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1.
Proc Natl Acad Sci U S A ; 117(35): 21785-21795, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32817553

RESUMEN

In Arabidopsis thaliana, the METTL3 homolog, mRNA adenosine methylase (MTA) introduces N6-methyladenosine (m6A) into various coding and noncoding RNAs of the plant transcriptome. Here, we show that an MTA-deficient mutant (mta) has decreased levels of microRNAs (miRNAs) but accumulates primary miRNA transcripts (pri-miRNAs). Moreover, pri-miRNAs are methylated by MTA, and RNA structure probing analysis reveals a decrease in secondary structure within stem-loop regions of these transcripts in mta mutant plants. We demonstrate interaction between MTA and both RNA Polymerase II and TOUGH (TGH), a plant protein needed for early steps of miRNA biogenesis. Both MTA and TGH are necessary for efficient colocalization of the Microprocessor components Dicer-like 1 (DCL1) and Hyponastic Leaves 1 (HYL1) with RNA Polymerase II. We propose that secondary structure of miRNA precursors induced by their MTA-dependent m6A methylation status, together with direct interactions between MTA and TGH, influence the recruitment of Microprocessor to plant pri-miRNAs. Therefore, the lack of MTA in mta mutant plants disturbs pri-miRNA processing and leads to the decrease in miRNA accumulation. Furthermore, our findings reveal that reduced miR393b levels likely contributes to the impaired auxin response phenotypes of mta mutant plants.


Asunto(s)
Metiltransferasas/metabolismo , MicroARNs/biosíntesis , MicroARNs/metabolismo , Adenosina/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Ciclo Celular/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Metilación , Metiltransferasas/fisiología , MicroARNs/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/metabolismo
2.
PLoS Genet ; 14(5): e1007412, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29799838

RESUMEN

The N6-methyladenosine (m6A) modification is the most prevalent internal RNA modification in eukaryotes. The majority of m6A sites are found in the last exon and 3' UTRs. Here we show that the nuclear m6A reader YTHDC1 is essential for embryo viability and germline development in mouse. Specifically, YTHDC1 is required for spermatogonial development in males and for oocyte growth and maturation in females; Ythdc1-deficient oocytes are blocked at the primary follicle stage. Strikingly, loss of YTHDC1 leads to extensive alternative polyadenylation in oocytes, altering 3' UTR length. Furthermore, YTHDC1 deficiency causes massive alternative splicing defects in oocytes. The majority of splicing defects in mutant oocytes are rescued by introducing wild-type, but not m6A-binding-deficient, YTHDC1. YTHDC1 is associated with the pre-mRNA 3' end processing factors CPSF6, SRSF3, and SRSF7. Thus, YTHDC1 plays a critical role in processing of pre-mRNA transcripts in the oocyte nucleus and may have similar non-redundant roles throughout fetal development.


Asunto(s)
Empalme Alternativo/genética , Ratones/crecimiento & desarrollo , Proteínas del Tejido Nervioso/genética , Oocitos/crecimiento & desarrollo , Poliadenilación/genética , Factores de Empalme de ARN/genética , Regiones no Traducidas 3'/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Animales , Núcleo Celular/metabolismo , Factor de Especificidad de Desdoblamiento y Poliadenilación/metabolismo , Desarrollo Embrionario/genética , Exones/genética , Femenino , Masculino , Ratones/genética , Ratones Transgénicos , Mutación , Proteínas del Tejido Nervioso/deficiencia , Proteínas del Tejido Nervioso/metabolismo , Oocitos/metabolismo , Precursores del ARN/genética , Factores de Empalme de ARN/deficiencia , Factores de Empalme de ARN/metabolismo , ARN Mensajero/genética , Factores de Empalme Serina-Arginina/metabolismo , Espermatogonias/crecimiento & desarrollo , Espermatogonias/metabolismo
3.
Plant Cell ; 28(10): 2385-2397, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27758893

