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Biomedical subjects

Cong Yu

Publications and source records attributed to Cong Yu.

At least 19 recordsLinked to original sources

Global contour processing in amblyopia.

The purpose of the experiments described here was to investigate global image processing using methods that require global processing while eliminating or compensating for low level abnormalities: visibility, shape perception and positional uncertainty. In order to accomplish this we used a closed figure made up of Gabor patches either in noise or on a blank field. The stimuli were circular or elliptical contours, formed by N equally spaced Gabor patches. We performed two separate experiments: In one experiment we fixed N and varied the aspect ratio using a staircase to determine the threshold aspect ratio; in the second experiment we held the aspect ratio constant (at twice the threshold aspect ratio) and varied N in order to measure the threshold number of elements required to judge the shape. Our results confirm and extend previous studies showing that humans with naturally occurring amblyopia show deficits in contour processing. Our results show that the deficits depend strongly on spatial scale (target size and spatial frequency). The deficit in global contour processing is substantially greater in noise (where contour-linking is required) than on a blank field. The magnitude of the deficits is modest when low-level deficits (reduced visibility, increased positional uncertainty, and abnormal shape perception) are minimized, and does not seem to depend much on acuity, crowding or stereoacuity. The residual deficits reported here cannot be simply ascribed to reduced visibility or increased positional uncertainty, and we therefore conclude that these are genuine deficits in global contour segregation and integration.

Adult↗

Single-stranded nucleic acid-induced helical self-assembly of alkynylplatinum(II) terpyridyl complexes.

Single-stranded nucleic acids, which carry multiple negative charges in an aqueous medium at near neutral pH, are found to induce the aggregation and self-assembly of the positively charged alkynylplatinum(II) terpyridyl complexes via electrostatic binding of the platinum complexes to the single-stranded nucleic acids, as revealed by the appearance of new UV-vis absorption and emission bands upon addition of single-stranded nucleic acids to a buffer solution of the complex. Changes in the intensity and pattern of circular dichroism (CD) spectroscopy are also observed, many of which are consistent with the assembly of the platinum complexes into helical structures, via metal...metal and pi...pi stacking interactions. The induced spectroscopic property changes are found to depend on the structural properties of the nucleic acids.

Nucleic Acid Conformation↗

Constant contour integration in peripheral vision for stimuli with good Gestalt properties.

The visual system integrates discrete but aligned local stimuli to form percept of global contours. Previous experiments using "snake" contours showed that contour integration was mainly present in foveal vision but absent or greatly weakened in peripheral vision. In this study, we demonstrated that, for contour stimuli such as circles and ellipses, which bore good Gestalt properties, contour integration for shape detection and discrimination was nearly constant from the fovea to up to 35 degrees visual periphery! Contour integration was impaired by local orientation and position jitters of contour elements, indicating that the same local contour linking mechanisms revealed with snake contour stimuli also played critical roles in integration of our good Gestalt stimuli. Contour integration was also unaffected by global position jittering up to 20% of the contour size and by dramatic shape jittering, which excluded non-contour integration processes such as detection of various local cues and template matching as alternative mechanisms for uncompromised peripheral perception of good Gestalt stimuli. Peripheral contour integration also presented an interesting upper-lower visual field symmetry after asymmetries of contrast sensitivity and shape discrimination were discounted. The constant peripheral performance might benefit from easy detection of good Gestalt stimuli, which popped out from background noise, from a boost of local contour linking by top-down influences and/or from multielement contour linking by long-range interactions.

Contrast Sensitivity↗

Michigan Molecular Interactions (MiMI): putting the jigsaw puzzle together.

