Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 129
Filtrar
Más filtros

Intervalo de año de publicación
1.
EMBO J ; 41(22): e111158, 2022 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-36245278

RESUMEN

Apicomplexan parasites possess secretory organelles called rhoptries that undergo regulated exocytosis upon contact with the host. This process is essential for the parasitic lifestyle of these pathogens and relies on an exocytic machinery sharing structural features and molecular components with free-living ciliates. However, how the parasites coordinate exocytosis with host interaction is unknown. Here, we performed a Tetrahymena-based transcriptomic screen to uncover novel exocytic factors in Ciliata and conserved in Apicomplexa. We identified membrane-bound proteins, named CRMPs, forming part of a large complex essential for rhoptry secretion and invasion in Toxoplasma. Using cutting-edge imaging tools, including expansion microscopy and cryo-electron tomography, we show that, unlike previously described rhoptry exocytic factors, TgCRMPs are not required for the assembly of the rhoptry secretion machinery and only transiently associate with the exocytic site-prior to the invasion. CRMPs and their partners contain putative host cell-binding domains, and CRMPa shares similarities with GPCR proteins. Collectively our data imply that the CRMP complex acts as a host-molecular sensor to ensure that rhoptry exocytosis occurs when the parasite contacts the host cell.


Asunto(s)
Toxoplasma , Toxoplasma/genética , Toxoplasma/metabolismo , Proteínas Protozoarias/metabolismo , Orgánulos/metabolismo , Exocitosis , Proteínas de la Membrana/metabolismo , Interacciones Huésped-Parásitos
2.
Cell ; 147(5): 1054-65, 2011 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-22118462

RESUMEN

Introns are removed from pre-mRNAs during transcription while the pre-mRNA is still tethered to the gene locus via RNA polymerase. However, during alternative splicing, it is important that splicing be deferred until all of the exons and introns involved in the choice have been synthesized. We have developed an in situ RNA imaging method with single-molecule sensitivity to define the intracellular sites of splicing. Using this approach, we found that the normally tight coupling between transcription and splicing is broken in situations where the intron's polypyrimidine tract is sequestered within strong secondary structures. We also found that in two cases of alternative splicing, in which certain exons are skipped due to the activity of the RNA-binding proteins Sxl and PTB, splicing is uncoupled from transcription. This uncoupling occurs only on the perturbed introns, whereas the preceding and succeeding introns are removed cotranscriptionally. PAPERCLIP:


Asunto(s)
Drosophila melanogaster/genética , Imagen Molecular/métodos , Empalme del ARN , Transcripción Genética , Empalme Alternativo , Animales , Secuencia de Bases , Proteínas de Drosophila/genética , Exones , Regulación de la Expresión Génica , Genes fos , Células HeLa , Humanos , Datos de Secuencia Molecular , Mutación , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Precursores del ARN/química , Precursores del ARN/metabolismo , Proteínas de Unión al ARN/genética
3.
Proc Natl Acad Sci U S A ; 120(5): e2219533120, 2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36693095

RESUMEN

Toxoplasmosis is a neglected parasitic disease necessitating public health control. Host cell invasion by Toxoplasma occurs at different stages of the parasite's life cycle and is crucial for survival and establishment of infection. In tachyzoites, which are responsible for acute toxoplasmosis, invasion involves the formation of a molecular bridge between the parasite and host cell membranes, referred to as the moving junction (MJ). The MJ is shaped by the assembly of AMA1 and RON2, as part of a complex involving additional RONs. While this essential process is well characterized in tachyzoites, the invasion process remains unexplored in bradyzoites, which form cysts and are responsible for chronic toxoplasmosis and contribute to the dissemination of the parasite between hosts. Here, we show that bradyzoites invade host cells in an MJ-dependent fashion but differ in protein composition from the tachyzoite MJ, relying instead on the paralogs AMA2 and AMA4. Functional characterization of AMA4 reveals its key role for cysts burden during the onset of chronic infection, while being dispensable for the acute phase. Immunizations with AMA1 and AMA4, alone or in complex with their rhoptry neck respective partners RON2 and RON2L1, showed that the AMA1-RON2 pair induces strong protection against acute and chronic infection, while the AMA4-RON2L1 complex targets more selectively the chronic form. Our study provides important insights into the molecular players of bradyzoite invasion and indicates that invasion of cyst-forming bradyzoites contributes to cyst burden. Furthermore, we validate AMA-RON complexes as potential vaccine candidates to protect against toxoplasmosis.


