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Trichoplax adhaerens is a small, ciliated marine animal that glides on surfaces grazing upon algae, which it digests externally. It has no muscles or nervous system and only six cell types, all but two of which are embedded in its epithelium. The epithelial cells are joined by apical adherens junctions; neither tight junctions nor gap junctions are present. Monociliated epithelial cells on the lower surface propel gliding. The cilia beat regularly, but asynchronously, and transiently contact the substrate with each stroke. The animal moves in random directions in the absence of food. We show here that it exhibits chemotaxis, moving preferentially toward algae embedded in a disk of agar. We present a mathematical model to explain how coherent, directional movements could arise from the collective actions of a set of ciliated epithelial cells, each independently sensing and responding to a chemoattractant gradient. The model incorporates realistic values for viscoelastic properties of cells and produces coordinated movements and changes in body shape that resemble the actual movements of the animal. The model demonstrates that an animal can move coherently in search of food without any need for chemical signaling between cells and introduces a different approach to modeling behavior in primitive multicellular organisms.
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Quimiotaxis/fisiología , Conducta Alimentaria , Alimentos , Microalgas , Placozoa/fisiología , Animales , Cilios , Transducción de SeñalRESUMEN
The shocking severity of the Covid-19 pandemic has woken up an unprecedented interest and accelerated effort of the scientific community to model and forecast epidemic spreading to find ways to control it regionally and between regions. Here we present a model that in addition to describing the dynamics of epidemic spreading with the traditional compartmental approach takes into account the social behaviour of the population distributed over a geographical region. The region to be modelled is defined as a two-dimensional grid of cells, in which each cell is weighted with the population density. In each cell a compartmental SEIRS system of delay difference equations is used to simulate the local dynamics of the disease. The infections between cells are modelled by a network of connections, which could be terrestrial, between neighbouring cells, or long range, between cities by air, road or train traffic. In addition, since people make trips without apparent reason, noise is considered to account for them to carry contagion between two randomly chosen distant cells. Hence, there is a clear separation of the parameters related to the biological characteristics of the disease from the ones that represent the spatial spread of infections due to social behaviour. We demonstrate that these parameters provide sufficient information to trace the evolution of the pandemic in different situations. In order to show the predictive power of this kind of approach we have chosen three, in a number of ways different countries, Mexico, Finland and Iceland, in which the pandemics have followed different dynamic paths. Furthermore we find that our model seems quite capable of reproducing the path of the pandemic for months with few initial data. Unlike similar models, our model shows the emergence of multiple waves in the case when the disease becomes endemic.
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BACKGROUND: Repetitive DNA elements such as direct and inverted repeat sequences are present in every genome, playing numerous biological roles. In amphibians, the functions and effects of the repeat sequences have not been extensively explored. We consider that the data of mitochondrial genomes in the NCBI database are a valuable alternative to generate a better understanding of the molecular dynamic of the repeat sequences in the amphibians. RESULTS: This work presents the development of a strategy to identify and quantify the total amount of repeat sequences with lengths from 5 to 30 base pairs in the amphibian mitogenomes. The results show differences in the abundance of repeat sequences among amphibians and bias to specific genomic regions that are not easily associated with the classical amphibian ancestry. CONCLUSIONS: Derived from these analyses, we show that great variability of the repeat sequences exists among amphibians, demonstrating that the mitogenomes of these organisms are dynamic.
