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Biomedical subjects

S Sokol

Publications and source records attributed to S Sokol.

At least 19 recordsLinked to original sources

Lexical factors in the word-superiority effect.

In the Reicher-Wheeler paradigm, fluent readers can identify letters better when they appear in a word than when they appear in either a pronounceable pseudoword (a lexicality effect) or a single letter (a word-letter effect). It was predicted that if both of these effects involve a lexical factor, then adult acquired dyslexic subjects whose deficit prevents access to visual word form should show disruptions of the normal effects on the Reicher-Wheeler task. The results were that dyslexic subjects as well as matched control subjects showed a lexicality effect; however, while the control subjects showed a normal word-letter effect, the dyslexic subjects showed a reverse letter-superiority effect. Both effects, however, showed a systematic variation: As performance on lexical decision improved, the subjects' performance on words in the Reicher-Wheeler task was better than that for all the other conditions. These subject correlations were replicated by using data from a second lexical decision experiment, which utilized the same words and pseudowords that were used in the Reicher-Wheeler task. In addition, an item analysis showed that the words that the subjects had discriminated correctly in lexical decision showed a significant advantage over those that they had not, as well as an improvement relative to the other conditions. These results suggest that there is a lexical factor underlying the lexicality and word-letter effects, and it is proposed that the abnormal letter-superiority effect can be accounted for as the manifestation of other competing factors.

Adult

Development of lateral interactions in the infant visual system.

The development of lateral inhibitory interactions in the infant visual system, as reflected by the visual-evoked potential (VEP), was studied using a radial, asymmetrical windmill-dartboard stimulus. This contrast-reversing stimulus generates VEP responses with a strong fundamental frequency component and an attenuated second harmonic component (relative to that obtained using a symmetrical stimulus). These two harmonic components reflect distinct phenomena, and appear to be the result of short-range (the fundamental) and long-range (attenuated second harmonic) lateral inhibitory interactions elicited by differential luminance-modulation of contiguous spatial regions. We studied the development of the short- and long-range interactions at 100% and 30% contrast in human infants using both VEP amplitude and phase measures. Attenuation of the second harmonic (long-range interactions) was adult-like by 8 weeks of age while the strength of the fundamental (short-range interactions) was adult-like by 20 weeks suggesting a differential development of long-range and short-range interactions. In contrast, corresponding phase data indicated significant immaturities at 20 weeks of age for both the short- and long-range components.

Contrast Sensitivity

Infant VEP and preferential looking acuity measured with phase alternating gratings.

Previously, infants' grating acuity was found to be temporally tuned, but adults' grating acuity was not. In infants, acuity was higher for gratings phase alternating at 7.5 and 14 reversals/sec than for stationary gratings and gratings alternating at 2.5 or 23 reversals/sec. Also, when preferential looking (PL) and visually evoked potential (VEP) acuity were estimated with phase alternating gratings (14 reversals/sec), the acuity difference between the two techniques was smaller than that obtained when phase alternating gratings were used to estimate VEP acuity and stationary gratings were used to estimate PL acuity. In the present study, it was determined if PL grating acuity was tuned in older children and if the smaller difference between VEP and PL acuity found when infants were tested with phase alternating gratings was independent of temporal rate. Grating acuity in infants older than 2 yr was found to be not tuned, and the smaller difference between VEP and PL grating acuity in infants when both were measured with phase-alternating gratings was not rate dependent. VEP acuity and PL acuity for phase alternating gratings developed at different rates, converging to nearly equivalent levels by 12 mo of age.

Aging

Injected Wnt RNA induces a complete body axis in Xenopus embryos.

Studies in Xenopus have shown that growth factors of the TGF beta and Wnt oncogene families can mimic aspects of dorsal axis formation. Here we directly compare the inductive properties of two Wnt proteins by injecting synthetic mRNA into developing embryos. The results show that Wnt-1 and Xwnt-8 can induce a new and complete dorsal axis and can rescue the development of axis-deficient, UV-irradiated embryos. In contrast, activin mRNA injection induces only a partial dorsal axis that lacks anterior structures. These studies demonstrate that the mechanism of Wnt-induced axis duplication results from the creation of an independent Spemann organizer. The relationship between the properties of the endogenous dorsal inducer and the effects of Wnts and activins is discussed.

Activins

Pre-existent pattern in Xenopus animal pole cells revealed by induction with activin.

