Anti-apolipoprotein A-I antibodies in the pathogenesis of Alzheimer disease : project plan

RESUMO: A doença de Alzheimer (AD) é a forma mais comum de demência em todo o mundo e sua prevalência deverá duplicar até 2050. Os mecanismos precisos responsáveis pela AD são desconhecidas mas as características histopatológicas estão bem caracterizadas. A hipótese mais importante para a perda neuronal e declínio cognitivo na AD é a cascata amilóide que indica que AD é o resultado da sobreprodução de beta amilóide (Aβ) e / ou remoção ineficaz; a acumulação do BA no cérebro seria o passo crítico na patogénese da AD. Actualmente, a identificação de proteínas que se ligam ao Aβ e modulam a sua agregação e neurotoxicidade pode proporcionar a base para novas abordagens terapêuticas. A apolipoproteína AI (ApoA-I), o principal componente das HDL humanas, interage com o domínio extracelular da proteína precursora de amilóide (APP), bem como com o Aβ. Estudos epidemiológicos têm mostrado uma diminuição acentuada da ApoA-I plasmática em doentes com AD, com uma correlação inversa entre o nível de ApoA-I e o risco de AD. Este trabalho pretende apresentar um projecto que tem como objectivo investigar se os anticorpos anti-apo AI podem impedir a formação de complexos Aβ / ApoA-I, bloqueando o efeito protector da ApoA-I. A hipótese baseia-se na possibilidade dos doentes com AD terem anticorpos anti-ApoA-I plasmáticos e de estes poderem interferir com a formação do complexo no LCR.------- ABSTRACT:Alzheimer’s disease (AD) is the most common form of dementia world-wide and its prevalence is expected to double by the year 2050. The precise mechanisms responsible for AD are unknown but the histopathologic features are well-characterised. The most compelling hypothesis for neuronal loss and cognitive decline in AD is the amyloid cascade hypothesis which states that AD is the result of amyloid beta (Aβ) overproduction and/or ineffective clearance and its accumulation in the brain would be the critical step in AD pathogenesis. Currently, identification of proteins that bind Aβ and modulate its aggregation and neurotoxicity could provide the basis for novel treatment approaches. Apolipoprotein A-I (ApoA-I), the main constituent of human HDL, ApoA-I interacts with the extracellular domain of amyloid precursor protein (APP), as well as with Aβ itself. Epidemiological studies have shown a marked decrease of plasma ApoA-I levels in AD patients, with an inverse correlation between the ApoA-I level and the risk of AD. This work intends to present a project that aims to investigate if anti-ApoA-I antibodies may prevent the formation of the Aβ /ApoA-I complex and by doing so blocking the protective effect of ApoA-I in AD. We base the hypothesis on the possibility that patients with AD might have anti-ApoA-I antibodies in plasma and that these can interfere with the complex formation in the cerebrospinal fluid (CSF).

Trypanosoma cruzi-like bloodstream trypomastigotes in bats from the State of Piauí, Northeastern Brazil

One-hundred and thirty-five bats from 12 species were examined for thepresence of trypomastigotes by means of direct blood examination, xenodiagnosis, and hemoculture. Of those, 44 specimens (32.6%) from 8 species were infected with trypanosomes. Phyllostomus discolor discolor presented the highest rate of infection, being captured only in one locality, while Phyllostomus hastatus hastatus captured in four localities showed high rates. Two species, Anoura geoffroyii and Pteronotus (Phillodia) pamelli rubiginosa, were found infected by T. cruzi-like trypanosomes, apparently described for thefirst time. Flagellates from Artibeus jamaisensis jamaisensisa and A. geoffroyii were able toproduce detectable parasitaemia in young mice. One triatomine bug was found infected in natural conditions, Triatoma brasiliensis was associated with a P.h. hastatus colony, in which six captured bats were also found infected.

Labrea-like hepatitis in Vitoria, Espirito Santo state, Brazil: report of a case

A case of fulminat hepatitis with microvesicular steatosis resembling Labrea 's fever, diagnosed in Vitoria (ES) is reported. The 16 year old bcy presented with severe epistaxis, agitation, jaundice and hemorrhagic vomiting and died two days after admission to the emergency unit of the Vnivesity Hospital. The disease started five days before with fever, myalgias, dark urine and jaundice andprogressed withpsychic agitation, torpor and coma. The liver andspleen were notpalpable. HBsAg was negative in the serum. The autopsy showed acute hepatitis with tylic necrosis confluent in the midizonal and periportal areas with massive microvesicular steatosis in the remaining hepatocytes. Mononuclear cellspredominated in the exudate. The reticulum showed condensation in the necrotic areas without typical bands of collapse. The portal tracts were edematous with mononuclear infiltration and mild bile duct proliferation. Absence of cholestasis. Exceptfor the confluent midzonalandperiportal necrosis this case showed several clinical and morphological aspects of the Labreafever describedfrom the East Amazon, demonstrating that the anatomical picture of this disease probabty is not in related to afactor peculiar to the Amazon region.