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Anfibios/genética , ADN Mitocondrial/química , Genoma Mitocondrial , Animales , Secuencias Invertidas Repetidas , Secuencias Repetitivas de Ácidos NucleicosRESUMEN
Although helminth-Plasmodium coinfections are common in tropical regions, the implications of this co-existence for the host immune response are poorly understood. In order to understand the effect of helminth infection at different times of coinfection on the immune response against Plasmodium infection, BALB/c mice were intraperitoneally infected with Taenia crassiceps (Tc). At 2 (Tc2) or 8 (Tc8) weeks post-infection, mice were intravenously infected with 1 × 103 Plasmodium yoelii (Py) 17XL-parasitized red blood cells. Py 17XL-single-infected mice developed cachexia, splenomegaly, and anemia, and died at 11 days post-infection. Importantly, Tc2 + Py-coinfected mice showed increased survival of 58% on day 11, but developed pathology (cachexia and splenomegaly) and succumbed on day 18 post-coinfection, this latter associated with high levels of IL-1ß and IL-12, and reduced IFN-γ in serum compared with Py 17XL-single-infected mice. Interestingly, Tc8 + Py-coinfected mice showed increased survival up to 80% on day 11 and succumbed on day 30 post-coinfection. This increased survival rate conferred by chronic helminth infection was associated with a decreased pathology and mixed inflammatory-type 1/anti-inflammatory-type 2 immune profile as evidenced by the production of high levels of IL-12 and IL-10, and reduced TNF-α from macrophages, high levels of IL-4 and IL-10, and low levels of IFN-γ from spleen cells. Also high serum levels of IL-1ß, TNF-α, IL-12, IL-4, and IL-10, but a significant reduction of IFN-γ were observed. Together, these data indicate that polarization of the cell-mediated response modulated by a pre-existing helminth infection differentially impacts on the host immune response to Py 17XL in a time-dependent manner.
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Coinfección/parasitología , Malaria/inmunología , Plasmodium yoelii/inmunología , Taenia/inmunología , Teniasis/inmunología , Anemia , Animales , Células Cultivadas , Eritrocitos/parasitología , Femenino , Interleucina-10/sangre , Subunidad p35 de la Interleucina-12/sangre , Macrófagos/inmunología , Malaria/sangre , Malaria/patología , Ratones , Ratones Endogámicos BALB C , Bazo/inmunología , Esplenomegalia/parasitología , Teniasis/sangre , Teniasis/patología , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Honesty plays a crucial role in any situation where organisms exchange information or resources. Dishonesty can thus be expected to have damaging effects on social coherence if agents cannot trust the information or goods they receive. However, a distinction is often drawn between prosocial lies ('white' lies) and antisocial lying (i.e. deception for personal gain), with the former being considered much less destructive than the latter. We use an agent-based model to show that antisocial lying causes social networks to become increasingly fragmented. Antisocial dishonesty thus places strong constraints on the size and cohesion of social communities, providing a major hurdle that organisms have to overcome (e.g. by evolving counter-deception strategies) in order to evolve large, socially cohesive communities. In contrast, white lies can prove to be beneficial in smoothing the flow of interactions and facilitating a larger, more integrated network. Our results demonstrate that these group-level effects can arise as emergent properties of interactions at the dyadic level. The balance between prosocial and antisocial lies may set constraints on the structure of social networks, and hence the shape of society as a whole.
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Decepción , Conducta Social , Apoyo Social , Animales , Humanos , Modelos Teóricos , ConfianzaRESUMEN
Although friendship networks have been extensively studied, few models and studies are available to understand the reciprocity of friendship and foes. Here a model is presented to explain the directed friendship and foes network formation observed in experiments of Mexican and Hungarian schools. Within the presented model, each agent has a private opinion and a public one that shares to the group. There are two kinds of interactions between agents. The first kind represent interactions with the neighbors while the other represents the attitude of an agent to the overall public available information. Links between agents evolve as a combination of the public and private information available. Friendship is defined using a fitness function according to the strength of the agent's bonds, clustering coefficient, betweenness centrality and degree. Enmity is defined as very negative links. The model allows us to reproduce the distribution of mentions for friends and foes observed in the experiments, as well as the topology of the directed networks.
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Instituciones Académicas , Red Social , Humanos , Análisis por Conglomerados , Ejercicio FísicoRESUMEN
[This corrects the article DOI: 10.3389/fvets.2023.1187271.].
