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Results for “Integrated functions”

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PubMed1998

The integral membrane protein snl1p is genetically linked to yeast nuclear pore complex function.

Integral membrane proteins are predicted to play key roles in the biogenesis and function of nuclear pore complexes (NPCs). Revealing how the transport apparatus is assembled will be critical for understanding the mechanism of nucleocytoplasmic transport. We observed that expression of the carboxyl-terminal 200 amino acids of the nucleoporin Nup116p had no effect on wild-type yeast cells, but it rendered the nup116 null strain inviable at all temperatures and coincidentally resulted in the formation of nuclear membrane herniations at 23 degrees C. To identify factors related to NPC function, a genetic screen for high-copy suppressors of this lethal nup116-C phenotype was conducted. One gene (designated SNL1 for suppressor of nup116-C lethal) was identified whose expression was necessary and sufficient for rescuing growth. Snl1p has a predicted molecular mass of 18.3 kDa, a putative transmembrane domain, and limited sequence similarity to Pom152p, the only previously identified yeast NPC-associated integral membrane protein. By both indirect immunofluorescence microscopy and subcellular fractionation studies, Snl1p was localized to both the nuclear envelope and the endoplasmic reticulum. Membrane extraction and topology assays suggested that Snl1p was an integral membrane protein, with its carboxyl-terminal region exposed to the cytosol. With regard to genetic specificity, the nup116-C lethality was also suppressed by high-copy GLE2 and NIC96. Moreover, high-copy SNL1 suppressed the temperature sensitivity of gle2-1 and nic96-G3 mutant cells. The nic96-G3 allele was identified in a synthetic lethal genetic screen with a null allele of the closely related nucleoporin nup100. Gle2p physically associated with Nup116p in vitro, and the interaction required the N-terminal region of Nup116p. Therefore, genetic links between the role of Snl1p and at least three NPC-associated proteins were established. We suggest that Snl1p plays a stabilizing role in NPC structure and function.

Amino Acid Sequence↗

PubMedDate not supplied

[Disorders of the integrative brain functions in posttraumatic hydrocephalus].

As many as 110 patients with posttraumatic hydrocephalus in the remote period of mild closed craniocerebral injury underwent routine neuropsychologic evaluation. 80.9% of the patients presented with disorders of higher integrative functions of the brain; of these, 72.7% appeared to get too easily fatigued, their mental processes running to exhaustion too soon. In decreasing rank order are disorders of attention, slowing down of those processes relating to abstract thought, power of apprehension and recent memory (62.7%, 60.9%, and 34.5% respectively). Mnestic disturbances prevailed among patients with moderate severity posttraumatic hydrocephalus (40%) and external hydrocephalus (47.8%). Mild degree hydrocephalus was free from disturbances to higher integrative functions of the brain. The aforesaid attests to the need of the nootropic, vasoactive agents, drugs having resolving and dehydrating effects to be included into the combined treatment of the above patient population.

Adolescent↗

PubMed2004

Invited review: formation of keratins in the bovine claw: roles of hormones, minerals, and vitamins in functional claw integrity.

Keratins are the characteristic structural proteins of the highly cornified epidermis of the skin, feathers, and hoof. Keratin proteins provide the structural basis for the unique properties of the biomaterial horn and its protective function against a wide range of environmental factors. Hoof horn is produced through a complex process of differentiation (keratinization) of epidermal cells. Formation and biochemical binding of keratin proteins and synthesis and exocytosis of intercellular cementing substance (ICS) are the hallmarks of keratinization. It is finalized by the programmed death of the living epidermal cells, i.e., cornification, that turns the living epidermal cells into dead horn cells. The latter become connected by the intercellular cementing substance. The functional integrity of hoof horn essentially depends on a proper differentiation, i.e., keratinization of hoof epidermal cells. Keratinization of hoof epidermis is controlled and modulated by a variety of bioactive molecules and hormones. This process is dependent on an appropriate supply of nutrients, including vitamins, minerals, and trace elements. Regulation and control of differentiation and nutrient flow to the epidermal cells play a central role in determining the quality and, consequently, the functional integrity of hoof horn. Decreasing nutrient supply to keratinizing epidermal cells leads to horn production of inferior quality and increased susceptibility to chemical, physical, or microbial damage from the environment. A growing body of evidence suggests that hormones, vitamins, minerals, and trace elements play critical roles in the normal development of claw horn and correct keratin formation.