Activin, a peptide growth factor related to tumour growth factor-beta, has been implicated in early inductive interactions in vertebrates and can induce Xenopus blastula ectodermal explants to develop a rudimentary axial pattern with anteroposterior and dorsoventral polarity. Here we demonstrate that prospective dorsal and ventral regions of the ectoderm respond differently to the same concentration of activin. Thus, activin does not seem to endow ectodermal cells with polarity but rather reveals a pre-existent pattern. Our results suggest that patterning of mesoderm is determined not only by a localized inducer, but also by the differential competence of cells in the responding tissue.

Activins

Activins are expressed early in Xenopus embryogenesis and can induce axial mesoderm and anterior structures.

We show that mammalian and Xenopus activins induce dorsal axial mesoderm and anterior structures in explants of Xenopus blastula cells that would otherwise form epidermis. The induced explants of animal cap cells can form notochord, muscle, neural tissue, and eyes all arranged in a rudimentary axial pattern. Activin A shares inductive properties and antigenic determinants with PIF, an inducing factor recently isolated from mouse macrophage culture supernatants. Genes encoding Xenopus activin beta A and beta B chains were cloned. Activin beta B transcripts are first detected in Xenopus blastula, whereas activin beta A transcripts do not appear until the late gastrula stage. Recombinant Xenopus activin beta B protein induces mesodermal and neural tissues similar to those induced by mammalian activin A and PIF. Furthermore, ectopic expression of Xenopus activin beta B produces a second body axis in embryos injected with synthetic mRNA. Our results suggest that early induction and axial patterning are accomplished by endogenous activin B, not activin A, in Xenopus.

Activins

A mouse macrophage factor induces head structures and organizes a body axis in Xenopus.

Soluble peptide factors have been implicated as the agents responsible for embryonic inductions in vertebrates. Here, a protein (PIF) secreted by a mouse macrophage cell line is shown to change the developmental fate of Xenopus embryonic cells. Exposure to PIF causes presumptive ectodermal explants to form anterior neural and mesodermal tissues, including brain and eye, instead of ciliated epidermis. In addition, the induced tissues are organized into a rudimentary embryonic axis. These results suggest that PIF or a closely related molecule is involved in inducing anterior structures and organizing the frog body plan.

Animals

A two-step model for the localization of maternal mRNA in Xenopus oocytes: involvement of microtubules and microfilaments in the translocation and anchoring of Vg1 mRNA.

In an effort to understand how polarity is established in Xenopus oocytes, we have analyzed the process of localization of the maternal mRNA, Vg1. In fully grown oocytes, Vg1 mRNA is tightly localized at the vegetal cortex. Biochemical fractionation shows that the mRNA is preferentially associated with a detergent-insoluble subcellular fraction. The use of cytoskeletal inhibitors suggests that (1) microtubules are involved in the translocation of the message to the vegetal hemisphere and (2) microfilaments are important for the anchoring of the message at the cortex. Furthermore, immunohistochemistry reveals that a cytoplasmic microtubule array exists during translocation. These results suggest a role for the cytoskeleton in localizing information in the oocyte.

Actin Cytoskeleton

Localization of mRNA and axis formation during Xenopus embryogenesis.

This paper summarizes our recent work concerned with the developmental polarity of the frog egg and the patterning of the embryonic body plan. In two separate projects, we are studying genes involved in setting up basic embryonic axes. One of these genes, Vg1, codes for a maternal mRNA that is localized in the frog egg. The Vg1 gene is used in studies on the induction of mesoderm and as a probe to understand how the polarity of an egg is established. A second gene, Xhox3, contains a homeodomain and is differentially expressed in the axial mesoderm. Our studies suggest that this homeobox gene is critically involved in setting up different positional values along the anteroposterior axis.

Animals

Evoked potential and preferential looking correlates of the oblique effect in 3-month-old infants.

Sensitivity for vertical and horizontal gratings is higher than for obliquely oriented gratings, a phenomenon known as the oblique effect. We compared visual evoken potential and preferential looking estimates of the oblique effect in nonastigmatic 3-month-old infants and found that orientation effects occurred more frequently by visual evoked potential measure than by preferential looking.

Evoked Potentials, Visual

The process of localizing a maternal messenger RNA in Xenopus oocytes.

