Thymic atrophy induced by Plasmodium berghei ANKA and Plasmodium yoelii 17XL infection.

The thymus is the anatomical site where T cells undergo a complex process of differentiation, proliferation, selection, and elimination of autorreactive cells which involves molecular signals in different intrathymic environment. However, the immunological functions of the thymus can be compromised upon exposure to different infections, affecting thymocyte populations. In this work, we investigated the impact of malaria parasites on the thymus by using C57BL/6 mice infected with Plasmodium berghei ANKA and Plasmodium yoelii 17XL; these lethal infection models represent the most severe complications, cerebral malaria, and anemia respectively. Data showed a reduction in the thymic weight and cellularity involving different T cell maturation stages, mainly CD4-CD8- and CD4+CD8+ thymocytes, as well as an increased presence of apoptotic cells, leading to significant thymic cortex reduction. Thymus atrophy showed no association with elevated serum cytokines levels, although increased glucocorticoid levels did. The severity of thymic damage in both models reached the same extend although it occurs at different stages of infection, showing that thymic atrophy does not depend on parasitemia level but on the specific host-parasite interaction.

The Pathophysiology of The Antiphospholipid Syndrome: A Perspective From The Blood Coagulation System.

The antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by a hypercoagulability associated to vascular thrombosis and/or obstetric morbidity, is caused by the presence of antiphospholipid antibodies such as lupus anticoagulant, anti-ß-2-glycoprotein 1, and/or anticardiolipin antibodies. In the obstetrical APS, antiphospholipid antibodies induce the production of proinflammatory cytokines and tissue factor by placental tissues and recruited neutrophils. Moreover, antiphospholipid antibodies activate the complement system which, in turn, induces a positive feedback leading to recruitment of neutrophils as well as activation of the placenta. Activation of these cells triggers myometrial contractions and cervical ripening provoking the induction of labor. In thrombotic and obstetrical APS, antiphospholipid antibodies activate endothelial cells, platelets, and neutrophils and they may alter the multimeric pattern and concentration of von Willebrand factor, increase the concentration of thrombospondin 1, reduce the inactivation of factor XI by antithrombin, increase the activation of factor XII, and reduce the activity of tissue plasminogen activator with the subsequent production of plasmin. All these effects result in less permeable clots, denser, thinner, and with more branched fibrin fibers which are more difficult to lysate. As a consequence, thrombosis, the defining clinical criterion of APS, complicates the clinical course of the patient.

Monocyte Locomotion Inhibitory Factor confers neuroprotection and prevents the development of murine cerebral malaria.

Cerebral malaria (CM) is a neurological complication derived from the Plasmodium falciparum infection in humans. The mechanisms involved in the disease progression are still not fully understood, but both the sequestration of infected red blood cells (iRBC) and leukocytes and an exacerbated host inflammatory immune response are significant factors. In this study, we investigated the effect of Monocyte Locomotion Inhibitory Factor (MLIF), an anti-inflammatory peptide, in a well-characterized murine model of CM. Our data showed that the administration of MLIF increased the survival and avoided the neurological signs of CM in Plasmodium berghei ANKA (PbA) infected C57BL/6 mice. MLIF administration down-regulated systemic inflammatory mediators such as IFN-γ, TNF-α, IL-6, CXCL2, and CCL2, as well as the in situ expression of TNF-α in the brain. In the same way, MLIF reduced the expression of CD31, CD36, CD54, and CD106 in the cerebral endothelium of infected animals and prevented the sequestration of iRBC and leucocytes in the brain microvasculature. Furthermore, MLIF inhibited the activation of astrocytes and microglia and preserved the integrity of the blood-brain barrier (BBB). In conclusion, our results demonstrated that the administration of MLIF increased survival and conferred neuroprotection by decreasing neuroinflammation in murine CM.

Directional control of charge and valley currents in a graphene-based device.

We propose a directional switching effect in a metallic device. To this end we exploit a graphene-based device with a three-terminal geometry in the presence of a magnetic field. We show that unidirectional charge and valley currents can be controlled by the Fermi energy and the magnetic field direction in the active device. Interestingly, unidirectional transport of charges and valleys is generated between two-terminals at the same bias voltage. Furthermore, we quantify the valley depolarization as a function of disorder concentration. Our results open a way for active graphene-based valleytronics devices.

In vitro and in silico studies of terpenes, terpenoids and related compounds with larvicidal and pupaecidal activity against Culex quinquefasciatus Say (Diptera: Culicidae).