Animals↗

PubMed2006

Differentiation of the gastric mucosa. I. Role of histamine in control of function and integrity of oxyntic mucosa: understanding gastric physiology through disruption of targeted genes.

Many physiological functions of the stomach depend on an intact mucosal integrity; function reflects structure and vice versa. Histamine in the stomach is synthesized by histidine decarboxylase (HDC), stored in enterochromaffin-like (ECL) cells, and released in response to gastrin, acting on CCK(2) receptors on the ECL cells. Mobilized ECL cell histamine stimulates histamine H(2) receptors on the parietal cells, resulting in acid secretion. The parietal cells express H(2), M(3), and CCK(2) receptors and somatostatin sst(2) receptors. This review discusses the consequences of disrupting genes that are important for ECL cell histamine release and synthesis (HDC, gastrin, and CCK(2) receptor genes) and genes that are important for "cross-talk" between H(2) receptors and other receptors on the parietal cell (CCK(2), M(3), and sst(2) receptors). Such analysis may provide insight into the functional significance of gastric histamine.

Animals↗

PubMed1994

The acute effect of straining on pelvic floor neurological function.

Integrity of sensory and motor function is essential in the maintenance of continence. The pudendal nerve assumes a central role being a mixed sensory and motor nerve. Neuropathic changes may therefore lead to incontinence and stretch injury to the pudendal nerve has been implicated as an aetiological factor. However pudendal neuropathy, altered anal sensation and perineal descent do not always correlate in the same patient. To investigate this further we evaluated the effect of a simulated defaecation strain on pelvic floor neurological function in a group of patients with constipation and incontinence. Pudendal nerve terminal motor latency (PNTML) and anal electrosensitivity (AS) were measured at rest and after a simulated defaecation strain of 1 minute. At rest PNTML correlated with AS (r = 0.461, P = 0.003). Twenty-five patients had perineal descent of more than 1 cm on straining, and 13 had descent below the ischial tuberosities. After 1 minute of straining AS was significantly (P < 0.001) blunted and PNTML was significantly (P < 0.001) prolonged both changes returning to normal after 3 minutes. AS was significantly (P = 0.01) more blunted in patients with perineal descent of more than 1 cm. PNTML was significantly (P = 0.01) more prolonged in patients with perineal descent of more than 2 cm. Age was significantly correlated with AS (r = 0.45, P = 0.004) and PNTML (r = 0.49, P = 0.002). Anal sensation and PNTML are acutely affected by defaecation straining, and changes may occur in patients without perineal descent. Functional changes occur equally in constipated and incontinent patients.

Adult↗

PubMed2003

Survival rate and antioxidant enzyme activity of ram spermatozoa after dilution with different extenders or selection by a dextran swim-up procedure.

The aim of this study was to evaluate the effect of four extenders (Sucrose (S), Galactose (G), milk-yolk (MY), and Fiser (F)) on the motility, membrane integrity, and functional integrity of ram spermatozoa during liquid storage at 15 degrees C. The use of either S or MY for the selection of high quality spermatozoa by a swim-up procedure was comparatively analyzed. Additionally, the activity of three antioxidant enzymes, superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx) was evaluated in both swim-up selected samples maintained at 15 degrees C for 6h. Sperm motility was better preserved in MY and was significantly higher after 6h of incubation than in either S or F (P<0.0001) and G (P<0.0005). Likewise, the incidence of spermatozoa with integral and functional membranes was higher in samples diluted in MY, with no significant decrease after 6h of incubation. The comparative analysis of the swim-up procedure performed with either MY or S revealed that not only was total sperm recovery significantly (P<0.001) higher (67.3%+/-3.21 versus 47.6%+/-3.78), but also that the best survival rate of spermatozoa was found in the MY stored sample. Sperm motility, viability and response to a hypoosmotic swelling (HOS) test were also significantly higher in the MY extended sample, maintaining still significantly higher values after 6h of incubation. In addition, this sample showed higher activity values for the antioxidant defense enzyme system.

