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At least 1,693 records · Page 94Linked to original sources
PubMed2002

Behavior of the point-spread function in photon-limited confocal microscopy.

We study the behavior of the point-spread function (PSF) of the confocal scanning optical microscope (CSOM) when the available optical energy density from the sample plane is low (<7.5 microJoule/micrometers2). The PSF profile is analyzed under three photon-limited imaging conditions: (1) reflection-type CSOM with a weak source and a perfectly reflecting sample, (2) reflection-type CSOM with a strong illumination source and a weak sample, and (3) fluorescence CSOM with a weak fluorescent sample. Linfoot's image quality criteria of fidelity, structural content, and correlation quality are used to assess the reproducibility of the PSF profile as a function of the photon number. Low photon numbers yield a PSF profile that is difficult to maintain from one location in the sample plane to another. The optical sectioning capability of the CSOM was found to deteriorate more quickly against light power reduction than its transverse resolving power. The signal-to-noise ratio of the scanned CSOM image improves exponentially with the photon number from the sample plane. The noise that is generated by an unstable PSF has an average amplitude that decreases exponentially with the photon number and is significant only at low photon numbers. The CSOM image quality deteriorates because of spurious high-frequency components, degradation in the PSF dynamic range, and varying resolving power.

Journal Article↗
PubMed2002

Cleavable substrate containing molecular beacons for the quantification of DNA-photolyase activity.

In order to gain deeper insight into the function and interplay of proteins in cells it is essential to develop methods that allow the profiling of protein function in real time, in solution, in cells, and in cell organelles. Here we report the development of a U-type oligonucleotide (molecular beacon) that contains a fluorophore and a quencher at the tips, and in addition a substrate analogue in the loop structure. This substrate analogue induces a hairpin cleavage in response to enzyme action, which is translated into a fluorescence signal. The molecular beacon developed here was used to characterize DNA-photolyase activity. These enzymes represent a challenge for analytical methods because of their low abundance in cells. The molecular beacon made it possible to measure the activity of purified class I and class II photolyases. Photolyase activity was even detectable in crude cell extracts.

DNA Repair↗
PubMed1981

Standardization of platelet function tests.

Methods for the standardization of several currently used platelet function tests (bleeding time, capillary fragility, platelet retention, platelet aggregation, platelet factor 3, and platelet volume profiles) are presented, Different variables than may interfere with the reproducibility of the results of each assay were identified and standardized. Using the standardized techniques, the range of normal values for each test was determined in a large population of normal volunteers and used to identify disease states by comparing patient results with those of the normal population. A format for presenting the entire profile of platelet function parameters is proposed.

Adult↗
PubMed2002

Delayed changes in regional brain energy metabolism following cerebral concussion in rats.

Traumatic brain injury (TBI) results in an acute altered metabolic profile of brain tissue which resolves within hours of initial insult and yet some of the functional deficits and cellular perturbations persist for days. It is hypothesized that a delayed change in energy status does occur and is a factor in the neural tissue's ability to survive and regain function. Regional metabolic profile and glucose consumption were determined at either 1 or 3 days following two different intensities of parasagittal fluid-percussion (F-P). A significant decrease in both 1CMRgluc and levels of ATP and P-creatine was evident in the hemisphere ipsilateral to the trauma at 1 day after the insult. The effect was greater in the cortical than the subcortical regions and was more pronounced at the higher trauma intensity. Normalization of glucose consumption and energy levels was essentially complete by 3 days. It would appear that the delayed metabolic changes at 1 day postinsult cannot be explained by a secondary ischemia since the changes in the metabolite profile do not elicit an increase in the consumption of glucose. These changes in energy metabolites may account for and contribute to the chronic neurological deficits following TBI.

Adenosine Triphosphate↗
PubMed2002

Emerging bioinformatics for the metabolome.

Metabolic profiling applied to functional genomics (metabolomics) is in an early stage of development. Here, the technologies used for metabolite profiling are briefly covered, illustrated by a few pioneering studies. Issues related to bioinformatics, namely data analysis, visualisation and archival, are the main focus of this review. Arguably there is already a need for databases containing metabolite profiles specific for a single organism, and a generic repository containing all metabolite profiling results, regardless of species. Data analyses and visualisations that combine the biological context with chemistry details are suggested as being the most promising.

