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Ampicillin-ceftriaxone has become a first-line therapy for Enterococcus faecalis endocarditis. We characterized the penicillin-binding protein (PBP) profiles of various E. faecalis strains and tested for synergy to better inform beta-lactam options for the treatment of E. faecalis infections. We assessed the affinity of PBP2B from elevated-MIC strain E. faecalis LS4828 compared to type strain JH2-2 using the fluorescent beta-lactam Bocillin FL. We also characterized pbp4 and pbpA structures and PBP4 and PBP2B expression and used deletion and complementation studies to assess the impact of PBP2B on the levels of resistance. We tested penicillin-susceptible and -resistant E. faecalis isolates against ceftriaxone or ceftaroline combinations with other beta-lactams in 24-h time-kill studies. Two penicillin-susceptible strains (JH2-2 and L2052) had identical pbp sequences and similar PBP expression levels. One reduced-penicillin-susceptibility strain (L2068) had pbp sequences identical to those of the susceptible strains but expressed more PBP4. The second decreased-penicillin-susceptibility strain (LS4828) had amino acid substitutions in both PBP4 and PBP2B and expressed increased quantities of both proteins. PBP2B did not appear to contribute significantly to the elevated beta-lactam MICs. No synergy was demonstrable against the strains with both mutated PBPs and increased expression (L2068 and LS4828). Meropenem plus ceftriaxone or ertapenem plus ceftriaxone demonstrated the most consistent synergistic activity. PBP2B of strain LS4828 does not contribute significantly to reduced penicillin susceptibility. Neither the MIC nor the level of PBP expression correlated directly with the identified synergistic combinations when tested at static subinhibitory concentrations.
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Enterococcus faecalis , beta-Lactamas , Proteínas de Unión a las Penicilinas/genética , Proteínas de Unión a las Penicilinas/metabolismo , beta-Lactamas/farmacología , beta-Lactamas/metabolismo , Enterococcus faecalis/genética , Enterococcus faecalis/metabolismo , Ceftriaxona/farmacología , Penicilinas/farmacología , Penicilinas/metabolismo , Pruebas de Sensibilidad Microbiana , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Antibacterianos/farmacología , Antibacterianos/metabolismoRESUMEN
Protein display approaches have been useful to endow the cell surface of yeasts with new catalytic activities so that they can act as enhanced whole-cell biocatalysts. Despite their biotechnological potential, protein display technologies remain poorly developed for filamentous fungi. The lignocellulolytic character of some of them coupled to the cell surface biosynthesis of valuable molecules by a single or a cascade of several displayed enzymes is an appealing prospect. Cell surface protein display consists in the co-translational fusion of a functional protein (passenger) to an anchor one, usually a cell-wall-resident protein. The abundance, spacing, and local environment of the displayed enzymes-determined by the relationship of the anchor protein with the structure and dynamics of the engineered cell wall-are factors that influence the performance of display-based biocatalysts. The development of protein display strategies in filamentous fungi could be based on the field advances in yeasts; however, the unique composition, structure, and biology of filamentous fungi cell walls require the customization of the approach to those microorganisms. In this prospective review, the cellular bases, the design principles, and the available tools to foster the development of cell surface protein display technologies in filamentous fungi are discussed.
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Técnicas de Visualización de Superficie Celular , Proteínas Fúngicas/metabolismo , Hongos/metabolismo , Proteínas de la Membrana/metabolismo , Biotecnología , Pared Celular/química , Pared Celular/metabolismo , Proteínas Fúngicas/genética , Hongos/genética , Glicosilfosfatidilinositoles/genética , Glicosilfosfatidilinositoles/metabolismo , Proteínas de la Membrana/genética , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismoRESUMEN
INTRODUCTION: Dense lower abdominal adhesions are known to cause urinary frequency by restricting expansion of the bladder. However, since preoperative diagnosis of adhesions has been difficult and there are multiple other causes of urinary frequency, such patients may go undiagnosed. With the improving resolution of ultrasound, ever smaller pathologic structures may be visualized, particularly if they are considered in the differential diagnosis. CASE PRESENTATION: To confirm the possibility that clinically significant lower abdominal adhesions may be visualized by ultrasound, we report on a patient who had developed disabling urinary frequency and pelvic pain after a cesarean section. Over a 5-year period, the patient underwent multiple diagnostic and therapeutic interventions at 2 large medical centers in multiple departments without success. Following this, a pelvic sonogram revealed a band of adhesions between the uterus and abdominal wall. Laparoscopic lysis of extensive pelvic adhesions was undertaken. Postoperatively, the patient was able to resume an active lifestyle, with good improvement in urinary frequency and pelvic pain. CONCLUSION: Ultrasound diagnosis of uterine adhesions to the abdominal wall led to successful laparoscopiclysis of adhesions with significant improvement in a patient's urinary tract symptoms and pelvic pain.