Protein interaction data exists in a number of repositories. Each repository has its own data format, molecule identifier and supplementary information. Michigan Molecular Interactions (MiMI) assists scientists searching through this overwhelming amount of protein interaction data. MiMI gathers data from well-known protein interaction databases and deep-merges the information. Utilizing an identity function, molecules that may have different identifiers but represent the same real-world object are merged. Thus, MiMI allows the users to retrieve information from many different databases at once, highlighting complementary and contradictory information. To help scientists judge the usefulness of a piece of data, MiMI tracks the provenance of all data. Finally, a simple yet powerful user interface aids users in their queries, and frees them from the onerous task of knowing the data format or learning a query language. MiMI allows scientists to query all data, whether corroborative or contradictory, and specify which sources to utilize. MiMI is part of the National Center for Integrative Biomedical Informatics (NCIBI) and is publicly available at: http://mimi.ncibi.org.

Databases, Protein↗

The essential role of stimulus temporal patterning in enabling perceptual learning.

Little is known about how temporal stimulus factors influence perceptual learning. Here we demonstrate an essential role of stimulus temporal patterning in enabling perceptual learning by showing that 'unlearnable' contrast and motion-direction discrimination (resulting from random interleaving of stimuli) can be readily learned when stimuli are practiced in a fixed temporal pattern. This temporal patterning does not facilitate learning by reducing stimulus uncertainty; further, learning enabled by temporal patterning can later generalize to randomly presented stimuli.

Analysis of Variance↗

Nicastrin functions as a gamma-secretase-substrate receptor.

gamma-secretase catalyzes the intramembrane cleavage of amyloid precursor protein (APP) and Notch after their extracellular domains are shed by site-specific proteolysis. Nicastrin is an essential glycoprotein component of the gamma-secretase complex but has no known function. We now show that the ectodomain of nicastrin binds the new amino terminus that is generated upon proteolysis of the extracellular APP and Notch domains, thereby recruiting the APP and Notch substrates into the gamma-secretase complex. Chemical- or antibody-mediated blocking of the free amino terminus, addition of purified nicastrin ectodomain, or mutations in the ectodomain markedly reduce the binding and cleavage of substrate by gamma-secretase. These results indicate that nicastrin is a receptor for the amino-terminal stubs that are generated by ectodomain shedding of type I transmembrane proteins. Our data are consistent with a model where nicastrin presents these substrates to gamma-secretase and thereby facilitates their cleavage via intramembrane proteolysis.

Amyloid Precursor Protein Secretases↗

Pulmonary function after complete unilateral phrenic nerve transection.

OBJECT: The status of pulmonary function following phrenic nerve transfer surgery is still largely unknown because of the high degree of variability in the accessory phrenic nerve that may be involved. In the present study, pulmonary functions were assessed in patients before and after full-length phrenic nerve transfer surgery, in whom the phrenic nerve was severed at a location just before its entry into the diaphragm. METHODS: Fifteen patients (average age 27.4 years) with complete brachial plexus palsy underwent full-length phrenic nerve transfer. The phrenic nerve was harvested from the thoracic cavity by means of video-assisted thoracic surgery and then transferred to the musculocutaneous nerve. Postoperative pulmonary functions were retrospectively analyzed. Patients underwent follow-up evaluation for 42 to 48 months; four patients were eventually lost to follow up. Although no patient experienced pulmonary problems following the surgery, all sustained varying degrees of diaphragmatic paralysis and elevation (for 1-1.5 intercostal spaces) on the surgically treated side as seen on chest x-ray films. Pulmonary functional parameters, including vital capacity, vital capacity in percentage of predicted values, residual volume, total lung capacity, forced vital capacity, and forced expiratory volume in 1 second, recovered to preoperative levels by 1 year postsurgery. In contrast, the postoperative maximal inspiratory pressure value was significantly decreased compared with the predicted values (average decrease approximately 20%) in all of the patients, even at 4 years after the surgery. CONCLUSIONS: In young patients with healthy lung function, unilateral phrenic nerve transection surgery can cause unilateral diaphragmatic paralysis and reduce the inspiration muscle force; however, most pulmonary function parameters gradually recover to preoperative levels within 1 year.

Adolescent↗

[Clinical application and efficiency of two stage multiple nerves transfer for treatment of root avulsion of brachial plexus].

