Amyloidogenic propensity of a natural variant of human apolipoprotein A-I: Stability and interaction with ligands

A number of naturally occurring mutations of human apolipoprotein A-I (apoA-I) have been associated with hereditary amyloidoses. The molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here we examined the effects of the Arg173Pro point mutation in apoA-I on the structure, stability, and aggregation propensity, as well as on the ability to bind to putative ligands. Our results indicate that the mutation induces a drastic loss of stability, and a lower efficiency to bind to phospholipid vesicles at physiological pH, which could determine the observed higher tendency to aggregate as pro-amyloidogenic complexes. Incubation under acidic conditions does not seem to induce significant desestabilization or aggregation tendency, neither does it contribute to the binding of the mutant to sodium dodecyl sulfate. While the binding to this detergent is higher for the mutant as compared to wt apoA-I, the interaction of the Arg173Pro variant with heparin depends on pH, being lower at pH 5.0 and higher than wt under physiological pH conditions. We suggest that binding to ligands as heparin or other glycosaminoglycans could be key events tuning the fine details of the interaction of apoA-I variants with the micro-environment, and probably eliciting the toxicity of these variants in hereditary amyloidoses.Facultad de Ciencias MédicasInstituto de Investigaciones Bioquímicas de La PlataInstituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Z_3 Quantum Criticality in a spin-1/2 chain model

The stability of the magnetization $m=1/3$ plateau phase of the XXZ spin-1/2 Heisenberg chain with competing interactions is investigated upon switching on a staggered transverse magnetic field. Within a bosonization approach, it is shown that the low-energy properties of the model are described by an effective two-dimensional XY model in a three-fold symmetry-breaking field. A phase transition in the three-state Potts universality class is expected separating the $m=1/3$ plateau phase to a phase where the spins are polarized along the staggered magnetic field. The Z$_3$ critical properties of the transition are determined within the bosonization approach.Comment: 5 pages, revised versio

Increased particle emissions from early fuel injection timing Diesel low temperature combustion

A clean premixed Diesel combustion strategy, called low temperature combustion (LTC), was able to achieve very low nitrogen oxide emissions (<35 ppm) through use of exhaust gas recirculation (12.1% inlet oxygen), and reduced particulate matter (PM) emissions (<0.05 FSN) through advanced fuel injection timing (-24°aTDC). When varying the injection timing by relatively small increments, large changes in PM mass and number emissions were measured within the premixed LTC regime. A discrepancy is investigated between expected reductions in PM emissions by simple fuel-air premixing and combustion temperature metrics, and actual PM emissions measurements when advancing the fuel injection timing earlier than -24°aTDC. For these earlier injection timings, particle numbers were seen to increase in two distinct particle size modes, whereas only one particle size mode existed at the minimum PM emissions -24°aTDC injection timing. Additional parameters from a 1D free fuel spray model were used to suggest new information that could explain the cause of these unexpected increases in PM. Using 0D and 1D calculations, the engine-out particle size and number emissions are analyzed to better understand their sensitivity to changes in the fuel injection timing within the early injection timing LTC regime. © 2011 Elsevier Ltd. All rights reserved.The authors sincerely thank Gabriel Alcantarilla, Rogerio Jorge Amorim, Simon Arthozoul, and Sara Goska for their great assistance in experimental data collection and post-analysis. The authors wish to acknowledge the Generalitat Valenciana for the financial support through the project GVA PROMETEO CMT 2010 (reference code: GR001/2009/00167539). Financial support of Christopher Kolodziej's research was provided by the Spanish Ministry of Education. This publication comes from a portion of the doctoral thesis work of Christopher Kolodziej.Benajes Calvo, JV.; García Oliver, JM.; Novella Rosa, R.; Kolodziej, CP. (2012). Increased particle emissions from early fuel injection timing Diesel low temperature combustion. Fuel. 94(1):184-190. https://doi.org/10.1016/j.fuel.2011.09.014S18419094

Amyloidogenic propensity of a natural variant of human apolipoprotein A-I: Stability and interaction with ligands