BACKGROUND: In order to develop new larvicidal agents derived from phytochemicals, the larvicidal activity of fifty molecules that are constituent of essential oils was evaluated against Culex quinquefasciatus Say. Terpenes, terpenoids and phenylpropanoids molecules were included in the in vitro evaluation, and QSAR models using genetic algorithms were built to identify molecular and structural properties of biological interest. Further, to obtain structural details on the possible mechanism of action, selected compounds were submitted to docking studies on sterol carrier protein-2 (SCP-2) as possible target. RESULTS: Results showed high larvicidal activity of carvacrol and thymol on the third and fourth larval stage with a median lethal concentration (LC50) of 5.5 and 11.1 µg/mL respectively. Myrcene and carvacrol were highly toxic for pupae, with LC50 values of 31.8 and 53.2 µg/mL. Structure-activity models showed that the structural property π-bonds is the largest contributor of larvicidal activity while ketone groups should be avoided. Similarly, property-activity models attributed to the molecular descriptor LogP the most contribution to larvicidal activity, followed by the absolute total charge (Qtot) and molar refractivity (AMR). The models were statistically significant; thus the information contributes to the design of new larvicidal agents. Docking studies show that all molecules tested have the ability to interact with the SCP-2 protein, wherein α-humulene and ß-caryophyllene were the compounds with higher binding energy. CONCLUSIONS: The description of the molecular properties and the structural characteristics responsible for larvicidal activity of the tested compounds were used for the development of mathematical models of structure-activity relationship. The identification of molecular and structural descriptors, as well as studies of molecular docking on the SCP-2 protein, provide insight on the mechanism of action of the active molecules, and the information can be used for the design of new structures for synthesis as potential new larvicidal agents.

Valley filtering by a line-defect in graphene: quantum interference and inversion of the filter effect.

Valley filters are crucial to any device exploiting the valley degree of freedom. By using an atomistic model, we analyze the mechanism leading to the valley filtering produced by a line-defect in graphene and show how it can be inverted by external means. Thanks to a mode decomposition applied to a tight-binding model we can resolve the different transport channels in k-space while keeping a simple but accurate description of the band structure, both close and further away from the Dirac point. This allows the understanding of a destructive interference effect, specifically a Fano resonance or antiresonance located on the p-side of the Dirac point leading to a reduced conductance. We show that in the neighborhood of this feature the valley filtering can be reversed by changing the occupations with a gate voltage, the mechanism is explained in terms of a valley-dependent Fano resonance splitting. Our results open the door for enhanced control of valley transport in graphene-based devices.

Line defects and quantum Hall plateaus in graphene.

Line defects in graphene can be either tailored-growth or arise naturally and are at the center of many discussions. Here we study the multiterminal conductance of graphene with an extended line defect in the quantum Hall regime analyzing the effects of the geometry of the setup, disorder and strain on the quantum Hall plateaus. We show that the defect turns out to affect the local and non-local conductance in very different ways depending on the geometrical configuration. When the defect is parallel to the sample edges one gets an equivalent circuit formed by parallel resistors. In contrast, when the defect bridges opposite edges, the Hall conductance may remain unaltered depending on the geometry of the voltage/current probes. The role of disorder, strain and the microscopic details of the defect in our results is also discussed. We show that the defect provides a realization of the electrical analog of an optical beam splitter. Its peculiar energy dependent inter-edge transmission allows it to be turned on or off at will and it may be used for routing the chiral edge states.

Multiterminal conductance of a Floquet topological insulator.

We report on simulations of the dc conductance and quantum Hall response of a Floquet topological insulator using Floquet scattering theory. Our results reveal that laser-induced edge states lead to quantum Hall plateaus once imperfect matching with the nonilluminated leads is lessened. The magnitude of the Hall plateaus, however, is not directly related to the number and chirality of all the edge states at a given energy, as usual. Instead, the plateaus are dominated by those edge states adding to the time-averaged density of states. Therefore, the dc quantum Hall conductance of a Floquet topological insulator is not directly linked to topological invariants of the full Floquet bands.

Perezone and its isomer isoperezone induce caspase-dependent and caspase-independent cell death.

In this study, we investigated the cytotoxic effect of perezone, a constituent isolated from the roots of Perezia spp. and of its synthetic isomer isoperezone on the K562 human leukemia cell line. Perezone showed greater cytotoxic effect than isoperezone but both compounds were found to induce cytotoxicity trough a caspase-dependent and a caspase-independent mechanisms; important changes in their light scattering properties, phosphatidylserine translocation and mitochondrial membrane potential disruption were detected by cytometry. The mechanism of death induction of each compound showed interesting concentration-dependent differences. Neither compound induced the apoptosis inducing factor.