OBJECTIVE: To investigate the results of two stage multiple nerves transfer for treatment of complete brachial plexus root avulsion. METHODS: Eight patients with complete brachial plexus avulsion, aging 18-38 years and with a mean 6 months interval of injury and repair, were surgically treated with the following procedures. One stage surgical procedure was that the contralateral C7 never root was transferred to the ulnar nerve, the phrenic nerve to the anterior division of upper trunci plexus brachialis and the accessory nerve to the suprascapular nerve. Two stage surgical procedure was that the ulnar nerve was transferred to the median nerve , the intercostal nerves to the radial nerve and the thoracodorsal nerve. RESULTS: All patients were followed up from 13 months to 25 months (21 months on average), muscle reinnervation was observed in all patients. Return of muscle power of M3 or better are regarded as effective. The effective recovery results were 75% in musculocutaneous nerve, 37.5% in suprascapular nerve, 37.5% in radial nerve, 75% in thoracodorsal nerve and 62.5% in median nerve. In sensory recovery of the median nerve, 4 patients obtained S3, 3 patients S2 and 1 patient S1. CONCLUSION: Two stage multiple nerves transfer for treatment of root avulsion of brachial plexus can achieve better motor function results and is safe and effective. The procedure should be recommended for treatment of root avulsion of brachial plexus in selected patients with complete brachial plexus root avulsion, especially in young patients with a short interval between injury and repair. It is one of the alternative options.

Adolescent↗

[Comparison of the suppressive effects of tramadol and low-dose ketamine on the patients with postoperative hyperalgesia after remifentanil-based anaesthesia].

OBJECTIVE: To compare the suppressive effects of tramadol and low-dose ketamine on postoperative hyperalgesia after remifentanil-based anaesthesia. METHODS: A total number of sixty ASA I - II adult patients who undergone the operation of cranio-cervical region were assigned to three groups randomly, controlled group (Group C), tramadol group (Group T) and low-dose ketamine group (Group K). Before the end of surgery, Group T was given tramadol 0.3 mg/kg, Group K was given ketamine 0.5 mg/kg and Group C wasn't given any medicine. When the visual analogue scale (VAS) score of the group C was over five, tramadol 0.3 mg/kg was given to the patients. The four-level verbal rating scale after trachea extubation, VAS score, the time of requiring analgesia again by patients and adverse drug reactions such as nausea, vomit, diplopia and hallucination were recorded for 24 hours after surgery. RESULTS: After operation, the VAS score of Group C was much higher than that of Group K in the first 4 hours and Group T was higher than Group K during 2, 3 and 4 hours (P < 0.05). The time of requiring analgesia by patients in Group C and Group T was earlier than Group K. The adverse drug reaction showed no significant difference in three groups. CONCLUSION: Low-dose ketamine had significant suppressive effect on patients with postoperative hyperalgesia and acute opioid tolerance after remifentanil-based anaesthesia.

Adult↗

Perceptual learning in contrast discrimination and the (minimal) role of context.

Unlike most visual tasks, contrast discrimination has been reported to be unchanged by practice (Dorais & Sagi, 1997; Adini, Sagi, & Tsodyks, 2002), unless practice is undertaken in the presence of flankers (context-enabled learning, Adini et al., 2002). Here we show that under experimental conditions nearly identical to those in the no-flanker practice experiment of Adini et al. (2002), practice significantly improved contrast discrimination. Moreover, in a separate experiment, we found that practice without flankers can improve contrast discrimination to a level only reached with flankers in Adini et al. (2002), but further practice with flankers produces no further improvement of contrast discrimination. These results call into question whether the "context-enabled learning" proposed by Adini et al. (2002) is different from regular contrast learning without flankers. In separate experiments, we found that contrast learning is tuned to spatial frequency, orientation, retinal location, and, unexpectedly, contrast. We also replicated Sagi, Adini, Tsodyks, and Wilkonsky's (2003) more recent finding that no regular contrast learning occurs if reference contrasts are randomly interleaved (contrast roving), and further demonstrated that flankers have no effect on contrast learning under contrast roving, another piece of evidence equating "context-enabled learning" to regular contrast learning. The contrast specificity of learning and the lack of learning under contrast roving provide new evidence in favor of a multiple contrast-selective channels model of contrast discrimination, and against saturating transducer models and multiplicative noise models.