Asunto(s)
Parásitos , Toxoplasma , Toxoplasmosis , Animales , Toxoplasma/metabolismo , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Infección Persistente , Toxoplasmosis/metabolismo , Parásitos/metabolismo , Vacunación
4.
Nucleic Acids Res ; 51(12): 6120-6142, 2023 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-37158274

RESUMEN

Iron metabolism is closely associated with the pathogenesis of obesity. However, the mechanism of the iron-dependent regulation of adipocyte differentiation remains unclear. Here, we show that iron is essential for rewriting of epigenetic marks during adipocyte differentiation. Iron supply through lysosome-mediated ferritinophagy was found to be crucial during the early stage of adipocyte differentiation, and iron deficiency during this period suppressed subsequent terminal differentiation. This was associated with demethylation of both repressive histone marks and DNA in the genomic regions of adipocyte differentiation-associated genes,  including Pparg, which encodes PPARγ, the master regulator of adipocyte differentiation. In addition, we identified several epigenetic demethylases to be responsible for iron-dependent adipocyte differentiation, with the histone demethylase jumonji domain-containing 1A and the DNA demethylase ten-eleven translocation 2 as the major enzymes. The interrelationship between repressive histone marks and DNA methylation was indicated by an integrated genome-wide association analysis, and was also supported by the findings that both histone and DNA demethylation were suppressed by either the inhibition of lysosomal ferritin flux or the knockdown of iron chaperone poly(rC)-binding protein 2. In summary, epigenetic regulations through iron-dependent control of epigenetic enzyme activities play an important role in the organized gene expression mechanisms of adipogenesis.


Asunto(s)
Estudio de Asociación del Genoma Completo , Hierro , Hierro/metabolismo , Metilación de ADN/genética , Epigénesis Genética , Adipocitos/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética , Histona Demetilasas con Dominio de Jumonji/metabolismo
5.
J Perinat Med ; 52(4): 399-405, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38404246

RESUMEN

OBJECTIVES: This study aims to show the relation between biomarkers in maternal and cord-blood samples and fetal heart rate variability (fHRV) metrics through a non-invasive fetal magnetocardiography (fMCG) technique. METHODS: Twenty-three women were enrolled for collection of maternal serum and fMCG tracings immediately prior to their scheduled cesarean delivery. The umbilical cord blood was collected for measurement of biomarker levels. The fMCG metrics were then correlated to the biomarker levels from the maternal serum and cord blood. RESULTS: Brain-derived neurotrophic factor (BDNF) had a moderate correlation with fetal parasympathetic activity (0.416) and fetal sympathovagal ratios (-0.309; -0.356). Interleukin (IL)-6 also had moderate-sized correlations but with an inverse relationship as compared to BDNF. These correlations were primarily in cord-blood samples and not in the maternal blood. CONCLUSIONS: In this small sample-sized exploratory study, we observed a moderate correlation between fHRV and cord-blood BDNF and IL-6 immediately preceding scheduled cesarean delivery at term. These findings need to be validated in a larger population.


Asunto(s)
Biomarcadores , Factor Neurotrófico Derivado del Encéfalo , Sangre Fetal , Frecuencia Cardíaca Fetal , Interleucina-6 , Humanos , Femenino , Embarazo , Factor Neurotrófico Derivado del Encéfalo/sangre , Frecuencia Cardíaca Fetal/fisiología , Adulto , Biomarcadores/sangre , Sangre Fetal/metabolismo , Sangre Fetal/química , Interleucina-6/sangre , Magnetocardiografía/métodos , Cesárea
6.
BMC Nephrol ; 24(1): 140, 2023 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-37217840