RESUMEN

RNA turnover is necessary for controlling proper mRNA levels posttranscriptionally. In general, RNA degradation is via exoribonucleases that degrade RNA either from the 5' end to the 3' end, such as XRN4, or in the opposite direction by the multisubunit exosome complex. Here, we use genome-wide mapping of uncapped and cleaved transcripts to reveal the global landscape of cotranslational mRNA decay in the Arabidopsis thaliana transcriptome. We found that this process leaves a clear three nucleotide periodicity in open reading frames. This pattern of cotranslational degradation is especially evident near the ends of open reading frames, where we observe accumulation of cleavage events focused 16 to 17 nucleotides upstream of the stop codon because of ribosomal pausing during translation termination. Following treatment of Arabidopsis plants with the translation inhibitor cycloheximide, cleavage events accumulate 13 to 14 nucleotides upstream of the start codon where initiating ribosomes have been stalled with these sequences in their P site. Further analysis in xrn4 mutant plants indicates that cotranslational RNA decay is XRN4 dependent. Additionally, studies in plants lacking CAP BINDING PROTEIN80/ABA HYPERSENSITIVE1, the largest subunit of the nuclear mRNA cap binding complex, reveal a role for this protein in cotranslational decay. In total, our results demonstrate the global prevalence and features of cotranslational RNA decay in a plant transcriptome.


Asunto(s)
Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Estabilidad del ARN/genética , ARN Mensajero/genética , Arabidopsis/efectos de los fármacos , Cicloheximida/farmacología , Exorribonucleasas/genética , Exorribonucleasas/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/genética , Complejo Proteico Nuclear de Unión a la Caperuza/genética , Complejo Proteico Nuclear de Unión a la Caperuza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estabilidad del ARN/fisiología , ARN de Planta/genética , Ribosomas/genética , Ribosomas/metabolismo
4.
J Opt Soc Am A Opt Image Sci Vis ; 36(4): B65-B70, 2019 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-31044957

RESUMEN

Recent studies on polarization perception have shown that humans are sensitive to patterned stimuli modulated by either angle of linear polarization (AoP) or degree of polarization (DoP). Here, we present a model of human polarization sensitivity that incorporates both AoP and DoP as spatially dependent input variables. Applying the model to both sinusoidal- and square-wave-modulated DoP and AoP inputs, we demonstrate the theoretical similarities and differences generated by such inputs. Our model indicates the following: (i) edge boundaries between two adjacent areas of different linear polarization are preserved for both AoP- and DoP-modulated stimuli; and (ii) compared with DoP stimuli, AoP stimuli generate greater luminance changes at the photoreceptor level, suggesting that AoP-modulated patterns are potentially more salient than DoP patterns. The computational model is supported experimentally with an optical test of the model comprising a radial diattenuating polarizing filter and modified liquid crystal displays generating DoP- and AoP-modulated outputs. Psychophysical measures of human sensitivity confirm the increased salience of AoP- relative to DoP-modulated stimuli. These findings have practical application to the selection of DoP- and AoP-modulated stimuli for the investigation of macular function and macular pigment density in healthy and diseased eyes.


Asunto(s)
Simulación por Computador , Percepción Espacial/fisiología , Percepción Visual , Adulto , Sensibilidad de Contraste , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Células Fotorreceptoras/citología
5.
Optom Vis Sci ; 96(8): 609-616, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31318800

RESUMEN

SIGNIFICANCE: Scrolling text can be an effective reading aid for those with central vision loss. Our results suggest that increased interword spacing with scrolling text may further improve the reading experience of this population. This conclusion may be of particular interest to low-vision aid developers and visual rehabilitation practitioners. PURPOSE: The dynamic, horizontally scrolling text format has been shown to improve reading performance in individuals with central visual loss. Here, we sought to determine whether reading performance with scrolling text can be further improved by modulating interword spacing to reduce the effects of visual crowding, a factor known to impact negatively on reading with peripheral vision. METHODS: The effects of interword spacing on reading performance (accuracy, memory recall, and speed) were assessed for eccentrically viewed single sentences of scrolling text. Separate experiments were used to determine whether performance measures were affected by any confound between interword spacing and text presentation rate in words per minute. Normally sighted participants were included, with a central vision loss implemented using a gaze-contingent scotoma of 8° diameter. In both experiments, participants read sentences that were presented with an interword spacing of one, two, or three characters. RESULTS: Reading accuracy and memory recall were significantly enhanced with triple-character interword spacing (both measures, P ≤ .01). These basic findings were independent of the text presentation rate (in words per minute). CONCLUSIONS: We attribute the improvements in reading performance with increased interword spacing to a reduction in the deleterious effects of visual crowding. We conclude that increased interword spacing may enhance reading experience and ability when using horizontally scrolling text with a central vision loss.