Observation of 2p3d(¹P°)→1s3d(¹Dᵉ) Radiative Transition in He-like Si, S, and Cl Ions

APS, Journals Phys. Rev. Lett., Volume 111, Issue 24

Smells Like Spleen Spirit: O Decadentismo na América da Segunda Metade do Século XX

Dissertação apresentada para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Línguas Literaturas e Culturas

Would Sacaca, Croton cajucara Benth (Euphorbiaceae) be an hepatotoxic plant like Germander, Teucrium chamaedrys L. (Labiatae)?

Clinical and experimental studies have consistently incriminated the medicinal plant germander (Teucrium chamaedrys L.) in epidemic and sporadic cases of liver diseases. The sacaca (Croton cajucara Benth), a common plant in Brazilian Amazon region also comes being incriminated in similar clinical cases. Of both plants were isolated diterpenoid coumpounds with similar chemical structures.

Absence of experimental cross-protection induced by a Trypanosoma cruzi-like strain isolated from bats

This study evaluated the possibility of inoculation and reinoculation with a trypanosomatid isolated from bats that is morphologically, biologically and molecularly similar to Trypanosoma cruzi, to protect against infection by virulent strains. Non-isogenic mice were divided into 24 groups that received from zero to three inoculations of Trypanosoma cruzi-like strain RM1, in the presence or absence of Freund's adjuvant, and were challenged with the VIC or JG strains of Trypanosoma cruzi. Parasitemia and survival were monitored and animals were sacrificed for histopathological analysis. Animals immunized with Trypanosoma cruzi-like strain RM1 presented decreased parasitemia, independently of the number of inoculations or the presence of adjuvant. In spite of this reduction, these animals did not present any protection against histopathological lesions. Severe eosinophilic infiltrate was observed and was correlated with the number of inoculations of Trypanosoma cruzi-like strain RM1. These findings suggest that prior inoculation with this strain did not protect against infection but, rather, aggravated the tissue inflammatory process.

American tripanosomiasis: a study on the prevalence of Trypanosoma cruzi and Trypanosoma cruzi-like organisms in wild rodents in San Luis province, Argentina

INTRODUCTION: Chagas disease is caused by Trypanosoma cruzi. Wild and perianthropic mammals maintain the infection/transmission cycle, both in their natural habitat and in the peridomestic area. The aim of this paper was to present the results from a study on wild rodents in the central and northern regions of San Luis province, Argentina, in order to evaluate the prevalence of this infection. METHODS: Sherman traps were set up in capture areas located between latitudes 32º and 33º S, and longitudes 65º and 66º W. The captured rodents were taxonomically identified and hemoflagellates were isolated. Morphological, biometric and molecular studies and in vitro cultures were performed. Infection of laboratory animals and histological examination of the cardiac muscle and inoculation area were also carried out. Parasites were detected in circulating blood in Calomys musculinus, Graomys griseoflavus, Phyllotis darwini and Akodon molinae. The parasites were identified using biological criteria. Molecular PCR studies were performed on some isolates, which confirmed the characterization of these hemoflagellates as Trypanosoma cruzi. RESULTS AND CONCLUSIONS: Forty-four percent of the 25 isolates were identified as Trypanosoma cruzi, and the remaining 56% as Trypanosoma cruzi-like. These findings provide evidence that wild rats infected with Trypanosoma cruzi and Trypanosoma cruzi-like organisms are important in areas of low endemicity.

Burkitt-like lymphoma in an infant: a case report

Childhood non-Hodgkin's lymphomas, including Burkitt and Burkitt-like, are rarely diagnosed in infants. A case of B-cell lymphoma in a 13-month-old girl with extensive abdominal disease, ascites, pleural effusion, and tumor lysis syndrome is reported. Phenotypic analysis showed a germinal center B-cell phenotype, and a B-cell clonality was confirmed by polymerase chain reaction. There was no evidence of Epstein-Barr and HIV infection. The case herein reported emphasizes the need for considering the diagnosis of lymphoma even in very young children.