Animals↗

PubMed1999

Activity of the Nurr1 carboxyl-terminal domain depends on cell type and integrity of the activation function 2.

Nurr1, a member of the nuclear hormone receptor superfamily, was recently demonstrated to be of critical importance in the developing central nervous system, where it is required for the generation of midbrain dopamine cells. Nuclear receptors encompass a transcriptional activation function (activation function 2; AF2) within their carboxyl-terminal domains important for ligand-induced transcriptional activation. Since a Nurr1 ligand remains to be identified, the role of the Nurr1 AF2 region in transcriptional activation is unclear. However, here we show that the Nurr1 AF2 contributes to constitutive activation independent of exogenously added ligands in human embryo kidney 293 cells and in neural cell lines. Extensive mutagenesis indicated a crucial role of the AF2 core region for transactivation but also identified unique features differing from previously characterized receptors. In addition, Nurr1 did not appear to interact with, and was not stimulated by, several previously identified coactivators such as the steroid receptor coactivator 1. In contrast, adenovirus protein E1A, stably expressed in 293 cells, was shown to contribute to AF2-dependent activation. Finally, while the AF2 core of RXR is required for ligand-induced transcriptional activation by Nurr1-RXR heterodimers, the functional integrity of Nurr1 AF2 core is not critical. These results establish that the ligand binding domain of Nurr1 has intrinsic capacity for transcriptional activation depending on cell type and mode of DNA binding. Furthermore, these results are consistent with the possibility that gene expression in the central nervous system can be modulated by an as yet unidentified ligand interacting with the ligand binding domain of Nurr1.

Adenovirus E1A Proteins↗

PubMed2005

Stratum corneum defensive functions: an integrated view.

Most epidermal functions can be considered as protective, or more specifically, as defensive in nature. Yet, the term "barrier function" is often used synonymously with only one such defensive function, though arguably its most important, i.e., permeability barrier homeostasis. Regardless of their relative importance, these protective cutaneous functions largely reside in the stratum corneum (SC). In this review, I first explore the ways in which the multiple defensive functions of the SC are linked and interrelated, either by their shared localization or by common biochemical processes; how they are co-regulated in response to specific stressors; and how alterations in one defensive function impact other protective functions. Then, the structural and biochemical basis for these defensive functions is reviewed, including metabolic responses and signaling mechanisms of barrier homeostasis. Finally, the clinical consequences and therapeutic implications of this integrated perspective are provided.

Animals↗

PubMed2003

Integrating advanced functionality in a microfabricated high-throughput fluorescent-activated cell sorter.

The integration of complete analyses systems "on chip" is one of the great potentials of microfabricated devices. In this study we present a new pressure-driven microfabricated fluorescent-activated cell sorter chip with advanced functional integration. Using this sorter, fluorescent latex beads are sorted from chicken red blood cells, achieving substantial enrichments at a sample throughput of 12000 cells s(-1). As a part of the sorter chip, we have developed a monolithically integrated single step coaxial flow compound for hydrodynamic focusing of samples in flow cytometry and cell sorting. The structure is simple, and can easily be microfabricated and integrated with other microfluidic components. We have designed an integrated chamber on the chip for holding and culturing of the sorted cells. By integrating this chamber, the risk of losing cells during cell handling processes is eliminated. Furthermore, we have also developed integrated optics for cell detection. Our new design contributes to the ongoing efforts for building a fully integrated micro cell sorting and analysing system.

Animals↗

PubMed2002

Intraoperative neurophysiological monitoring in pediatric neurosurgery: why, when, how?

