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1.
Nature ; 600(7889): 553-558, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34695838

RESUMEN

The voltage-dependent motor protein prestin (also known as SLC26A5) is responsible for the electromotive behaviour of outer-hair cells and underlies the cochlear amplifier1. Knockout or impairment of prestin causes severe hearing loss2-5. Despite the key role of prestin in hearing, the mechanism by which mammalian prestin senses voltage and transduces it into cellular-scale movements (electromotility) is poorly understood. Here we determined the structure of dolphin prestin in six distinct states using single-particle cryo-electron microscopy. Our structural and functional data suggest that prestin adopts a unique and complex set of states, tunable by the identity of bound anions (Cl- or SO42-). Salicylate, a drug that can cause reversible hearing loss, competes for the anion-binding site of prestin, and inhibits its function by immobilizing prestin in a new conformation. Our data suggest that the bound anion together with its coordinating charged residues and helical dipole act as a dynamic voltage sensor. An analysis of all of the anion-dependent conformations reveals how structural rearrangements in the voltage sensor are coupled to conformational transitions at the protein-membrane interface, suggesting a previously undescribed mechanism of area expansion. Visualization of the electromotility cycle of prestin distinguishes the protein from the closely related SLC26 anion transporters, highlighting the basis for evolutionary specialization of the mammalian cochlear amplifier at a high resolution.


Asunto(s)
Proteínas de Transporte de Anión , Células Ciliadas Auditivas Externas , Animales , Proteínas de Transporte de Anión/metabolismo , Aniones/metabolismo , Microscopía por Crioelectrón , Células Ciliadas Auditivas Externas/metabolismo , Mamíferos/metabolismo , Proteínas/metabolismo , Transportadores de Sulfato/metabolismo
2.
Nature ; 583(7814): 145-149, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32461693

RESUMEN

Voltage-gated potassium (Kv) channels coordinate electrical signalling and control cell volume by gating in response to membrane depolarization or hyperpolarization. However, although voltage-sensing domains transduce transmembrane electric field changes by a common mechanism involving the outward or inward translocation of gating charges1-3, the general determinants of channel gating polarity remain poorly understood4. Here we suggest a molecular mechanism for electromechanical coupling and gating polarity in non-domain-swapped Kv channels on the basis of the cryo-electron microscopy structure of KAT1, the hyperpolarization-activated Kv channel from Arabidopsis thaliana. KAT1 displays a depolarized voltage sensor, which interacts with a closed pore domain directly via two interfaces and indirectly via an intercalated phospholipid. Functional evaluation of KAT1 structure-guided mutants at the sensor-pore interfaces suggests a mechanism in which direct interaction between the sensor and the C-linker hairpin in the adjacent pore subunit is the primary determinant of gating polarity. We suggest that an inward motion of the S4 sensor helix of approximately 5-7 Å can underlie a direct-coupling mechanism, driving a conformational reorientation of the C-linker and ultimately opening the activation gate formed by the S6 intracellular bundle. This direct-coupling mechanism contrasts with allosteric mechanisms proposed for hyperpolarization-activated cyclic nucleotide-gated channels5, and may represent an unexpected link between depolarization- and hyperpolarization-activated channels.


Asunto(s)
Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Arabidopsis , Microscopía por Crioelectrón , Activación del Canal Iónico , Canales de Potasio de Rectificación Interna/química , Canales de Potasio de Rectificación Interna/metabolismo , Regulación Alostérica , Arabidopsis/química , Arabidopsis/ultraestructura , Proteínas de Arabidopsis/ultraestructura , Sitios de Unión , Lípidos , Modelos Moleculares , Canales de Potasio de Rectificación Interna/ultraestructura , Conformación Proteica
3.
Biochem Biophys Res Commun ; 586: 107-113, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34837834