Asunto(s)
Reconocimiento Visual de Modelos/fisiología , Lectura , Escotoma/fisiopatología , Percepción Espacial/fisiología , Adulto , Femenino , Humanos , Lenguaje , Masculino , Adulto Joven
6.
J Opt Soc Am A Opt Image Sci Vis ; 35(6): 946-952, 2018 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-29877338

RESUMEN

Haidinger's brushes (HB) are entoptic phenomena resulting from differential absorption of linear polarized light by the human macula. Computational models have assisted in understanding the behavior of these subjective phenomena but have been limited in their application. This study presents a revised computational model that incorporates known determinants of the form and behavior of HB. The model generates both static and animated simulations of HB that can be quantified by their density, contrast, and radial/circumferential extent. Measured physiological parameters are used to demonstrate the dependency of HB on macular pigment (MP) density, MP distribution, and ocular retardation. Physiological variations in these parameters explain the reported variations in the perception of HB.


Asunto(s)
Simulación por Computador , Luz , Mácula Lútea/efectos de la radiación , Visión Entóptica/fisiología , Percepción Visual/fisiología , Humanos , Visión Ocular/fisiología
7.
Optom Vis Sci ; 95(4): 399-404, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29554010

RESUMEN

SIGNIFICANCE: Poor peripheral visual acuity in myopia may reflect, in part, photoreceptor misalignment with the exit pupil of the eye. We speculate that if such misalignment causes sufficient visual deprivation and/or disrupts retinal feedback processes, it may influence eye growth itself. PURPOSE: It is known that myopic eyes have a reduced peripheral resolution acuity relative to emmetropic eyes, though it remains unclear how mechanical stretching of the retina in myopia impacts on peripheral visual performance. Our aim was to determine how retinal stretching affects the properties of sampling units in peripheral vision. METHODS: Three-dimensional magnetic resonance imaging provided a depiction in vivo of ocular shape, allowing the inter-eye ratio of retinal image surface areas and the relative alignment of surfaces to be determined in our observer, who was unique in having severe myopia in the right eye (~21 D) but only modest myopia in the left (~3 D). Visual performance was assessed for the detection and direction discrimination of drifting sinusoids positioned 40° in the temporal retina. Applying the sampling theorem to our measures, we estimated the density and cut-off frequency of the underlying sampling units. RESULTS: The retinal image surface area of the right eye was 40% larger than that of the left and was rotated 8.9° anticlockwise relative to the left eye's image surface. In agreement with a linear stretch model of myopia, the sampling density of the right eye was reduced by approximately the same ratio as that predicted from the inter-eye MRI data, namely, 1.18. However, the cut-off frequency (cycles/mm) of the right eye was approximately half that of the left, a reduction that cannot be explained solely by a linear areal expansion of retinal sampling units. CONCLUSIONS: Poor peripheral acuity in severe myopia may be caused, at least in part, by receptoral misalignment with the exit pupil.


Asunto(s)
Miopía/fisiopatología , Refracción Ocular/fisiología , Retina/fisiopatología , Agudeza Visual/fisiología , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Miopía/diagnóstico por imagen , Psicometría , Retina/diagnóstico por imagen , Retinoscopía
8.
Pharmacol Res ; 107: 229-233, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-27025785

RESUMEN

This review synthesizes examples of pharmacological agents who have off-target effects of an epigenetic nature. We expand upon the paradigm of epigenetics to include "quasi-epigenetic" mechanisms. Quasi-epigenetics includes mechanisms of drugs acting upstream of epigenetic machinery or may themselves impact transcription factor regulation on a more global scale. We explore these avenues with four examples of conventional pharmaceuticals and their unintended, but not necessarily adverse, biological effects. The quasi-epigenetic drugs identified in this review include the use of beta-lactam antibiotics to alter glutamate receptor activity and the action of cyclosporine on multiple transcription factors. In addition, we report on more canonical epigenome changes associated with pharmacological agents such as lithium impacting autophagy of aberrant proteins, and opioid drugs whose chronic use increases the expression of genes associated with addictive phenotypes. By expanding our appreciation of transcriptomic regulation and the effects these drugs have on the epigenome, it is possible to enhance therapeutic applications by exploiting off-target effects and even repurposing established pharmaceuticals. That is, exploration of "pharmacoepigenetic" mechanisms can expand the breadth of the useful activity of a drug beyond the traditional drug targets such as receptors and enzymes.