The maternal mRNA Vg1 is localized to the vegetal pole during oogenesis in Xenopus. We have cultured oocytes in vitro to begin to understand how this localization occurs. Endogenous Vg1 mRNA undergoes localization when oocytes are cultured in vitro, and synthetic Vg1 mRNA injected into such oocytes is localized in the same fashion. Vg1 mRNA is associated with a detergent-insoluble fraction from homogenized oocytes, suggesting a possible cytoskeletal association. The use of cytoskeletal inhibitors reveals a two-step process for localizing Vg1 mRNA. Microtubule inhibitors such as nocodazole and colchicine inhibit the localization of Vg1 mRNA in late stage III/early stage IV oocytes, but have no effect on Vg1 mRNA once it is localized. The microfilament inhibitor cytochalasin B, however, has little effect on the translocation of Vg1 mRNA in middle-stage oocytes but causes a release of the message in late-stage oocytes. We propose a model for the localization of Vg1 mRNA in which translocation of the message to the vegetal cortex is achieved via cytoplasmic microtubules and the anchoring of the message at the cortex involves cortical microfilaments.

Actin Cytoskeleton

Infant grating acuity is temporally tuned.

Studies of infant visual development have shown that acuity estimated with pattern visually evoked potential (VEP) techniques is higher than acuity estimated with preferential looking (PL) techniques. A major difference is that VEP stimuli are temporally modulated while PL stimuli are typically stationary. We measured PL acuity in 2-10-month-old infants for stationary gratings and for gratings phase alternating at 2.5, 7.5, 14 and 23 reversals/sec using a computer generated staircase method. The acuity functions were temporally tuned at 7.5 or 14 rev/sec for infants 3 months and older. Acuity for 7.5 and 14 rev/sec gratings was 0.5 to 1.0 octave higher than for stationary, 2.5 and 23 rev/sec gratings. When adults' grating acuity was measured foveally and 5 deg eccentrically, tuning occurred only for the eccentric targets, suggesting that the retinal area used by the infants to detect gratings acts like the adult perifovea. In a second experiment, VEP and PL acuity were both measured from the same infants using 14 reversals/sec gratings. The VEP/PL acuity difference was less for phase alternating gratings than for stationary gratings. The magnitude of the difference was age dependent, decreasing from 2 octaves at 2 months to 0.5 octave at 12 months. Even though the use of phase alternating gratings results in improved PL acuity, temporal modulation does not completely account for the difference between VEP and PL acuity.

Adult

Electrophysiological evidence for the oblique effect in human infants.

Visually-evoked potentials (VEPs) were recorded from infants between the ages of 2 and 11 months in response to 2.5 c/deg main axis and oblique square wave gratings. The oblique effect first appears at 3 months of age; some infants showed smaller VEP amplitude and/or longer VEP latency for obliquely oriented gratings. Regarding the age of onset of the oblique effect, VEP data from this study agree with the results obtained with preferential looking (PL) studies which have directly paired vertical and oblique gratings, but the current study found that fewer infants show an oblique effect by VEP than by PL.

Aging

Diagnosing functional visual deficits with the P300 component of the visual evoked potential.

The visual evoked potential (VEP) is routinely used to assess visual function, though it occasionally does not reflect a patient's conscious experience. Reports of normal flash or pattern VEPs obtained from blind persons are extreme examples of this problem. The difficulty in interpreting VEPs in light of such findings can be partly overcome by obtaining a cognitive component of the evoked potential, P300. We obtained traditional visual acuity measurements, pattern-reversal VEPs, and VEPs containing P300s from three patients with clinically diagnosed functional visual deficits. The P300s were obtained in response to stimuli that the patients claimed they could not see, supporting the clinical conclusions that malingering or hysteria was involved. The P300 component can be helpful in assessing the subjective visual experience of patients suspected of having functional visual loss.

Clinical Trials as Topic

Contrast sensitivity in diabetics with and without background retinopathy.

Contrast sensitivity measurements were obtained from 64 patients with insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus who had normal Snellen acuity and minimal or no visible diabetic retinopathy. Contrast thresholds were determined for stationary gratings at six spatial frequencies, ranging from 0.5 to 22.8 cycles/degree (c/deg), and for 1.0-c/deg gratings phase-alternated at 15 Hz. Data from each group of diabetic patients were compared with data from age-matched normal subjects. We found that (1) patients with IDDM and no retinopathy had normal contrast sensitivity, (2) patients with NIDDM and no retinopathy had abnormal contrast sensitivity at only one spatial frequency (22.8 c/deg), and (3) patients with NIDDM and background retinopathy had abnormal contrast sensitivity at all spatial frequencies tested. We also found a dissociation of Snellen acuity and contrast sensitivity, indicating that contrast sensitivity can be used as an early index of changes in the retina not demonstrated by measurements of visual acuity.

Adolescent