Contrast Sensitivity↗

BRL1 and BRL3 are novel brassinosteroid receptors that function in vascular differentiation in Arabidopsis.

Plant steroid hormones, brassinosteroids (BRs), are perceived by the plasma membrane-localized leucine-rich-repeat-receptor kinase BRI1. Based on sequence similarity, we have identified three members of the BRI1 family, named BRL1, BRL2 and BRL3. BRL1 and BRL3, but not BRL2, encode functional BR receptors that bind brassinolide, the most active BR, with high affinity. In agreement, only BRL1 and BRL3 can rescue bri1 mutants when expressed under the control of the BRI1 promoter. While BRI1 is ubiquitously expressed in growing cells, the expression of BRL1 and BRL3 is restricted to non-overlapping subsets of vascular cells. Loss-of-function of brl1 causes abnormal phloem:xylem differentiation ratios and enhances the vascular defects of a weak bri1 mutant. bri1 brl1 brl3 triple mutants enhance bri1 dwarfism and also exhibit abnormal vascular differentiation. Thus, Arabidopsis contains a small number of BR receptors that have specific functions in cell growth and vascular differentiation.

Amino Acid Sequence↗

A conserved GXXXG motif in APH-1 is critical for assembly and activity of the gamma-secretase complex.

The multipass membrane protein APH-1, found in the gamma-secretase complex together with presenilin, nicastrin, and PEN-2, is essential for Notch signaling in Caenorhabditis elegans embryos and is required for intramembrane proteolysis of Notch and beta-amyloid precursor protein in mammalian and Drosophila cells. In C. elegans, a mutation of the conserved transmembrane Gly123 in APH-1 (mutant or28) leads to a notch/glp-1 loss-of-function phenotype. In this study, we show that the corresponding mutation in mammalian APH-1aL (G122D) disrupts the physical interaction of APH-1aL with hypoglycosylated immature nicastrin and the presenilin holoprotein as well as with mature nicastrin, presenilin, and PEN-2. The G122D mutation also reduced gamma-secretase activity in intramembrane proteolysis of membrane-tethered Notch. Moreover, we found that the conserved transmembrane Gly122, Gly126, and Gly130 in the fourth transmembrane region of mammalian APH-1aL are part of the membrane helix-helix interaction GXXXG motif and are essential for the stable association of APH-1aL with presenilin, nicastrin, and PEN-2. These findings suggest that APH-1 plays a GXXXG-dependent scaffolding role in both the initial assembly and subsequent maturation and maintenance of the active gamma-secretase complex.

Amino Acid Motifs↗

Cross- and iso- oriented surrounds modulate the contrast response function: the effect of surround contrast.

The detectability and appearance of visual targets can be modulated by surround stimuli. In this study we asked how cross- and iso-oriented surrounds modulate contrast detection and discrimination in foveal vision. We systematically measured the Threshold-versus-Contrast (TvC) functions over a wide range of pedestal and surround contrasts. Our results show that cross-oriented surrounds lower the contrast threshold over the entire range of pedestal and surround contrasts, but iso-surround modulation of the TvC function is dependent on the relative contrast, being facilitative when the surround/pedestal contrast ratio Csur/Cped < 1 and suppressive when Csur/Cped > 1. Data fitting indicates that cross-surround modulation (facilitation) is mainly due to improved gain, except at very low and high surround contrasts. Iso-surround modulation on the other hand is more complicated, probably reflecting more than one surround process as determined by the relative contrast.

Adult↗

Flow control valves for analytical microfluidic chips without mechanical parts based on thermally responsive monolithic polymers.