RESUMEN

The Rad, Rem, Rem2, and Gem/Kir (RGK) sub-family of small GTP-binding proteins are crucial in regulating high voltage-activated (HVA) calcium channels. RGK proteins inhibit calcium current by either promoting endocytosis or reducing channel activity. They all can associate directly with Ca2+ channel ß subunit (CaVß), and the binding between CaVα1/CaVß appears essential for the endocytic promotion of CaV1.X, CaV2.1, and CaV2.2 channels. In this study, we investigated the inhibition of CaV2.3 channels by RGK proteins in the absence of CaVß. To this end, Xenopus laevis oocytes expressing CaV2.3 channels devoid of auxiliary subunit were injected with purified Gem and Rem and found that only Gem had an effect. Ca currents and charge movements were reduced by injection of Gem, pointing to a reduction in the number of channels in the plasma membrane. Since this reduction was ablated by co-expression of the dominant-negative mutant of dynamin K44A, enhanced endocytosis appears to mediate this reduction in the number of channels. Thus, Gem inhibition of CaV2.3 channels would be the only example of a CaVß independent promotion of dynamin-dependent endocytosis.


Asunto(s)
Potenciales de Acción/fisiología , Canales de Calcio Tipo R/genética , Proteínas de Transporte de Catión/genética , Dinaminas/genética , Proteínas de Unión al GTP Monoméricas/genética , Sustitución de Aminoácidos , Animales , Canales de Calcio Tipo R/metabolismo , Proteínas de Transporte de Catión/metabolismo , Dinaminas/metabolismo , Endocitosis/genética , Femenino , Expresión Génica , Humanos , Proteínas de Unión al GTP Monoméricas/metabolismo , Mutación , Oocitos/citología , Oocitos/metabolismo , Técnicas de Placa-Clamp , Plásmidos/química , Plásmidos/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transfección , Transgenes , Xenopus laevis
4.
Curr Opin Organ Transplant ; 27(4): 243-249, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-36354249

RESUMEN

PURPOSE OF REVIEW: Human cytomegalovirus (CMV) infection is one of the most important infectious complications in solid organ transplant (SOT) recipients, leading to significant morbidity and mortality. Therefore, early detection and prompt treatment are imperative to improve transplant outcomes. This article highlights the clinical characteristics of the most common CMV end-organ diseases in SOT recipients and their diagnostic modalities and challenges. RECENT FINDINGS: CMV can cause a variety of end-organ diseases in SOT recipients. Although CMV nucleic acid amplification by polymerase chain reaction (PCR) is frequently employed to detect CMV reactivation or infection, its predictive value for various CMV end-organ diseases remains uncertain. Given the limitation of PCR or other noninvasive tests, confirmation of CMV end-organ disease may require tissue biopsy, which may not be feasible or available, or may cause untoward complications. SUMMARY: The utility of PCR to diagnose CMV end-organ disease is limited. As CMV can infect any organ system(s), clinicians caring for SOT recipients need to maintain vigilance for any signs and symptoms of end-organ disease to allow early recognition and prompt treatment. Invasive procedures might be needed to confirm the diagnosis and minimize the empirical use of antiviral therapy that may have substantial drug toxicities.


Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Órganos , Humanos , Citomegalovirus/genética , Trasplante de Órganos/efectos adversos , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/tratamiento farmacológico , Receptores de Trasplantes
5.
Proc Natl Acad Sci U S A ; 112(15): 4809-14, 2015 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-25825713

RESUMEN

Being activated by depolarizing voltages and increases in cytoplasmic Ca(2+), voltage- and calcium-activated potassium (BK) channels and their modulatory ß-subunits are able to dampen or stop excitatory stimuli in a wide range of cellular types, including both neuronal and nonneuronal tissues. Minimal alterations in BK channel function may contribute to the pathophysiology of several diseases, including hypertension, asthma, cancer, epilepsy, and diabetes. Several gating processes, allosterically coupled to each other, control BK channel activity and are potential targets for regulation by auxiliary ß-subunits that are expressed together with the α (BK)-subunit in almost every tissue type where they are found. By measuring gating currents in BK channels coexpressed with chimeras between ß1 and ß3 or ß2 auxiliary subunits, we were able to identify that the cytoplasmic regions of ß1 are responsible for the modulation of the voltage sensors. In addition, we narrowed down the structural determinants to the N terminus of ß1, which contains two lysine residues (i.e., K3 and K4), which upon substitution virtually abolished the effects of ß1 on charge movement. The mechanism by which K3 and K4 stabilize the voltage sensor is not electrostatic but specific, and the α (BK)-residues involved remain to be identified. This is the first report, to our knowledge, where the regulatory effects of the ß1-subunit have been clearly assigned to a particular segment, with two pivotal amino acids being responsible for this modulation.