RESUMEN

BACKGROUND: Patients with COVID-19 have a high incidence of acute kidney injury (AKI), which is associated with mortality. The objective of the study was to determine the factors associated with AKI in patients with COVID-19. METHODOLOGY: A retrospective cohort was established in two university hospitals in Bogotá, Colombia. Adults hospitalized for more than 48 h from March 6, 2020, to March 31, 2021, with confirmed COVID-19 were included. The main outcome was to determine the factors associated with AKI in patients with COVID-19 and the secondary outcome was estimate the incidence of AKI during the 28 days following hospital admission. RESULTS: A total of 1584 patients were included: 60.4% were men, 738 (46.5%) developed AKI, 23.6% were classified as KDIGO 3, and 11.1% had renal replacement therapy. The risk factors for developing AKI during hospitalization were male sex (OR 2.28, 95% CI 1.73-2.99), age (OR 1.02, 95% CI 1.01-1.03), history of chronic kidney disease (CKD) (OR 3.61, 95% CI 2.03-6.42), High Blood Pressure (HBP) (OR 6.51, 95% CI 2.10-20.2), higher qSOFA score to the admission (OR 1.4, 95% CI 1.14-1.71), the use of vancomycin (OR 1.57, 95% CI 1.05-2.37), piperacillin/tazobactam (OR 1.67, 95% CI 1.2-2.31), and vasopressor support (CI 2.39, 95% CI 1.53-3.74). The gross hospital mortality for AKI was 45.5% versus 11.7% without AKI. CONCLUSIONS: This cohort showed that male sex, age, history of HBP and CKD, presentation with elevated qSOFA, in-hospital use of nephrotoxic drugs and the requirement for vasopressor support were the main risk factors for developing AKI in patients hospitalized for COVID-19.


Asunto(s)
Lesión Renal Aguda , COVID-19 , Hipertensión , Insuficiencia Renal Crónica , Adulto , Humanos , Masculino , Femenino , Antibacterianos/efectos adversos , Estudios Retrospectivos , COVID-19/epidemiología , COVID-19/complicaciones , Factores de Riesgo , Hipertensión/complicaciones , Lesión Renal Aguda/etiología , Insuficiencia Renal Crónica/complicaciones , Mortalidad Hospitalaria
7.
BMC Nephrol ; 22(1): 335, 2021 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-34625046

RESUMEN

BACKGROUND: A bundle of preventive measures can be taken to avoid acute kidney injury (AKI) or progression of AKI. We performed a systematic review and meta-analysis to evaluate the compliance to AKI care bundles in hospitalized patients and its impact on kidney and patient outcomes. METHODS: Randomized controlled trials, observational and interventional studies were included. Studied outcomes were care bundle compliance, occurrence of AKI and moderate-severe AKI, use of kidney replacement therapy (KRT), kidney recovery, mortality (ICU, in-hospital and 30-day) and length-of-stay (ICU, hospital). The search engines PubMed, Embase and Google Scholar were used (January 1, 2012 - June 30, 2021). Meta-analysis was performed with the Mantel Haenszel test (risk ratio) and inverse variance (mean difference). Bias was assessed by the Cochrane risk of bias tool (RCT) and the NIH study quality tool (non-RCT). RESULTS: We included 23 papers of which 13 were used for quantitative analysis (4 RCT and 9 non-randomized studies with 25,776 patients and 30,276 AKI episodes). Six were performed in ICU setting. The number of trials pooled per outcome was low. There was a high variability in care bundle compliance (8 to 100%). Moderate-severe AKI was less frequent after bundle implementation [RR 0.78, 95%CI 0.62-0.97]. AKI occurrence and KRT use did not differ between the groups [resp RR 0.90, 95%CI 0.76-1.05; RR 0.67, 95%CI 0.38-1.19]. In-hospital and 30-day mortality was lower in AKI patients exposed to a care bundle [resp RR 0.81, 95%CI 0.73-0.90, RR 0.95 95%CI 0.90-0.99]; this could not be confirmed by randomized trials. Hospital length-of-stay was similar in both groups [MD -0.65, 95%CI -1.40,0.09]. CONCLUSION: This systematic review and meta-analysis shows that implementation of AKI care bundles in hospitalized patients reduces moderate-severe AKI. This result is mainly driven by studies performed in ICU setting. Lack of data and heterogeneity in study design impede drawing firm conclusions about patient outcomes. Moreover, compliance to AKI care bundles in hospitalized patients is highly variable. Additional research in targeted patient groups at risk for moderate-severe AKI with correct and complete implementation of a feasible, well-tailored AKI care bundle is warranted. (CRD42020207523).


