latency in laryngeal adductor dystonia.

Although the latency between the initiation of thyroarytenoid electrical activity and the onset of phonation generally is increased in patients with adductor laryngeal dystonia, there is disagreement about whether there is overlap of latency values in these patients and normal subjects. The goal of this article was to compare the severity of dysphonia with the latency between electrophysiological activation of the thyroarytenoid muscle (TA) and the onset of phonation in patients with adductor laryngeal dystonia and compare the values with normal controls. Twenty-one patients with adductor dystonia and 15 control patients underwent laryngeal electromyographic (EMG) examination of the left TA.

The low molecular weight S-nitrosothiol, S-nitroso-N-acetylpenicillamine, promotes cell cycle progression in rabbit aortic endothelial cells.

S-Nitrosylation reactions are considered to be a major mechanism by which NO-related bioactivities are regulated in vivo. In the present study, we show the effects of the low molecular weight S-nitrosothiol, S-nitroso-N-acetylpenicillamine (SNAP), on cell cycle progression of rabbit aortic endothelial cells (RAEC). SNAP at low concentrations (0.

Adduction laryngeal dystonia: proposal and evaluation of nasofibroscopy.

Unlabelled: Dystonias are organic central motor processing disorders characterized by involuntary muscular contractions or incontrollable spasms induced by task-specific movements. Adduction laryngeal dystonias present with important speech impairments, with inappropriate spasms and abrupt voice breaks. The diagnosis is based on clinical features, evaluation by a speech therapist and transnasal fiber optic laryngoscopy.

c-Ki-ras oncogene amplification and FGF2 signaling pathways in the mouse Y1 adrenocortical cell line.

The mouse Y1 adrenocortical tumor cell line is highly responsive to FGF2-(Fibroblast Growth Factor 2) and possesses amplified and over-expressed c-Ki-ras proto-oncogene. We previously reported that this genetic lesion leads to high constitutive levels of activation of the c-Ki-Ras-GTP-->PI3K-->Akt signaling pathway (Forti et al. 2002).

Tyrosine phosphorylation in nitric oxide-mediated signaling events.

In this chapter, we provide an overview of nitric oxide (NO)-tyrosine phosphorylation signal transduction pathways, integrating them with the cyclic guanosine monophosphate (cGMP) and S-nitrosylation-mediated pathways that are triggered by NO. The second half of this chapter includes a description of the methods that our laboratory has used extensively to characterize the mechanisms involved in signaling events mediated by this pathway. These include assays for detecting protein tyrosine phosphorylation, tyrosine phosphorylation of the epidermal growth factor (EGF) receptor, phosphorylation of the ERK1/2 mitogen-activated protein (MAP) kinases, transfection of cells with modified forms of p21Ras, and an assay of p21Ras.

Molecular mechanisms of cell cycle control in the mouse Y1 adrenal cell line.

Y1 adrenocortical tumor cells possess amplified and overexpressed c-Ki-ras proto-oncogene, displaying chronic high levels of the c-Ki-Ras-GTP protein. Despite this oncogenic lesion, we previously reported that Y1 cells retain tight regulatory mechanisms of cell cycle control typified by the mitogenic response triggered by FGF2 in G0/G1-arrested cells. ACTH, on the other hand, elicits cAMP/PKA-mediated antimitogenic mechanisms involving Akt/PKB dephosphorylation/deactivation and c-Myc protein degradation, blocking G1 phase progression stimulated by FGF2.

c-Myc protein is stabilized by fibroblast growth factor 2 and destabilized by ACTH to control cell cycle in mouse Y1 adrenocortical cells.

ACTH is the hormone known to control adrenal cortex function and maintenance in the intact animal but, in culture, it inhibits proliferation of adrenocortical cells from different mammalian species, a puzzle that has remained unsolved for nearly 30 years. In this paper we compare ACTH and fibroblast growth factor 2 (FGF2) antagonistic effects on the cell cycle in the Y1 cell line, a functional lineage of mouse adreno-cortical tumor cells. This cell line displays chronic high levels of c-Ki-Ras-GTP, high active constitutive levels of phosphatidylinositol 3-OH kinase/Protein Kinase B (PI3K/AKT) and low constitutive basal expression of c-Myc, which accounts for a minor deregulation of the cell cycle.