A number of naturally occurring mutations of human apolipoprotein A-I (apoA-I) have been associated with hereditary amyloidoses. The molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here we examined the effects of the Arg173Pro point mutation in apoA-I on the structure, stability, and aggregation propensity, as well as on the ability to bind to putative ligands. Our results indicate that the mutation induces a drastic loss of stability, and a lower efficiency to bind to phospholipid vesicles at physiological pH, which could determine the observed higher tendency to aggregate as pro-amyloidogenic complexes. Incubation under acidic conditions does not seem to induce significant desestabilization or aggregation tendency, neither does it contribute to the binding of the mutant to sodium dodecyl sulfate. While the binding to this detergent is higher for the mutant as compared to wt apoA-I, the interaction of the Arg173Pro variant with heparin depends on pH, being lower at pH 5.0 and higher than wt under physiological pH conditions. We suggest that binding to ligands as heparin or other glycosaminoglycans could be key events tuning the fine details of the interaction of apoA-I variants with the micro-environment, and probably eliciting the toxicity of these variants in hereditary amyloidoses.Facultad de Ciencias MédicasInstituto de Investigaciones Bioquímicas de La PlataInstituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Peptides Derived From the α-Core and γ-Core Regions of a Putative Silybum marianum Flower Defensin Show Antifungal Activity Against Fusarium graminearum

Fusarium graminearum is the etiological agent of Fusarium head blight (FHB), a disease that produces a significant decrease in wheat crop yield and it is further aggravated by the presence of mycotoxins in the affected grains that may cause health problems to humans and animals. Plant defensins and defensin-like proteins are antimicrobial peptides (AMPs); they are small basic, cysteine-rich peptides (CRPs) ubiquitously expressed in the plant kingdom and mostly involved in host defence. They present a highly variable sequence but a conserved structure. The γ-core located in the C-terminal region of plant defensins has a conserved β-hairpin structure and is a well-known determinant of the antimicrobial activity among disulphide-containing AMPs. Another conserved motif of plant defensins is the α-core located in the N-terminal region, not conserved among the disulphide-containing AMPs, it has not been yet extensively studied. In this report, we have cloned the putative antimicrobial protein DefSm2, expressed in flowers of the wild plant Silybum marianum. The cDNA encodes a protein with two fused basic domains of an N-terminal defensin domain (DefSm2-D) and a C-terminal Arg-rich and Lys-rich domain. To further characterize the DefSm2-D domain, we built a 3D template-based model that will serve to support the design of novel antifungal peptides. We have designed four potential antifungal peptides: two from the DefSm2-D α-core region (SmAPα1-21 and SmAPα10-21) and two from the γ-core region (SmAPγ27-44 and SmAPγ29-35). We have chemically synthesized and purified the peptides and further characterized them by electrospray ionization mass spectrometry (ESI-MS) and Circular dichroism (CD) spectroscopy. SmAPα1-21, SmAPα10-21, and SmAPγ27-44 inhibited the growth of the phytopathogen F. graminearum at low micromolar concentrations. Conidia exposure to the fungicidal concentration of the peptides caused membrane permeabilization to the fluorescent probe propidium iodide (PI), suggesting that this is one of the main contributing factors in fungal cell killing. Furthermore, conidia treated for 0.5h showed cytoplasmic disorganization as observed by transmission electron microscopy (TEM). Remarkably, the peptides derived from the α-core induced morphological changes on the conidia cell wall, which is a promising target since its distinctive biochemical and structural organization is absent in plant and mammalian cells.Centro de Investigación de Proteínas VegetalesCentro de Investigaciones en Fitopatologí

A Pliocene-Pleistocene continental biota from Venezuela

The Pliocene-Pleistocene transition in the Neotropics is poorly understood despite the major climatic changes that occurred at the onset of the Quaternary. The San Gregorio Formation, the younger unit of the Urumaco Sequence, preserves a fauna that documents this critical transition. We report stingrays, freshwater bony fishes, amphibians, crocodiles, lizards, snakes, aquatic and terrestrial turtles, and mammals. A total of 49 taxa are reported from the Vergel Member (late Pliocene) and nine taxa from the Cocuiza Member (Early Pleistocene), with 28 and 18 taxa reported for the first time in the Urumaco sequence and Venezuela, respectively. Our findings include the first fossil record of the freshwater fishes Megaleporinus, Schizodon, Amblydoras, Scorpiodoras, and the pipesnake Anilius scytale, all from Pliocene strata. The late Pliocene and Early Pleistocene ages proposed here for the Vergel and Cocuiza members, respectively, are supported by their stratigraphic position, palynology, nannoplankton, and 86 Sr/ 88 Sr dating. Mammals from the Vergel Member are associated with the first major pulse of the Great American Biotic Interchange. In contrast to the dry conditions prevailing today, the San Gregorio Formation documents mixed open grassland/forest areas surrounding permanent freshwater systems, following the isolation of the northern South American basin from western Amazonia. These findings support the hypothesis that range contraction of many taxa to their current distribution in northern South America occurred rapidly during at least the last 1.5 million years

