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At least 505 records · Page 28Linked to original sources
PubMed2003

Elevated free calcium levels in the subretinal space elevate the absolute dark-adapted threshold in hypopigmented mice.

Abundant evidence spanning 25 years demonstrates that hypopigmentation is associated with sensory abnormalities manifested most clearly as elevated absolute dark-adapted thresholds in hypopigmented mice. Here we show that when ocular melanin is increased in the himalayan mouse via alpha-melanocyte stimulating hormone (alpha-MSH) injections, dark-adapted thresholds drop in proportion to the change in ocular melanin. We further measured free calcium concentration with calcium-sensitive microelectrodes in both albino and black mouse retinal eyecups in living subjects. The recordings were done in anesthetized animals as the defect is not present in isolated retinas or in the superfused eye preparation. A double-barreled electrode--pCa and Vref--was used to simultaneously record the calcium concentration and the electroretinogram (ERG) at each of many depths as the electrode was driven through the retina. The position of the electrode was confirmed with ERG and 1,1'-dioctadecyl-3, 3,3',3'-tetramethylindocarbocyanine perchlorate electrode tract reconstruction. Dark-adapted albinos (n = 6) had 1.4 +/- 0.015 mM calcium in the subretinal space compared with 0.80 +/- 0.025 mM in black mice (n = 6). The results of these experiments are consistent with the hypothesis that ocular hypopigmentation causes elevated calcium levels in the subretinal space that in turn mimic light adaptation in hypopigmented mice.

Albinism↗
PubMed2026

Stem Cell Differentiation Disperses Transcriptional Clusters via a Conserved Surface-Condensate Trajectory.

Stem cells exhibit exceptionally prominent transcriptional clusters, which dissolve with progressing differentiation. Although these clusters are assigned central roles in embryonic gene regulation, their formation and loss during differentiation remain poorly understood. This study reveals that these prominent clusters disperse along a conserved trajectory in mouse embryonic stem cells, fruit fly testes, and zebrafish embryos. Imaging and lattice simulations show that these clusters form via surface condensation on H3K27ac-marked super-enhancer regions, which act as genomic scaffolds. Upon differentiation, partial loss of these active epigenetic marks and transcription-driven unfolding lead to dispersal of the prominent clusters. The block copolymer-based lattice simulations explain this process as a conserved trajectory through a three-dimensional state space, governed by surface condensation principles that extend beyond canonical liquid-liquid phase separation. This work marks surface condensation as a biophysical mechanism for the dynamic organization of stem cell-specific transcriptional hubs and demonstrates evolutionary conservation in several organisms. By uncovering a conserved biophysical mechanism for transcriptional organization in development, our work illustrates how polymer properties can contribute to the control of cell identity and fate.

Animals↗
PubMed2003

The evolution of resource use.

The evolution of a consumer exploiting two resources is investigated. The strategy x under selection represents the fraction of time or energy an individual invests into extracting the first resource. In the model, a dimensionless parameter alpha quantifies how simultaneous consumption of both resources influences consumer growth; alpha<0 corresponds to hemi-essential resources, 0 1 corresponds to antagonistic resources. An analysis of the ecological and evolutionary dynamics leads to five conclusions. First, when alpha< or =1, there is a unique singular strategy x* for the adaptive dynamics and it is evolutionarily stable and globally convergent stable. Second, when alpha=1, the singular strategy x* corresponds to the populations exhibiting an ideal free distribution and a population playing this strategy can invade and displace populations playing any other strategy. Third, when alpha>1, the strategies x=0 and x=1 are evolutionarily stable and convergent stable. Hence, if the populations initially specialize on one resource, evolution amplifies this specialization. Fourth, when alpha is slightly larger than one (i.e. the resources are slightly antagonistic), there is a convergent stable singular strategy whose basin of attraction is almost the entire strategy space (0,1). This singular strategy is evolutionarily unstable and serves as an evolutionary branching point. Following evolutionary branching, our analysis and numerical simulations suggest that evolutionary dynamics are driven toward an end state consisting of two populations specializing on different resources. Fifth, when alpha>>1, there is only one singular strategy and it is convergent unstable and evolutionarily unstable. Hence, if resources are overly antagonistic, evolutionary branching does not occur and ultimately only one resource is exploited.

Animals↗
PubMed1992

Purification of complex protein mixtures by ion-exchange displacement chromatography using spacer displacers.