INTRODUCTION: This review is primarily based on peer-reviewed scientific publications and on the authors' experience in the field of intraoperative neurophysiology. The purpose is a critical analysis of the role of intraoperative neurophysiological monitoring (INM) during various neurosurgical procedures, emphasizing the aspects that mainly concern the pediatric population. Original papers related to the field of intraoperative neurophysiology were collected using medline. INM consists in monitoring (continuous "on-line" assessment of the functional integrity of neural pathways) and mapping (functional identification and preservation of anatomically ambiguous nervous tissue) techniques. We attempted to delineate indications for intraoperative neurophysiological techniques according to their feasibility and reliability (specificity and sensitivity). DISCUSSION AND CONCLUSIONS: In compiling this review, controversies about indications, methodologies and the usefulness of some INM techniques have surfaced. These discrepancies are often due to lack of familiarity with new techniques in groups from around the globe. Accordingly, internationally accepted guidelines for INM are still far from being established. Nevertheless, the studies reviewed provide sufficient evidence to enable us to make the following recommendations. (1) INM is mandatory whenever neurological complications are expected on the basis of a known pathophysiological mechanism. INM becomes optional when its role is limited to predicting postoperative outcome or it is used for purely research purposes. (2) INM should always be performed when any of the following are involved: supratentorial lesions in the central region and language-related cortex; brain stem tumors; intramedullary spinal cord tumors; conus-cauda equina tumors; rhizotomy for relief of spasticity; spina bifida with tethered cord. (3) Monitoring of motor evoked potentials (MEPs) is now a feasible and reliable technique that can be used under general anesthesia. MEP monitoring is the most appropriate technique to assess the functional integrity of descending motor pathways in the brain, the brain stem and, especially, the spinal cord. (4) Somatosensory evoked potential (SEP) monitoring is of value in assessment of the functional integrity of sensory pathways leading from the peripheral nerve, through the dorsal column and to the sensory cortex. SEPs cannot provide reliable information on the functional integrity of the motor system (for which MEPs should be used). (5) Monitoring of brain stem auditory evoked potentials remains a standard technique during surgery in the brain stem, the cerebellopontine angle, and the posterior fossa. (6) Mapping techniques (such as the phase reversal and the direct cortical/subcortical stimulation techniques) are invaluable and strongly recommended for brain surgery in eloquent cortex or along subcortical motor pathways. (7) Mapping of the motor nuclei of the VIIth, IXth-Xth and XIIth cranial nerves on the floor of the fourth ventricle is of great value in identification of "safe entry zones" into the brain stem. Techniques for mapping cranial nerves in the cerebellopontine angle and cauda equina have also been standardized. Other techniques, although safe and feasible, still lack a strong validation in terms of prognostic value and correlation with the postoperative neurological outcome. These techniques include monitoring of the bulbocavernosus reflex, monitoring of the corticobulbar tracts, and mapping of the dorsal columns. These techniques, however, are expected to open up new perspectives in the near future.

Brain Mapping↗

PubMed2006

A scalable method for integration and functional analysis of multiple microarray datasets.

MOTIVATION: The diverse microarray datasets that have become available over the past several years represent a rich opportunity and challenge for biological data mining. Many supervised and unsupervised methods have been developed for the analysis of individual microarray datasets. However, integrated analysis of multiple datasets can provide a broader insight into genetic regulation of specific biological pathways under a variety of conditions. RESULTS: To aid in the analysis of such large compendia of microarray experiments, we present Microarray Experiment Functional Integration Technology (MEFIT), a scalable Bayesian framework for predicting functional relationships from integrated microarray datasets. Furthermore, MEFIT predicts these functional relationships within the context of specific biological processes. All results are provided in the context of one or more specific biological functions, which can be provided by a biologist or drawn automatically from catalogs such as the Gene Ontology (GO). Using MEFIT, we integrated 40 Saccharomyces cerevisiae microarray datasets spanning 712 unique conditions. In tests based on 110 biological functions drawn from the GO biological process ontology, MEFIT provided a 5% or greater performance increase for 54 functions, with a 5% or more decrease in performance in only two functions.

