Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “functional experiments”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed1996

Studies of mechanoreceptors in skin of the snout of the echidna Tachyglossus aculeatus.

The echidna Tachyglossus aculeatus, together with the platypus, belongs to the monotremes, a group of mammals with a number of reptilian characteristics. A structure unique to the skin of monotremes is the push rod-a compacted column of epidermal cells that is 20 microns wide and 100 microns long with its tip at the skin surface, and that is able to move relatively independently of adjacent tissue. At the base of each push rod is a cluster of encapsulated nerve endings. Push rods are common in skin of the snout and have been postulated to have a mechanosensory function. Experiments were carried out on four anesthetized echidnas with the aim of determining the function of push rods. Recordings made from the infraorbital nerve, which supplies the skin of the upper jaw, yielded responses from a total of 46 afferents. Two were electroreceptors; the others were mechanoreceptors. Within the group of mechanoreceptors with rapidly adapting responses, three responded to high-frequency vibration and resembled pacinian corpuscles. There were 26 slowly adapting (SA) mechanoreceptors, which, based on the regularity of their discharge, could be divided into two groups: SA I or Merkel type, and SA II or Ruffini type. SA I receptors had very discrete receptive fields with diameters of 100 microns. The receptive fields of two SA I receptors were marked, and after histological processing, one was seen to lie near two push rods. It is concluded that mechanoreceptor responses in the echidna's snout skin resemble those in other mammals in many aspects. We could not unequivocally associate responses to mechanical stimulation with the push rods.

Afferent Pathways↗
PubMed2004

Mitochondrial uncoupling proteins--facts and fantasies.

Instead of a comprehensive review, we describe the basic undisputed facts and a modest contribution of our group to the fascinating area of the research on mitochondrial uncoupling proteins. After defining the terms uncoupling, leak, protein-mediated uncoupling, we discuss the assumption that due to their low abundance the novel mitochondrial uncoupling proteins (UCP2 to UCP5) can provide only a mild uncoupling, i.e. can decrease the proton motive force by several mV only. Contrary to this, the highly thermogenic role of UCP1 in brown adipose tissue is not given only by its high content (approximately 5 % of mitochondrial proteins) but also by the low ATP synthase content and high capacity respiratory chain. Fatty acid cycling mechanism as a plausible explanation for the protonophoretic function of all UCPs and some other mitochondrial carriers is described together with the experiments supporting it. The phylogenesis of all UCPs, estimated UCP2 content in several tissues, and details of UCP2 activation are described on the basis of our experiments. Functional activation of UCP2 is proposed to decrease reactive oxygen species (ROS) production. Moreover, reaction products of lipoperoxidation such as cleaved hydroperoxy-fatty acids and hydroxy-fatty acid can activate UCP2 and promote feedback down-regulation of mitochondrial ROS production.

Animals↗
PubMed2026

OLR1 drives gastric cancer progression through NF-κB activation and immunosuppressive macrophage polarization.

Gastric cancer remains a leading cause of cancer-related mortality worldwide, and the identification of clinically relevant biomarkers is critical for improving patient outcomes. Oxidized low-density lipoprotein receptor 1 (OLR1) has been implicated in tumor progression; however, its role in gastric cancer and the tumor microenvironment remains unclear. OLR1 expression and clinical significance were analyzed using The Cancer Genome Atlas (TCGA) dataset and validated in gastric cancer cell lines. Gain- and loss-of-function experiments, together with in vitro and in vivo assays, were performed to investigate the biological functions and underlying mechanisms of OLR1 in gastric cancer progression. OLR1 was significantly upregulated in gastric cancer and associated with unfavorable prognosis. Functional analyses demonstrated that OLR1 promoted gastric cancer cell proliferation, migration, and tumor growth. Mechanistically, OLR1 activated NF-κB signaling and facilitated macrophage polarization toward the M2 phenotype, thereby contributing to a protumorigenic microenvironment. OLR1 promotes gastric cancer progression through activation of NF-κB signaling and modulation of macrophage polarization. These findings identify OLR1 as a potential prognostic biomarker and therapeutic target for gastric cancer.