Epidermis recreation in spongy-like hydrogels: New opportunities to explore epidermis-like analogues

[Excerpt] On the road to successfully achieving skin regeneration, 3D matrices/scaffolds that provide the adequate physico-chemical and biological cues to recreate the ideal healing environment are believed to be a key element [1], [2] and [3]. Numerous polymeric matrices derived from both natural [4] and [5] and synthetic [6], [7] and [8] sources have been used as cellular supports; nowadays, fewer matrices are simple carriers, and more and more are ECM analogues that can actively participate in the healing process. Therefore, the attractive characteristics of hydrogels, such as high water content, tunable elasticity and facilitated mass transportation, have made them excellent materials to mimic cells’ native environment [9]. Moreover, their hygroscopic nature [10] and possibility of attaining soft tissues-like mechanical properties mean they have potential for exploitation as wound healing promoters [11], [12], [13] and [14]. Nonetheless, hydrogels lack natural cell adhesion sites [15], which limits the maximization of their potential in the recreation of the cell niche. This issue has been tackled through the use of a range of sophisticated approaches to decorate the hydrogels with adhesion sequences such as arginine-glycine-aspartic acid (RGD) derived from fibronectin [16], [17] and [18], and tyrosine-isoleucine-glycine-serine-arginine (YIGSR) derived from laminin [18] and [19], which not only aim to modulate cell adhesion, but also influencing cell fate and survival [18]. Nonetheless, its widespread use is still limited by significant costs associated with the use of recombinant bioactive molecules.

Search for vector-like B quarks in events with one isolated lepton, missing transverse momentum and jets at s√= 8 TeV with the ATLAS detector

A search has been performed for pair production of heavy vector-like down-type (B) quarks. The analysis explores the lepton-plus-jets final state, characterized by events with one isolated charged lepton (electron or muon), significant missing transverse momentum and multiple jets. One or more jets are required to be tagged as arising from b-quarks, and at least one pair of jets must be tagged as arising from the hadronic decay of an electroweak boson. The analysis uses the full data sample of pp collisions recorded in 2012 by the ATLAS detector at the LHC, operating at a center-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 20.3 fb−1. No significant excess of events is observed above the expected background. Limits are set on vector-like B production, as a function of the B branching ratios, assuming the allowable decay modes are B→Wt/Zb/Hb. In the chiral limit with a branching ratio of 100% for the decay B→Wt, the observed (expected) 95% CL lower limit on the vector-like B mass is 810 GeV (760 GeV). In the case where the vector-like B quark has branching ratio values corresponding to those of an SU(2) singlet state, the observed (expected) 95% CL lower limit on the vector-like B mass is 640 GeV (505 GeV). The same analysis, when used to investigate pair production of a colored, charge 5/3 exotic fermion T5/3, with subsequent decay T5/3→Wt, sets an observed (expected) 95% CL lower limit on the T5/3 mass of 840 GeV (780 GeV).

Search for production of vector-like quark pairs and of four top quarks in the lepton-plus-jets final state in pp collisions at root 8=8 TeV with the ATLAS detector

A search for pair production of vector-like quarks, both up-type (T) and down-type (B), as well as for four-top-quark production, is presented. The search is based on pp collisions at s√=8 TeV recorded in 2012 with the ATLAS detector at the CERN Large Hadron Collider and corresponding to an integrated luminosity of 20.3 fb−1. Data are analysed in the lepton-plus-jets final state, characterised by an isolated electron or muon with high transverse momentum, large missing transverse momentum and multiple jets. Dedicated analyses are performed targeting three cases: a T quark with significant branching ratio to a W boson and a b-quark (TT¯→Wb+X), and both a T quark and a B quark with significant branching ratio to a Higgs boson and a third-generation quark (TT¯→Ht+X and BB¯→Hb+X respectively). No significant excess of events above the Standard Model expectation is observed, and 95% CL lower limits are derived on the masses of the vector-like T and B quarks under several branching ratio hypotheses assuming contributions from T→Wb, Zt, Ht and B→Wt, Zb, Hb decays. The 95% CL observed lower limits on the T quark mass range between 715 GeV and 950 GeV for all possible values of the branching ratios into the three decay modes, and are the most stringent constraints to date. Additionally, the most restrictive upper bounds on four-top-quark production are set in a number of new physics scenarios.

Global vs. local nonlinear optimization techniques for human-like movement of an anthropomorphic robot

In this paper a comparison between using global and local optimization techniques for solving the problem of generating human-like arm and hand movements for an anthropomorphic dual arm robot is made. Although the objective function involved in each optimization problem is convex, there is no evidence that the admissible regions of these problems are convex sets. For the sequence of movements for which the numerical tests were done there were no significant differences between the optimal solutions obtained using the global and the local techniques. This suggests that the optimal solution obtained using the local solver is indeed a global solution.