The anion-exchange separation of complex protein mixtures by displacement chromatography using spacer displacers driven by high-affinity final displacers is demonstrated. Guinea pig serum was separated on a medium-resolution adsorbent using a single heterogeneous mixture of carboxymethyldextran displacers to space the protein components. Mouse liver cytosol was separated on a low-resolution adsorbent using six carboxymethyldextran spacer displacers of increasing column affinity. The demonstration of the purification of alkaline phosphatase from E. coli periplasm by displacement chromatography on a high-performance liquid chromatography column is reviewed. The benefits of spacer displacers for separating minor components from complex biological protein mixtures is discussed. A simplified method for preparing carboxymethyldextran displacers is presented.

Adsorption↗
PubMed2000

Early postoperative capsular block syndrome related to saccadic-eye-movement-induced fluid flow into the capsular bag.

PURPOSE: To determine the relationship between saccadic eye movements and the development of early postoperative capsular block syndrome. SETTING: Fundacion Oftalmologica, Los Andes, Santiago, Chile. METHODS: An artificial experimental setup was designed to reproduce the anatomical, hydrodynamic, and kinetic conditions of an early postoperative pseudophakic eye with a capsulorhexis and intracapsular intraocular lens (IOL) implantation. An electromechanical transducer driven by a digital-to-analog converter was used to mimic saccadic eye movements at physiological speeds and accelerations. Position information and differential pressure measurements between the intracapsular space and the extracapsular space were digitized. Various anterior capsule-IOL configurations were tested including partial adhesion of the anterior capsule to the lens. RESULTS: Saccadic movements increased intracapsular pressure by displacing fluid into the capsular bag. This finding was inconstant and only observed when the capsular rim adhered to the IOL optic by more than 70%. Development of positive intracapsular pressure was noted above 4 mm Hg. CONCLUSION: A valve-like mechanism formed by the capsulorhexis rim partially adhered to the IOL optic can occur postoperatively. Under these conditions, saccadic eye movements can increase intracapsular pressure by a unidirectional inertial displacement of fluid into the capsular bag.

Aqueous Humor↗
PubMed1999

New mode of DNA binding of multi-zinc finger transcription factors: deltaEF1 family members bind with two hands to two target sites.

SIP1, a Smad-interacting protein, and deltaEF1, a transcriptional repressor involved in skeletal and T-cell development, belong to the same family of DNA binding proteins. SIP1 and deltaEF1 contain two separated clusters of zinc fingers, one N-terminal and one C-terminal. These clusters show high sequence homology and are highly conserved between SIP1 and deltaEF1. Each zinc finger cluster binds independently to a 5'-CACCT sequence. However, high-affinity binding sites for full-length SIP1 and deltaEF1 in the promoter regions of candidate target genes like Xenopus Xbra2, and human alpha4-integrin and E-cadherin, are bipartite elements composed of one CACCT and one CACCTG sequence, the orientation and spacing of which can vary. Using transgenic Xenopus embryos, we demonstrate that the integrity of these two sequences is necessary for correct spatial expression of a Xbra2 promoter-driven reporter gene. Both zinc finger clusters must be intact for the high-affinity binding of SIP1 to DNA and for its optimal repressor activity. Our results show that SIP1 binds as monomer and contacts one target sequence with the first zinc finger cluster, and the other with the second cluster. Our work redefines the optimal binding site and, consequently, candidate target genes for vertebrate members of the deltaEF1 family.

Animals↗
PubMed2006

Radiatively generated maximal mixing scenario for the Higgs boson mass and the least fine-tuned minimal supersymmetric standard model.

We argue that given the experimental constraints on the Higgs boson mass the least fine-tuned parameter space of the minimal supersymmetric standard model is with negative top-squark masses squared at the grand unification scale. While the top-squark mass squared is typically driven to positive values at the weak scale, the contribution to the Higgs boson mass squared parameter from the running can be arbitrarily small, which reduces the fine-tuning of electroweak symmetry breaking. At the same time the top-squark mixing is necessarily enhanced and the maximal mixing scenario for the Higgs boson mass can be generated radiatively even when starting with negligible mixing at the unification scale. This highly alleviates constraints on possible models for supersymmetry breaking in which fine-tuning is absent.

Journal Article↗
PubMed2003

Spatiotemporal patterns of excitation and inhibition evoked by the horizontal network in layer 2/3 of ferret visual cortex.

The horizontal network in visual cortex layer 2/3 is implicated in numerous psychophysical and physiological properties. To investigate the spatial and temporal distribution of excitation and inhibition evoked by this network, we used voltage-sensitive dyes to image the responses to focal electrical stimulation in tangential slices of ferret visual cortex layer 2/3. The resulting optical patterns included a diffuse zone of activation near the stimulation site and numerous ovoid domains throughout the slice. In contrast to the fixed anatomy of the horizontal connections, substantial shifts in both space and time were evident in the distribution of population-based neuronal activity during stimulus trains. Both of these shifts relied on inhibitory synaptic potentials, suggesting that inhibition driven by horizontal connections sculpts the distribution of activity in this cortical network.