Humans↗
PubMed1997

Molecular basis of the diversity of calcium channels in cardiovascular tissues.

Voltage-dependent calcium (Ca2+) channels control a variety of physiological functions, such as excitation-contraction coupling in cardiac and smooth muscle. secretion of hormones and release of neurotransmitters. Studies on dissociated or cultured cells enabled us to compare their electrophysiological and pharmacological properties and their regulation in various tissues. Molecular genetics has provided a structural basis with which to observe the functional diversity of Ca2+ channels, which are composed of several subunits (alpha 1, alpha 2-delta, beta, gamma). Structure-function experiments, using expression in Xenopus oocytes, were designed to explain the molecular basis underlying this functional diversity. Six genes have been identified encoding the pore subunit (alpha 1) which determines the basic profile, i.e. the pharmacology of any Ca2+ channel. However, using a reconstitution model, the auxiliary subunits, but mainly beta subunits, for which four genes and several variants have been isolated, are able to modify the level of expression and the properties of a Ca2+ current directed by an alpha 1 subunit. Our structure-function studies are mainly designed to investigate the functional consequences of alpha 1-beta interaction on electrophysiological and pharmacological properties, especially in the case of cardiovascular Ca2+ channels. These studies should lead to a better understanding of the molecular basis underlying the differences between cardiac and vascular Ca2+ channels and also their implication in pathophysiology. Functional expression of the various combinations of subunit isoforms and identification of the precise oligomeric structure of voltage-dependent Ca2+ channels in specific cell types should help in the development of new therapeutic drugs.

Animals↗
PubMed1994

Successful methods of pancreas transplantation in the rat using a cuff technique.

Two models of pancreas transplantation were examined in the rat with a view to choosing one for regular use in functional experiments. A cuff technique applied to the renal vessels of the recipient was used. The histology and endocrine functioning of whole pancreas-duodenal transplant (Tx) plus bladder drainage (drainage model), and the pancreatic duct ligated segmental pancreas Tx (ligated model) were examined. Syngeneic operations were performed using either Lewis or Wistar rats. Streptozotocin (STZ) 60 mg/kg intravenously (i.v.) was used to render the recipient rats diabetic. A cuff technique was used with both models to anastomose the grafts to the renal vessels instead of the conventional technique of hand suturing to the abdominal vessels. This allows a shorter warm ischaemia time for the donor pancreas and leaves the systemic circulation intact leading to a high success rate for both techniques. Operation survival rates were 93% (n = 30) and 90% (n = 10) in the ligated and drainage models, respectively. The recipients in both groups were normoglycaemic for > 100 days. Histological examination revealed atrophic exocrine tissue early in the ligated group but only two from the drainage group showed exocrine atrophy at > 100 days. There was no statistical difference in i.v. glucose tolerance tests with both models showing a normal pattern. Thus, endocrine function remained independent of exocrine function. Both models are quicker than the conventional techniques. The duct ligation model was a simpler transplant to perform, suggesting that this should be the technique of choice in future experiments.

Anastomosis, Surgical↗
PubMed2003

Wave functions derived from experiment. V. Investigation of electron densities, electrostatic potentials, and electron localization functions for noncentrosymmetric crystals.