Monolithic plugs of poly(N-isopropylacrylamide) cross-linked with 5% methylenebisacrylamide have been prepared by photoinitiated polymerization within the channel of a microfluidic device. The volume change associated with the polymer phase transition at its lower critical solution temperature of 32 degrees C allows both the rapid swelling and the deswelling of the monoliths enabling the polymer to close or open the channel as it functions as a nonmechanical valve. Thermoelectric elements capable of changing the temperature of the system between 17 and 57 degrees C were used to actuate the valve. Flow through the device was monitored by fluorescence measurements via the laser-triggered photobleaching of a dye contained in the liquid phase. Photobleaching occurs quickly once the flow is stopped, and the time required to open and close the valve was 3.5 and 5.0 s, respectively. No changes in function were observed even after 120 open-close cycles. Although the 2-mm-long valve was prepared from a polymerization mixture consisting of only a 5% aqueous solution of monomers, it resists pressures of up to 1.38 MPa (200 psi) without observable structural damage.

Acrylic Resins↗

Dog leukocyte antigen-haploidentical stem cell allografts after anti-CD44 therapy and reduced-intensity conditioning in a preclinical canine model.

OBJECTIVE: We previously described a nonmyeloablative hematopoietic stem cell transplantation regimen in dog leukocyte antigen (DLA)-identical littermate recipients consisting of low-dose total body irradiation (TBI) before and mycophenolate mofetil (MMF)/cyclosporine (CSP) given after transplant to control both graft-vs-host and residual host-vs-graft reactions. In this study, we sought to develop a reduced-intensity regimen to achieve engraftment across major histocompatibility complex barriers in DLA-haploidentical littermate recipients. MATERIALS AND METHODS: We tested a regimen of 450-cGy TBI with or without postgrafting MMF/CSP for 28 and 35 days, respectively, and with the administration of monoclonal antibody (mAb) S5 (anti-CD44), at a dose of 0.2 mg/kg/day from days -7 through -2, prior to receiving TBI. RESULTS: One of six dogs conditioned with 450-cGy TBI alone achieved engraftment of granulocyte colony-stimulating factor-mobilized peripheral blood stem cells. Three of six dogs achieved sustained donor cell engraftment using 450-cGy TBI and posttransplantation MMF/CSP. None of three dogs given mAb S5 followed by 450-cGy TBI showed signs of donor cell engraftment. However, when S5 mAb pretreatment was added to 450-cGy TBI and postgrafting MMF/CSP, 10 of 12 dogs achieved sustained engraftment (p = 0.008 or 0.007 vs 450-cGy alone or to S5 + 450-cGy TBI without MMF/CSP, respectively), with only three dogs developing severe graft-vs-host disease on this short regimen of immunosuppression. CONCLUSION: These results show that engraftment across a DLA haplotype-mismatched barrier can be achieved after reduced-intensity conditioning when mAb S5 directed at CD44 is added to this regimen.

Animals↗

Effective integration of protein data through better data modeling.

Protein data, from sequence and structure to interaction, is being generated through many diverse methodologies; it is stored and reported in numerous forms and multiple places. The magnitude of the data limits researchers abilities to utilize all information generated. Effective integration of protein data can be accomplished through better data modeling. We demonstrate this through the MIPD project.

Models, Molecular↗

Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch.

Presenilin and nicastrin are essential components of the gamma-secretase complex that is required for the intramembrane proteolysis of an increasing number of membrane proteins including the amyloid-beta precursor protein (APP) and Notch. By using co-immunoprecipitation and nickel affinity pull-down approaches, we now show that mammalian APH-1 (mAPH-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain. Similar to the loss of presenilin or nicastrin, the inactivation of endogenous mAPH-1 using small interfering RNAs results in the decrease of presenilin levels, accumulation of gamma-secretase substrates (APP carboxyl-terminal fragments), and reduction of gamma-secretase products (amyloid-beta peptides and the intracellular domains of APP and Notch). These data indicate that mAPH-1 is probably a functional component of the gamma-secretase complex required for the intramembrane proteolysis of APP and Notch.

Amino Acid Sequence↗