Asunto(s)
Analgésicos Opioides/farmacología , Ciclosporina/farmacología , Epigénesis Genética , Regulación de la Expresión Génica/efectos de los fármacos , Compuestos de Litio/farmacología , beta-Lactamas/farmacología , Sistema de Transporte de Aminoácidos X-AG/genética , Antibacterianos/farmacología , Inmunosupresores/farmacología , Fármacos Neuroprotectores/farmacología , Receptores Opioides/metabolismo
9.
Ophthalmic Physiol Opt ; 36(4): 459-64, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27061397

RESUMEN

PURPOSE: Technological devices such as smartphones and tablets are widely available and increasingly used as visual aids. This study evaluated the use of a novel app for tablets (MD_evReader) developed as a reading aid for individuals with a central field loss resulting from macular degeneration. The MD_evReader app scrolls text as single lines (similar to a news ticker) and is intended to enhance reading performance using the eccentric viewing technique by both reducing the demands on the eye movement system and minimising the deleterious effects of perceptual crowding. Reading performance with scrolling text was compared with reading static sentences, also presented on a tablet computer. METHODS: Twenty-six people with low vision (diagnosis of macular degeneration) read static or dynamic text (scrolled from right to left), presented as a single line at high contrast on a tablet device. Reading error rates and comprehension were recorded for both text formats, and the participant's subjective experience of reading with the app was assessed using a simple questionnaire. RESULTS: The average reading speed for static and dynamic text was not significantly different and equal to or greater than 85 words per minute. The comprehension scores for both text formats were also similar, equal to approximately 95% correct. However, reading error rates were significantly (p = 0.02) less for dynamic text than for static text. The participants' questionnaire ratings of their reading experience with the MD_evReader were highly positive and indicated a preference for reading with this app compared with their usual method. CONCLUSIONS: Our data show that reading performance with scrolling text is at least equal to that achieved with static text and in some respects (reading error rate) is better than static text. Bespoke apps informed by an understanding of the underlying sensorimotor processes involved in a cognitive task such as reading have excellent potential as aids for people with visual impairments.


Asunto(s)
Movimientos Oculares/fisiología , Lectura , Escotoma/fisiopatología , Auxiliares Sensoriales , Agudeza Visual , Campos Visuales/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Computadoras de Mano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Escotoma/terapia , Encuestas y Cuestionarios , Baja Visión/fisiopatología , Baja Visión/terapia
10.
J Immunol ; 191(7): 3789-98, 2013 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-23997217

RESUMEN

The phenylalanyl-glycyl-glycyl-alanyl-prolyl (FG-GAP) domain plays an important role in protein-protein interactions, including interaction of integrins with their ligands. Integrin-α FG-GAP repeat-containing protein 2 (Itfg2) is a highly conserved protein in vertebrates that carries two FG-GAP domains, but its role in mammalian physiology is unknown. In this article, we show that Itfg2 is an intracellular protein and it plays a critical role in B cell differentiation and development of autoimmunity. Itfg2-deficient mice displayed a phenotype consistent with retention of B cells in the spleen and had a lower concentration of IgG in the blood when compared with wild-type littermates. Itfg2-deficient splenocytes also showed a defect in cell migration in vitro. After immunization with a thymus-dependent Ag, the absence of Itfg2 caused a shift in B cell maturation from the germinal centers to the extrafollicular regions of the spleen and blocked deposition of Ag-specific plasma cells in the bone marrow. In support of hematopoietic cell intrinsic activity of Itfg2, bone marrow transplantation of Itfg2-deficient cells was sufficient to impair germinal center development in wild-type mice. Furthermore, Itfg2 deficiency exacerbated development of autoimmune disease in MRL/lpr lupus-prone mice. These results identify Itfg2 as a novel contributor to B cell differentiation and a negative regulator of the autoimmune response during lupus.