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Cesárea/efectos adversos , Dolor Pélvico/etiología , Complicaciones Posoperatorias/cirugía , Adherencias Tisulares/complicaciones , Incontinencia Urinaria/etiología , Adulto , Femenino , Humanos , Laparoscopía , Adherencias Tisulares/diagnóstico por imagen , UltrasonografíaRESUMEN
Twenty years ago, governments agreed that the right to have control over and decide freely and responsibly on all matters related to one's sexuality, free from coercion, discrimination and violence, is a fundamental human right. Since then, many aspects of sexual rights have been agreed by consensus at the global level, but the term "sexual rights" itself continues to be removed from negotiated outcomes and left out of international agreements, often at the last stages of negotiations. This commentary represents our point of view on the unfinished business of the UN with regards to the fight for sexual rights. Our perspective draws from lessons learned in cross-movement organizing in various regional UN spaces and outlines some of the tactics by conservative forces to push sexual rights to the periphery. The article reaffirms the position that broadening the debate and concepts surrounding sexual rights to be more inclusive, has enormous transformational potential and should inform collective advocacy efforts moving forward.
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Derechos Humanos , Sexualidad , Naciones Unidas , Salud Global , Humanos , Política , Salud Reproductiva , Conducta Sexual , Minorías Sexuales y de GéneroRESUMEN
Life history parameters were established under controlled laboratory conditions for the green stink bug, Chinavia hilaris (Say) (= Acrosternum hilare), to improve pest control in pistachios in California. Parameters measured and calculated included survival and development at seven constant temperatures (ranging from 15 to 35 degrees C), development time, upper and lower development thresholds, thermal constants, fecundity, generation time, net reproductive rate, and intrinsic rate of increase. C. hilaris did not complete development at 15 and 35 degrees C. Within the range of 20-27.5 degrees C, development time decreased linearly with temperature; it increased again at 30 degrees C. The lower threshold was calculated by linear methods to be 12.3 degrees C, and the thermal constant was calculated to be 588 degree days. Fastest development was recorded at 27.5 degrees C, whereas greatest survival was observed at 22.5 degrees C. At 27.5 degrees C, mean fecundity was 53.5 eggs per female, mean generation time was 74.4 d, net reproductive rate was 20.09, and intrinsic rate of increase was 0.04. Use of a nonlinear model yielded estimates of 13.2, 28.4, and 33.4 degrees C, for the lower threshold, optimum temperature, and upper threshold, respectively. Results were compared with similar studies and interpreted in the light of pest management needs in pistachio. Increased emphasis on monitoring and management ofoverwintering sites and early-season migration are recommended.
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Heterópteros/crecimiento & desarrollo , Animales , California , Femenino , Longevidad , Masculino , Pistacia , Reproducción , TemperaturaRESUMEN
INTRODUCTION: Epidermal inclusion cysts are common discrete nodules often formed in areas of previous trauma or surgery. A literature review indicated that large epidermal inclusion cysts of the pelvis are extremely rare. Accordingly, we present a case of a woman with a large pelvic epidermal inclusion cyst of the vaginal cuff, along with imaging studies and a review of the literature. CASE PRESENTATION: A 49-year-old woman, 13 years after vaginal hysterectomy, was found to have a 7-cm soft tissue pelvic mass, discovered on a computed tomography (CT) scan performed for abdominal pain. The transvaginal ultrasound showed typical findings of an unruptured epidermal inclusion cyst with a hypoechoic background with diffuse small variable echodensities (some intense echogenic reflectors), a thin wall, and no internal Doppler flow. A 7-cm epidermal inclusion cyst was removed laparoscopically from her vaginal cuff without complication. DISCUSSION: Epidermal inclusion cysts of clinical significance are rarely formed at the vaginal cuff or elsewhere in the pelvis. Increased utilization of abdominal/pelvic CT imaging is increasing the frequency in which benign pelvic cysts are encountered. The trauma of surgery may sequester portions of vaginal epithelium, which may form epidermal inclusion cysts. As the cyst increases in size, the cyst may be viewed as an incidental pelvic mass requiring clinical decision making.