Animals↗
PubMed2001

Colocalization of plastid division proteins in the chloroplast stromal compartment establishes a new functional relationship between FtsZ1 and FtsZ2 in higher plants.

Chloroplast division is driven by a macromolecular complex containing components that are positioned on the cytosolic surface of the outer envelope, the stromal surface of the inner envelope, and in the intermembrane space. The only constituents of the division apparatus identified thus far are the tubulin-like proteins FtsZ1 and FtsZ2, which colocalize to rings at the plastid division site. However, the precise positioning of these rings relative to the envelope membranes and to each other has not been previously defined. Using newly isolated cDNAs with open reading frames longer than those reported previously, we demonstrate here that both FtsZ2 proteins in Arabidopsis, like FtsZ1 proteins, contain cleavable transit peptides that target them across the outer envelope membrane. To determine their topological arrangement, protease protection experiments designed to distinguish between stromal and intermembrane space localization were performed on both in vitro imported and endogenous forms of FtsZ1 and FtsZ2. Both proteins were shown to reside in the stromal compartment of the chloroplast, indicating that the FtsZ1- and FtsZ2-containing rings have similar topologies and may physically interact. Consistent with this hypothesis, double immunofluorescence labeling of various plastid division mutants revealed precise colocalization of FtsZ1 and FtsZ2, even when their levels and assembly patterns were perturbed. Overexpression of FtsZ2 in transgenic Arabidopsis inhibited plastid division in a dose-dependent manner, suggesting that the stoichiometry between FtsZ1 and FtsZ2 is an important aspect of their function. These studies raise new questions concerning the functional and evolutionary significance of two distinct but colocalized forms of FtsZ in plants and establish a revised framework within which to understand the molecular architecture of the plastid division apparatus in higher plants.

Arabidopsis↗
PubMed1988

Voltage gradients and ionic currents in injured and regenerating axons.

When an axon is damaged, a strong, persistent, injury current enters the damaged area, driven by the ionic pumps of the healthy portion of the cell. This current is associated with an electrical field, existing within the damaged axon and in the extracellular space around it. Such currents and fields are a common feature of neuronal damage and probably play a role in Ca2+-mediated degenerative events soon after transection, retrograde die-back, a structuring of the axonal terminus into zones, and perhaps organelle movement within damaged fibers. The long-term persistent currents may be a common feature of growing axons and might play a role in development and regeneration. Altogether, electrical effects of injury provide an alternative to conjecture concerning the physiological basis for immediate cellular responses to axonal injury. They also provide a possible basis for modulating the responses of neurons to injury by applied electric fields.

Action Potentials↗
PubMed2000

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗
PubMed2001

Apocytochrome c requires the TOM complex for translocation across the mitochondrial outer membrane.

The import of proteins into the mitochondrial intermembrane space differs in various aspects from the classical import pathway into the matrix. Apocytochrome c defines one of several pathways known to reach the intermembrane space, yet the components and pathways involved in outer membrane translocation are poorly defined. Here, we report the reconstitution of the apocytochrome c import reaction using proteoliposomes harbouring purified components. Import specifically requires the protease-resistant part of the TOM complex and is driven by interactions of the apoprotein with internal parts of the complex (involving Tom40) and the 'trans-side receptor' cytochrome c haem lyase. Despite the necessity of TOM complex function, the translocation pathway of apocytochrome c does not overlap with that of presequence-containing preproteins. We conclude that the TOM complex is a universal preprotein translocase that mediates membrane passage of apocytochrome c and other preproteins along distinct pathways. Apocytochrome c may provide a paradigm for the import of other small proteins into the intermembrane space such as factors used in apoptosis and protection from stress.

Apoproteins↗
PubMed2006

x-f Choice: reconstruction of undersampled dynamic MRI by data-driven alias rejection applied to contrast-enhanced angiography.