Asunto(s)
Enfermedades Autoinmunes/genética , Linfocitos B/citología , Linfocitos B/metabolismo , Diferenciación Celular/genética , Cadenas alfa de Integrinas/genética , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/metabolismo , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/metabolismo , Secuencia de Bases , Diferenciación Celular/inmunología , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Modelos Animales de Enfermedad , Orden Génico , Marcación de Gen , Genotipo , Centro Germinal/inmunología , Centro Germinal/metabolismo , Células Madre Hematopoyéticas/metabolismo , Inmunoglobulinas/sangre , Cadenas alfa de Integrinas/química , Cadenas alfa de Integrinas/metabolismo , Lupus Eritematoso Sistémico/inmunología , Ratones , Ratones Noqueados , Datos de Secuencia Molecular , Fenotipo , Alineación de Secuencia , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo
11.
Clin Exp Optom ; : 1-5, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38373889

RESUMEN

CLINICAL RELEVANCE: The electronic storage of patient records and modern-day search engines present private practitioners with a unique opportunity to extract valuable data for investigative research purposes. However, practitioners seldom harness this resource and consequently a vast repository of clinical data remains largely unexplored. BACKGROUND: This study, based on real-world data from an optometric practice, stands as an example of how clinicians can actively contribute to research. In doing so it underscores the role played by age in determining the rate of natural myopia progression. METHODS: A retrospective data analysis of the refractive status, age and optical correction type of participants, was conducted over six years. Forty-four participants were recruited (25 contact lens and 19 spectacle wearers), with a presenting age varying from 5 to 20 years (median, 11 years). Non-cycloplegic, monocular foveal refractions were completed using a ShinNippon open-field autorefractor, corroborated with subjective refraction. The mean spherical equivalent refractive error was calculated for the participants' initial visit (baseline measure) and for a six-year follow-up visit (progression measure), with myopia progression defined as the difference between these measures. Statistical analyses were computed using Decision Tree Analysis, with a significance level set at 95%. RESULTS: The participant age at first visit exerted a significant influence on natural myopia progression over the assessment period (F 1,42 = 17.11, p < 0.001). Individuals aged ≤ 10 years had approximately twice the myopic progression (mean, -2.27 D) of those aged > 10 years (mean, -1.13 D). Neither degree of myopia at the initial visit nor optical correction type had a significant effect on progression (p > 0.05). CONCLUSIONS: Utilizing the advantage of small real-world data samples, the benefit of research by private practitioners was demonstrated, providing evidence that the age at which a child first presents for an eye examination is highly influential in determining their rate of myopia progression.

12.
J Immunol ; 187(2): 664-75, 2011 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-21690328

RESUMEN

αß and γδ lineage T cells are thought to arise from a common CD4(-)CD8(-) progenitor in the thymus. However, the molecular pathways controlling fate selection and maturation of these two lineages remain poorly understood. We demonstrated recently that a ubiquitously expressed ribosomal protein, Rpl22, is selectively required for the development of αß lineage T cells. Germline ablation of Rpl22 impairs development of αß lineage, but not γδ lineage, T cells through activation of a p53-dependent checkpoint. In this study, we investigate the downstream effectors used by p53 to impair T cell development. We found that many p53 targets were induced in Rpl22(-/-) thymocytes, including miR-34a, PUMA, p21(waf), Bax, and Noxa. Notably, the proapoptotic factor Bim, while not a direct p53 target, was also strongly induced in Rpl22(-/-) T cells. Gain-of-function analysis indicated that overexpression of miR-34a caused a developmental arrest reminiscent of that induced by p53 in Rpl22-deficient T cells; however, only a few p53 targets alleviated developmental arrest when individually ablated by gene targeting or knockdown. Co-elimination of PUMA and Bim resulted in a nearly complete restoration of development of Rpl22(-/-) thymocytes, indicating that p53-mediated arrest is enforced principally through effects on cell survival. Surprisingly, co-elimination of the primary p53 regulators of cell cycle arrest (p21(waf)) and apoptosis (PUMA) actually abrogated the partial rescue caused by loss of PUMA alone, suggesting that the G1 checkpoint protein p21(waf) facilitates thymocyte development in some contexts.


Asunto(s)
Diferenciación Celular/inmunología , Marcación de Gen , Inhibidores de Crecimiento/inmunología , Proteínas Ribosómicas/deficiencia , Subgrupos de Linfocitos T/inmunología , Proteína p53 Supresora de Tumor/fisiología , Animales , Apoptosis/genética , Apoptosis/inmunología , Proteínas Reguladoras de la Apoptosis/biosíntesis , Proteínas Reguladoras de la Apoptosis/deficiencia , Proteína 11 Similar a Bcl2 , Diferenciación Celular/genética , Línea Celular , Linaje de la Célula/genética , Linaje de la Célula/inmunología , Regulación hacia Abajo/genética , Regulación hacia Abajo/inmunología , Marcación de Gen/métodos , Inhibidores de Crecimiento/genética , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/deficiencia , Ratones , Ratones Noqueados , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Proto-Oncogénicas/deficiencia , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/deficiencia , Proteínas Ribosómicas/biosíntesis , Proteínas Ribosómicas/genética , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/patología , Timo/inmunología , Timo/metabolismo , Timo/patología , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/deficiencia , Proteínas Supresoras de Tumor/biosíntesis , Proteínas Supresoras de Tumor/deficiencia , Proteína X Asociada a bcl-2/biosíntesis
13.
Vision (Basel) ; 7(1)2023 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-36810315