Asunto(s)
Lesión Renal Aguda/terapia , Paquetes de Atención al Paciente , Hospitalización , Humanos , Riñón , Resultado del Tratamiento
8.
J Cell Physiol ; 235(10): 6725-6735, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32056205

RESUMEN

The imbalance between food intake and energy expenditure causes high accumulation of triglycerides in adipocytes. Obesity is related with the increased lipid accumulation in white adipose tissue, which is a major risk factor for the development of metabolic disorders, such as type 2 diabetes and cardiovascular disease. This study highlights the role of E1A-like inhibitor of differentiation 1 (EID1) in the modulation of adipogenesis through the downregulation of glycerol-3-phosphate dehydrogenase (GPDH), which is a key enzyme in the synthesis of triglycerides and is considered to be a marker of adipogenesis. By analyzing DNA microarray data, we found that when EID1 is overexpressed in preadipocytes (3T3-L1 cells) during adipocyte differentiation, EID1 inhibits lipid accumulation through the downregulation of GPDH. In contrast, EID1 is not involved in the regulation of intracellular glucose via the translocation of glucose transporter. A confocal image analysis showed that EID1 is located in the nucleus of preadipocytes in the form of speckles, which could be involved as a regulator of the transcriptional process. We further confirmed that EID1 is able to bind to the promoter sequence of GPDH in the nucleus. These findings provide a molecular explanation for the inhibitory effect of EID1 on lipid accumulation in adipocytes.


Asunto(s)
Glicerolfosfato Deshidrogenasa/metabolismo , Metabolismo de los Lípidos/fisiología , Proteínas Nucleares/metabolismo , Proteínas Represoras/metabolismo , Células 3T3-L1 , Adipocitos/metabolismo , Adipogénesis/fisiología , Tejido Adiposo Blanco/metabolismo , Animales , Diferenciación Celular/fisiología , Línea Celular , Núcleo Celular/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Regulación hacia Abajo/fisiología , Glucosa/metabolismo , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Ratones , Obesidad/metabolismo , Regiones Promotoras Genéticas/genética , Triglicéridos/metabolismo
9.
Malar J ; 18(1): 129, 2019 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-30971233

RESUMEN

BACKGROUND: Avian haemosporidia are obligate blood parasites with an ample range of hosts worldwide. To understand how host communities may influence the diversity of parasites of the neotropics, the spatial genetic variation of avian Plasmodium, Haemoproteus, and Leucocytozoon was examined between areas of host endemism and along the elevational gradient in the tropical Andes. METHODS: A total of 1686 accessions of the cytochrome b gene of avian haemosporidia were selected from 43 publications, that further provides additional information on 14.2% of bird species in the Neotropics. Haplotype groups were identified using a similarity-based clustering of sequences using a cut-off level ≥ 99.3% of sequence identity. Phylogenetic-based analyses were implemented to examine the spatial genetic structure of avian haemosporidia among areas of host endemism and the elevation gradient in the tropical Andes. RESULTS: The areas of avian endemism, including the tropical Andes, can explain the differential distribution of the haemosporidia cytochrome b gene variation. In the tropical Andes region, the total number of avian haemosporidia haplotypes follows a unimodal pattern that peaks at mid-elevation between 2000 and 2500 m above sea level. Furthermore, the haplotype assemblages of obligate blood parasites tend to overlap towards mid-elevation, where avian host diversity tends to be maximized. CONCLUSIONS: Spatial analyses revealed that richness and turnover in haemosporidia suggest an association with montane host diversity, according to elevation in the tropical Andes. In addition, the spatial distribution of haemosporidia diversity is closely associated with patterns of host assemblages over large geographical scale in the tropical Andes and areas of avian endemism nearby.