The constrained Hartree-Fock method using experimental X-ray diffraction data is extended and applied to the case of noncentrosymmetric molecular crystals. A new way to estimate the errors in derived properties as a derivative with respect to added Gaussian noise is also described. Three molecular crystals are examined: ammonia [NH(3)], urea [CO(NH(2))(2)], and alloxan [(CO)(4)(NH)(2)]. The energetic and electrical properties of these molecules in the crystalline state are presented. In all cases, an enhancement of the dipole moment is observed upon application of the experimental constraint. It is found that the phases of the structure factors are robustly determined by the constrained Hartree-Fock model, even in the presence of simulated noise. Plots of the electron density, electrostatic potential, and the electron localization function for the molecules in the crystal are displayed. In general, relative to the Hartree-Fock model, there is a depletion of charge around hydrogen atoms and lone pair regions, and a build-up of charge within the molecular framework near nuclei, directed along the bonds. The electron localization function plots reveal an increase in the pair density between vicinal hydrogen atoms.

Journal Article↗
PubMed2005

Xenopus aristaless-related homeobox (xARX) gene product functions as both a transcriptional activator and repressor in forebrain development.

Mutations in the aristaless-related homeobox (ARX) gene have been found in patients with a variety of X-linked mental retardation syndromes with forebrain abnormalities, including lissencephaly. Arx is expressed in the developing mouse, Xenopus, and zebrafish forebrain. We have used whole-mount in situ hybridization, overexpression, and loss-of-function studies to investigate the involvement of xArx in Xenopus brain development. We verified that xArx is expressed in the prospective diencephalon, as the forebrain is patterned and specified during neural plate stages. Expression spreads into the ventral and medial telencephalon as development proceeds through neural tube and tadpole stages. Overexpression of xArx resulted in morphological abnormalities in forebrain development, including loss of rostral midline structures, syn- or anophthalmia, dorsal displacement of the nasal organ, and ventral neural tube hyperplasia. Additionally, there is a delay in expression of many molecular markers of brain and retinal development. However, expression of some markers, dlx5 and wnt8b, was enhanced in xArx-injected embryos. Loss-of-function experiments indicated that xArx was necessary for normal forebrain development. Expansion of wnt8b expression depended on xArx function as a transcriptional repressor, whereas ectopic expression of dlx5, accompanied by development of ectopic otic structures, depended on function of Arx as a transcriptional activator. These results suggest that Arx acts as a bifunctional transcriptional regulator in brain development.

Animals↗
PubMed2002

Aftereffects of the surprising presentation and omission of appetitive reinforcers on key-pecking performance in pigeons.

The reinforcement-omission effect (ROE), also known as frustration effect, refers to greater response strength immediately after nonreinforcement (N) than reinforcement (R). The ROE was traditionally interpreted as transient invigoration after N induced by primary frustration. Pigeons demonstrate similar ROEs whether outcomes are surprising (partial R) or expected (discrimination training) in runway (Experiment 1) and Skinner box situations (Experiments 2-3). Variations in the interval between N and the opportunity to respond indicate that the ROE results from an aftereffect of food consumption (Experiment 4). Increasing reinforcer magnitude increased the after-R effect, without modifying the after-N function (Experiment 5). These results are reviewed in the context of comparative research on spaced-trial successive negative contrast and related phenomena that have failed to appear in experiments involving nonmammalian vertebrates.

Animals↗
PubMed1995

A far-upstream sequence of the wheat histone H3 promoter functions differently in rice and tobacco cultured cells.

The cis-regulatory function of a far-upstream sequence (-1,711 to -186) of the promoter of the wheat gene for histone H3 (TH012) was analyzed in cultured rice and tobacco cells in a transient expression system with the gene for beta-D-glucuronidase as a reporter gene. The far-upstream sequence was necessary for full activity of the H3 promoter in rice cells but did not enhance the activity of the proximal promoter in tobacco cells. Dissection analysis of the far-upstream sequence revealed the existence of several positive and negative cis-acting sequences in this region, some of which functioned differently in rice and tobacco cells. In gain-of-function experiments with rice cells, the sequence from -848 to -704, containing the CCAAT and octamer (CaCGGATC) motifs, functioned in an orientation-independent manner, whereas the sequence from -703 to -486 functioned in an orientation-dependent manner. By contrast, both sequences exhibited an orientation-dependent cis-function in tobacco cells. These findings suggest that some cis-regulatory sequences in the far-upstream region of the H3 promoter function differently in rice and tobacco cells.