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A global disaster, such as the recent Covid-19 pandemic, affects every aspect of our lives and there is a need to investigate these highly complex phenomena if one aims to diminish their impact in the health of the population, as well as their socio-economic stability. In this paper we present an attempt to understand the role of the governmental authorities and the response of the rest of the population facing such emergencies. We present a mathematical model that takes into account the epidemiological features of the pandemic and also the actions of people responding to it, focusing only on three aspects of the system, namely, the fear of catching this serious disease, the impact on the economic activities and the compliance of the people to the mitigating measures adopted by the authorities. We apply the model to the specific case of Spain, since there are accurate data available about these three features. We focused on tourism as an example of the economic activity, since this sector of economy is one of the most likely to be affected by the restrictions imposed by the authorities, and because it represents an important part of Spanish economy. The results of numerical calculations agree with the empirical data in such a way that we can acquire a better insight of the different processes at play in such a complex situation, and also in other different circumstances.
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COVID-19 , Desastres , Humanos , España/epidemiología , Pandemias , COVID-19/epidemiología , Factores SocioeconómicosRESUMEN
Neurocysticercosis (NC) is a clinically and radiologically heterogeneous parasitic disease caused by the establishment of larval Taenia solium in the human central nervous system. Host and/or parasite variations may be related to this observed heterogeneity. Genetic differences between pig and human-derived T. solium cysticerci have been reported previously. In this study, 28 cysticerci were surgically removed from 12 human NC patients, the mitochondrial gene that encodes cytochrome b was amplified from the cysticerci and genetic variations that may be related to NC heterogeneity were characterised. Nine different haplotypes (Ht), which were clustered in four haplogroups (Hg), were identified. Hg 3 and 4 exhibited a tendency to associate with age and gender, respectively. However, no significant associations were found between NC heterogeneity and the different T. solium cysticerci Ht or Hg. Parasite variants obtained from patients with similar NC clinical or radiological features were genetically closer than those found in groups of patients with a different NC profile when using the Mantel test. Overall, this study establishes the presence of genetic differences in the Cytb gene of T. solium isolated from human cysticerci and suggests that parasite variation could contribute to NC heterogeneity.
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Citocromos b/genética , Variación Genética/genética , Neurocisticercosis/parasitología , Taenia solium/genética , Animales , Secuencia de Bases , Humanos , Datos de Secuencia Molecular , Taenia solium/aislamiento & purificaciónRESUMEN
Introduction: In veterinary medicine, cancer is the leading cause of death in companion animals, and mammary gland tumors represent the most common neoplasm in female dogs. Several epidemiological risk factors, such as age, breed, hormones, diet, and obesity have been reported to be relevant for canine mammary tumors. Nowadays, the gold standard for diagnosis of canine mammary tumors is the pathological examination of the suspected tissue. However, tumor grade can only be assessed after surgical removal or biopsy of the altered tissue. Therefore, in cases of tumors that could be surgically removed, it would be very helpful to be able to predict the biological behavior of the tumor, before performing any surgery. Since, inflammation constitutes part of the tumor microenvironment and it influences each step of tumorigenesis, cellular and biochemical blood markers of systemic inflammation, such as the neutrophil to lymphocyte ratio (NLR) and the albumin to globulin ratio (AGR) have been proposed as prognostic factors for human cancer development. The NLR and the AGR have not been explored enough as prognostic factors for cancer development in veterinary medicine. Methods: To determine the prognostic value of NLR in canine mammary tumors, clinical records including biochemistry and hematological studies of female dogs with mammary tumors and of control healthy dogs, were used to determine the pre-treatment NLR and AGR. Other clinical data included age, breed, tumor size, histological tumor grade, and survival time after surgery. Results and discussion: It was found that a higher pre-treatment NLR value (NLR > 5) associates with less survival rate. In contrast, the AGR did not show any predictive value on the malignancy of the tumor. However, by combining the NLR with AGR, age of the dog, and tumor size in a principal component analysis (PCA), the grade of the tumor and survival after surgery could be appropriately predicted. These data strongly suggest that pre-treatment NLR values have a prognostic value for the survival rate after surgery of dogs with mammary tumors.