Algorithms↗

PubMed2000

The primate cranial base: ontogeny, function, and integration.

Understanding the complexities of cranial base development, function, and architecture is important for testing hypotheses about many aspects of craniofacial variation and evolution. We summarize key aspects of cranial base growth and development in primates that are useful for formulating and testing hypotheses about the roles of the chondrocranium and basicranium in cranial growth, integration, and function in primate and human evolution. We review interspecific, experimental, and ontogenetic evidence for interactions between the cranial base and brain, and between the cranial base and the face. These interactions indicate that the cranial base plays a key role in craniofacial growth, helping to integrate, spatially and functionally, different patterns of growth in various adjoining regions of the skull such as components of the brain, the eyes, the nasal cavity, the oral cavity, and the pharynx. Brain size relative to cranial base length appears to be the dominant influence on many aspects of basicranial variation, especially the angle of the cranial base in the midsagittal plane, but other factors such as facial size, facial orientation, and posture may also be important. Major changes in cranial base shape appear to have played crucial roles in the evolution of early primates, the origin of anthropoids, and the origin of Homo sapiens.

Animals↗

PubMed1999

Integration of functional magnetic resonance imaging supported by magnetoencephalography in functional neuronavigation

OBJECTIVE: In this study, the intraoperative visualization of functional data provided by functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) leading to functional neuronavigation is demonstrated in surgery around the motor strip. METHODS: In seven patients with lesions adjacent to the central region, fMRI was performed with a 1.5-Tesla magnetic resonance system, using axial echo-planar imaging with a motor and a sensory task. Somatosensory and motor evoked fields were recorded with a biomagnetometer. fMRI and MEG were matched to an anatomic three-dimensional magnetic resonance image set by a contour fit. Then this three-dimensional image data set was transferred to the navigation microscope and displayed in the eyepieces of the microscope during surgery. Additionally, intraoperative recording of somatosensory evoked potentials was performed for verification of the central sulcus. RESULTS: In all cases, the projection of fMRI and MEG data into the operating viewing field allowed easy identification of the central region, which was confirmed by phase reversal of somatosensory evoked potentials in each case. fMRI and MEG measurements yielded corresponding results in each patient. CONCLUSION: Functional neuronavigation with integration of fMRI and MEG allows the fast identification of eloquent brain areas. The widespread availability of fMRI will result in a broad availability of functional neuronavigation, which will, in turn, contribute to the successful surgery of lesions in eloquent brain areas with lower morbidity.

Journal Article↗

PubMed2004

A path integral influence functional for excess electron in fluids: Density-functional formulation.

In this paper, we propose a path integral influence functional from a solvent to determine a self-correlation function of a quantum particle in classical simple fluid. It is shown that the influence functional is related to a grand potential functional of the pure solvent under a three-dimensional external field arising from a classical isomorphic polymer, on which the quantum particle is mapped. The influence functional can be calculated from the self-correlation function, the solute-solvent and the solvent-solvent pair correlation function. The obtained equation of the self-correlation function is applied to an excess electron problem in fluid helium. The Fourier path-integral Monte Carlo method is employed to perform the path integral of the electron. The solute-solvent pair correlation function is estimated from a reference interaction site model integral equation. These results obtained form our proposed influence functional and from that proposed by Chandler, Singh, and Richardson are compared with those provided by a path integral Monte Carlo simulation with the explicit helium solvent.

Journal Article↗

PubMed2001

Preservation of endothelial integrity and function in experimental vascular anastomosis with non-penetrating clips.