RESUMEN

The relationship of macular pigments and foveal anatomy to the perception of Maxwell's spot (MS) and Haidinger's brushes (HB) entoptic phenomena were investigated. Dual-wavelength-autofluorescence and OCT were used to define macular pigment density and foveal anatomy in 52 eyes. MS was generated by alternating unpolarized red/blue and red/green uniform field illumination. HB was generated by alternating the linear polarization axis of a uniform blue field. In Experiment 1, horizontal widths of MS and HB were measured using a micrometer system and compared with macular pigment densities and OCT-defined morphometry. MS radius (mean 1.4°) was significantly less than HB radius (mean 1.6°), with the spatial extent of both phenomena falling between the boundaries of the foveola and foveal pit. Multiple regression showed MS and HB radii to be significantly associated with the macular pigment spatial profile radius. HB radius, but not MS radius, was also significantly associated with foveolar morphometry. Experiment 2 compared perceptual profiles of MS with macular pigment distribution patterns and demonstrated close agreement. The size and appearance of MS is a direct indicator of macular pigment density and distribution. Measures of HB radii are less specific, with dependence on both macular pigment density and foveal structure.

14.
J Immunol ; 185(1): 327-34, 2010 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-20505138

RESUMEN

Sh2d3c is an adaptor protein that has been implicated in T cell activation and shown to associate with different components of the integrin signaling pathway ex vivo. However, the in vivo significance of Sh2d3c expression in the regulation of the immune response and/or hematopoietic cell lineage development is not known. In this study, we show that expression of Sh2d3c is more critical for development and function of marginal zone B (MZB) cells than for T cell maturation. Mice deficient in Sh2d3c expression (Sh2d3c(-/-)) had a reduced number of MZB cells, and the residual MZB cells failed to properly capture polysaccharide Ags. Activation-induced proliferation, cytokine production, and migration of Sh2d3c(-)(/)(-) splenic B cells were also significantly reduced in vitro compared with wild-type (Sh2d3c(+/+)) cells. In contrast, T cell development and function were largely normal in Sh2d3c(-/-) mice. The thymi of Sh2d3c(-/-) mice showed no maturational abnormalities, the number of splenic T cells was only modestly reduced, and the T cells responded normally to in vitro polyclonal activation. The observed B cell deficiency in the Sh2d3c(-/-) mice led to diminished humoral immune response against thymus-independent type 2, but not thymus-dependent Ags, which highlights the primary in vivo role of Sh2d3c in regulating B cell development and function.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/fisiología , Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/metabolismo , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Transducción de Señal/inmunología , Bazo/inmunología , Bazo/metabolismo , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Antígenos T-Independientes/inmunología , Subgrupos de Linfocitos B/patología , Señalización del Calcio/genética , Señalización del Calcio/inmunología , Quimiotaxis de Leucocito/genética , Quimiotaxis de Leucocito/inmunología , Femenino , Linfopenia/genética , Linfopenia/inmunología , Linfopenia/patología , Masculino , Ratones , Ratones Noqueados , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Transducción de Señal/genética , Bazo/patología , Subgrupos de Linfocitos T/citología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Timo/citología , Timo/inmunología , Timo/metabolismo
15.
Cancer Cell ; 4(5): 349-60, 2003 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-14667502

RESUMEN

Wnt5a is a member of the Wnt family of secreted glycoproteins that play essential organizing roles in development. Similar to other Wnt members, Wnt5a can upregulate cell proliferation and has been proposed to have oncogenic function. Here we report that Wnt5a signals through the noncanonical Wnt/Ca++ pathway to suppress cyclin D1 expression and negatively regulate B cell proliferation in a cell-autonomous manner. Wnt5a hemizygous mice develop myeloid leukemias and B cell lymphomas that are clonal in origin and display loss of Wnt5a function in tumor tissues. Furthermore, analysis of human primary leukemias reveals deletion of the WNT5A gene and/or loss of WNT5A expression in a majority of the patient samples. These results demonstrate that Wnt5a suppresses hematopoietic malignancies.


