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At least 199 records · Page 11Linked to original sources

Structural and biophysical simulation of angiogenesis and vascular remodeling.

The purpose of this report is to introduce a new computer model for the simulation of microvascular growth and remodeling into arteries and veins that imitates angiogenesis and blood flow in real vascular plexuses. A C++ computer program was developed based on geometric and biophysical initial and boundary conditions. Geometry was defined on a two-dimensional isometric grid by using defined sources and drains and elementary bifurcations that were able to proliferate or to regress under the influence of random and deterministic processes. Biophysics was defined by pressure, flow, and velocity distributions in the network by using the nodal-admittance-matrix-method, and accounting for hemodynamic peculiarities like Fahraeus-Lindqvist effect and exchange with extravascular tissue. The proposed model is the first to simulate interdigitation between the terminal branches of arterial and venous trees. This was achieved by inclusion of vessel regression and anastomosis in the capillary plexus and by remodeling in dependence from hemodynamics. The choice of regulatory properties influences the resulting vascular patterns. The model predicts interdigitating arteriovenous patterning if shear stress-dependent but not pressure-dependent remodeling was applied. By approximating the variability of natural vascular patterns, we hope to better understand homogeneity of transport, spatial distribution of hemodynamic properties and biomass allocation to the vascular wall or blood during development, or during evolution of circulatory systems.

Algorithms↗

Biophysical and pharmacological characterization of spermatogenic T-type calcium current in mice lacking the CaV3.1 (alpha1G) calcium channel: CaV3.2 (alpha1H) is the main functional calcium channel in wild-type spermatogenic cells.

Mammalian acrosome reaction (AR) requires successive activation of three different types of calcium channels (T-type channels, Inositol-3-phosphate (InsP3) receptors, and TRPC2 channels). All the calcium signaling is under the control of the activation of the first-one, a T-type calcium channel. The molecular characterization of the T-type calcium channel is still a matter of debate, previous reports showing the presence of transcripts for Ca(V)3.1 and Ca(V)3.2 subunits. Using mice deficient for Ca(V)3.1 subunit, we show that the T-type current density in spermatogenic cells is not reduced in deficient mice versus control mice. We characterized the biophysical and pharmacological properties of T-type current in spermatogenic cells from Ca(V)3.1 deficient mice. Biophysical and pharmacological properties of spermatogenic T-type current from wild-type and Ca(V)3.1 deficient mice demonstrate that Ca(V)3.3 does not contribute to T-type current. Moreover, nickel and amiloride inhibit T-type currents in deficient and wild-type mice with similar potencies. These results demonstrate that T-type currents in spermatogenic cells is due to Ca(V)3.2 subunit and that Ca(V)3.1 contributes to a very negligible extent to the T-type currents. Thus, the deficient Ca(V)3.1 mouse model allows the characterization of native Ca(V)3.2 currents in spermatogenic cells. Spermatogenic Ca(V)3.2 currents present specific feature in comparison to the cloned Ca(V)3.2 current so far. More particularly, the time-dependence of recovery from short-term inactivation of native spermatogenic Ca(V)3.2 is close to 100 millisecond, a value expected for Ca(V)3.1 current.

Amiloride↗

Biophysical study of porcine ear skin in vitro and its comparison to human skin in vivo.

The goal of this work was to establish, using biophysical characterization, that porcine ear skin in vitro is a valid model for its human counterpart. Specifically, stratum corneum (SC) barrier function was evaluated during its progressive removal by adhesive tape-stripping using the techniques of transepidermal water loss (TEWL) and impedance spectroscopy. TEWL increased slowly at first and then more rapidly with the degree of SC impairment. In contrast, low-frequency skin impedance declined exponentially as a function of progressive SC removal. The methods provide complementary and correlated information about SC barrier function. Biophysical parameters, including the diffusivity and permeability coefficient of water across the SC, and the thickness of the barrier were determined from the TEWL data using Fick's first law of diffusion. Furthermore, an ionic partition coefficient-mobility product was estimated from the skin impedance measurements. Comparison of the results with those previously reported for human skin in vivo strongly supports the validity of the porcine membrane as an in vitro model.

Animals↗

Biophysical characteristics of the Meibomian lipid layer under in vitro conditions.