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Quiste Epidérmico/diagnóstico por imagen , Quiste Epidérmico/cirugía , Enfermedades Vaginales/diagnóstico por imagen , Enfermedades Vaginales/cirugía , Diagnóstico Diferencial , Femenino , Humanos , Histerectomía , Laparoscopía , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
Resistance to ampicillin and imipenem in Enterococcus faecalis is infrequent. However, the evolution of resistance can occur through prolonged antibiotic exposure during the treatment of chronic infections. In this study, we conducted a Long-Term Evolution Experiment (LTEE) using four genetically diverse strains of E. faecalis with varying susceptibilities to ampicillin and imipenem. Each strain was subjected to increasing concentrations of either ampicillin or imipenem over 200 days, with three independent replicates for each strain. Selective pressure from imipenem led to the rapid selection of highly resistant lineages across all genetic backgrounds, compared to ampicillin. In addition to high resistance, we describe, for the first time, the evolution of a ß-lactam dependent phenotype observed in lineages from all backgrounds. WGS and bioinformatic analysis revealed mutations in three main functional classes: genes involved in cell wall synthesis and degradation, genes in the walK/R two-component system, and genes in the c-di-AMP pathway. Our analysis identified new mutations in genes known to be involved in resistance as well as novel genes potentially associated with resistance. Furthermore, the newly described ß-lactam dependent phenotype was correlated with the inactivation of c-di-AMP degradation, resulting in high levels of this second messenger. Together, these data highlight the diverse genetic mechanisms underlying resistance to ampicillin and imipenem in E. faecalis . The emergence of high resistance levels and ß-lactam dependency underscores the importance of understanding evolutionary dynamics in the development of antibiotic resistance. Importance: E. faecalis is a major human pathogen, and treatment is frequently compromised by poor response to first-line antibiotics such ampicillin. Understanding the factors that play a role in susceptibility/resistance to these drugs will help guide the development of much needed treatments.
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BACKGROUND AND PURPOSE: The determination of Aneurysm wall enhancement (AWE) by human readers on visual inspection alone is subjective and prone to error. A three-dimensional (3D) method for quantifying the aneurysm wall's signal intensity (SI) enables objective determination of AWE. Inter-reader agreement and agreement between subjective and objective determination of AWE were assessed in this study. MATERIALS AND METHODS: Patients with saccular intracranial aneurysms (IAs) were imaged with high-resolution MRI. Subjective assessment: Two internal adjudicators visually determined AWE if the degree of enhancement was equal to or higher than the pituitary stalk. An experienced internal neuroradiologist resolved disagreements. This internal adjudication was compared with an external adjudication to assess inter-rater agreement among centers. Objective assessment: The distribution of SI across the aneurysm wall after normalizing the SI to the corpus callosum was determined with an in-house code. The normalized mean SI on post-contrast T1 MRI was defined as 3D-circumferential AWE (3D-CAWE). If the 3D-CAWE value was higher than one, an IA was defined as objectively "enhancing." Inter-rater agreement was analyzed with kappa coefficients. Inter-technique agreement between subjective and objective assessment was performed using kappa statistics. Univariate regressions were performed to identify which morphological characteristics influenced subjective adjudication of enhancement. RESULTS: A total of 113 IAs were analyzed. The agreement of the internal assessment was moderate (k = 0.63), 49.5% of IAs (56) were classified as "enhancing" and 50.5% (57) as "non-enhancing" after consensus. Inter-rater agreement between internal and external adjudication was weak (k = 0.52) for the presence of AWE. There was no agreement between the subjective assessment of AWE and objective 3D-CAWE (k = 0.16, p 0.02). Subjective assessment was less likely to reliably adjudicate enhancement when assessing multiple aneurysms (OR 0.4, 95% CI 0.16 -0.97, p 0.04) and IAs larger than > 7 mm (OR 0.22, 95% CI 0.09 -0.55, p 0.002) despite being objectively "non-enhancing". CONCLUSIONS: Subjective adjudication of AWE has poor inter-rater agreement, and no agreement with an objective 3D method of determining AWE. It is also less likely than objective quantification to identify enhancement in aneurysms larger than 7 mm or when multiple aneurysms are present. Objective 3D quantification, such as the technique used in this study, should therefore be considered when assessing AWE, especially in patients with multiple aneurysms and aneurysms larger than 7 mm in size. ABBREVIATIONS: 3D, three-dimensional; 3D-CAWE, three-dimensional circumferential aneurysm wall enhancement; AWE, aneurysm wall enhancement; Gd, gadolinium; HR-MRI, high resolution MRI; HR 3D T1 VWI, high-resolution 3D T1 weighted black blood vessel wall imaging; IA, intracranial aneurysm; SI, signal intensity.