Asunto(s)
Linfocitos B/metabolismo , División Celular/fisiología , Leucemia Mieloide/metabolismo , Linfoma de Células B/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Animales , Calcio/metabolismo , Células Cultivadas , Ciclina D1/metabolismo , Citometría de Flujo , Sistema Hematopoyético/metabolismo , Sistema Hematopoyético/fisiopatología , Humanos , Interleucina-7/metabolismo , Leucemia Mieloide/patología , Pérdida de Heterocigocidad/fisiología , Tejido Linfoide/fisiopatología , Linfoma de Células B/patología , Ratones , Ratones Noqueados , Proteínas Proto-Oncogénicas/genética , Transducción de Señal/fisiología , Trasplante Heterólogo , Proteínas Wnt , Proteína Wnt-5a
16.
PLoS One ; 16(12): e0261762, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34941940

RESUMEN

Short-term study-abroad (STSA) programs provide a more accessible alternative for students who would otherwise not consider engaging in academic activities overseas. Though improvements in the levels of intercultural sensitivity and general academic aspects attained by STSA programs have been previously examined, much less is known regarding the impact such programs have in the mood of students. Here, we examined changes in mood state associated with participation in an STSA program in a group of Japanese university students. Mood states were assessed using the Profile of Mood States (POMS), the Satisfaction With Life Scale (SWLS), and the Gratitude Questionnaire (GQ-6). Results indicated that the POMS mean scores of Vigor-Activity and SWLS peaked at the time immediately following participation in the STSA program; moreover, the same scores were found to be at comparable levels even one month after the end of the program. These results indicate that participation in STSA programs can positively influence the mood state of university students, suggesting that the benefits associated with participation in such programs extend beyond typically reported improvements in the academic domain.


Asunto(s)
Afecto , Estrés Psicológico/psicología , Encuestas y Cuestionarios , Universidades , Adolescente , Adulto , Femenino , Humanos , Japón , Masculino
17.
Transl Vis Sci Technol ; 10(9): 8, 2021 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-34351366

RESUMEN

Purpose: The purpose of this study was to determine if a battery of polarization-modulated stimuli, quantified as a single metric, is effective in identifying macular disease in the presence/absence of cataract or pseudophakia. Methods: Using a modified liquid crystal display, polarization pattern perception (PPP) for a formulated battery of geometric and logMAR stimuli was evaluated in participants that had either no eye pathology (healthy participants) or were grouped according to the presence of cataract, pseudophakia, and/or age-related macular degeneration (AMD). PPP was quantified as response frequencies to individual stimuli, and as a novel monocular polarization sensitivity score (Ps) based on perception of the stimulus battery set. Results: Stimulus response frequencies were pattern-dependent and, compared with healthy participants, reduced for cataract and AMD groups but not for subjects with pseudophakia. Compared with healthy eyes (n = 47, median Ps = 17), Ps was significantly reduced by AMD (n = 59, median Ps = 1, P < 0.001) and, to a lesser extent, by cataracts (n = 80, median Ps = 6, P < 0.001). There was no significant difference between Ps for healthy and pseudophakic eyes (n = 47, median Ps = 13, P = 0.323). There was no significant correlation between Ps and logMAR visual acuity. Conclusions: In the absence of significant cataract, or in pseudophakia, a set of polarization-modulated visual stimuli, quantified as the Ps score, distinguishes AMD from healthy maculae. Translational Relevance: Perception of polarization-modulated stimuli, previously shown to be macula-dependent in a laboratory setting, is effective as a test of macular function in health and disease in a clinic setting.