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Herein, we rigorously develop novel 3-dimensional algebraic models called Genetic Hotels of the Standard Genetic Code (SGC). We start by considering the primeval RNA genetic code which consists of the 16 codons of type RNY (purine-any base-pyrimidine). Using simple algebraic operations, we show how the RNA code could have evolved toward the current SGC via two different intermediate evolutionary stages called Extended RNA code type I and II. By rotations or translations of the subset RNY, we arrive at the SGC via the former (type I) or via the latter (type II), respectively. Biologically, the Extended RNA code type I, consists of all codons of the type RNY plus codons obtained by considering the RNA code but in the second (NYR type) and third (YRN type) reading frames. The Extended RNA code type II, comprises all codons of the type RNY plus codons that arise from transversions of the RNA code in the first (YNY type) and third (RNR) nucleotide bases. Since the dimensions of remarkable subsets of the Genetic Hotels are not necessarily integer numbers, we also introduce the concept of algebraic fractal dimension. A general decoding function which maps each codon to its corresponding amino acid or the stop signals is also derived. The Phenotypic Hotel of amino acids is also illustrated. The proposed evolutionary paths are discussed in terms of the existing theories of the evolution of the SGC. The adoption of 3-dimensional models of the Genetic and Phenotypic Hotels will facilitate the understanding of the biological properties of the SGC.
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Evolución Molecular , Modelos Genéticos , ARN/genética , Fractales , Código Genético , HumanosRESUMEN
Fish skin colouration has been widely studied because it involves a variety of processes that are important to the broad field of the developmental biology. Mathematical modelling of fish skin patterning first predicted the existence of morphogens and helped to elucidate the mechanisms of pattern formation. The catfishes of the genus Pseudoplatystoma offer a good biological study model, since its species exhibit the most spectacular and amazing variations of colour patterns on the skin. They present labyrinths, closed loops (or cells), alternate spots and stripes, only spots and combinations of these. We have extended a well known mathematical model to study the skin of Pseudoplatystoma. The basic model is a two component, non-linear reaction diffusion system that presents a richness of bifurcations. The extended model assumes that there are two interacting cell/tissue layers in which morphogens diffuse and interact giving rise to the skin colouration pattern. We have found that by varying only two parameters we are able to accurately reproduce the distinct patterns found in all species of Pseudoplatystoma. The histological analysis of skin samples of two species of this genus, with different patterns, revealed differences on the disposition of the colouration cells that are consistent with our theoretical predictions.
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Bagres/fisiología , Modelos Biológicos , Pigmentación de la Piel/fisiología , Animales , Color , Geografía , Ríos , Piel/citología , América del SurRESUMEN
Cytochrome P4501A1 (CYP1A1) is involved in the metabolism of several genotoxic/carcinogenic environmental xenobiotics including polycyclic aromatic hydrocarbons (PAHs) like benzo[a]pyrene. Several authors had proposed CYP1A inhibition as a plausible strategy for cancer chemoprevention. Using ethoxyresorufin O-deethylase activity (EROD), we tested the inhibitory properties of nine flavonoids: quercetin, miricetin, luteolin, fisetin, morin, kaempferol, 5-hydroxyflavone (5-HF), 3-hydroxyflavone (3-HF), and flavone (F) against human recombinant CYP1A1. The last three compounds exerted the highest inhibitory effect with IC50 values of 0.07, 0.10 and 0.08⯵M respectively; the more hydroxyl-groups were present, the lower the potency of inhibition was. Biochemical characterization leads to the conclusion that flavone and its hydroxy derivatives are mixed-type inhibitors. In silico studies have shown that, Phe224 and other aromatic residues in the human CYP1A1 active site play an important role in flavonoid-CYP interaction, through a π/π stacking between the aminoacid and the flavonoid C-ring. Outside the active site, the three flavonoids bind preferentially between A and K helices of the enzyme. Results from the Ames test using human S9 fraction revealed that none of the three compounds was mutagenic. We can consider 5-HF, 3-HF, and F as potential chemopreventive agents against genotoxic damage caused by metabolites resulting from CYP1A1 activity.