Epidemiology and outcomes of non-cardiac surgical patients in Brazilian intensive care units

OBJECTIVES: Due to the dramatic medical breakthroughs and an increasingly ageing population, the proportion of patients who are at risk of dying following surgery is increasing over time. The aim of this study was to evaluate the outcomes and the epidemiology of non-cardiac surgical patients admitted to the intensive care unit. METHODS: A multicenter, prospective, observational, cohort study was carried out in 21 intensive care units. A total of 885 adult surgical patients admitted to a participating intensive care unit from April to June 2006 were evaluated and 587 patients were enrolled. Exclusion criteria were trauma, cardiac, neurological, gynecologic, obstetric and palliative surgeries. The main outcome measures were postoperative complications and intensive care unit and 90-day mortality rates. RESULTS: Major and urgent surgeries were performed in 66.4% and 31.7% of the patients, respectively. The intensive care unit mortality rate was 15%, and 38% of the patients had postoperative complications. The most common complication was infection or sepsis (24.7%). Myocardial ischemia was diagnosed in only 1.9% of the patients. A total of 94 % of the patients who died after surgery had co-morbidities at the time of surgery (3.4 ± 2.2). Multiple organ failure was the main cause of death (53%). CONCLUSION: Sepsis is the predominant cause of morbidity in patients undergoing non-cardiac surgery. In this patient population, multiple organ failure prevailed as the most frequent cause of death in the hospital.OBJETIVO: Devido aos avanços da medicina e ao envelhecimento da população, a proporção de pacientes em risco de morte após cirurgias está aumentando. Nosso objetivo foi avaliar o desfecho e a epidemiologia de cirurgias não cardíacas em pacientes admitidos em unidade de terapia intensiva. MÉTODOS: Estudo prospectivo, observacional, de coorte, realizado em 21 unidades de terapia intensiva. Um total de 885 pacientes adultos, cirúrgicos, consecutivamente admitidos em unidades de terapia intensiva no período de abril a junho de 2006 foi avaliado e destes, 587 foram incluídos. Os critérios de exclusão foram; trauma, cirurgias cardíacas, neurológicas, ginecológicas, obstétricas e paliativas. Os principais desfechos foram complicações pós-cirúrgicas e mortalidade na unidade de terapia intensiva e 90 dias após a cirurgia. RESULTADOS: Cirurgias de grande porte e de urgência foram realizadas em 66,4% e 31,7%, dos pacientes, respectivamente. A taxa de mortalidade na unidade de terapia intensiva foi de 15%, e 38% dos pacientes tiveram complicações no pós-operatório. A complicação mais comum foi infecção ou sepse (24,7%). Isquemia miocárdica foi diagnosticada em apenas 1,9%. Um total de 94 % dos pacientes que morreram após a cirurgia tinha co-morbidades associadas (3,4 ± 2,2). A principal causa de óbito foi disfunção de múltiplos órgãos (53%). CONCLUSÃO: Sepse é a causa predominante de morbidade em pacientes submetidos a cirurgias não cardíacas. A grande maioria dos óbitos no pós-operatório ocorreu por disfunção de múltiplos órgãos.Faculdade de Medicina de São José do Rio PretoServidor Público Estadual Serviço de Terapia IntensivaHospital São Lucas Unidade Coronariana IntensivaHospital Moinhos de Vento Centro de Terapia IntensivaClínica Sorocaba Centro de Terapia IntensivaClínica São Vicente Centro de Terapia IntensivaUniversidade Federal da Paraíba Hospital Universitário Unidade de Terapia Intensiva de AdultosUniversidade Federal de São Paulo (UNIFESP)Hospital Pró-Cardíaco Centro de Terapia IntensivaUniversidade Federal do Mato Grosso do Sul Hospital Universitário Centro de Terapia Intensiva AdultoUniversidade Estadual de LondrinaHospital de Terapia IntensivaUniversidade Estadual do PiauíHospital Santa Luzia Centro de Terapia IntensivaUniversidade Estadual do Oeste do ParanáFaculdade de Medicina de São José do Rio Preto Hospital de BaseHospital do Servidor Público EstadualHospital Cardiotrauma IpanemaSanta Casa de Misericórdia Centro de Terapia IntensivaUNIFESPSciEL