Base Sequence↗
PubMed2002

The basic helix-loop-helix factor olig2 is essential for the development of motoneuron and oligodendrocyte lineages.

Sonic hedgehog (Shh), an organizing signal from ventral midline structures, is essential for the induction and maintenance of many ventral cell types in the embryonic neural tube. Olig1 and Olig2 are related basic helix-loop-helix factors induced by Shh in the ventral neural tube. Although expression analyses and gain-of-function experiments suggested that these factors were involved in motoneuron and oligodendrocyte development, they do not clearly define the functional differences between Olig1 and Olig2. We generated mice with a homozygous inactivation of Olig2. These mice did not feed and died on the day of birth. In the spinal cord of the mutant mice, motoneurons are largely eliminated and oligodendrocytes are not produced. Olig2(-/-) neuroepithelial cells in the ventral spinal cord failed to differentiate into motoneurons or oligodendrocytes and expressed an astrocyte marker, S100beta, at the time of oligodendrogenesis. Olig1 or Olig3, other family members, were expressed in the descendent cells that should have expressed Olig2. We concluded that Olig2 is an essential transcriptional regulator in motoneuron and oligodendrocyte development. Our data provide the first evidence that a single gene mutation leads to the loss of two cell types, motoneuron and oligodendrocyte.

Animals↗
PubMed2002

Functional limitations of school-aged children seen in primary care.

OBJECTIVE: The purpose of the present study was to assess the prevalence of functional limitations in children seen in a large paediatric practice network and to identify sociodemographic, family and psychosocial factors related to functional limitations. STUDY DESIGN: Cross-sectional analysis. POPULATION: Children were recruited from two large, practice-based primary care research networks during their paediatric office visits. For the present study, participants included 14 630 school-aged children (ages 6-15 years) and their caregivers. OUTCOMES MEASURED: Parents completed written questionnaires including the Pediatric Symptom Checklist, the Family Apgar and the Functional Limitations Index. RESULTS: Findings indicated that 15% of children surveyed had some limitation in their daily functioning. More children had schoolwork and physical function limitations than limitations in personal and self-care. Logistic regression equations predicted functional limitations and health status in children from a model of sociodemographic factors, psychosocial symptoms and family functioning. CONCLUSIONS: A low but significant number of school-age children seen in the primary care setting experience functional limitations. Children with any psychosocial symptoms were at increased risk for functional limitations, indicating the critical need to screen for functional impairment in children with suspected behavioural or emotional problems. A screening tool of functional limitations may be useful for assessing the presence or absence of such limitations in children's daily function and warrants further investigation.

Activities of Daily Living↗
PubMed1989

Interaction of selected vasodilating beta-blockers with adrenergic receptors in human cardiovascular tissues.

beta- And alpha 1-adrenoceptor antagonist properties of bufuralol, carvedilol, celiprolol, dilevalol, labetalol, and pindolol were investigated in human myocardium and mammary artery using binding techniques and functional studies. In myocardial membranes, beta-adrenoceptor antagonists showed monophasic competition isotherms for [125I]pindolol binding with high affinity (Ki from 1-100 nM), except for celiprolol which displayed a biphasic competition isotherm (pKi = 6.4 +/- 0.06 for beta 1- and 4.8 +/- 0.07 for beta 2-adrenoceptors). Drug interactions with alpha 1-adrenoceptors were evaluated in human mammary artery by [3H]prazosin binding and by measuring contractile responses to norepinephrine (NE). Labetalol and carvedilol showed a moderate affinity for alpha 1-adrenoceptors (pKi = 6.2 +/- 0.01 and 6.1 +/- 0.06, respectively), and inhibited NE-induced contractions (pA2 = 6.93 +/- 0.23 and 8.64 +/- 0.24, respectively). Dilevalol, bufuralol, and pindolol displayed weak effect both in binding (Ki in micromolar range) and functional experiments (pA2 = 5.98, 5.54, and 6.23, respectively). Celiprolol did not show antagonist properties up to 100 microM in functional studies, but displayed a slight affinity for alpha 1-adrenoceptors in binding studies. The data indicate that the vasodilating activity of these beta-adrenoceptor antagonists is caused in some instances by an alpha 1-adrenoceptor antagonism (labetalol, carvedilol), whereas for the others alternative mechanisms should be considered.