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Antineoplásicos Fitogénicos/farmacología , Citocromo P-450 CYP1A1/antagonistas & inhibidores , Flavonoides/farmacología , Aminoácidos/metabolismo , Antimutagênicos/farmacología , Simulación por Computador , Flavonas/química , Flavonas/farmacología , Humanos , Modelos Moleculares , Simulación del Acoplamiento Molecular , Pruebas de Mutagenicidad , Mutágenos/farmacología , Proteínas Recombinantes , Relación Estructura-ActividadRESUMEN
RecBCD and RecFOR homologous recombination pathways induced bacterial chromosomal duplication-segregation by sodium selenite (SSe) at sub-inhibitory concentrations. This evidence suggests that SSe induces both, double and single DNA strand damage with a concomitant DNA repair response, however the strong dependence for recombinogenic activity of RecB product suggests that the main DNA repair pathway copes with dsDNA breaks. A role for SSe recombinogenic induction is proposed to explain its effect on DNA instability.
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Deleción Cromosómica , Cromosomas Bacterianos/efectos de los fármacos , Cromosomas Bacterianos/genética , Exodesoxirribonucleasa V/metabolismo , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Selenito de Sodio/toxicidad , Proteínas Bacterianas/metabolismo , Daño del ADN , Reparación del ADN , Proteínas de Unión al ADN/metabolismo , Genes Bacterianos , Recombinación Genética , Salmonella typhimurium/metabolismoRESUMEN
Mexico City's Metropolitan Area (MCMA) includes Mexico City and 60 municipalities of the neighbor states. Inhabitants are exposed to emissions from over five million vehicles and stationary sources of air pollutants such as particulate matter (PM) and ozone. MCMA PM contains elemental carbon and organic carbon (OC). OCs include polycyclic aromatic hydrocarbons (PAHs), many of which induce mutagenic and carcinogenic DNA adducts. Gestational exposure to air pollution has been associated with increased risk of intrauterine growth restriction, preterm birth or low birth weight risk, and PAH-DNA adducts. These effects also depend on the presence of risk alleles. We investigated the presence of bulky PAH-DNA adducts, plasma 8-iso-PGF2α (8-iso-prostaglandin F2α ) and risk allele variants in neonates cord blood and their non-smoking mothers' leucocytes from families that were living in a highly polluted area during 2014-2015. The presence of adducts was significantly associated with both PM2.5 and PM10 levels, mainly during the last trimester of gestation in both neonates and mothers, while the last month of pregnancy was significant for the association between ozone levels and maternal plasma 8-iso-PGF2α . Fetal CYP1B1*3 risk allele was associated with increased adduct levels in neonates while the presence of the maternal allele significantly reduced the levels of fetal adducts. Maternal NQO1*2 was associated with lower maternal levels of adducts. Our findings suggest the need to reduce actual PM limits in MCMA. We did not observe a clear association between PM and/or adduct levels and neonate weight, length, body mass index, Apgar or Capurro score. Environ. Mol. Mutagen. 60:428-442, 2019. © 2019 Wiley Periodicals, Inc.