Asunto(s)
Calcio/metabolismo , Activación del Canal Iónico/fisiología , Subunidades beta de los Canales de Potasio de Gran Conductancia Activados por el Calcio/fisiología , Potasio/metabolismo , Animales , Sitios de Unión/genética , Femenino , Humanos , Activación del Canal Iónico/genética , Subunidades beta de los Canales de Potasio de Gran Conductancia Activados por el Calcio/química , Subunidades beta de los Canales de Potasio de Gran Conductancia Activados por el Calcio/genética , Lisina/química , Lisina/genética , Lisina/fisiología , Potenciales de la Membrana/genética , Potenciales de la Membrana/fisiología , Modelos Moleculares , Mutación , Oocitos/metabolismo , Oocitos/fisiología , Estructura Terciaria de Proteína , Subunidades de Proteína/química , Subunidades de Proteína/genética , Subunidades de Proteína/fisiología , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Xenopus laevis
6.
Pharmacol Res ; 101: 56-64, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26305431

RESUMEN

Voltage-gated ion channels are the molecular determinants of cellular excitability. This group of ion channels is one of the most important pharmacological targets in excitable tissues such as nervous system, cardiac and skeletal muscle. Moreover, voltage-gated ion channels are expressed in non-excitable cells, where they mediate key cellular functions through intracellular biochemical mechanisms rather than rapid electrical signaling. This review aims at illustrating the pharmacological impact of these ion channels, highlighting in particular the structural details and physiological functions of two of them - the high conductance voltage- and Ca(2+)-gated K(+) (BK) channels and voltage-gated proton (Hv1) channels- in non-excitable cells. BK channels have been implicated in a variety of physiological processes ranging from regulation of smooth muscle tone to modulation of hormone and neurotransmitter release. Interestingly, BK channels are also involved in modulating K(+) transport in the mammalian kidney and colon epithelium with a potential role in the hyperkalemic phenotype observed in patients with familial hyperkalemic hypertension type 2, and in the pathophysiology of hypertension. In addition, BK channels are responsible for resting and stimulated Ca(2+)-activated K(+) secretion in the distal colon. Hv1 channels have been detected in many cell types, including macrophages, blood cells, lung epithelia, skeletal muscle and microglia. These channels have a central role in the phagocytic system. In macrophages, Hv1 channels participate in the generation of reactive oxygen species in the respiratory burst during the process of phagocytosis.


Asunto(s)
Canales Iónicos/fisiología , Canales de Potasio de Gran Conductancia Activados por el Calcio/fisiología , Quimioterapia , Humanos , Canales Iónicos/química , Canales Iónicos/efectos de los fármacos , Canales de Potasio de Gran Conductancia Activados por el Calcio/química , Canales de Potasio de Gran Conductancia Activados por el Calcio/efectos de los fármacos , Modelos Biológicos , Modelos Moleculares , Terapia Molecular Dirigida
7.
Proc Natl Acad Sci U S A ; 109(46): 18991-6, 2012 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-23112204