Asunto(s)
Aves , Variación Genética , Haemosporida/genética , Malaria Aviar/genética , Altitud , Animales , Biota , Plasmodium/genética , América del Sur
10.
Neurourol Urodyn ; 38(1): 151-157, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30387530

RESUMEN

AIMS: To characterize levator ani muscle (LAM) activity in nulligravidas using magnetomyography (MMG) and define MMG characteristics associated with LAM activity with and without accessory muscle contributions. METHODS: MMG data were collected from eight nulligravidas during rest and voluntary LAM contractions (Kegels) of varying intensity. We utilized simultaneous vaginal manometry and surface electromyography (sEMG) to evaluate for accessory muscle recruitment. Moderate Kegel (MK) MMG trials were sub-selected based on the presence or absence of accessory muscle interaction. Amplitude and spectral-related indicators were calculated across MK epochs: root-mean square (RMS) amplitude, percentage amplitude relative to rest, and relative power spectrum density (rPSD) in three frequency bands (low, middle, high). Ternary diagram characterized rPSD from selected Kegels and ROC analysis was performed to identify cut-points to differentiate MKs from interacting MKs. RESULTS: Nineteen MMG recordings were obtained. Amplitude and spectral parameters were significantly different between isolated and interacting MK epochs. Mean RMS and power values of the isolated MK were, respectively, 120.66 ± 43.8 fT and 1.72 ± 1.44 (T2 /Hz)*10-28 . Amplitudes of MK were 64% and 117 higher than baseline activities for the isolated and interacting epochs, respectively. ROC curves reveled cut-off points on low and middle frequency bands that achieved perfect separation (ROC-AUC = 1.0) between isolated and interacting MK. CONCLUSIONS: Our study demonstrates that MMG, a novel biomagnetic technique, allows precise detection and characterization of normal female pelvic floor function. Results show that isolated moderate voluntary contraction of the LAMs produces distinct MMG amplitude and spectral characteristics compared with Kegels involving co-activation of other muscle groups.


Asunto(s)
Electromiografía/métodos , Diafragma Pélvico/fisiología , Adulto , Estudios de Cohortes , Femenino , Voluntarios Sanos , Humanos , Campos Magnéticos , Manometría , Contracción Muscular , Músculo Esquelético/fisiología , Curva ROC , Vagina/fisiología
12.
Pediatr Crit Care Med ; 20(1): 27-37, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30395106

RESUMEN

OBJECTIVES: Examine the relationship between perioperative renal regional tissue oximetry, urinary biomarkers, and acute kidney injury in infants after congenital cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, observational. SETTING: Cardiac operating room and cardiac ICU. PATIENTS: Neonates and infants without history of kidney injury or anatomic renal abnormality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Renal regional tissue oximetry was measured intraoperatively and for 48 hours postoperatively. Urinary levels of neutrophil gelatinase-associated lipocalin and tissue inhibitor of metalloproteinases 2 together with insulin-like growth factor-binding protein 7 were measured preoperatively, 2, 12, and 24 hours postoperatively. Patients were categorized as no acute kidney injury, stage 1, or Stage 2-3 acute kidney injury using the Kidney Disease: Improving Global Outcomes criteria with 43 of 70 (61%) meeting criteria for any stage acute kidney injury. Stage 2-3 acute kidney injury patients had higher tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7 at 2 hours (0.3 vs 0.14 for stage 1 acute kidney injury and 0.05 for no acute kidney injury; p = 0.052) and 24 hours postoperatively (1.71 vs 0.27 for stage 1 acute kidney injury and 0.19 for no acute kidney injury, p = 0.027) and higher neutrophil gelatinase-associated lipocalin levels at 24 hours postoperatively (10.3 vs 3.4 for stage 1 acute kidney injury and 6.2 for no acute kidney injury, p = 0.019). Stage 2-3 acute kidney injury patients had lower mean cardiac ICU renal regional tissue oximetry (66% vs 79% for stage 1 acute kidney injury and 84% for no acute kidney injury, p = 0.038). Regression analyses showed that tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7 at 2 hours postoperatively and nadir intraoperative renal regional tissue oximetry to be independent predictors of postoperative kidney damage as measured by urinary neutrophil gelatinase-associated lipocalin. CONCLUSIONS: We observed modest differences in perioperative renal regional tissue oximetry and urinary biomarker levels compared between acute kidney injury groups classified by creatinine-dependent Kidney Disease: Improving Global Outcomes criteria, but there were significant correlations between renal regional tissue oximetry, tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7, and postoperative neutrophil gelatinase-associated lipocalin levels. Kidney injury after infant cardiac surgery may be undetectable by functional assessment (creatinine) alone, and continuous monitoring of renal regional tissue oximetry may be more sensitive to important subclinical acute kidney injury.


