RESUMEN
Coronavirus disease 2019 (COVID-19) has caused significant morbidity and mortality and new cases are on the rise globally, yet malaria-endemic areas report statistically significant lower incidences. We identified potential shared targets for an immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by immune determinants' shared identities with P. falciparum using the Immune Epitope Database and Analysis Resource Immune 9.0 browser tool. Probable cross-reactivity is suggested through HLA-A∗02:01 and subsequent CD8+ T-cell activation. The apparent immunodominant epitope conservation between SARS-CoV-2 (N and open reading frame (ORF) 1ab) and P. falciparum thrombospondin-related anonymous protein (TRAP) may underlie the low COVID-19 incidence in the malaria-endemic zone by providing immunity against virus infection to those previously infected with Plasmodium. Additionally, we hypothesize that the shared epitopes which lie within antigens that aid in the establishment of the P. falciparum erythrocyte invasion may be an alternative route for SARS-CoV-2 via the erythrocyte CD147 receptor, although this remains to be proven.
RESUMEN
Dendritic spines, the bulbous protrusions that form the postsynaptic half of excitatory synapses, are one of the most prominent features of neurons and have been imaged and studied for over a century. In that time, changes in the number and morphology of dendritic spines have been correlated to the developmental process as well as the pathophysiology of a number of neurodegenerative diseases. Due to the sheer scale of synaptic connectivity in the brain, work to date has merely scratched the surface in the study of normal spine function and pathology. This review will highlight traditional approaches to the imaging of dendritic spines and newer approaches made possible by advances in microscopy, protein engineering, and image analysis. The review will also describe recent work that is leading researchers toward the possibility of a systematic and comprehensive study of spine anatomy throughout the brain.
Asunto(s)
Espinas Dendríticas/ultraestructura , Microscopía/métodos , Imagen Óptica/métodos , Tinción con Nitrato de Plata/métodosRESUMEN
A critical component of flagellar assembly, the kinesin-2 heterotrimeric complex powers the anterograde movement of proteinaceous rafts along the outer doublet of axonemes in intraflagellar transport (IFT). We present the first high-resolution structures of a kinesin-2 motor domain and an ATP hydrolysis-deficient motor domain mutant from the parasitic protist Giardia intestinalis. The high-resolution crystal structures of G. intestinalis wild-type kinesin-2 (GiKIN2a) motor domain, with its docked neck linker and the hydrolysis-deficient mutant GiKIN2aT104N were solved in a complex with ADP and Mg(2+) at 1.6 and 1.8 A resolutions, respectively. These high-resolution structures provide unique insight into the nucleotide coordination within the active site. G. intestinalis has eight flagella, and we demonstrate that both kinesin-2 homologues and IFT proteins localize to both cytoplasmic and membrane-bound regions of axonemes, with foci at cell body exit points and the distal flagellar tips. We demonstrate that the T104N mutation causes GiKIN2a to act as a rigor mutant in vitro. Overexpression of GiKIN2aT104N results in significant inhibition of flagellar assembly in the caudal, ventral, and posterolateral flagellar pairs. Thus we confirm the conserved evolutionary structure and functional role of kinesin-2 as the anterograde IFT motor in G. intestinalis.
Asunto(s)
Cinesinas/química , Animales , Membrana Celular/metabolismo , Cristalografía por Rayos X/métodos , Citoplasma/metabolismo , Evolución Molecular , Flagelos/metabolismo , Giardia lamblia , Proteínas Fluorescentes Verdes/metabolismo , Cinesinas/metabolismo , Microdominios de Membrana/química , Modelos Moleculares , Mutación , Conformación Proteica , Estructura Terciaria de ProteínaRESUMEN
A pregnant woman with an undiagnosed pheochromocytoma is described. Her presentation at 29 weeks' gestation was consistent with preeclampsia. Noninvasive measurement of cardiac output and ambulatory monitoring of blood pressure provided data that facilitated making the appropriate diagnosis and managing the patient until delivery at term.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/diagnóstico , Hemodinámica , Feocromocitoma/diagnóstico , Complicaciones Neoplásicas del Embarazo/diagnóstico , Neoplasias de las Glándulas Suprarrenales/fisiopatología , Neoplasias de las Glándulas Suprarrenales/terapia , Adulto , Atención Ambulatoria , Determinación de la Presión Sanguínea , Gasto Cardíaco , Diagnóstico Diferencial , Femenino , Humanos , Feocromocitoma/fisiopatología , Feocromocitoma/terapia , Preeclampsia/diagnóstico , Embarazo , Complicaciones Neoplásicas del Embarazo/fisiopatologíaRESUMEN
BACKGROUND AND OBJECTIVES: Reports have emphasized the importance of spinal needle tip configuration in the development of post dural puncture headache (PDPH). METHODS: Charts from 366 consecutive obstetric patients receiving spinal anesthesia for labor, cesarean delivery, postpartum surgical procedures, or postpartum tubal ligations were reviewed retrospectively for evidence of PDPH in the five days after dural puncture. Spinal anesthesia was administered to these patients using 25-gauge Quincke (n = 74), 26-gauge Quincke (n = 160), or 24-gauge Sprotte (n = 132) spinal needles. RESULTS: The groups were well matched demographically. The incidence of PDPH in the three groups was 9%, 8%, and 1.5%, respectively. Half of the patients developing PDPH in each group were treated with an epidural blood patch. CONCLUSIONS: Our data indicate that the Sprotte spinal needle, with its non-cutting tip, results in a significantly lower (p less than 0.05) incidence of PDPH than Quincke cutting-tip needles of smaller gauge.