A technique for reconstructing dynamic undersampled MRI data, termed "x-f choice," was developed and applied to dynamic contrast-enhanced MR angiography (DCE-MRA). Regular undersampling in k-t space (a hybrid of k-space and time) creates aliasing in the conjugate x-f space that must be resolved. When regions in the object containing fast dynamic change are sparse, as in DCE-MRA, signal overlap caused by aliasing is often much less than the undersample factor would imply. x-f Choice reconstruction identifies overlapping signals using a model of the full non-aliased x-f space that is automatically generated from the undersampled data, and applies parallel imaging (PI) to separate them. No extra reference scans are required to generate either the model or the coil sensitivity maps. At each location in the reconstructed images, g-factor noise amplification is compared with predicted reconstruction errors to obtain an optimized solution. Acceleration factors greater than the number of receiver coils are possible, but are limited by the sparseness of the dynamic content and the signal-to-noise ratio (SNR) (in DCE-MRA the latter is dominant). Temporal fidelity was validated for up to a factor 10 speed-up using retrospectively undersampled data from a six-coil array. The method was tested on volunteers using fivefold prospective undersampling.

Blood Flow Velocity↗
PubMed2000

On selection mechanisms during initial evolution and on the possible role of ionic balance.

Initial evolution at the molecular level can proceed through mechanisms that enhance either the generation or the survival of certain molecules. Phenomena related to ionic balance can be the basis for both generative and survival selection mechanisms that may have driven the initial evolution of macromolecules. An important advantage of mechanisms based on ionic balance phenomena is that they can conceivably generate spatial and temporal inhomogeneities in semi-enclosed spaces within cavities of porous materials and/or membranes. Under certain circumstances, such inhomogeneities are required for initial evolution to proceed.

Animals↗
PubMed2000

Antigenic drift of viruses within a host: a finite site model with demographic stochasticity.

We theoretically study the antigenic drift of viruses within an infected host, as observed in human immunodeficiency virus (HIV) and equine infectious anemia virus (EIAV) infections, assuming that a finite number of antigen-determining sites at the viral envelop gene are responsible for the specific immune response. The pattern of antigen evolution becomes more complex than that predicted from the previous one-dimensional antigen space models. If the viral growth rate is sufficiently large, the demographic stochasticity for the fate of a new antigen mutant can be neglected. The high dimensionality in the way a virus escapes the immune defense in genotype space could then causes a rapid increase in the antigenic diversity and the total viral density, until finally the whole antigen genotypes are used up. The viral population is then driven to extinction in a host by the enhanced immune response to all genotypes. In contrast, if the viral growth rate is moderate or small so that only a small fraction of new antigen mutants can survive during the initial endangered period of random extinction, the viral antigenic diversity and the total density remain bounded, thereby enabling them to persist for a prolonged period by shifting the dominant antigen types. The phylogenetic pattern of antigen divergence is well characterized by the mean number of surviving antigen mutants from an antigen genotype. The substitution rate at antigen-determining sites increases as the efficiency of host immune response increases.

Animals↗
PubMedDate not supplied

A comparison of the accuracy and safety of vertebral body pin placement using a fluoroscopically guided versus an open surgical approach: an in vitro study.

OBJECTIVE: To compare the safety and accuracy of Steinmann pin placement in vertebral bodies T10 through L7 using either an open or closed fluoroscopic method. STUDY DESIGN: In vitro radiographic and anatomic study. ANIMALS: Ten medium-sized canine cadavers. METHODS: Cadavers were randomly assigned to 2 groups: open and closed. Steinmann pins were placed in vertebral bodies through a standard dorsal incision in the open group and percutaneously with the aid of fluoroscopy in the closed group. Pins were placed bilaterally in vertebral bodies T10 through L7 at approximately 30 degrees from horizontal and driven to a uniform depth. Necropsies were performed to examine potential pulmonary, vascular, or neurological trauma as a result of pin placement. Spines were cross-sectioned through intervertebral disc spaces, and radiographs were performed to evaluate accuracy of pin placement. Descriptive statistics were determined for pin angle, percentage of bone purchase, and penetration length. Means of interest between groups were compared using a Student t test. Complication incidence was compared using Chi;(2) analysis. Significance was P <.05. RESULTS: Mean pin insertion angle was significantly different than 30 degrees for the open group in thoracic and lumbar vertebrae and for the closed group in thoracic vertebrae. Mean pin insertion angle for all vertebrae was significantly greater than 30 degrees for the open group. Mean pin penetration distance in each vertebra was significantly different between groups with the closed group having less penetration and lower variance. Both groups were significantly different from the ideal penetration distance. The mean percentage of bone purchase was greater in the closed group for all vertebrae except T10 and T11. The complication incidence was significantly greater in the open group for thoracic vertebrae. CONCLUSION AND CLINICAL RELEVANCE: The results of this study suggest that a closed technique for placement of Steinmann pins in lumbar vertebrae for use in external skeletal fixation is a reasonable and safer alternative to the traditional open technique. Use of either technique in thoracic vertebrae should be avoided.

Animals↗