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Gastrointestinal Stromal Tumors (GIST) are the most frequent mesenchymal neoplasia of the digestive tract. Genomic alterations in KIT, PDFGRA, SDH, and BRAF genes are essential in GIST oncogenesis. Therefore, the mutations in these genes have demonstrated clinical implications. Tumors with deletions in KIT-exon 11 or duplications in exon 9 are associated with a worse prognosis. In contrast, KIT-exon 11 substitutions and duplications are associated with a better clinical outcome. Moreover, mutations in Kit exon 9 and 11 are actionable, due to their response to imatinib, while mutations in PDGFRA respond to sunitinib and/or avapritinib. Although, molecular testing on tissue samples is effective; it is invasive, requires adequate amounts of tissue, and a long experimental process is needed for results. In contrast, liquid biopsy has been proposed as a simple and non-invasive method to test biomarkers in cancer. The most common molecule analyzed by liquid biopsy is circulating tumor DNA (ctDNA). GISTs ctDNA testing has been demonstrated to be effective in identifying known and novel KIT mutations that were not detected using traditional tissue DNA testing and have been useful in determining progression risk and response to TKI therapy. This allows the clinician to have an accurate picture of the genetic changes of the tumor over time. In this work, we aimed to discuss the implications of mutational testing in clinical outcomes, the methods to test ctDNA and the future challenges in the establishment of alternatives of personalized medicine.
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Tumores del Estroma Gastrointestinal , Humanos , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/genética , Mesilato de Imatinib/farmacología , Mesilato de Imatinib/uso terapéutico , Sunitinib/uso terapéutico , Pronóstico , Mutación , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/uso terapéutico , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genéticaRESUMEN
California pistachios are threatened by several stink bug species (Hemiptera: Pentatomidae), including the native Thyanta pallidovirens (Stål) and Chlorochroa uhleri (Stål), as well as the invasive Nezara viridula (L.). In pistachio, control tactics often target specific life stages, which makes knowledge about life histories fundamental to successful IPM programs. For that purpose, life history parameters of these stink bug species were assessed. Nymphal development and survivorship at seven constant temperatures, upper and lower development thresholds, thermal constants, adult longevity and fecundity, and life table parameters were evaluated. No species completed development at 15°C or 35°C. For N. viridula, egg to adult development was fastest at 30°C, whereas for T. pallidovirens there was no significant difference between 27.5 and 30°C and C. uhleri development was similar between 25 and 30°C. Egg to adult survival was highest at 22.5°C and 27.5°C. The thermal requirements as degree-days (DD) to complete immature development were estimated to be 714.3, 370.4, and 434.8 for C. uhleri, T. pallidovirens, and N. viridula, respectively. For C. uhleri, life table calculations produced a value of 56.7 d for mean generation time (To), 24.89 for net reproductive rate (Ro) and 0.057 for the intrinsic rate of increase (r). Thyanta pallidovirens had a To of 39.9 d, a Ro of 81.10 and a r of 0.11. The results are discussed with respect to the improvement of IPM in California pistachios, and the information presented may contribute to the control of these pest species in other ecosystems.