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Aductos de ADN/análisis , Exposición Materna , Intercambio Materno-Fetal/fisiología , Ozono/toxicidad , Material Particulado/toxicidad , Hidrocarburos Policíclicos Aromáticos/análisis , Efectos Tardíos de la Exposición Prenatal/patología , Adulto , Contaminación del Aire/análisis , Citocromo P-450 CYP1B1/genética , Aductos de ADN/genética , Femenino , Sangre Fetal/química , Humanos , Recién Nacido , Isoprostanos/sangre , México , NAD(P)H Deshidrogenasa (Quinona)/genética , Embarazo , Emisiones de Vehículos/análisis , Adulto JovenRESUMEN
Extracellular and intraneuronal formation of amyloid-beta aggregates have been demonstrated to be involved in the pathogenesis of Alzheimer's disease. However, the precise mechanism of amyloid-beta neurotoxicity is not completely understood. Previous studies suggest that binding of amyloid-beta to a number of targets have deleterious effects on cellular functions. In the present study we have shown for the first time that amyloid-beta 1-42 bound to a peptide comprising the microtubule binding domain of the heavy chain of microtubule-associated protein 1B by the screening of a human brain cDNA library expressed on M13 phage. This interaction may explain, in part, the loss of neuronal cytoskeletal integrity, impairment of microtubule-dependent transport and synaptic dysfunction observed previously in Alzheimer's disease.
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Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Neuronas/metabolismo , Fragmentos de Péptidos/metabolismo , Encéfalo/fisiopatología , Línea Celular Tumoral , Humanos , Microtúbulos/metabolismo , Péptidos/metabolismo , Unión Proteica/fisiología , Estructura Terciaria de Proteína/fisiología , Transporte de Proteínas/fisiología , Transmisión Sináptica/fisiologíaRESUMEN
Human macrophage migration inhibitory factor (MIF) is a cytokine that plays a role in several metabolic and inflammatory processes. Single nucleotide polymorphism (SNP) -173 G/C (rs755622) on MIF gene has been associated with numerous diseases, such as arthritis and cancer. However, most of the reports concerning the association of MIF with these and other pathologies are inconsistent and remain quite controversial. Therefore, we performed a meta-analysis from 96 case-control studies on -173 G/C MIF SNP and stratified the data according to the subjects geographic localization or the disease pathophysiology, in order to determine a more meaningful significance to this SNP. The polymorphism was strongly associated with an increased risk in autoimmune-inflammatory, infectious and age-related diseases on the dominant (OR: 0.74 [0.58-0.93], P < 0.01; OR: 0.81 [0.74-0.89], P < 0.0001; and OR: 0.81 [0.76-0.87], P < 0.0001, respectively) and the recessive models (OR: 0.74 [0.57-0.095], P < 0.01; OR: 0.66 [0.48-0.92], P < 0.0154; and OR: 0.70 [0.60-0.82], P < 0.0001, respectively). Also, significant association was found in the geographic localization setting for Asia, Europe and Latin America subdivisions in the dominant (OR: 0.76 [0.69-0.84], P < 0.0001; OR: 0.77 [0.72-0.83], P < 0.0001; OR: 0.61 [0.44-0.83], P-value: 0.0017, respectively) and overdominant models (OR: 0.85 [0.77-0.94], P < 0.0001; OR: 0.80 [0.75-0.86], P < 0.0001; OR: 0.73 [0.63-0.85], P-value: 0.0017, respectively). Afterwards, we implemented a network meta-analysis to compare the association of the polymorphism for two different subdivisions. We found a stronger association for autoimmune than for age-related or autoimmune-inflammatory diseases, and stronger association for infectious than for autoimmune-inflammatory diseases. We report for the first time a meta-analysis of rs755622 polymorphism with a variety of stratified diseases and populations. The study reveals a strong association of the polymorphism with autoimmune and infectious diseases. These results may help direct future research on MIF-173 G/C in diseases in which the relation is clearer and thus assist the search for more plausible applications.