Animals↗
PubMed2005

Families of membranous proteins can be characterized by the amino acid composition of their transmembrane domains.

SUMMARY: In eukaryotes, membranous proteins account for 20-30% of the proteome. Most of these proteins contain one or more transmembrane (TM) domains. These are short segments that transverse the bilayer lipid membrane. Various properties of the TM domains, such as their number, their topology and their arrangement within the membrane, are closely related to the protein's cellular functions. The properties of the TM domains also determine the cellular targeting and localization of these proteins. It is not known, however, whether the information encoded by TM domains suffices for the purpose of classifying proteins into their functional families. This is the question we address here. We introduce an algorithm that creates a profile of each functional family of membranous proteins based only on the amino acid composition of their TM domains. This is complemented by a classifier program for each such family (to determine whether a given protein belongs to it or not). We find that in most instances TM domains contain enough information to allow an accurate discrimination of approximately 80% sensitivity and approximately 90% specificity among unrelated polytopic functional families with the same number of TM domains. SUPPLEMENTARY INFORMATION: Available at www.protonet.cs.huji.ac.il/TM/

Algorithms↗
PubMed2002

Novel retroviral vectors to facilitate expression screens in mammalian cells.

As tools for functional genomics, expression profiling and proteomics provide correlative data, while expression cloning screens can link genes directly to biological function. However, technical limitations of gene transfer, expression, and recovery of candidate genes have limited wider application of genome-wide expression screens. Here we describe the pEYK retroviral vectors, which maintain high titers and robust gene expression while addressing the major bottleneck of expression cloning--efficient candidate gene recovery. By exploiting schemes for enhanced PCR rescue or strategies for direct isolation of proviral DNA as plasmids in bacterial hosts, the pEYK vectors facilitate cDNA isolation from selected cells and enable rapid iteration of screens and genetic reversion analyses to validate gene candidates. These vectors have proven useful to identify genes linked to cell proliferation, senescence and apoptosis.

Animals↗
PubMed2004

Long-term outcome of Fowler-Stephens orchiopexy in boys with prune-belly syndrome.

PURPOSE: Intra-abdominal testes in boys with prune-belly syndrome have been conventionally managed by 1 or 2-stage orchiopexy with division of the gonadal vessels. We reviewed a series of adults with prune-belly syndrome to assess the morphological and functional outcome of orchiopexy in childhood with specific reference to the spontaneous onset of puberty, hormonal profiles and sexual function. MATERIALS AND METHODS: A total of 41 boys were divided into 3 groups depending on the type of orchiopexy performed, namely group 1-20 with bilateral 1-stage orchiopexy, group 2-10 with unilateral 1-stage and contralateral 2-stage orchiopexy, and group 3-11 with bilateral 2-stage orchiopexy. RESULTS: In group 1 9 of 20 patients had good scrotal testes bilaterally, 6 had a good scrotal testis on 1 side and 3 had small testes on each side. Two boys required testosterone supplementation but 18 had normal hormonal and sexual function. In group 2 6 of 10 patients had good scrotal testes bilaterally and 4 had a good scrotal testis on 1 side. All patients underwent spontaneous puberty with good sexual function. In group 3 7 of 11 boys had good scrotal testes bilaterally and 3 had 1 good testis with normal puberty and sexual function. These 10 patients underwent spontaneous puberty with good sexual function. CONCLUSIONS: The majority of boys with prune-belly syndrome had a satisfactory outcome after orchiopexy with division of the gonadal vessels with testicular function sufficient to induce puberty and maintain satisfactory sexual function in adult life.

Adolescent↗
PubMed2001

Genomewide function conservation and phylogeny in the Herpesviridae.

The Herpesviridae are a large group of well-characterized double-stranded DNA viruses for which many complete genome sequences have been determined. We have extracted protein sequences from all predicted open reading frames of 19 herpesvirus genomes. Sequence comparison and protein sequence clustering methods have been used to construct herpesvirus protein homologous families. This resulted in 1692 proteins being clustered into 243 multiprotein families and 196 singleton proteins. Predicted functions were assigned to each homologous family based on genome annotation and published data and each family classified into seven broad functional groups. Phylogenetic profiles were constructed for each herpesvirus from the homologous protein families and used to determine conserved functions and genomewide phylogenetic trees. These trees agreed with molecular-sequence-derived trees and allowed greater insight into the phylogeny of ungulate and murine gammaherpesviruses.