RESUMEN

Calcium- and voltage-activated potassium channels (BK) are regulated by a multiplicity of signals. The prevailing view is that different BK gating mechanisms converge to determine channel opening and that these gating mechanisms are allosterically coupled. In most instances the pore forming α subunit of BK is associated with one of four alternative ß subunits that appear to target specific gating mechanisms to regulate the channel activity. In particular, ß1 stabilizes the active configuration of the BK voltage sensor having a large effect on BK Ca(2+) sensitivity. To determine the extent to which ß subunits regulate the BK voltage sensor, we measured gating currents induced by the pore-forming BK α subunit alone and with the different ß subunits expressed in Xenopus oocytes (ß1, ß2IR, ß3b, and ß4). We found that ß1, ß2, and ß4 stabilize the BK voltage sensor in the active conformation. ß3 has no effect on voltage sensor equilibrium. In addition, ß4 decreases the apparent number of charges per voltage sensor. The decrease in the charge associated with the voltage sensor in α ß4 channels explains most of their biophysical properties. For channels composed of the α subunit alone, gating charge increases slowly with pulse duration as expected if a significant fraction of this charge develops with a time course comparable to that of K(+) current activation. In the presence of ß1, ß2, and ß4 this slow component develops in advance of and much more rapidly than ion current activation, suggesting that BK channel opening proceeds in two steps.


Asunto(s)
Activación del Canal Iónico/fisiología , Canales de Potasio de Gran Conductancia Activados por el Calcio/metabolismo , Subunidades de Proteína/metabolismo , Regulación Alostérica/fisiología , Animales , Calcio/metabolismo , Humanos , Canales de Potasio de Gran Conductancia Activados por el Calcio/genética , Oocitos/citología , Oocitos/metabolismo , Potasio/metabolismo , Subunidades de Proteína/genética , Xenopus laevis
8.
Gac Med Mex ; 150 Suppl 3: 306-10, 2014 Dec.
Artículo en Español | MEDLINE | ID: mdl-25643881

RESUMEN

BACKGROUND: Endovascular aneurysm repair (EVAR) generally is not recommend for patients with unfavorable neck anatomy. This study examines the short-term results according to the characteristics of the proximal aortic neck treated with EVAR. METHODS: Between December 2010 and January 2013, 21 patients were treated with EVAR. Patients were classified as those with favorable neck anatomy (FNA) and hostile neck anatomy (HNA). The parameters for HNA were considered as one or more of the following criteria: neck length < 15 mm, angle > 60°, diameter > 28 mm, ≥ 50% of thrombus in the proximal neck circumference, inverted tapered neck. Clinical and demographic characteristics were compared within the short-term (30 days). RESULTS: A total of 47.7% of the stents were placed in FNA. Perioperative complications were vascular injury and bleeding, which occurred at the same frequency in both groups, and postoperative complications were acute renal failure and pulmonary complications in both groups. The mortality rate was 0% FNA vs. 20% ANA. Intraoperative type I endoleaks occurred in FNA in one case (9%) and HNA in two cases (20%). The cuffs were used in the FNA endoleak and in a HNA case and the other case was treated by angioplasty over dilatation subsequently presenting early endoleak. CONCLUSIONS: Patients presenting a hostile neck are at increased risk of complications related to endoleaks and second interventions, so close monitoring of these patients should be maintained. However, no incidence of open surgical conversion, rupture, or death related to aortic aneurysm was seen. This being so, it is possible to treat these patients with challenging aortic characteristics. Increased vigilance in these patients should be considered.

9.
Infect Control Hosp Epidemiol ; 45(2): 241-243, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37746805

RESUMEN

We used a strand-specific RT-qPCR to evaluate viral replication as a surrogate for infectiousness among 242 asymptomatic inpatients with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) admission test. Only 21 patients (9%) had detectable SARS-CoV-2 minus-strand RNA. Because most patients were found to be noninfectious, our findings support the suspension of asymptomatic admission testing.


Asunto(s)
COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/epidemiología , SARS-CoV-2/genética , Prueba de COVID-19 , Centros de Atención Terciaria , Técnicas de Laboratorio Clínico , ARN Viral/genética
10.
Viruses ; 15(2)2023 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-36851544