Collective Effervescence, Self-Transcendence, and Gender Differences in Social Well-Being During 8 March Demonstrations

8 March (8M), now known as International Women’s Day, is a day for feminist claims where demonstrations are organized in over 150 countries, with the participation of millions of women all around the world. These demonstrations can be viewed as collective rituals and thus focus attention on the processes that facilitate different psychosocial effects. This work aims to explore the mechanisms (i.e., behavioral and attentional synchrony, perceived emotional synchrony, and positive and transcendent emotions) involved in participation in the demonstrations of 8 March 2020, collective and ritualized feminist actions, and their correlates associated with personal well-being (i.e., affective well-being and beliefs of personal growth) and collective well-being (i.e., social integration variables: situated identity, solidarity and fusion), collective efficacy and collective growth, and behavioral intention to support the fight for women’s rights. To this end, a cross-cultural study was conducted with the participation of 2,854 people (age 18–79; M = 30.55; SD = 11.66) from countries in Latin America (Mexico, Chile, Argentina, Brazil, Peru, Colombia, and Ecuador) and Europe (Spain and Portugal), with a retrospective correlational cross-sectional design and a convenience sample. Participants were divided between demonstration participants (n = 1,271; 94.0% female) and non-demonstrators or followers who monitored participants through the media and social networks (n = 1,583; 75.87% female). Compared with non-demonstrators and with males, female and non-binary gender respondents had greater scores in mechanisms and criterion variables. Further random-effects model meta-analyses revealed that the perceived emotional synchrony was consistently associated with more proximal mechanisms, as well as with criterion variables. Finally, sequential moderation analyses showed that proposed mechanisms successfully mediated the effects of participation on every criterion variable. These results indicate that participation in 8M marches and demonstrations can be analyzed through the literature on collective rituals. As such, collective participation implies positive outcomes both individually and collectively, which are further reinforced through key psychological mechanisms, in line with a Durkheimian approach to collective rituals.Fil: Zumeta, Larraitz N.. Universidad del País Vasco; EspañaFil: Castro Abril, Pablo. Universidad del País Vasco; EspañaFil: Méndez, Lander. Universidad del País Vasco; EspañaFil: Pizarro, José J.. Universidad del País Vasco; EspañaFil: Włodarczyk, Anna. Universidad Católica del Norte; ChileFil: Basabe, Nekane. Universidad del País Vasco; EspañaFil: Navarro Carrillo, Ginés. Universidad de Jaén; EspañaFil: Padoan De Luca, Sonia. Universidad del País Vasco; EspañaFil: da Costa, Silvia. Universidad del País Vasco; EspañaFil: Alonso Arbiol, Itziar. Universidad del País Vasco; EspañaFil: Torres Gómez, Bárbara. Universidad del País Vasco; EspañaFil: Cakal, Huseyin. Keele University; Reino UnidoFil: Delfino, Gisela Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; ArgentinaFil: Techio, Elza M.. Universidade Federal da Bahia; BrasilFil: Alzugaray, Carolina. Universidad de Santo Tomas; ChileFil: Bilbao, Marian. Universidad Alberto Hurtado; ChileFil: Villagrán, Loreto. Universidad de Concepción; ChileFil: López López, Wilson. Pontificia Universidad Javeriana; ColombiaFil: Ruiz Pérez, José Ignacio. Universidad Nacional de Colombia; ColombiaFil: Cedeño, Cynthia C.. Universidad Politécnica Salesiana; EcuadorFil: Reyes Valenzuela, Carlos. Universidad Andina Simon Bolivar - Sede Ecuador.; EcuadorFil: Alfaro Beracoechea, Laura. Universidad de Guadalajara; MéxicoFil: Contreras Ibáñez, Carlos César. Universidad Autónoma Metropolitana; MéxicoFil: Ibarra, Manuel Leonardo. Universidad Autónoma del Estado de México; MéxicoFil: Reyes Sosa, Hiram. Universidad Autonoma de Coahuila; MéxicoFil: Cueto, Rosa María. Pontificia Universidad Católica de Perú; PerúFil: Carvalho, Catarina L.. Universidad de Porto; PortugalFil: Pinto, Isabel R.. Universidad de Porto; Portuga