Asunto(s)
Lesión Renal Aguda/fisiopatología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Creatinina/sangre , Cardiopatías Congénitas/cirugía , Complicaciones Posoperatorias/fisiopatología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/orina , Biomarcadores , Femenino , Humanos , Lactante , Recién Nacido , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Lipocalina 2/orina , Masculino , Oximetría , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/orina , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Espectroscopía Infrarroja Corta , Inhibidor Tisular de Metaloproteinasa-2/orina
13.
Endocr J ; 66(2): 115-125, 2019 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-30606913

RESUMEN

Adipose tissue harbors plasticity to adapt to environmental thermal changes. While brown adipocyte is a thermogenic cell which produces heat acutely in response to cold stimuli, beige (or brite) adipocyte is an inducible form of thermogenic adipocytes which emerges in the white adipose depots in response to chronic cold exposure. Such adaptability of adipocytes is regulated by epigenetic mechanisms. Among them, histone methylation is chemically stable and thus is an appropriate epigenetic mark for mediating cellular memory to induce and maintain the beige adipocyte characteristics. The enzymes that catalyze the methylation or demethylation of H3K27 and H3K9 regulate brown adipocyte biogenesis through their catalytic activity-dependent and -independent mechanisms. Resolving the bivalency of H3K4me3 and H3K27me3 as well as "opening" the chromatin structure by demethylation of H3K9 both mediate beige adipogenesis. In addition, it is recently reported that maintenance of beige adipocyte, beige-to-white transition, and cellular memory of prior cold exposure in beige adipocyte are also regulated by histone methylation. A further understanding of the epigenetic mechanism of beige adipocyte biogenesis would unravel the mechanism of the cellular memory of environmental stimuli and provide a novel therapeutics for the metabolic disorders such as obesity and diabetes that are influenced by environmental factors.


Asunto(s)
Adipocitos Beige/metabolismo , Adipogénesis/fisiología , Metilación de ADN , Histonas/metabolismo , Animales , Epigénesis Genética , Humanos , Termogénesis/fisiología
14.
Proc Natl Acad Sci U S A ; 113(2): 398-403, 2016 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-26712012

RESUMEN

Plasmodium falciparum and Toxoplasma gondii are widely studied parasites in phylum Apicomplexa and the etiological agents of severe human malaria and toxoplasmosis, respectively. These intracellular pathogens have evolved a sophisticated invasion strategy that relies on delivery of proteins into the host cell, where parasite-derived rhoptry neck protein 2 (RON2) family members localize to the host outer membrane and serve as ligands for apical membrane antigen (AMA) family surface proteins displayed on the parasite. Recently, we showed that T. gondii harbors a novel AMA designated as TgAMA4 that shows extreme sequence divergence from all characterized AMA family members. Here we show that sporozoite-expressed TgAMA4 clusters in a distinct phylogenetic clade with Plasmodium merozoite apical erythrocyte-binding ligand (MAEBL) proteins and forms a high-affinity, functional complex with its coevolved partner, TgRON2L1. High-resolution crystal structures of TgAMA4 in the apo and TgRON2L1-bound forms complemented with alanine scanning mutagenesis data reveal an unexpected architecture and assembly mechanism relative to previously characterized AMA-RON2 complexes. Principally, TgAMA4 lacks both a deep surface groove and a key surface loop that have been established to govern RON2 ligand binding selectivity in other AMAs. Our study reveals a previously underappreciated level of molecular diversity at the parasite-host-cell interface and offers intriguing insight into the adaptation strategies underlying sporozoite invasion. Moreover, our data offer the potential for improved design of neutralizing therapeutics targeting a broad range of AMA-RON2 pairs and apicomplexan invasive stages.