RESUMEN

Human adenoviruses (HAdV) are one of the most important pathogens detected in acute respiratory diseases in pediatrics and immunocompromised patients. In 1953, Wallace Rowe described it for the first time in oropharyngeal lymphatic tissue. To date, more than 110 types of HAdV have been described, with different cellular tropisms. They can cause respiratory and gastrointestinal symptoms, even urinary tract inflammation, although most infections are asymptomatic. However, there is a population at risk that can develop serious and even lethal conditions. These viruses have a double-stranded DNA genome, 25-48 kbp, 90 nm in diameter, without a mantle, are stable in the environment, and resistant to fat-soluble detergents. Currently the diagnosis is made with lateral flow immunochromatography or molecular biology through a polymerase chain reaction. This review aimed to highlight the HAdV variability and the pandemic potential that a HAdV3 and 7 recombinant could have considering the aggressive outbreaks produced in health facilities. Herein, we described the characteristics of HAdV, from the infection to treatment, vaccine development, and the evaluation of the social determinants of health associated with HAdV, suggesting the necessary measures for future sanitary control to prevent disasters such as the SARS-CoV-2 pandemic, with an emphasis on the use of recombinant AdV vaccines to control other potential pandemics.


Asunto(s)
Adenovirus Humanos , COVID-19 , Humanos , Niño , Adenoviridae , Pandemias/prevención & control , Amigos , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2/genética , Adenovirus Humanos/genética
11.
Infect Control Hosp Epidemiol ; 44(12): 2078-2080, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37381726

RESUMEN

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) real-time reverse-transcription polymerase chain reaction (rRT-PCR) strand-specific assay can be used to identify active SARS-CoV-2 viral replication. We describe the characteristics of 337 hospitalized patients with at least 1 minus-strand SARS-CoV-2 assay performed >20 days after illness onset. This test is a novel tool to identify high-risk hospitalized patients with prolonged SARS-CoV-2 replication.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Replicación Viral , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
12.
Life (Basel) ; 12(4)2022 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-35455024

RESUMEN

In December 2019, a case of atypical pneumonia was reported in Wuhan, China. It was named COVID-19 and caused by SARS-CoV-2. In a few months, scientific groups around the world developed vaccines to reduce the disease's severity. The objective was to evaluate the humoral and cellular immune response post immunization with three different vaccination schedules administered in Chile until January 2022. Sixty volunteers were recruited with a three-dose schedule, who had no history of infection nor close contact with a positive patient. IgG against the spike antigenic domain was detected, and the neutralization capacity against two groups of variants, Original/Alpha and Beta/Gamma, was also measured. Finally, the cellular response with interferon release was measured through IGRA. Results showed that there were significant differences in the neutralizing antibodies for the original and alpha variant when comparing three Comirnaty doses with Coronavac and Vaxzevria. A high number of reactive subjects against the different SARS-CoV-2 variants, alpha, gamma, and delta, were observed, with no significant differences between any of the three schemes, confirming the existence of a cellular immune response against SARS-CoV-2. In conclusion, the three vaccine schemes generated a cellular immune response in these volunteers.

13.
Rev Chilena Infectol ; 38(2): 144-151, 2021 04.
Artículo en Español | MEDLINE | ID: mdl-34184703

RESUMEN

BACKGROUND: The SARS-CoV-2 outbreak originated in the Hubei province in China spread rapidly throughout the world during the first months of 2020. On March 3, the first case was reported in Chile; at 17 days the first case of COVID-19 healthcare worker (HCW) was notified in our institution. AIM: To describe the demographic characteristics and the incidence of SARS-CoV-2 infection in the HCW of a university hospital in Chile. MATERIAL AND METHOD: Retrospective study of SARS-CoV-2 infection on HCW in a university hospital between March 1 and May 31, 2020. RESULTS: There were 273 positive cases. In the period under study, we had an incidence of 5.8%. When we separated the cases into clinical and non-clinical personnel, it was observed that their incidences were practically identical (5.8 vs. 5.7% p = 0.9430). 88% of the officials were oligosymptomatic or asymptomatic at the beginning of the clinical presentation and only 12% had a fever before the medical consultation. CONCLUSION: The incidence reported in the study was around 5 times that reported in Wuhan. If we apply the current definition of cases, we would lose 4 out of 5 cases. 88% of HPW did not present criteria to be considered suspicious, so it would be advisable in HCW to eliminate fever as a criterion to improve the research and trace their contacts on time.