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BACKGROUND: Extraparenchymal neurocysticercosis (ExPNCC), an infection caused by Taenia solium cysticerci that mainly occurs in the ventricular compartment (Ve) or the basal subarachnoid space (SAb), is more severe but less frequent and much less studied than parenchymal neurocysticercosis (ParNCC). Demographic, clinical, radiological, and lumbar cerebrospinal fluid features of patients affected by ExPNCC are herein described and compared with those of ParNCC patients. METHODOLOGY AND PRINCIPAL FINDINGS: 429 patients with a confirmed diagnosis of neurocysticercosis, attending the Instituto Nacional de Neurología y Neurocirugía, a tertiary reference center in Mexico City, from 2000 through 2014, were included. Demographic information, signs and symptoms, radiological patterns, and lumbar cerebrospinal fluid (CSF) laboratory values were retrieved from medical records for all patients. Data were statistically analyzed to assess potential differences depending on cyst location and to determine the effects of age and sex on the disease presentation. In total, 238 ExPNCC and 191 ParNCC patients were included. With respect to parenchymal cysts, extraparenchymal parasites were diagnosed at an older age (P = 0.002), chiefly caused intracranial hypertension (P < 0.0001), were more frequently multiple and vesicular (P < 0.0001), and CSF from these patients showed higher protein concentration and cell count (P < 0.0001). SAb patients were diagnosed at an older age than Ve patients, and showed more frequently seizures, vesicular cysticerci, and higher CSF cellularity. Gender and age modulated some traits of the disease. CONCLUSIONS: This study evidenced clear clinical, radiological, and inflammatory differences between ExPNCC and ParNCC, and between SAb and Ve patients, and demonstrated that parasite location determines different pathological entities.
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Inflamación/patología , Neurocisticercosis/patología , Adulto , Encéfalo/parasitología , Encéfalo/patología , Humanos , Inflamación/parasitología , México/epidemiología , Persona de Mediana Edad , Neurocisticercosis/epidemiología , Estudios RetrospectivosRESUMEN
Extracellular and intraneuronal formation of amyloid-beta (Abeta) deposits have been demonstrated to be involved in the pathogenesis of Alzheimer's disease (AD). However, the precise mechanism of Abeta neurotoxicity is not completely understood. Previous studies suggest that binding of Abeta with a number of targets have deleterious effects on cellular functions. It has been shown that Abeta directly interacted with intracellular protein ERAB (endoplasmic reticulum amyloid beta-peptide-binding protein) also known as ABAD (Abeta-binding alcohol dehydrogenase) resulting in mitochondrial dysfunction and cell death. In the present study we have identified another mitochondrial enzyme, ND3 of the human complex I, that binds to Abeta1-42 by the screening of a human brain cDNA library expressed on M13 phage. Our results indicated a strong interaction between Abeta and a phage-displayed 25 amino acid long peptide TTNLPLMVMSSLLLIIILALSLAYE corresponding to C-terminal peptide domain of NADH dehydrogenase, subunit 3 (MTND3) encoded by mitochondrial DNA (mtDNA). This interaction may explain, in part, the inhibition of complex I activity in astrocytes and neurons in the presence of Abeta, described recently. To our knowledge, the present study is the first demonstration of interaction between Abeta and one of the subunits of the human complex I.
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Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Biblioteca de Genes , Pruebas Genéticas/métodos , Fragmentos de Péptidos/metabolismo , Proteínas/metabolismo , Southern Blotting/métodos , Fragmentación del ADN/fisiología , Complejo I de Transporte de Electrón , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Reacción en Cadena de la Polimerasa/métodosRESUMEN
Neuroinflammation is an important feature in the pathogenesis and progression of neurodegenerative diseases. Molecules with anti-inflammatory properties have been evaluated in animal models of neuroinflammation and neurodegeneration as an adjuvant therapeutic strategy. In the present study we have demonstrated that alpha-mangostin (α-MG), a natural xanthone purified from mangosteen pericarp, reduced brain levels of pro-inflammatory cytokine interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and 18 kDa translocator protein (TSPO) in an animal model of peripheral LPS-induced neuroinflammation. We think that evaluation of α-MG as an adjuvant treatment in preclinical models of AD, PD, multiple sclerosis and other diseases with known shared pathology merits further consideration.