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Ecosistema , Heterópteros , Animales , Ninfa , Reproducción , TemperaturaRESUMEN
Bipolar disorder is a psychiatric disorder that affects a significant part of the world's population; however, its diagnosis is difficult, mainly because of the lack of biomarkers and objective tests that aid the clinical evaluation. Proton magnetic resonance spectroscopy (MRS) is a tool that is relatively unused in the medical field. Its application arises from conventional magnetic resonance, and allows non-invasive, in vivo, the study of various metabolites and compounds in the human brain. This method may allow the assessment of neurobiochemical alterations in bipolar patients. One of the main advantages of this study type is the simplicity in its use since it only needs a standard magnetic resonator. All these characteristics make it an attractive diagnostic tool that can be used anywhere, including in low-middle-income countries. In conclusion, MRS has potential as a diagnostic tool for bipolar disorder; nevertheless, using it for this purpose still requires additional steps.
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Symbiosis of green algae with protozoa and invertebrates has been studied for more than 100 years. Endosymbiotic green algae are widely distributed in ciliates (e.g. Paramecium, Stentor, Climacostomum, Coleps, Euplotes), heliozoa (e.g. Acanthocystis) and invertebrates (e.g. Hydra, Spongilla), and have traditionally been identified as named or unnamed species of Chlorella Beij. or Zoochlorella K. Brandt or referred to as Chlorella-like algae or zoochlorellae. We studied 17 strains of endosymbionts isolated from various hosts and geographical localities using an integrative approach (nuclear encoded small subunit and internal transcribed spacer regions of rRNA gene sequences including their secondary structures, morphology, physiology and virus sensitivity). Phylogenetic analyses have revealed them to be polyphyletic. The strains examined belong to five independent clades within the Trebouxiophyceae (Choricystis-, Elliptochloris-, Auxenochlorella- and Chlorella-clades) and Chlorophyceae (Scenedesmus-clade). The most studied host organism, Paramecium bursaria, harbours endosymbionts representing at least five different species. On the basis of our results, we propose a taxonomic revision of endosymbiotic 'Chlorella'-like green algae. Zoochlorella conductrix K. Brandt is transferred to Micractinium Fresen. and Zoochlorella parasitica K. Brandt to Choricystis (Skuja) Fott. It was shown that Choricystis minor (Skuja) Fott, the generitype, is a later heterotypic synonym of Choricystis parasitica (K. Brandt) comb. nov. A new species, Chlorella heliozoae, is proposed to accommodate the endosymbiont of Acanthocystis turfacea.
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Chlorella/clasificación , Chlorella/genética , Filogenia , Secuencia de Bases , ADN de Plantas/genética , ADN Espaciador Ribosómico/genética , Genes de ARNr , Conformación de Ácido Nucleico , Paramecium/microbiología , SimbiosisRESUMEN
The structures of three related keto diester and diester ylides, namely diethyl 3-oxo-2-(triphenylphosphoranylidene)glutarate, C(27)H(27)O(5)P, (I), diethyl 3-oxo-2-(triphenylphosphoranylidene)glutarate acetic acid monosolvate, C(27)H(27)O(5)P·C(2)H(4)O(2), (II), and diethyl 2-(triphenylphosphoranylidene)succinate, C(26)H(27)O(4)P, (III), are presented. The syn-keto anti-ester conformations in the crystalline keto diesters are governed by electronic delocalization between the P-C and ylidic bonds and an acyl group, and by intra- and intermolecular interactions. There are also intramolecular attractive and repulsive interactions of different types (C-H...O and C-H...π) controlling the molecular conformations. The mono-ylidic diester (III) has an anti-ester conformation, while those for (I) and (II) are related to pyrolytic formation of acetylene derivatives. The terminal nonylidic ester group in (I) was disordered over two sets of almost equally populated positions.
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Enteropathogenic Escherichia coli (EPEC) infection causes a histopathological lesion including recruitment of F-actin beneath the attached bacteria and formation of actin-rich pedestal-like structures. Another important target of EPEC is the tight junction (TJ), and EspF induces displacement of TJ proteins and increased intestinal permeability. Previously, we determined that an EPEC strain lacking EspF did not cause TJ disruption; meanwhile, pedestals were located on the TJ and smaller than those induced by the wild-type strain. Therefore, EspF could be playing an important role in both phenotypes. Here, using different cell models, we found that EspF was essential for pedestal maturation through ZO-1 disassembly from TJ, leading to (a) ZO-1 recruitment to the pedestal structure; no other main TJ proteins were required. Recruited ZO-1 allowed the afadin recruitment. (b) Afadin recruitment caused an afadin-ZO-1 transient interaction, like during TJ formation. (c) Afadin and ZO-1 were segregated to the tip and the stem of pedestal, respectively, causing pedestal maturation. Initiation of these three discrete phases for pedestal maturation functionally and physically required EspF expression. Pedestal maturation process could help coordinate the epithelial actomyosin function by maintaining the actin-rich column composing the pedestal structure and could be important in the dynamics of the pedestal movement on epithelial cells.