Animals↗
PubMed1998

IgG-Fc-mediated effector functions: molecular definition of interaction sites for effector ligands and the role of glycosylation.

The Fc region of human IgG expresses interaction sites for many effector ligands. In this review the topographical distributions of ten of these sites are discussed in relation to functional requirement. It is apparent that interaction sites localised to the inter-CH2-CH3 domain region of the Fc allow for functional divalency, whereas sites localised to the hinge proximal region of the CH2 domain are functionally monovalent, with expression of the latter sites being particularly dependent on glycosylation. All x-ray crystal structures for Fc and Fc-ligand complexes report that the protein structure of the hinge proximal region of the CH2 domain is "disordered", suggesting "internal mobility". We propose a model in which such "internal mobility" results in the generation of a dynamic equilibrium between multiple conformers, certain of which express interaction sites specific to individual ligands. The emerging understanding of the influence of oligosaccharide/protein interactions on protein conformation and biological function of IgG antibodies suggests a potential to generate novel glycoforms of antibody molecules having unique profiles of effector functions.

Animals↗
PubMed2005

Light-induced global structural changes in phytochrome A regulating photomorphogenesis in plants.

Phytochromes are photoreceptor proteins that monitor the light environment and regulate a variety of photomorphogenic responses to optimize the growth and development of plants. Phytochromes comprise N-terminal photosensory and C-terminal regulatory domains. They are mutually photoconvertible between a red-light-absorbing (Pr) and a far-red-light-absorbing (Pfr) form. Their interconversion by light stimuli initiates downstream signaling cascades. Here we report the molecular structures of pea phytochrome A lacking the N-terminal 52 amino-acid residues in the Pr and Pfr forms studied by small-angle X-ray scattering. A new purification protocol yielded monodispersive sample solutions. The molecular mass and the maximum dimension of Pr determined from scattering data indicated its dimeric association. The molecular structure of Pr predicted by applying the ab initio simulation method to the scattering profile was approximated as a stack of two flat bodies, comprising two lobes assignable to the functional regions. Scattering profiles recorded under red-light irradiation showed small but definite changes from those of Pr. The molecular dimensions and predicted molecular structure of Pfr suggest global structural changes such as movement of the C-terminal domains in the Pr-to-Pfr phototransformation. Red-light-induced structural changes in Pfr were reversible, mostly due to thermal relaxation processes.

Light↗
PubMed2006

Extraction of phylogenetic network modules from the metabolic network.

BACKGROUND: In bio-systems, genes, proteins and compounds are related to each other, thus forming complex networks. Although each organism has its individual network, some organisms contain common sub-networks based on function. Given a certain sub-network, the distribution of organisms common to it represents the diversity of its function. RESULTS: We extracted such "common" sub-networks, defined as "phylogenetic network modules," using phylogenetic profiles and cluster analysis. The enzymes in the same "phylogenetic network module" have similar phylogenetic profiles and related functions. These modules are shown to be phylogenetic building blocks. Furthermore, the network of the modules illustrated hierarchical feature as well as the network of enzymes involved in the metabolism. CONCLUSION: We conclude that phylogenetic network modules are evolutionary conserved functional units in the metabolic network. We claim that our concept of phylogenetic modules provides a more accurate understanding of the evolution of biological networks.

Animals↗
PubMed2005

Metabolic remodeling in the aging heart.

The aim of this study was to investigate the effects of aging on the profile of myocardial substrate utilization and cardiac function using a physiological profile of substrates. Hearts from 6-, 15- and 24-month male Wistar rats were perfused in the isovolumic Langendorff mode, with physiological concentrations of 13C labeled palmitate, and either 13C labeled lactate or 13C glucose. 13C-NMR glutamate isotopomer analysis was performed to determine the contribution of the different substrates to oxidative metabolism. Palmitate oxidation was significantly increased and lactate oxidation depressed in the 24-month old, senescent hearts compared to the mature 6-month hearts. This metabolic remodeling was paralleled with a marked decline in cardiac function and efficiency. These results highlight that adaptations in substrate utilization occur during senescence and may contribute to the age-related increase in the incidence of heart failure.