The biophysical behaviour of the Meibomian gland secretion was tested under in vitro conditions. Thereby, simultaneous recording of surface pressure and surface potential was performed. The Meibomian lipid layer was compared with other surface-active components like polyvinylalcohol and polyvinylpyrrolidone. On the other hand, Eledoisin was tested as an example for a surface-inactive substance. An attempt was made to describe the biophysical interaction between a given artificial tear substitute and the Meibomian lipid layer. With respect to the surface potential Dipalmitoyl-phosphatidyl-choline was established as an analogue for Meibomian gland secretion. Fluorescence measurements in the presence of a cyanine dye (1 N,N'dioctadecyloxacarbocyanine) were used as a method to localize the site of the characteristic potential change. From the fluorescence spectra under compression we conclude that the molecular change takes place at the lipid-subphase interface of the Meibomian lipid layer.

1,2-Dipalmitoylphosphatidylcholine↗

Biophysical behaviour of the infant Meibomian lipid layer.

Infants have been known occasionally to stare without blinking for almost a minute. This puts great demands on the stability of their tear-film. To verify the stability of infant tears, we performed biophysical experiments on Meibomian gland secretion, which forms the outermost layer of the tear-film. The secretion was taken from infants belonging to one of three age-groups (1.5 years, 4-5 years, 7-10 years). Under in vitro conditions we determined the surface pressure and the surface potential of the film by spreading the secretion over a water surface and subsequently compressing and decompressing it. Sufficient amounts of Meibomian gland secretion were expressed in all age-groups. The surface pressure and the surface potential of the tears in infants corresponded to those in healthy adults. It was also found that the younger the patient was, the better was the consistency of the surface potential under repeated periods of compression and expansion. In comparison with the secretion of healthy adults, the infant Meibomian gland secretion showed better biophysical characteristics and a correspondingly higher stability in the tear-film.

Biophysical Phenomena↗

Leukocyte biophysics. An invited review.

The biophysical properties of leukocytes in the passive and active state are discussed. In the passive unstressed state, leukocytes are spherical with numerous membrane folds. Passive leukocytes exhibit viscoelastic properties, and the stress is carried largely by the cell cytoplasm and the nucleus. The membrane is highly deformable in shearing and bending, but resists area expansion. Membrane tension can usually be neglected but plays a role in cases of large deformation when the membrane becomes unfolded. The constant membrane area constraint is a determinant of phagocytic capacity, spreading of cells, and passage through narrow pores. In the active state, leukocytes undergo large internal cytoplasmic deformation, pseudopod projection, and granule redistribution. Several different measurements for assessment of biophysical properties and the internal cytoplasmic deformation in form of strain and strain rate tensors are presented. The current theoretical models for active cytoplasmic motion in leukocytes are discussed in terms of specific macromolecular reactions.

Biophysical Phenomena↗

Biophysical properties of heteromultimeric erg K+ channels.

The three ether-à-go-go-related gene (erg) K(+) channel subunits are able to form heteromultimers within their subfamily. The functional importance of this finding is indicated by in situ hybridization experiments showing that the different erg subunits have overlapping expression patterns in several regions of the brain. To investigate the biophysical properties of heteromultimeric erg channels, concatemers of two erg subunits were constructed and expressed heterologously in Chinese hamster ovary (CHO) cells. The resulting currents were measured using the patch-clamp technique. The heteromultimers exhibited an intermediate potential dependence of activation compared with the corresponding wild-type (WT) erg channels. In contrast, the time course of activation was clearly dominated by the faster activating subunit. The kinetics of recovery from inactivation and the deactivation kinetics of all heteromultimers were similar to those of WT erg1 channels, the rat homologue of the human erg1 K(+) channel (HERG), even if erg1 was not part of the concatemer. Taken together, the biophysical properties of heteromultimeric erg channels result in larger current amplitudes upon both depolarization and repolarization. Thus, through heteromeric assembly erg channels may contribute significantly to different physiological functions such as setting and stabilizing the resting membrane potential and modulation of action potential frequency.

Animals↗

The role of membrane biophysical properties in the regulation of protein kinase C activity.

Under physiological conditions, protein kinase C is active when bound to membranes. Like most membrane-bound enzymes, its activity is dependent on the nature of its lipid environment. In this article, Richard Epand and David Lester describe the relationship between the ability of specific membrane-active agents to alter the biophysical properties of the lipid environment and their potential to modulate protein kinase C activity. They argue that this can lead to a greater understanding of the mechanism of inhibition and activation of protein kinase C through modulation of the bulk biophysical properties of the membrane, and may provide a new approach to the development of a more specific set of inhibitors.

Animals↗

Resonance induced alterations of intracellular biophysical properties.

A treatment of cancer by the application of external electromagnetic energy at a resonant frequency capable of the generation of heat intracellularly to induce selective thermal death of cancer cells is described. This process also allows for the detection of cancer cells by the use of differential resonant frequencies including nuclear magnetic resonance and electron spin resonance techniques. This process permits the selective treatment of cancer cells by the compartmentalized alteration of biophysical properties in the cancer cells and the detection of cancer cells by determination of their biophysical properties. The process comprises an ability to determine the respective resonant frequencies of cancer cells and normal cells at a cellular level. An external alternating electromagnetic field is then applied at the resonant frequency of the cancer cells which differs from the resonant frequency of the normal cells. The cancer cells absorb significant energy at this resonant frequency whereas the normal cells absorb minimal energy at this frequency. Generating the heat intracellularly instead of extracellularly results in the cell's membrane, which is an effective thermal barrier, enhancing the process by keeping the heat within the cell instead of outside of the cell. This process is enhanced by the nuclear differences between cancer cells and normal cells and by the energy changes characteristic of structural and conformational changes in the deoxyribonucleic acid and the histones of the nucleus including their interrelationship. This process promises great efficacy in the diagnosis and the treatment of neoplastic and also perhaps of artherosclerotic diseases.

Arteriosclerosis↗

Biophysical shunt theory for neuropsychopathology: Part I.

We present a new model of the origin of schizophrenia based on biophysical ionic shunts in neuronal (electrical) pathways. Microstructural and molecular evidence is presented for the way in which changes in the neuronal membrane ionic channels may facilitate membrane property rearrangement, leading to a change in the density and composition of the ion channel charge which in turn causes a change in ionic flow orientation and distribution. We suggest that, under abnormal conditions, ionic flow shunts are created which redirect the biophysical collateral neuronal (electrical) pathways, resulting in psychiatric signs and symptoms. This model is complementary to the biological basis of schizophrenia.

Biophysical Phenomena↗

In vivo plasma membrane organization: results of biophysical approaches.

In the last two decades, various biophysical techniques have been used to investigate the organization of the plasma membrane in live cells. This review describes some of the most important experimental findings and summarizes the characteristics and limitations of a few frequently used biophysical techniques. In addition, the current knowledge about three membrane organizational elements: the membrane-associated cytoskeleton, caveolae and lipid microdomains, is described in detail. Unresolved issues, experimental contradictions and future directions to integrate the variety of experimental data into a revised model of the plasma membrane of eukaryotic cells are discussed in the last section.

Actins↗

Measuring metabolism and biophysical flux in the tissue, cellular and sub-cellular domains: recent developments in self-referencing amperometry for physiological sensing.

Ultimately, advances in genomics, proteomics and metabolomics will be realized by combining these approaches with biophysical sensors for understanding the functional and structural (physiological) aspects of sub-cellular systems (cytomics). Therefore, the emergence of the new fields of cytomics and physiomics will require new technologies to probe the functional realm of living cells. While amperometric sensors have been used, their sensitivity and reliability are significantly improved through the development of new strategies and data acquisition systems for the operation of the sensors. This includes the application of the principles of the vibrating or self-referencing microsensor to the operation of amperometric sensors. The development of self-referencing amperometry (SRA) is significant because it effectively converts static concentration sensors into dynamic biophysical sensors that directly monitor physiological flux. SRA has been developed for analytes such as O2, NO, H2O2 and ascorbate. These sensors have been validated against non-biological microscopic flux sources that were theoretically modeled, before being applied to biological research. This new sensor technology has been shown, through research in a wide variety of biological and biomedical research projects, to be an important new tool in the arsenal of the cell biologist. SRA technology has been adapted through SRA-H2O2 and SRA-NADH sensors, for electrochemically coupled enzyme based self-referencing biosensors (SRB) for glucose, glutamate and ethanol. These developments in self-referencing sensor technologies offer great promise in extending electroanalytical chemistry and biosensor technologies from the micro to the nanoscale where researchers can study physiology at the sub-cellular and organellar levels.

Animals↗

Synaptic modifications depend on synapse location and activity: a biophysical model of STDP.

In spike-timing-dependent plasticity (STDP) the synapses are potentiated or depressed depending on the temporal order and temporal difference of the pre- and post-synaptic signals. We present a biophysical model of STDP which assumes that not only the timing, but also the shapes of these signals influence the synaptic modifications. The model is based on a Hebbian learning rule which correlates the NMDA synaptic conductance with the post-synaptic signal at synaptic location as the pre- and post-synaptic quantities. As compared to a previous paper [Saudargiene, A., Porr, B., Worgotter, F., 2004. How the shape of pre- and post-synaptic signals can influence stdp: a biophysical model. Neural Comp.], here we show that this rule reproduces the generic STDP weight change curve by using real neuronal input signals and combinations of more than two (pre- and post-synaptic) spikes. We demonstrate that the shape of the STDP curve strongly depends on the shape of the depolarising membrane potentials, which induces learning. As these potentials vary at different locations of the dendritic tree, model predicts that synaptic changes are location dependent. The model is extended to account for the patterns of more than two spikes of the pre- and post-synaptic cells. The results show that STDP weight change curve is also activity dependent.

Action Potentials↗

Biophysical properties of homomeric and heteromultimeric channels formed by cardiac connexins.

Substantial advances have been made in characterizing the biophysical properties of channels formed exclusively by connexin isoforms expressed mainly in the heart, e.g., Cx43, Cx45 or Cx40. These properties include transjunctional and transmembrane voltage gating as well as their perm-selectivity, chemical gating and, at a single channel level, their multiple open states and changes in mode behavior. Nonetheless, these connexins are rarely expressed individually in a cell and the presence of functional channels constituted by distinct connexin isoforms is now suspected to be a norm. In fact, combinations of the connexins that form heteromeric channels have been described in some tissues, increasing the necessity to reinforce the research that leads to understanding the effects of these heteromeric interaction on the gating and conducting characteristics of the channels. Furthermore, protein-protein interaction studies will help to understand which connexin domains are involved in these interactions and how they affect the physiology of channels and their interaction with other biological and structural molecules in the cell. New information on the biophysical properties of heteromultimeric channels suggests that interaction between connexins and connexons is not as simple as once thought. Theoretically, changes in the coupling of homomeric connexons (Cx43) in the myocardium may not be significant enough to change the physiology of the heart or to incite arrhythmias, but when heteromeric channels are present, alteration in conductance, differential gating sensitivity to bio-gating molecules and changes in voltage sensitivity increase substantially the cell resources to modulate intercellular coupling, which may participate in the physiology and/or pathology of the cardiovascular tissues.

Animals↗

Biophysical and morphological changes in the stratum corneum lipids induced by UVB irradiation.

BACKGROUND: UV irradiation induces a variety of responses in the epidermis, including sunburn cell formation, epidermal hyperplasia, and epidermal permeability barrier disruption. OBJECTIVE: The aim of present study was to assess the effects of UVB irradiation in the intercellular lipids in murine stratum corneum. METHODS: Adult hairless mice were exposed to a single UVB dose (0.15 J/cm(2)), the Fourier transform infrared (FT-IR) spectroscopic study was performed to investigate the effect on the biophysical changes in the stratum corneum lipids, barrier function was monitored by transepidermal water loss (TEWL) measurement, and the morphological alterations of stratum corneum was examined by electron microscopy using ruthenium tetroxide postfixation. RESULTS: The FT-IR spectroscopic study revealed that there was the shift to higher wavenumbers of the symmetric and asymmetric stretching peaks near 2850 and 2920 cm(-1) respectively at days 3-4 after a single UVB irradiation, reflecting to the increase in motional freedom of lipids hydrocarbon chains, call as disordering of lipids. Moreover, A single UVB irradiation also caused a significant increase in TEWL, the increase in TEWL began after 2 days and peaked at day 4. Electron microscopic observations revealed that marked morphological abnormalities in the intercellular domains, including abnormal profile of lamellar granules and its contents at the interface between stratum corneum and stratum granulosum and the persistence of the nuclei in the stratum corneum. Moreover, the separated fragmentary lipid lamellae, excessive numbers of lamellae in stacks, both the elongated and enlarged lacuna as well as the extracellular whorls were present within the widen space of the stratum corneum. CONCLUSION: The both of biophysical and morphological changes of the stratum corneum lipids may reflect to the mechanisms of perturbation of the epidermal permeability barrier induced by UVB irradiation.

Animals↗

Management of a chronic lumbar disk herniation with chiropractic biophysics methods after failed chiropractic manipulative intervention.

OBJECTIVE: To discuss the use of chiropractic biophysics methods in the treatment and rehabilitation of a patient with a chronic disk herniation at the L5-S1 disk, retrolisthesis of L5, and a reduced lumbar lordosis. CLINICAL FEATURES: A 23-year-old woman suffered from chronic unremitting symptoms of lower back pain and left-leg pain. She was treated five years prior, without relief. Diagnosis at that time was low-back pain and lumbar subluxation. Approximately 3 years later, she was evaluated by an orthopedic surgeon. Magnetic resonance imaging showed a moderate posterior disk protrusion at L5-S1 with degeneration. INTERVENTION AND OUTCOME: Chiropractic treatment of this patient consisted of mirror-image chiropractic adjustments, 3-point bending lumbar extension traction, and postural exercises. The patient responded well with a complete resolution of her symptoms and a restoration of her lumbar lordosis. CONCLUSION: This article suggests that successful management of chronic low-back pain symptoms may require a close analysis of a patient's postural deviations and sagittal plane curves. This study suggests that it is possible to restore lumbar lordosis in some cases and this may have an unforeseen benefit to the patient. Further study is warranted into the treatment of chronic low-back pain with chiropractic biophysics methods.

Adult↗

Fetal assessment based on fetal biophysical profile scoring: experience in 19,221 referred high-risk pregnancies. II. An analysis of false-negative fetal deaths.

The incidence of false-negative fetal death, which is defined as stillbirth unrelated to major anomaly or alloimmunization occurring after a last normal fetal biophysical score, was determined in 19,221 referred high-risk pregnancies. The calculated rate of fetal death after a last normal test was 0.726/1000 (14 deaths), which remained relatively constant despite a progressive increase in tests and patients studied. We conclude that a normal fetal biophysical profile score confers a high probability of perinatal survival.

Amniotic Fluid↗

Structural elements in domain IV that influence biophysical and pharmacological properties of human alpha1A-containing high-voltage-activated calcium channels.

We have cloned two splice variants of the human homolog of the alpha1A subunit of voltage-gated Ca2+ channels. The sequences of human alpha1A-1 and alpha1A-2 code for proteins of 2510 and 2662 amino acids, respectively. Human alpha1A-2alpha2bdeltabeta1b Ca2+ channels expressed in HEK293 cells activate rapidly (tau+10mV = 2.2 ms), deactivate rapidly (tau-90mV = 148 micros), inactivate slowly (tau+10mV = 690 ms), and have peak currents at a potential of +10 mV with 15 mM Ba2+ as charge carrier. In HEK293 cells transient expression of Ca2+ channels containing alpha1A/B(f), an alpha1A subunit containing a 112 amino acid segment of alpha1B-1 sequence in the IVS3-IVSS1 region, resulted in Ba2+ currents that were 30-fold larger compared to wild-type (wt) alpha1A-2-containing Ca2+ channels, and had inactivation kinetics similar to those of alpha1B-1-containing Ca2+ channels. Cells transiently transfected with alpha1A/B(f)alpha2bdeltabeta1b expressed higher levels of the alpha1, alpha2bdelta, and beta1b subunit polypeptides as detected by immunoblot analysis. By mutation analysis we identified two locations in domain IV within the extracellular loops S3-S4 (N1655P1656) and S5-SS1 (E1740) that influence the biophysical properties of alpha1A. alpha1AE1740R resulted in a threefold increase in current magnitude, a -10 mV shift in steady-state inactivation, and an altered Ba2+ current inactivation, but did not affect ion selectivity. The deletion mutant alpha1ADeltaNP shifted steady-state inactivation by -20 mV and increased the fast component of current inactivation twofold. The potency and rate of block by omega-Aga IVA was increased with alpha1ADeltaNP. These results demonstrate that the IVS3-S4 and IVS5-SS1 linkers play an essential role in determining multiple biophysical and pharmacological properties of alpha1A-containing Ca2+ channels.

Amino Acid Sequence↗