Asunto(s)
Interacciones Huésped-Parásitos , Parásitos/fisiología , Proteínas Protozoarias/metabolismo , Toxoplasma/metabolismo , Animales , Ratones , Modelos Moleculares , Filogenia , Unión Proteica , Proteínas Protozoarias/química
15.
J Obstet Gynaecol Res ; 45(10): 1989-1996, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31297963

RESUMEN

AIM: Pregnant women undergoing treatment for opioid use disorder (OUD) may be exposed to multiple QT prolonging agents. We used magnetocardiography to measure fetal QT intervals in mothers with OUD on buprenorphine therapy. METHODS: Fetal and maternal magnetocardiography was performed in pregnant women receiving buprenorphine-assisted treatment (Disorder group); these were matched by gestational age to pregnant women who were opiate naïve (Reference group). Corrected QT intervals were determined using Bazett's formula and compared between groups. RESULTS: A total of eight women in the Disorder group matched to eight in the Reference group. Seven of the mothers (88%) in the Disorder group were smokers; there were no smokers in the Reference group. The average fetal corrected QT was significantly longer (P = 0.022) in the Disorder group than that in the Reference group (505 milliseconds [ms] ± 68.6 [standard deviation] vs 383 ms ± 70.3 [standard deviation]). CONCLUSION: Novel data from this small sample demonstrate prolongation of fetal corrected QT in women with OUD participating in buprenorphine assisted therapy. Additional investigation from a larger sample is needed to clarify if fetal buprenorphine and/or tobacco exposure is associated with changes in fetal QT which would warrant further prenatal and postnatal testing.


Asunto(s)
Buprenorfina/efectos adversos , Corazón Fetal/efectos de los fármacos , Antagonistas de Narcóticos/efectos adversos , Tratamiento de Sustitución de Opiáceos/efectos adversos , Adulto , Estudios de Cohortes , Femenino , Humanos , Magnetocardiografía , Trastornos Relacionados con Opioides/tratamiento farmacológico , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Adulto Joven
16.
Bull Environ Contam Toxicol ; 102(4): 538-543, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30868178

RESUMEN

The karstic aquifer of Yucatan features a high permeability, therefore, all contaminants placed in the soil surface, can reach it through infiltration along with the rain water. The purpose of the present study is to determine the spatial distribution of the aromatic hydrocarbons in the underground water of Merida City. Fifty wells inside the city were sampled. The sampling took place during the dry season, from October 2007 to March 2008. Liquid-liquid Hydrocarbon extraction was performed using hexane and purification was made by previously packed chromatography columns. Regarding the occurrence of polynuclear aromatic hydrocarbon (PAHs) traces, 28 water samples (56%) contained residues of these compounds. The following PAHs presented the highest concentrations: benzo(a)anthracene y benzo(k)fluoranthene 13.26 and 7.88 µg L-1 respectively. Only three of the sampled wells showed levels above those allowed by EPA and WHO norms. The origin of these compounds is mainly pyrogenic.


Asunto(s)
Agua Subterránea/química , Hidrocarburos Policíclicos Aromáticos/química , Ciudades , México , Lluvia , Estaciones del Año , Suelo/química , Contaminantes del Suelo/química
17.
Prenat Diagn ; 37(2): 193-196, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27891637

RESUMEN

Fetal magnetocardiography provides the requisite precision for diagnostic measurement of electrophysiological events in the fetal heart. Despite its significant benefits, this technique with current cryogenic based sensors has been limited to few centers, due to high cost of maintenance. In this study, we show that a less expensive non-cryogenic alternative, optically pumped magnetometers, can provide similar electrophysiological and quantitative characteristics when subjected to direct comparison with the current technology. Further research can potentially increase its clinical use for fetal magnetocardiography. © 2016 John Wiley & Sons, Ltd.