Asunto(s)
Catarata , Degeneración Macular , Catarata/diagnóstico , Humanos , Degeneración Macular/diagnóstico , Seudofaquia , Refracción Ocular , Agudeza Visual
18.
Mil Med ; 186(Suppl 1): 122-128, 2021 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-33499475

RESUMEN

INTRODUCTION: The purpose of this investigation was to evaluate the efficacy of currently employed commercial disinfectants in a simulated austere surgical environment similarly faced by ground surgical teams in forward deployed positions. Severe contamination of traumatic combat wounds along with limitations of operations in austere environments may result in available disinfectants providing inadequate surgical instrument decontamination. MATERIALS AND METHODS: The study consisted of nine experimental groups and two control groups evaluating hemostatic forceps found in kits of ground surgical teams. Hemostats were contaminated in a manner replicating the use in austere wartime surgery, cleaned by manual debridement and soaked in a disinfectant. Initially, instruments were debrided in one of three initial liquids (potable water, sterile water, or potable water with Envirocleanse A) and subsequently treated with one of three terminal disinfectants (Cidex OPA, CaviCide, or Neutral Disinfectant Cleaner). Treated hemostats were placed in sterile wire-closure bags for various storage times and tested for viable bacteria measured by colony-forming units. RESULTS: Our findings indicated that mechanical debridement in water, independent of Envirocleanse A, followed by soaking in any of the three terminal disinfectants achieved a marked reduction in recovered bacteria from hemostats regardless of storage length. Of the three disinfectants tested, Cidex OPA appeared to be the most robust in terms of decontamination, followed by CaviCide and Neutral Disinfectant Cleaner. CONCLUSIONS: This study supports the conclusion that all evaluated disinfectants are capable of rapidly producing instruments with minimal bacterial contaminants when standard sterilization is unavailable. Therefore, when lifesaving surgical intervention must be performed in a deployed environment, austere surgical teams can confidently utilize either product with minimal risk of infection. However, of the disinfectants, Cidex OPA appears to be most effective in reducing bacterial contamination for both rapid and slow turnover of instrument usage, and thus, the disinfectants are recommended for application when sterilization is not available.


Asunto(s)
Desinfección , Bacterias , Desinfectantes/farmacología , Glutaral , Humanos , Instrumentos Quirúrgicos
19.
Proc Biol Sci ; 277(1699): 3421-6, 2010 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-20534611

RESUMEN

Visual perception is dependent not only on low-level sensory input but also on high-level cognitive factors such as attention. In this paper, we sought to determine whether attentional processes can be internally monitored for the purpose of enhancing behavioural performance. To do so, we developed a novel paradigm involving an orientation discrimination task in which observers had the freedom to delay target presentation--by any amount required--until they judged their attentional focus to be complete. Our results show that discrimination performance is significantly improved when individuals self-monitor their level of visual attention and respond only when they perceive it to be maximal. Although target delay times varied widely from trial-to-trial (range 860 ms-12.84 s), we show that their distribution is Gaussian when plotted on a reciprocal latency scale. We further show that the neural basis of the delay times for judging attentional status is well explained by a linear rise-to-threshold model. We conclude that attentional mechanisms can be self-monitored for the purpose of enhancing human decision-making processes, and that the neural basis of such processes can be understood in terms of a simple, yet broadly applicable, linear rise-to-threshold model.


Asunto(s)
Atención , Concienciación , Adulto , Humanos , Reconocimiento Visual de Modelos
20.
Vision Res ; 174: 1-9, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32492477

RESUMEN

Recent reports indicate that the subjective ability of humans to discriminate between polarization E-vector orientations approaches that of many invertebrates. Here, we show that polarization-modulated patterned stimuli generate an objectively recordable electrophysiological response in humans with normal vision. We investigated visual evoked potential (VEP) and electroretinographic (ERG) responses to checkerboard patterns defined solely by their polarization E-vector orientation alternating between ± 45°. Correcting for multiple comparisons, paired-samples t-tests were conducted to assess the significance of post-stimulus deflections from baseline measures of noise. Using standard check pattern sizes for clinical electrophysiology, and a pattern-reversal protocol, participants showed a VEP response to polarization-modulated patterns (PolVEP) with a prominent and consistent positive component near 150 ms (p < 0.01), followed by more variable negative components near 200 ms and 300 ms. The effect was unrecordable with visible wavelengths >550 nm. Further, pseudo-depolarization negated the responses, while control studies provided confirmatory evidence that the PolVEP response was not the product of luminance artefacts. Polarization-modulated patterns did not elicit a recordable ERG response. The possible origins of the PolVEP signals, and the absence of recordable ERG signals, are discussed. We conclude that evoked cortical responses to polarization-modulated patterns provide an objective measure of foveal function, suitable for both humans and non-human primates with equivalent macular anatomy.


Asunto(s)
Electrorretinografía , Potenciales Evocados Visuales , Animales , Fóvea Central , Refracción Ocular , Visión Ocular
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