Asunto(s)
COVID-19 , SARS-CoV-2 , Chile/epidemiología , Personal de Salud , Hospitales Universitarios , Humanos , Estudios Retrospectivos
14.
Rev. chil. infectol ; 40(3): 266-269, jun. 2023.
Artículo en Español | LILACS | ID: biblio-1515133

RESUMEN

Desde la segunda mitad de 2022 se ha reportado un aumento de casos de influenza en aves migratorias en Latinoamérica. Los virus influenza A y B son los principales agentes asociados a influenza estacional epidémica en humanos. Los virus influenza A circulan no solo en humanos sino también en animales, incluyendo aves migratorias. El intercambio de segmentos de ARN genómico entre dos virus del mismo tipo aumenta la diversidad de los subtipos circulantes e incluso puede facilitar la generación de progenie viral potencialmente pandémica. La naturaleza zoonótica del virus influenza A puede generar infecciones en humanos con virus de origen animal. El virus influenza A de origen aviar ha ocasionado transmisiones en humanos, incluyendo casos graves y muertes, siendo la influenza A H5N1 la más destacada. Es importante tomar medidas de prevención y control en caso de aumento de casos de influenza en aves migratorias para prevenir posibles pandemias en Chile y el mundo.


Since the second half of 2022, an increase in influenza cases in migratory birds has been reported in Latin America. Influenza A and B viruses are the main agents associated with seasonal epidemic influenza in humans. Influenza A viruses circulate not only in humans but also in animals, including migratory birds. The exchange of genomic RNA segments among two viruses increases the diversity of circulating subtypes and may even facilitate the generation of potentially pandemic viral progeny. The zoonotic nature of influenza A virus can generate infections in humans with animal-origin viruses. Avian-origin influenza A virus has caused transmissions in humans, including severe cases and deaths, with influenza A H5N1 being the most prominent. It is important to take preventive and control measures in case of an increase in influenza cases in migratory birds to prevent possible pandemics in Chile and the world.


Asunto(s)
Humanos , Animales , Gripe Humana/epidemiología , Subtipo H5N1 del Virus de la Influenza A , Gripe Aviar/epidemiología , Aves , Infecciones por Orthomyxoviridae , Gripe Humana/prevención & control , Gripe Humana/transmisión , Pandemias/prevención & control , Gripe Aviar/prevención & control , Gripe Aviar/transmisión
15.
J Gen Physiol ; 150(5): 697-711, 2018 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-29643172

RESUMEN

Mutations in connexin 26 (Cx26) hemichannels can lead to syndromic deafness that affects the cochlea and skin. These mutations lead to gain-of-function hemichannel phenotypes by unknown molecular mechanisms. In this study, we investigate the biophysical properties of the syndromic mutant Cx26G12R (G12R). Unlike wild-type Cx26, G12R macroscopic hemichannel currents do not saturate upon depolarization, and deactivation is faster during hyperpolarization, suggesting that these channels have impaired fast and slow gating. Single G12R hemichannels show a large increase in open probability, and transitions to the subconductance state are rare and short-lived, demonstrating an inoperative fast gating mechanism. Molecular dynamics simulations indicate that G12R causes a displacement of the N terminus toward the cytoplasm, favoring an interaction between R12 in the N terminus and R99 in the intracellular loop. Disruption of this interaction recovers the fast and slow voltage-dependent gating mechanisms. These results suggest that the mechanisms of fast and slow gating in connexin hemichannels are coupled and provide a molecular mechanism for the gain-of-function phenotype displayed by the syndromic G12R mutation.