Asunto(s)
Corazón Fetal/diagnóstico por imagen , Magnetocardiografía/instrumentación , Magnetocardiografía/métodos , Diagnóstico Prenatal , Análisis Costo-Beneficio , Estudios de Factibilidad , Femenino , Humanos , Magnetocardiografía/economía , Magnetometría/economía , Magnetometría/instrumentación , Magnetometría/métodos , Óptica y Fotónica/instrumentación , Embarazo , Tercer Trimestre del Embarazo , Diagnóstico Prenatal/economía , Diagnóstico Prenatal/instrumentación , Diagnóstico Prenatal/métodos
18.
J Environ Qual ; 44(2): 668-75, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26023984

RESUMEN

Agricultural activities have heavily altered the nitrogen (N) cycle in stream ecosystems draining croplands, particularly in the midwestern United States. However, our knowledge about dissolved organic N (DON) biogeochemistry in agricultural ecosystems is limited. From January 2011 to June 2012, we investigated DON dynamics in an agricultural headwater stream in the midwestern United States. We quantified the contribution of DON to the total dissolved N (TDN) pool and examined the role of DON as a source of N for microbial metabolism. For this we measured N-acquiring enzyme activities (aminopeptidases) and whole-stream DON uptake through short-term releases of amino acids. To investigate potential coupling between the N and C cycles occurring via simultaneous uptake of these two elements during assimilation of amino acids, seven of the short-term releases were performed concurrently with acetate. We found minimal contribution of DON to the TDN pool in this stream as a result of high concentrations of nitrate. Acetate uptake suggested that C was a limiting factor for microbial metabolism in this stream. In contrast, we were not able to detect amino acid uptake during any of the 13 short-term releases we conducted, likely as a result of high availability of dissolved inorganic N. Aminopeptidase (AMP) activity did not reflect N demand. Large spatial variability in AMP was observed within and among sites, possibly as result of physicochemical characteristics of the sediments. In contrast to other human-dominated streams, DON appeared to play a minor role in microbial metabolic processes and contributed minimally to the N pool of the study stream.

19.
Environ Monit Assess ; 187(1): 4208, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25504195

RESUMEN

Traditional sampling methods for dissolved organic matter (DOM) in streams limit opportunities for long-term studies due to time and cost constraints. Passive DOM samplers were constructed following a design proposed previously which utilizes diethylaminoethyl (DEAE) cellulose as a sampling medium, and they were deployed throughout a temperate stream network in Indiana. Two deployments of the passive samplers were conducted, during which grab samples were frequently collected for comparison. Differences in DOM quality between sites and sampling methods were assessed using several common optical analyses. The analyses revealed significant differences in optical properties between sampling methods, with the passive samplers preferentially collecting terrestrial, humic-like DOM. We assert that the differences in DOM composition from each sampling method were caused by preferential binding of complex humic compounds to the DEAE cellulose in the passive samplers. Nonetheless, the passive samplers may provide a cost-effective, integrated sample of DOM in situations where the bulk DOM pool is composed mainly of terrestrial, humic-like compounds.


Asunto(s)
Monitoreo del Ambiente/instrumentación , Sustancias Húmicas/análisis , Ríos/química , Contaminantes del Agua/análisis , Celulosa/análisis , Ambiente , Monitoreo del Ambiente/métodos , Indiana
20.
ScientificWorldJournal ; 2014: 524367, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24757424

RESUMEN

We study the use of nonparametric multicompare statistical tests on the performance of simulated annealing (SA), genetic algorithm (GA), particle swarm optimization (PSO), and differential evolution (DE), when used for electroencephalographic (EEG) source localization. Such task can be posed as an optimization problem for which the referred metaheuristic methods are well suited. Hence, we evaluate the localization's performance in terms of metaheuristics' operational parameters and for a fixed number of evaluations of the objective function. In this way, we are able to link the efficiency of the metaheuristics with a common measure of computational cost. Our results did not show significant differences in the metaheuristics' performance for the case of single source localization. In case of localizing two correlated sources, we found that PSO (ring and tree topologies) and DE performed the worst, then they should not be considered in large-scale EEG source localization problems. Overall, the multicompare tests allowed to demonstrate the little effect that the selection of a particular metaheuristic and the variations in their operational parameters have in this optimization problem.


Asunto(s)
Algoritmos , Electroencefalografía/métodos , Cómputos Matemáticos , Simulación por Computador
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA