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PubMedDate not supplied

[The effect of the drug-induced activation and deprivation of the sympathetic nervous system on aldosterone receptor binding by the kidney with disturbed neurotrophic support].

The results of studies are presented on the determination of aldosterone accumulation by mineralocorticoid receptors on cytoplasm and nuclei of normal rat renal tubules as well as in disturbed neurotrophic supply of the kidney including that against the background of activation and deprivation of the sympathetic nervous system function. It was shown that a pharmacological stimulation of sympathetic nervous system potentiated functional disturbances of the renal mineralocorticoid receptor apparatus in reflex dystrophy of the kidney. A simultaneous pharmacological blockade both of neural and of humoral transmission of pathological stimuli from damaged sciatic nerve to the kidney prevented the development of these disturbances. A belief is stated that there is a possibility of using adrenoceptor blockers as means to prevent or inhibit the development of dystrophic alterations in the organism which appear under the lesion of one or other part of the nervous system.

Aldosterone↗

PubMed1997

Functional activation of cerebral blood flow after cardiac arrest in rat.

After a period of global cerebral ischemia, CO2 reactivity and the hemodynamic-metabolic activation to functional stimulation are transiently suppressed. This raises the question of whether the impaired functional coupling reflects disturbances of functional integrity of the brain or an impaired cerebrovascular reactivity. We, therefore, compared the recovery of CO2 reactivity with that of somatosensory evoked potentials, functional flow activation and neurologic deficits in a rodent model of cardiac arrest-induced cerebral ischemia, followed by up to 7 days of reperfusion. Cardiac arrest of 10 minutes' duration was produced in 24 animals by electrical fibrillation of the heart. Five animals were sham-operated controls. Resuscitation was performed by external cardiac massage, using standard resuscitation procedures. Functional activation was carried out under chloralose anesthesia by electrical stimulation of forepaws. CO2 reactivity was tested by ventilation of animals with 6% CO2. During functional and hypercapnic stimulation CBF was measured in the somatosensory cortex using laser-Doppler flowmetry, and at the end of the experiment by 14C-iodoantipyrine autoradiography. Neurologic deficits were scored by evaluating consciousness and various sensory and motor functions. In control animals 6% CO2 increased CBF measured by laser-Doppler flowmetry by 28.8% +/- 8.7%. Forepaw stimulation generated somatosensory evoked potentials with an amplitude of 750 +/- 217 microV and increased CBF measured by laser-Doppler flowmetry by 86.0% +/- 18.1%. After return of spontaneous circulation, CO2 reactivity was transiently reduced to about 30% of control at 1 hour of reperfusion (P < 0.05) but returned to near control at 5 hours. Somatosensory evoked potential amplitudes were reduced to 15% of control at 45 minutes of reperfusion and returned to only 50% to 60% at 3 and 7 days after return of spontaneous circulation (P < 0.05). Functional activation of blood flow was completely suppressed during the first hour after return of spontaneous circulation but also recovered to 50% to 60% of control at 3 days after return of spontaneous circulation (P < 0.05). Linear regression analysis revealed a significant correlation between recovery of functional activation of blood flow and both recovery of the amplitude of somatosensory evoked potentials (P = 0.03) and the neurologic deficit score (P = 0.02), but not between neurologic deficit score and recovery of CO2 reactivity or somatosensory evoked potential amplitudes. These data demonstrate that the suppression of functional activation of blood flow after 10 minutes cardiac arrest is not related to impairment of coupling mechanisms but reflects ongoing disturbances of the functional integrity of the brain. Assessment of functional flow coupling is a reliable way to study postischemic recovery of the brain.

Animals↗

PubMed2003

Timing of neural responses in cortical organotypic slices.

Timing is a fundamental part of sensory and motor processing. However, little is known about the neural mechanisms underlying timing in the range of tens to hundreds of milliseconds. Although many theoretical hypotheses have been put forth on the possible underpinnings of temporal processing, there is little cellular experimental data, particularly in vitro, as to the neural mechanisms that could potentially function as timers. We use organotypic cortical slices to show that reliably timed action potentials (or excitatory postsynaptic potentials) can be observed up to 300 ms after a single stimulus. There was no relationship between the latency of the late responses and distance from the stimulating electrode. Paired recordings and pharmacological manipulations suggest that the timed late responses are the result of the propagation of activity throughout functionally defined networks. These results show that cortical networks may be intrinsically able to process temporal information.

2-Amino-5-phosphonovalerate↗

PubMed1997

Expression and function of the cardiac Na+/Ca2+ exchanger in postnatal development of the rat, in experimental-induced cardiac hypertrophy and in the failing human heart.

The diastolic and systolic dysfunction in the failing heart appear to be related to the altered Ca2+ handling of the cardiac myocyte. Disturbed Ca2+ handling might also affect influx and efflux of other ions, including Na+. In this context, the cardiac sarcolemmal Na+/Ca2+ exchanger represents an important exchange mechanism of Ca2+ versus Na+ transport across the sarcolemma. Expression and function of cardiac Na+/Ca2+ exchanger is highest in newborn rats and declines gradually in postnatal development. In pressure overload-induced hypertrophy, expression of cardiac Na+/Ca2+ exchanger is increased and translated into increased Na+/Ca2+ exchanger activity similar to the early phase of postnatal development in the rat. This suggests a common underlying mechanism in the control of Na+/ Ca2+ exchanger expression in the immature and the hypertrophied myocardium. Similar to experimental-induced hypertrophy, mRNA, protein and activity of Na+/ Ca2+ exchanger is increased in the failing human heart suggesting an increase in the number of functional exchanger molecules rather than an enhanced exchange rate by preexisting exchanger molecules. The potential functional implications of an increased cardiac Na+/Ca2+ exchanger activity in human heart failure may be limitation of diastolic intracellular Ca2+ overload. However, this may increase the arrhythmogenic potential of the failing heart, since additional Na+ influx via Na+/Ca2+ exchanger may affect the membrane potential.

Aging↗

PubMed2001

Bose-Einstein condensates in standing waves: the cubic nonlinear Schrödinger equation with a periodic potential.

We present a new family of stationary solutions to the cubic nonlinear Schrödinger equation with an elliptic function potential. In the limit of a sinusoidal potential our solutions model a quasi-one-dimensional dilute gas Bose-Einstein condensate trapped in a standing light wave. Provided that the ratio of the height of the variations of the condensate to its dc offset is small enough, both trivial phase and nontrivial phase solutions are shown to be stable. Recent developments allow for experimental investigation of these predictions.

Journal Article↗

PubMed1999

Concepts in functional foods: the case of inulin and oligofructose.

Recent advances in biosciences support the hypothesis that diet modulates various body functions. Diet may maintain well-being and reduce the risk of some diseases. Such discoveries have led to the concept of "functional food" and the development of the new discipline, i.e., "functional food science." A practical and simple definition of a "functional food" is a food for which a claim has been authorized. The food components to be discussed as potential "functional food ingredients" are the inulin-type fructans, i.e., chicory inulin and oligofuctose. The targets for their effects are the colonic microflora, the gastrointestinal physiology, the immune functions, the bioavailability of minerals, the metabolism of lipids and colonic carcinogenesis. Potential health benefits include reduction of risk of colonic diseases, noninsulin-dependent diabetes, obesity, osteoporosis and cancer. The documentation of such benefits requires scientific evidence that must be evaluated in terms of "health claims." Previous assessments have concluded that, in terms of "functional claims," strong evidence exists for a prebiotic effect and improved bowel habit. The evidence for calcium bioavailability is promising, and positive modulation of triglyceride metabolism is undergoing preliminary evaluation. Scientific research still must be done to support any "disease risk reduction claim," but sound hypotheses do already exist for designing the relevant human nutrition trials.

Biological Availability↗

PubMed2005

Akt3 overexpression in the heart results in progression from adaptive to maladaptive hypertrophy.

Akt is a serine/threonine kinase that mediates a variety of cellular responses to external stimuli. Among the three members of mammalian Akt (Akt1, Akt2 and Akt3), Akt3 is unique in that it has an alternatively spliced variant that lacks the carboxy-terminal regulatory phosphorylation site. However, little is known regarding in vivo functions of Akt3 and its spliced variant. In this study we investigated the potential functions of the Akt3 spliced variant by overexpressing its activated form in the heart. Cardiac-specific Akt3 transgenic (TG) mice exhibited marked cardiac hypertrophy. Contractile function of TG hearts was preserved at 4 and 12 weeks, but was impaired at 20 weeks of age. When treated with cardiotoxic drug doxorubicin (Dox), TG mice at 4 weeks of age exhibited improved survival and preserved contractile function. However, these cardioprotective effects were not evident when Dox was injected at 12 weeks of age, and TG mice exhibited even higher mortality rate than wild-type animals when Dox was injected at 20 weeks of age. Endogenous Akt1 and Akt2 protein and phosphorylation levels were downregulated in Akt3 TG hearts, suggesting the existence of negative feedback regulation of Akt signaling at the level of Akt protein amount. Taken together, the Akt3 spliced variant is functional in vivo, promotes cardiac growth and mediates cardioprotective effects. However, continuous overexpression of Akt3 results in contractile dysfunction and increased susceptibility to cardiac injury. Thus, sustained activation of Akt signaling results in progression from adaptive to maladaptive hypertrophy.

Animals↗

PubMed2000

Direct molecular interaction of a conserved yolk granule protein in sea urchins.

The regulation of yolk storage in oocytes and subsequent utilization in embryos is critical for embryogenesis. In sea urchins, the major yolk protein is made in the intestines, transported to the ovaries and accumulated in developing oocytes within membrane-bound vesicles comprising approximately 10% of the mass of an egg. Here, a non-yolk protein that accumulates specifically in yolk granules is reported. This protein was identified by cDNA cloning and, by use of antibodies to the recombinant protein, it was shown that this molecule is stored selectively in yolk granules of oocytes and embryos. No accumulation was seen in the accessory cells, testis, or intestines. In situ ribonucleic acid (RNA) hybridizations showed that the transcript accumulated only in oocytes, and was more highly concentrated in young oocytes. However, later in oogenesis, the messenger ribonucleic acid (mRNA) levels decreased significantly so that no signal was detectable in mature haploid eggs or at any later stage in development. However, by immunofluorescence and western blot analysis, the 30 kDa band was present throughout development. The predicted sequence of this protein shows that it is a member of the bep, HLC-32, EBP family of sea urchin proteins, but as it does not accumulate at the cell surface, nor in the hyaline layer in the two species studied here, as do other members of the family, it has been referred to as YP30 (30 kDa protein of the yolk platelet). To address its potential function, yeast two-hybrid analysis was performed to screen for proteins that potentially interact with YP30. It was found that it binds itself, and forms strongly interacting dimers. It is hypothesized that YP30 participates in the packaging and storage of major yolk protein during oogenesis, or in the utilization of the major yolk protein in development.

Amino Acid Sequence↗

PubMed2004

A common cross-species function for the double epidermal growth factor-like modules of the highly divergent plasmodium surface proteins MSP-1 and MSP-8.

An understanding of structural and functional constraints on the C-terminal double epidermal growth factor (EGF)-like modules of merozoite surface protein (MSP)-1 and related proteins is of importance to the development of these molecules as malaria vaccines and drug targets. Using allelic replacement, we show that Plasmodium falciparum parasites can invade erythrocytes and grow efficiently in the absence of an MSP-1 protein with authentic MSP-1 EGF domains. In this mutant parasite line, the MSP-1 EGFs were replaced by the corresponding double EGF module from P. berghei MSP-8, the sequence of which shares only low identity with its MSP-1 counterpart. Hence, the C-terminal EGF domains of at least some Plasmodium surface proteins appear to perform the same function in asexual blood-stage development. Mapping the surface location of the few residues that are common to these functionally complementary EGF modules revealed the presence of a highly conserved pocket of potential functional significance. In contrast to MSP-8, an even more divergent double EGF module, that from the sexual stage protein PbS25, was not capable of complementing MSP-1 EGF function. More surprisingly, two chimeric double EGF modules comprising hybrids of the EGF domains from P. falciparum and P. chabaudi MSP-1 were also not capable of replacing the P. falciparum MSP-1 EGF module. Together, these data suggest that although the MSP-1 EGFs can accommodate extensive sequence diversity, there appear to be constraints that may restrict the simple accumulation of point mutations in the face of immune pressure in the field.

Alleles↗

PubMed2005

Relativistic kicked rotor.

Transport properties in the relativistic analog of the periodically kicked rotor are contrasted under classically and quantum mechanical dynamics. The quantum rotor is treated by solving the Dirac equation in the presence of the time-periodic delta-function potential resulting in a relativistic quantum mapping describing the evolution of the wave function. The transition from the quantum suppression behavior seen in the nonrelativistic limit to agreement between quantum and classical analyses in the relativistic regime is discussed. The absence of quantum resonances in the relativistic case is also addressed.

Journal Article↗

PubMed1997

Tie2 expression and phosphorylation in angiogenic and quiescent adult tissues.

Angiogenesis, the process of new vessels sprouting from the existing vasculature, is a critical process during early development. However, angiogenesis rarely occurs in the adult, except in response to cyclic hormonal stimulation in the ovary and uterus, in response to injury, and in response to pathological conditions such as tumorigenesis and diabetes mellitus. Tie2 (also known as Tek) is a novel endothelium-specific receptor tyrosine kinase, which has been demonstrated to be essential for the development of the embryonic vasculature; Tie2 knockout mice die by embryonic day 10.5 with specific defects in the formation of microvessels. Tie2 is downregulated later in embryogenesis, and its function in the adult has been relatively unexplored. To gain insight into the potential functions of Tie2 in the adult vasculature, Tie2 expression was examined in adult tissues undergoing angiogenesis and in quiescent tissues. Tie2 expression was localized by immunohistochemistry to the endothelium of neovessels in rat tissues undergoing angiogenesis during hormonally stimulated follicular maturation and uterine development and in healing skin wounds. Immunoprecipitation and RNase protection assay demonstrated upregulation of Tie2 protein and mRNA in rat and mouse skin wounds, respectively. Moreover, Tie2 immunoprecipitated from skin wounds was tyrosine-phosphorylated, indicating active downstream signaling. Surprisingly, Tie2 was also expressed in the entire spectrum of the quiescent vasculature (arteries, veins, and capillaries) in a wide range of adult tissues, and Tie2 immunoprecipitated from quiescent adult tissues was also tyrosine-phosphorylated. Together, these results suggest a dual function for Tie2 in adult tissues involving both angiogenesis and vascular maintenance.

Aging↗

PubMed2002

Proteomic tools for biomedicine.

Proteomic tools measure gene expression, protein activity and interactions of biological events at the protein level. Proteins are the major catalysts of biological functions and contain several dimensions of information that collectively indicate the actual rather than the potential functional state as indicated by mRNA analysis. Measurements can be made in terms of protein quantity, location, and time-point. For the future we see a further integration of existing and new technologies for proteomics from a wide range of areas of biochemistry, chemistry, physics, computing science and molecular biology. This will further advance our knowledge of how biological systems are built up and what mechanisms control these systems. However, the potential of proteomics to comprehensively answer all biological questions is limited as only protein activity is measured. A unification of genomics, proteomics, and other technologies is needed if we are to start to understand the complexity of biological function in the context of disease and health.

Proteome↗

PubMed2006

Semaphorin3A regulates synaptic function of differentiated hippocampal neurons.

Semaphorins are major chemorepellents for developing neuronal projections. Their persistent expression at adult stages suggests that they may contribute to the functioning of neuronal circuits. We investigated the functional properties of semaphorin3A (Sema3A) in adult hippocampal neurons, and report that exogenous application of this cue decreases the efficacy of synaptic transmission evoked in the CA1 region of hippocampal slices. In situ hybridization, imaging and biochemical techniques showed that the Sema3A receptor component neuropilin-1 is present at hippocampal synapses and localizes in the presynaptic membrane. In differentiated cultured hippocampal neurons, Sema3A elicited Erk1/2 phosphorylation in somata and neuritic compartments. Furthermore, Sema3A application resulted in a striking reduction of synaptophysin and postsynaptic density 95 puncta without affecting the axon diameter. These observations reveal novel functional potentialities for secreted semaphorins, which suggest that these cues could modulate the morphology and function of synapses in the adult brain.

Animals↗

PubMed2002

Contribution of cytophaga-like bacteria to the potential of turnover of carbon, nitrogen, and phosphorus by bacteria in the rhizosphere of barley (Hordeum vulgare L.).

The functional potential of bacteria isolated from the rhizosphere of barley (Hordeum vulgare L.) in May, July, and August and cultivated on nutrient-rich substrate (1/10 TSBA) and nutrient-poor substrate (cold soil extract agar) was determined. There was no significant difference in numbers of CFU when counted on nutrient rich or poor substrate. Bacterial numbers increased approximately 3-fold in the rhizosphere soil from May to August but was unchanged in bulk soil over the same period. A total of 4474 randomly isolated bacteria were screened for enzymatic activities involved in carbon turnover (amylase, cellulase, mannanase, xylanase, and chitinase), nitrogen turnover (protease, nitrate and nitrite reductase), and phosphate turnover (phosphatase). In the rhizosphere soil, bacteria carrying C and P turnover enzymes were not stimulated by the growing plant whereas protease and nitrate and nitrite reductase were stimulated by the growing plant. No changes were observed in the bulk soil. Two taxonomic groups were followed: Cytophaga-like bacteria (CLB) and fluorescent pseudomonads, the latter being abundant in the rhizosphere and important contributors to the cycling of organic matter in soil. Unexpectedly in the spring samples, CLB were around 25% of all bacteria isolated, whereas fluorescent pseudomonads made up less than 10%. The relative proportion of these bacterial groups then decreased during the plant growth season but at all times showing a clear rhizosphere effect. Furthermore, up to 70% of the isolates carrying enzymes involved in the turnover of carbon, in the May sample, were identified as CLB, indicating the importance of this group in early colonization of the rhizosphere. The fluorescent pseudomonad group contributed less than 3%.

Carbon↗

PubMed1996

Identification of functional elements in unaligned nucleic acid sequences by a novel tuple search algorithm.

We present an algorithm to identify potential functional elements like protein binding sites in DNA sequences, solely from nucleotide sequence data. Prerequisites are a set of at least seven not closely related sequences with a common biological function which is correlated to one or more unknown sequence elements present in most but not necessarily all of the sequences. The algorithm is based on a search for n-tuples which occur at least in a minimum percentage of the sequences with no or one mismatch, which may be at any position of the tuple. In contrast to functional tuples, random tuples show no preferred pattern of mismatch locations within the tuple nor is the conservation extended beyond the tuple. Both features of functional tuples are used to eliminate random tuples. Selection is carried out by maximization of the information content first for the n-tuple, then for a region containing the tuple and finally for the complete binding site. Further matches are found in an additional selection step, using the ConsInd method previously described. The algorithm is capable of identifying and delimiting elements (e.g. protein binding sites) represented by single short cores (e.g. TATA box) in sets of unaligned sequences of about 500 nucleotides using no information other than the nucleotide sequences. Furthermore, we show its ability to identify multiple elements in a set of complete LTR sequences (more than 600 nucleotides per sequence).

Algorithms↗

PubMed2003

A thin-film electrochemical study of the "blue" copper proteins, auracyanin A and auracyanin B, from the photosynthetic bacterium Chloroflexus aurantiacus: the reduction potential as a function of pH.

The reversible formal potentials of auracyanin A and auracyanin B, two closely related "blue" copper proteins from the photosynthetic bacterium Chloroflexus aurantiacus, have been determined by protein film voltammetry in the range 4<or=pH<or=9. At pH 7 in 0.1 M NaCl, the values of for auracyanin A and auracyanin B are 205+/-7 mV and 215+/-7 mV, respectively, versus the standard hydrogen electrode. In both cases there is a smooth but non-sigmoidal change in from approximately 190 mV at pH 9 to approximately 240 mV at pH 4. The small changes in as a function of pH indicate that auracyanin A and auracyanin B differ from those "blue" copper proteins in which the Cu site in the reduced (Cu(I)) state switches to a redox-inhibited form at low pH. For auracyanin A, the results obtained by protein film voltammetry are closely similar to those obtained by the conventional spectroelectrochemical method. The findings are discussed in relation to the putative role of auracyanin in biological electron transfer.

Azurin↗

PubMed2005

The transcript composition of egg cells changes significantly following fertilization in wheat (Triticum aestivum L.).

Here, we report the transcript profile of wheat egg cells and proembryos, just after the first cell division. Microdissected female gametophytes of wheat were used to isolate eggs and two-celled proembryos to construct cell type-specific cDNA libraries. In total, 1197 expressed sequence tags (ESTs) were generated. Analysis of these ESTs revealed numerous novel transcripts. In egg cells, 17.6% of the clustered ESTs represented novel transcripts, while 11.4% novel clusters were identified in the two-celled proembryo. Functional classification of sequences with similarity to previously characterized proteins indicates that the unfertilized egg cell has a higher metabolic activity and protein turnover than previously thought. Transcript composition of two-celled proembryos was significantly distinct from egg cells, reflecting DNA replication as well as high transcriptional and translational activity. Several novel transcripts of the egg cell are specific for this cell. In contrast, some fertilization induced novel mRNAs are abundant also in sporophytic tissues indicating a more general role in plant growth and development. The potential functions of genes based on similarity to known genes involved in developmental processes are discussed. Our analysis has identified numerous genes with potential roles in embryo sac function such as signaling, fertilization or induction of embryogenesis.

Computational Biology↗

PubMed2005

Phosphodiesterase-Ialpha/autotaxin (PD-Ialpha/ATX): a multifunctional protein involved in central nervous system development and disease.

Phosphodiesterase-Ialpha/autotaxin (PD-Ialpha/ATX) was originally identified as a cell-motility-stimulating factor secreted by a variety of tumor cells. Thus, studies related to its potential functional roles have traditionally focused on tumorigenesis. PD-Ialpha/ATX's catalytic activity, initially defined as nucleotide pyrophosphatase/phosphodiesterase, was soon recognized as being necessary for its tumor cell-motility-stimulating activity. However, only the discovery of PD-Ialpha/ATX's identity with lysophospholipase D, an extracellular enzyme that converts lysophosphatidylcholine into lysophosphatidic acid (LPA) and potentially sphingosylphosphoryl choline into sphingosine 1-phosphate (S1P), revealed the actual effectors responsible for PD-Ialpha/ATX's ascribed motogenic functions, i.e., its catalytic products. PD-Ialpha/ATX has also been detected during normal development in a number of tissues, in particular, the central nervous system (CNS), where expression levels are high. Similar to tumor cells, PD-Ialpha/ATX-expressing CNS cells secrete catalytically active PD-Ialpha/ATX into the extracellular environment. Thus, it appears reasonable to assume that PD-Ialpha/ATX's CNS-related functions are mediated via lysophospholipid, LPA and potentially S1P, signaling. However, recent studies identified PD-Ialpha/ATX as a matricellular protein involved in the modulation of oligodendrocyte-extracellular matrix interactions and oligodendrocyte remodeling. This property of PD-Ialpha/ATX was found to be independent of its catalytic activity and to be mediated by a novel functionally active domain. These findings, therefore, uncover PD-Ialpha/ATX, at least in the CNS, as a multifunctional protein able to induce complex signaling cascades via distinct structure-function domains. This Mini-Review describes PD-Ialpha/ATX's multifunctional roles in the CNS and discusses their potential contributions to CNS development and pathology.

Animals↗