BACKGROUND: Vascular repair with sutures is associated with disruption of the endothelial lining and subsequent thrombus formation on the intraluminal lesions. This experimental study was designed to determine whether the use of non-penetrating clips improved endothelial preservation. METHODS: In ten female pigs, 25-mm arteriotomies were made in both carotid arteries. The arteriotomies were repaired with jugular vein patches. On the left side, the repair was done with 1.4-mm titanium clips, and on the right side with two running 6/0 polypropylene sutures. Next, the aorta was divided and subsequently repaired with 2-mm clips in five of these pigs, and with two running 5/0 polypropylene sutures in the remaining five pigs. Endothelial function was studied at the anastomotic site in the carotid arteries by determination of endothelium-dependent and -independent relaxatory responses. Morphometric examination of the carotid arteries and inspection of the aortic endothelium were performed by means of scanning electron microscopy. RESULTS: Maximal endothelium-dependent relaxation to adenosine 5'-diphosphate was less in sutured than in clipped carotid arteries (P < 0.05), while there was no difference in maximal endothelium-independent relaxation to sodium nitrite. This result in clipped carotid arteries was not accompanied by less intimal hyperplasia. Screening of the aortic anastomotic line showed better preservation of endothelial architecture after clip anastomosis. Mean cross-clamp time for carotid patch repair was significantly less when using clips than with sutures. CONCLUSION: The use of non-penetrating clips for vascular anastomoses preserved endothelial function and structural integrity better than running sutures, although the degree of intimal hyperplasia was similar.

Anastomosis, Surgical↗

PubMed1997

Integration of functional and anatomical brain images.

This article concerns the integration of functional and anatomical volumetric brain images. Integration consists of two steps: matching or registration, where the images are brought into spatial agreement, and fusion or simultaneous display where the registered multimodal image information is presented in an integrated fashion. Approaches to register multiple images are divided into extrinsic methods based on artificial markers, and intrinsic matching methods based solely on the patient related image data. The various methods are compared by a number of characteristics, which leads to a clear preference for one class of intrinsic methods, viz. voxel-based matching. Furthermore, two- and three-dimensional techniques to display multimodality image information are outlined.

Brain↗

PubMedDate not supplied

[New approaches in correcting disorders of higher integrative brain functions in the pharmacotherapy of arterial hypertension with propranolol].

In experiments on rats it is found that propranolol in a dose of 2 mg/kg has a negative effect on higher integrative functions of the brain. Nootropics--pyracetam (200 mg/kg), AKF-94 (20 mg/kg), PIR-87-6-O (50 mg/kg) and actoprotector bemityl (40 mg/kg)--normalized orientative-trying behavior, memory, and emotionality of the animals. A possible mechanism of the drug action and prospects of their clinical application are discussed.

Animals↗

PubMed2004

Integration of functional brain information into stereotactic irradiation treatment planning using magnetoencephalography and magnetic resonance axonography.

PURPOSE: To minimize the risk of neurologic deficit after stereotactic irradiation, functional brain information was integrated into treatment planning. METHODS AND MATERIALS: Twenty-one magnetoencephalography and six magnetic resonance axonographic images were made in 20 patients to evaluate the sensorimotor cortex (n = 15 patients, including the corticospinal tract in 6), visual cortex (n = 4), and Wernicke's area (n = 2). One radiation oncologist was asked to formulate a treatment plan first without the functional images and then to modify the plan after seeing them. The pre- and postmodification values were compared for the volume of the functional area receiving > or =15 Gy and the volume of the planning target volume receiving > or =80% of the prescribed dose. RESULTS: Of the 21 plans, 15 (71%) were modified after seeing the functional images. After modification, the volume receiving > or =15 Gy was significantly reduced compared with the values before modification in those 15 sets of plans (p = 0.03). No statistically significant difference was found in the volume of the planning target volume receiving > or =80% of the prescribed dose (p = 0.99). During follow-up, radiation-induced necrosis at the corticospinal tract caused a minor motor deficit in 1 patient for whom magnetic resonance axonography was not available in the treatment planning. No radiation-induced functional deficit was observed in the other patients. CONCLUSION: Integration of magnetoencephalography and magnetic resonance axonography in treatment planning has the potential to reduce the risk of radiation-induced functional dysfunction without deterioration of the dose distribution in the target volume.

Adult↗