Asunto(s)
Conexina 26/metabolismo , Sordera/genética , Ictiosis/genética , Activación del Canal Iónico , Queratitis/genética , Mutación Missense , Animales , Conexina 26/química , Conexina 26/genética , Humanos , Simulación de Dinámica Molecular , Xenopus
16.
Rev. chil. infectol ; 38(2): 144-151, abr. 2021. ilus, tab
Artículo en Español | LILACS | ID: biblio-1388224

RESUMEN

INTRODUCCIÓN: El brote de SARS-CoV-2 originado en la provincia de Hubei en la República Popular China, se fue extendiendo aceleradamente en el mundo durante los primeros meses del año 2020. El 3 de marzo se notificó el primer caso en Chile; a los 17 días se notificó el primer caso de un Personal de Salud (PS) COVID-19 en nuestra institución. OBJETIVO: Describir las características demográficas y la incidencia de infección por SARS-CoV-2 en el PS de un hospital universitario de alta complejidad. MATERIAL Y MÉTODO: Estudio retrospectivo de los casos de infección por SARS-CoV-2 del PS entre el 1 de marzo y 31 de mayo de 2020. RESULTADOS: Hubo 273 casos positivos, con una incidencia de 5,8% en el período en estudio. Al dividir los casos en personal clínico y no clínico se observó que sus incidencias fueron prácticamente idénticas (5,8 vs 5,7% p = 0,9430). El 88% de los funcionarios fue oligo-sintomático o asintomático al inicio del cuadro clínico y sólo 12% tuvo fiebre antes de la consulta médica. CONCLUSIÓN: La incidencia reportada en el estudio fue alrededor de cinco veces la reportada en Wuhan. Al aplicar la definición de casos vigente, se perderían cuatro de cada cinco casos. Destaca que 88% del PS no presentaba criterios para ser considerado sospechoso, por lo que sería recomendable en el PS eliminar la fiebre como criterio para mejorar la pesquisa y trazar sus contactos de forma oportuna.


BACKGROUND: The SARS-CoV-2 outbreak originated in the Hubei province in China spread rapidly throughout the world during the first months of 2020. On March 3, the first case was reported in Chile; at 17 days the first case of COVID-19 healthcare worker (HCW) was notified in our institution. AIM: To describe the demographic characteristics and the incidence of SARS-CoV-2 infection in the HCW of a university hospital in Chile. MATERIAL AND METHOD: Retrospective study of SARS-CoV-2 infection on HCW in a university hospital between March 1 and May 31, 2020. RESULTS: There were 273 positive cases. In the period under study, we had an incidence of 5.8%. When we separated the cases into clinical and non-clinical personnel, it was observed that their incidences were practically identical (5.8 vs. 5.7% p = 0.9430). 88% of the officials were oligosymptomatic or asymptomatic at the beginning of the clinical presentation and only 12% had a fever before the medical consultation. CONCLUSION: The incidence reported in the study was around 5 times that reported in Wuhan. If we apply the current definition of cases, we would lose 4 out of 5 cases. 88% of HPW did not present criteria to be considered suspicious, so it would be advisable in HCW to eliminate fever as a criterion to improve the research and trace their contacts on time.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Personal de Salud , COVID-19/epidemiología , Chile/epidemiología , Incidencia , Estudios Retrospectivos , SARS-CoV-2 , Hospitales Universitarios
18.
FEBS Lett ; 589(22): 3471-8, 2015 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-26296320

RESUMEN

The main role of voltage-gated proton channels (Hv1) is to extrude protons from the intracellular milieu when, mediated by different cellular processes, the H(+) concentration increases. Hv1 are exquisitely selective for protons and their structure is homologous to the voltage sensing domain (VSD) of other voltage-gated ion channels like sodium, potassium, and calcium channels. In clear contrast to the classical voltage-dependent channels, Hv1 lacks a pore domain and thus permeation necessarily occurs through the voltage sensing domain. Hv1 channels are activated by depolarizing voltages, and increases in internal proton concentration. It has been proposed that local conformational changes of the transmembrane segment S4, driven by depolarization, trigger the molecular rearrangements that open Hv1. However, it is still unclear how the electromechanical coupling is achieved between the VSD and the potential pore, allowing the proton flux from the intracellular to the extracellular side. Here we provide a revised view of voltage activation in Hv1 channels, offering a comparative scenario with other voltage sensing channels domains.