Coherent versus sequential electron tunneling in quantum dots.

Manifestations of quantum coherence in the electronic conductance through nearly closed quantum dots in the Coulomb-blockade regime are addressed. We show that quantum coherent tunneling processes explain some puzzling statistical features of the conductance peak heights observed in recent experiments at low temperatures. We employ the constant interaction model and the random matrix theory to model the quantum dot electronic interactions and its single-particle statistical fluctuations, taking full account of the finite decay width of the quantum dot levels.

[Serine protease of Bacillus subtilis R]. / Serinovaia proteasa Bacillus subtilis R.

Properties of a protease preparation obtained by ethanol precipitation of a concentrate of the culture fluid of Bacillus subtilis R (1 : 4 v/v; 4 degrees C) grown under the conditions of deep cultivation were studied. The use of specific inhibitors, EDTA and phenylmethylsulfonyl fluoride, made it possible to show that the enzyme belongs to the group of serine proteases. The preparation exhibited high stability in alkaline medium and thermostability; it hydrolyzed protein substrates and retained catalytic properties in the presence of a multicomponent detergent system. The preparation is recommended for use in those branches of industry where proteolysis is required and in the production of detergents (as a biological additive).

Biosynthetic control of molecular weight in the polymerization of the octasaccharide subunits of succinoglycan, a symbiotically important exopolysaccharide of Rhizobium meliloti.

Succinoglycan, a symbiotically important exopolysaccharide of Rhizobium meliloti, is composed of polymerized octasaccharide subunits, each of which consists of one galactose and seven glucoses with succinyl, acetyl, and pyruvyl modifications. Production of specific low molecular weight forms of R. meliloti exported and surface polysaccharides, including succinoglycan, appears to be important for nodule invasion. In a previous study of the roles of the various exo gene products in succinoglycan biosynthesis, exoP, exoQ, and exoT mutants were found to synthesize undecaprenol-linked fully modified succinoglycan octasaccharide subunits, suggesting possible roles for their gene products in polymerization or transport. Using improved techniques for analyzing succinoglycan biosynthesis by these mutants, we have obtained evidence indicating that R. meliloti has genetically separable systems for the synthesis of high molecular weight succinoglycan and the synthesis of a specific class of low molecular weight oligosaccharides consisting of dimers and trimers of the octasaccharide subunit. Models to account for our unexpected findings are discussed. Possible roles for the ExoP, ExoQ, and ExoT proteins are compared and contrasted with roles that have been suggested on the basis of homologies to key proteins involved in the biosynthesis of O-antigens and of certain exported or capsular cell surface polysaccharides.

Influence of propranolol plasma levels on hemodynamics during coronary artery bypass surgery.

Hemodynamic effects of propranolol during coronary artery surgery were investigated in 26 patients who chronically took propranolol and who received a standardized morphine/diazepam/pancuronium/halothane anesthetic. Effects were shown by correlating logarithm of the plasma propranolol concentrations versus percentage change in hemodynamics following stressful events (induction, intubation, skin incision, sternotomy, and sternal retraction). Log propranolol and hemodynamics following cardiopulmonary bypass also were correlated. A broad range of propranolol levels were observed. Levels (range and mean +/- SD) were preinduction 0-96 (25.6 +/- 21.6) ng/ml; preincision 0-86 (27.2 +/- 24.4) ng/ml; and sternal retraction 0-92 (28.2 +/- 25.4) ng/ml. The range of hemodynamic responses to stressful events also was broad. Representative changes between preincision control and sternotomy were (range and mean +/- SD): HR-8-30 (7 +/- 10) beats/min; PCWP 1-21 (8.5 +/- 4.6) mmHg; CI -0.2-1.1 (-0.2 +/- 0.7) 1 X min-1 X m-2, and SVR -244-1,288 (310 +/- 388) dyn X s X cm-3. By the time of sternal retraction, CI had declined from preincision values in 14 patients. Linear regression analysis demonstrated an inverse correlation between log propranolol and magnitude of HR, MAP, PCWP, and CI response to stressful stimulation. A direct but statistically weaker correlation with SVR also was seen. Significant correlations between log propranolol versus hemodynamic response to anesthetic induction and versus postcardiopulmonary bypass hemodynamics were not observed.