Adrenergic beta-Antagonists↗
PubMed1993

Estimation of competitive antagonist affinity from functional inhibition curves using the Gaddum, Schild and Cheng-Prusoff equations.

1. The estimation of antagonist affinity from functional experiments in which the effect of a fixed agonist concentration is reduced by a range of antagonist concentrations ('functional inhibition curves') has been considered from both a theoretical and experimental viewpoint. 2. Theoretical predictions are compared with results obtained from the stimulation of [35S]-GTP gamma S binding by acetylcholine to membranes of Chinese hamster ovary (CHO) cells stably transfected with human m1-m4 muscarinic receptors, and inhibition of the stimulated binding by pirenzepine and AQ-RA 741. 3. The usual procedure of applying the Cheng-Prusoff correction is shown to be theoretically invalid, and predictions are made of the size and distribution of errors associated with this procedure. 4. A different procedure for estimating antagonist affinity, using the principles of dose-ratio analysis and analogous to use of the Gaddum equation, is found to be accurate and theoretically valid. 5. A novel method of analysis allows accurate estimation of both antagonist affinity and Schild slope, by fitting the combined data from an antagonist inhibition curve and an agonist activation curve directly to a form of the Schild equation (derived by Waud) using non-linear regression analysis. 6. It is shown that the conventional Schild analysis can be enhanced by treating part of the data as a family of inhibition curves and including in the Schild plot dose-ratios estimated from the inhibition curves.

Acetylcholine↗
PubMed2000

Temporal integration in the presence of off-frequency maskers.

Temporal integration was measured at a relatively low and a relatively high signal frequency under conditions of off-frequency masking. The masker was typically gated for 300 ms, and the signal was presented 70 ms after masker onset. In experiment 1, the signal frequency was 500 or 2000 Hz. Temporal integration was measured in quiet and in the presence of a masker whose frequency was lower or higher than the signal frequency. In all listening situations, there was less integration at 2000 Hz than at 500 Hz. This effect of frequency was particularly dramatic in the presence of a lower frequency masker, where there was almost no integration at 2000 Hz. Experiment 2 showed that this dramatic effect of frequency cannot be understood in terms of the underlying psychometric functions. Experiment 3 measured temporal integration at 750 and 2000 Hz for a large number of masker-signal frequency separations for both a tonal and a noise masker, and in conditions where the masker was gated or continuous. The results with the gated tonal masker largely confirmed the results of experiment 1. The results with the continuous tonal masker and the gated or continuous noise masker, however, were quite different. In those cases, the amount of temporal integration at both signal frequencies was more or less independent of the masker-signal separation; the masked temporal integration was nearly equal to the integration in quiet. Thus based on the conditions evaluated here, off-frequency masked temporal integration differs substantially from integration in quiet only for gated tonal maskers located considerably lower in frequency than the signal. It is unclear how to account for this finding, although it may be related to attentional factors.

Adult↗
PubMed1991

Use of invertebrate animals to teach physiological principles.

Experiments with invertebrate animals offer valuable opportunities in the teaching of physiology. In some cases, exercises that use these animals may demonstrate physiological principles more clearly than experiments that use vertebrates. Other experiments are easy to perform because of the latitude of conditions in which the tissues of many invertebrates function. Experiments with invertebrates can also illustrate a far wider range of physiological mechanisms than occurs in vertebrates and are especially suited for opportunities for independent original investigation by the students. Since at this time invertebrates are underutilized in teaching, much can be gained by the design, testing, and dissemination of innovative experimental protocols for student use.