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Escherichia coli Enteropatógena/fisiología , Infecciones por Escherichia coli/metabolismo , Infecciones por Escherichia coli/microbiología , Proteínas de Escherichia coli/genética , Proteínas de Microfilamentos/metabolismo , Fosfoproteínas/genética , Uniones Estrechas/metabolismo , Proteína de la Zonula Occludens-1/metabolismo , Actinas/metabolismo , Células Epiteliales/metabolismo , Infecciones por Escherichia coli/patología , Proteínas de Escherichia coli/metabolismo , Técnica del Anticuerpo Fluorescente , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Permeabilidad , Fosfoproteínas/metabolismo , Unión ProteicaRESUMEN
The adhesion G protein-coupled receptors latrophilins have been in the limelight for more than 20 years since their discovery as calcium-independent receptors for α-latrotoxin, a spider venom toxin with potent activity directed at neurotransmitter release from a variety of synapse types. Latrophilins are highly expressed in the nervous system. Although a substantial amount of studies has been conducted to describe the role of latrophilins in the toxin-mediated action, the recent identification of endogenous ligands for these receptors helped confirm their function as mediators of adhesion events. Here we hypothesize a role for latrophilins in inter-neuronal contacts and the formation of neuronal networks and we review the most recent information on their role in neurons. We explore molecular, cellular and behavioral aspects related to latrophilin adhesion function in mice, zebrafish, Drosophila melanogaster and Caenorhabditis elegans, in physiological and pathophysiological conditions, including autism spectrum, bipolar, attention deficit and hyperactivity and substance use disorders.
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The goal of a taxonomist should be to contribute to the construction of a framework that expresses interrelationships among taxa and provides pegs to which information from all possible sources may be attached. It is essential that this information be attached to the correct peg. Throughout the history of taxonomy, attempts have been made to reduce the subjectivity involved in determining the correct peg. Illustrations, which initially were relied on to produce accurate determinations, have maintained their importance, keeping pace with miraculous advances in the technologies of microscopy, electronics, graphics, and communication. The type method was introduced to provide an anchor for each name in a sea of ever-changing circumscriptions. The physical nature of types has kept pace with advances in taxonomic methodology and now includes the possibility of designating a living culture as type if it is preserved in a metabolically inactive state. The number of characters associated with a name has been greatly increased by studying organisms in culture, by using transmission and scanning electron microscopy, and by nucleotide sequence analysis. A marked increase in the number of discriminatory characters has resulted in greater assurance that the correct peg has been chosen on which to hang accumulated information. Integration of molecular and morphological data should theoretically strengthen the certainty of identification, but this certainty will always be tempered by some degree of subjectivity. Taxonomists form opinions on the basis of data that are reputedly objective, but that in fact are subject to varying interpretations. Genomic analysis is a very important taxonomic tool, but its application should not be assumed to be free of subjectivity.
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Clasificación/métodos , Eucariontes/clasificación , Eucariontes/citología , Investigación/normas , Proyectos de InvestigaciónRESUMEN
The conformations of organic compounds determined in the solid state are important because they can be compared with those in solution and/or from theoretical calculations. In this work, the crystal and molecular structures of four closely related diesters, namely methyl isopropyl 2-(triphenylphosphoranylidene)malonate, C(25)H(25)O(4)P, ethyl isopropyl 2-(triphenylphosphoranylidene)malonate, C(26)H(27)O(4)P, methyl tert-butyl 2-(triphenylphosphoranylidene)malonate, C(26)H(27)O(4)P, and ethyl tert-butyl 2-(triphenylphosphoranylidene)malonate, C(27)H(29)O(4)P, have been analysed as a preliminary step for such comparative studies. As a result of extensive electronic delocalization, as well as intra- and intermolecular interactions, a remarkably similar pattern of preferred conformations in the crystal structures results, viz. a syn-anti conformation of the acyl groups with respect to the P atom, with the bulkier alkoxy groups oriented towards the P atom. The crystal structures are controlled by nonconventional hydrogen-bonding and intramolecular interactions between cationoid P and acyl and alkoxy O atoms in syn positions.