Asunto(s)
Activación del Canal Iónico , Canales Iónicos/química , Canales Iónicos/metabolismo , Secuencia de Aminoácidos , Animales , Humanos , Datos de Secuencia Molecular , Estructura Terciaria de Proteína
19.
J Gen Physiol ; 145(1): 61-74, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25548136

RESUMEN

Large-conductance Ca(2+)- and voltage-activated K(+) channel (BK) open probability is enhanced by depolarization, increasing Ca(2+) concentration, or both. These stimuli activate modular voltage and Ca(2+) sensors that are allosterically coupled to channel gating. Here, we report a point mutation of a phenylalanine (F380A) in the S6 transmembrane helix that, in the absence of internal Ca(2+), profoundly hinders channel opening while showing only minor effects on the voltage sensor active-resting equilibrium. Interpretation of these results using an allosteric model suggests that the F380A mutation greatly increases the free energy difference between open and closed states and uncouples Ca(2+) binding from voltage sensor activation and voltage sensor activation from channel opening. However, the presence of a bulky and more hydrophobic amino acid in the F380 position (F380W) increases the intrinsic open-closed equilibrium, weakening the coupling between both sensors with the pore domain. Based on these functional experiments and molecular dynamics simulations, we propose that F380 interacts with another S6 hydrophobic residue (L377) in contiguous subunits. This pair forms a hydrophobic ring important in determining the open-closed equilibrium and, like an integration node, participates in the communication between sensors and between the sensors and pore. Moreover, because of its effects on open probabilities, the F380A mutant can be used for detailed voltage sensor experiments in the presence of permeant cations.


Asunto(s)
Activación del Canal Iónico , Canales de Potasio de Gran Conductancia Activados por el Calcio/metabolismo , Secuencia de Aminoácidos , Animales , Calcio/metabolismo , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Canales de Potasio de Gran Conductancia Activados por el Calcio/química , Canales de Potasio de Gran Conductancia Activados por el Calcio/genética , Lisina/genética , Datos de Secuencia Molecular , Fenilalanina/genética , Mutación Puntual , Estructura Terciaria de Proteína , Xenopus
20.
Int J Fertil Womens Med ; 48(2): 74-82, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12779293

RESUMEN

UNLABELLED: To evaluate the clinical impact of the use of an indirect immunofluorescence assay (IFA) against Chlamydia as a method to identify patients with tubal factor infertility (TFI) in a population of infertile Mexican women. METHODS: This was a retrospective analysis made on 100 patients attending the infertility clinic who underwent laparoscopy. Blood and cervical samples were collected during the clinical examination. The presence of anti-Chlamydia trachomatis IgG antibodies was documented using the IFA test, and the presence of active chlamydial infection was evaluated using the nucleic acid hybridization assay. RESULTS: The sensitivity and specificity values of the IFA test to identify patients with periadnexal adhesions were 45% and 82%, respectively; and the positive predictive and negative predictive values were 42% and 84%, and the positive and negative likelihood ratios were 2.5 and 0.7, respectively. CONCLUSION: The IFA test was not usable for the identification of patients with periadnexal adhesions as a cause of infertility in this population. However, it could be useful as a screening test to decide which patients might receive laparoscopic treatment. Furthermore, it could be useful for identifying patients with active chlamydial infections in the upper genital tract, but a study with a larger sample needs to be done.


Asunto(s)
Anticuerpos Antibacterianos/análisis , Anticuerpos Antibacterianos/sangre , Infecciones por Chlamydia/diagnóstico , Chlamydia trachomatis/aislamiento & purificación , Técnica del Anticuerpo Fluorescente Indirecta/métodos , Infertilidad Femenina/microbiología , Adolescente , Adulto , Infecciones por Chlamydia/complicaciones , Chlamydia trachomatis/inmunología , Femenino , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina G/sangre , Infertilidad Femenina/diagnóstico , Laparoscopía/estadística & datos numéricos , México , Persona de Mediana Edad , Hibridación de Ácido Nucleico/métodos , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Salpingitis/diagnóstico , Salpingitis/microbiología , Sensibilidad y Especificidad , Uretra/microbiología , Salud de la Mujer
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