Animal Welfare↗
PubMed1997

Orthotopic lower urinary tract reconstruction in women using the Kock ileal neobladder: updated experience in 34 patients.

PURPOSE: Orthotopic lower urinary tract reconstruction has revolutionized urinary diversion following cystectomy. Initially performed solely in male patients, orthotopic diversion has now become a viable option in women. Currently, the orthotopic neobladder is the diversion of choice for women requiring lower urinary tract reconstruction at our institution. We evaluate and update our clinical and functional experience with orthotopic reconstruction in female patients. MATERIALS AND METHODS: Since June 1990, 34 women 31 to 86 years old (median age 67) have undergone orthotopic lower urinary tract reconstruction following cystectomy. Indications for cystectomy included transitional cell carcinoma in 29 patients, urachal adenocarcinoma in 1, mesenchymal tumor of endometrial origin in 1, cervical carcinoma in 1 and a fibrotic radiated bladder in 1. In addition, 1 woman underwent undiversion to the native urethra following a previous simple cystectomy and cutaneous diversion for eosinophilic cystitis. Data were analyzed according to postoperative early and late complications, survival, tumor recurrence, pathological evaluation of the cystectomy specimen, continence status, voiding pattern and patient satisfaction. The median followup in this group of patients was 30 months (range 17 to 70). RESULTS: There were no perioperative deaths, and 4 early (11%) and 3 (9%) late complications. Four patients died, none with a urethral recurrence, including 3 of metastatic bladder cancer and 1 of unrelated causes. In another patient with an extensive mesenchymal tumor of the uterus a sigmoid tumor recurred requiring conversion of the orthotopic reservoir to a cutaneous diversion. All of the remaining 29 patients are alive without evidence of disease. Intraoperative frozen section of the distal surgical margin (proximal urethra) accurately evaluated (confirmed by permanent section) the proximal urethra prospectively for tumor in all 29 specimens removed for transitional cell carcinoma, including 28 specimens (97%) without evidence of tumor and 1 specimen with carcinoma in situ. Complete daytime and nighttime continence was reported by 29 (88%) and 27 (82%) of 33 evaluable patients, respectively. A total of 28 patients (85%) void to completion, while 5 (15%) require some form of intermittent catheterization to empty the neobladder. Patient satisfaction is overwhelming. CONCLUSIONS: The excellent clinical and functional results demonstrated with further followup confirm our initial experience with orthotopic diversion in women. Careful selection of appropriate female candidates for orthotopic diversion is critical, and includes preoperative evaluation of the bladder neck and intraoperative frozen section analysis of the distal cystectomy margin. Furthermore, close monitoring of the retained urethra is mandatory in all women undergoing orthotopic diversion. We believe that the orthotopic neobladder is the urinary diversion of choice in women following cystectomy.

Adult↗
PubMed2003

Modulo is a target of Myc selectively required for growth of proliferative cells in Drosophila.

In Drosophila, the homologue of the proto-oncogene Myc is a key regulator of both cell size and cell growth. The identities and roles of dMyc target genes in these processes, however, remain largely unexplored. Here, we investigate the function of the modulo (mod) gene, which encodes a nucleolus localized protein. In gain of function or loss of function experiments, we demonstrate that mod is directly controlled by dMyc. Strikingly, in proliferative imaginal cells, mod loss-of-function impairs both cell growth and cell size, whereas larval endoreplicative tissues grow normally. In contrast to dMyc, over-expressing Mod in wing imaginal discs is not sufficient to induce cell growth. Taken together, our results indicate that mod does not possess the full spectrum of dMyc activities, but is required selectively in proliferative cells to sustain their growth and to maintain their specific size.

Animals↗