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Malonatos/química , Compuestos Organofosforados/química , Cristalografía , Conformación MolecularRESUMEN
The intestinal epithelium consists of a single cell layer, which is a critical selectively permeable barrier to both absorb nutrients and avoid the entry of potentially harmful entities, including microorganisms. Epithelial cells are held together by the apical junctional complexes, consisting of adherens junctions, and tight junctions (TJs), and by underlying desmosomes. TJs lay in the apical domain of epithelial cells and are mainly composed by transmembrane proteins such as occludin, claudins, JAMs, and tricellulin, that are associated with the cytoplasmic plaque formed by proteins from the MAGUK family, such as ZO-1/2/3, connecting TJ to the actin cytoskeleton, and cingulin and paracingulin connecting TJ to the microtubule network. Extracellular bacteria such as EPEC and EHEC living in the intestinal lumen inject effectors proteins directly from the bacterial cytoplasm to the host cell cytoplasm, where they play a relevant role in the manipulation of the eukaryotic cell functions by modifying or blocking cell signaling pathways. TJ integrity depends on various cell functions such as actin cytoskeleton, microtubule network for vesicular trafficking, membrane integrity, inflammation, and cell survival. EPEC and EHEC effectors target most of these functions. Effectors encoded inside or outside of locus of enterocyte effacement (LEE) disrupt the TJ strands. EPEC and EHEC exploit the TJ dynamics to open this structure, for causing diarrhea. EPEC and EHEC secrete effectors that mimic host proteins to manipulate the signaling pathways, including those related to TJ dynamics. In this review, we focus on the known mechanisms exploited by EPEC and EHEC effectors for causing TJ disruption.
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Escherichia coli Enterohemorrágica/metabolismo , Escherichia coli Enteropatógena/metabolismo , Uniones Estrechas/metabolismo , Sistemas de Secreción Tipo III/metabolismo , Escherichia coli Enterohemorrágica/genética , Escherichia coli Enterohemorrágica/patogenicidad , Escherichia coli Enteropatógena/genética , Escherichia coli Enteropatógena/patogenicidad , Infecciones por Escherichia coli/microbiología , Proteínas de Escherichia coli/metabolismo , Uniones Intercelulares/efectos de los fármacos , Mucosa Intestinal/microbiología , Ocludina/metabolismo , Transporte de Proteínas , Uniones Estrechas/químicaRESUMEN
The objective of this article was to identify the association between motorcycle deaths and variables related to Samaja's theory of social reproduction in the period 2000-2005 in the state of Pernambuco. An ecological, case-control study was carried out, with municipalities as the unit of analysis. Cases were defined as the 20% of municipalities with the highest local empirical Bayesian coefficients for mortality due to motorcycle accidents, and controls as the 40% with the lowest coefficients. The municipalities with the greatest chances of high coefficients for mortality due to motorcycle accidents showed high population growth factors and increases in the total fleet of motorcycles, with low population densities, low GDP per capita, and more than 20 motorcycles per thousand inhabitants. We conclude that the variables related to macro-policies proved to have greater force in explaining higher chances of motorcycle death.
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Accidentes de Tránsito/mortalidad , Motocicletas , Accidentes de Tránsito/economía , Teorema de Bayes , Brasil/epidemiología , Estudios de Casos y Controles , Humanos , Renta , Densidad de Población , Crecimiento Demográfico , Teoría SocialRESUMEN
BACKGROUND: Rapidly progressive hirsutism or virilization in the postmenopausal woman raises the suspicion of an androgen-secreting tumor. Hormonal testing and imaging studies usually rule out an adrenal tumor. However, small, androgenizing ovarian tumors may not be detectable by imaging studies. CASE: A postmenopausal woman presented with rapidly progressive hirsutism and elevated androgens. Imaging studies did not localize the tumor. Bilateral laparoscopic oophorectomy was performed, and a small, androgenizing Brenner cell tumor of the left ovary was demonstrated on histologic examination. CONCLUSION: Because of the low morbidity associated with laparoscopic salpingo-oophorectomy, it may be reasonable to remove the ovaries of postmenopausal women who display virilization or rapidly progressive hirsutism and elevated androgens, even if imaging studies do not detect the ovarian tumor.