Aging↗
PubMed2006

Pregnancy-related hyperlipidemia and endothelial function in healthy women.

BACKGROUND: The purpose of the present study was to investigate pregnancy-related changes in the maternal serum lipid profile and endothelial function. METHODS AND RESULTS: As part of the population-based, prospective cohort Cardiovascular Risk in Young Finns study conducted in Finland, 57 pregnant Finnish women and 62 control women matched for age and smoking were examined throughout gestation. Serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined and concomitantly endothelium-dependent brachial artery flow mediated dilation (FMD) was measured by ultrasound. During pregnancy serum TC, LDL-C, HDL-C, TG and very-low-density lipoprotein cholesterol increased significantly when compared with the non-pregnant state (p<0.001 for each) and towards the end of pregnancy (p<0.001, p<0.001, p=0.007, p<0.001, p<0.001). FMD increased towards the end of pregnancy and there was a statistically significant direct correlation between gestational age and FMD% (r=0.345, p=0.010). Brachial artery diameter at rest and FMD% were negatively correlated in pregnant (r=-0.280, p=0.035) and non-pregnant women (r=-0.360, p<0.004). The univariate correlation analysis showed a direct correlation between maternal serum TC (r=0.333, p=0.012) and TG (r=0.366, p=0.006) and FMD%, whereas a negative non-significant correlation was found in non-pregnant women. In a multivariate model, vessel size (beta=-0.436, p=0.001) and TG (beta=0.502, p<0.001) were the most powerful predictors for FMD% in pregnancy, the influence of other lipids was non-significant. CONCLUSIONS: In healthy pregnant women increased gestational age is associated with improved endothelium-dependent vasodilation responses regardless of concurrently appearing lipid changes.

Blood Flow Velocity↗
PubMed2026

Amplicon and metagenomic sequencing reveal thifluzamide drive rhizosphere microbial structural shifts and functional adaption.

Thifluzamide (TF) is a widely used phenyl urea fungicide in rice production; however, its impacts on the structural composition and functional dynamics of the rhizosphere microbiome remain poorly understood. Here, we systematically investigated the effects of TF on the structure, interactions, and functional potential of the rice (Oryza sativa L.) rhizosphere microbiome using integrated amplicon sequencing and metagenomic approaches. TF application significantly altered both bacterial and fungal community composition, bacterial diversity was markedly reduced, whereas fungal diversity increased. With bacterial diversity markedly reduced while fungal diversity increased. Beta-diversity analyses revealed strong treatment-driven community separation, indicating pronounced TF-induced microbial restructuring. Co-occurrence network analysis demonstrated reduced complexity and connectivity in bacterial networks but increased negative co-occurrence patterns within fungal communities, suggesting contrasting stability responses between microbial kingdoms. Metagenomic profiling further revealed substantial functional shifts, including the differential enrichment of KEGG and COG pathways associated with xenobiotic metabolism. Notably, while total ARG abundance remained stable, TF exposure altered the resistome profile by selectively enriching specific classes of antibiotic resistance genes (ARGs), biocide resistance genes (BRGs), and mobile genetic elements (MGEs). Strong positive correlations between MGEs and ARGs highlighted an elevated potential for horizontal gene transfer. Metagenome-assembled genome (MAG) analysis identified specific TF-enriched bacterial taxa, including Methylophilus, Sulfurospirillum, and Azospirillum, which harbored genes involved in pesticide degradation and xenobiotic transformation. Collectively, these findings demonstrate that TF profoundly reshapes the rice rhizosphere microbiome by altering microbial diversity, interaction networks, resistance gene profiles, and functional capacities. This study provides genomic insights into fungicide-microbiome interactions, underscoring the potential ecological implications associated with TF application, while identifying candidate microbial taxa that may contribute to pesticide degradation and rhizosphere microecology resilience.

Rhizosphere↗
PubMed2004

Serum profiles of luteinizing hormone, oestradiol and cholesterol and ovarian functions in layer poultry birds (Gallus domesticus) fed diets containing furazolidone.

This study was carried out to assess the serum profiles of luteinizing hormone (LH), oestradiol, cholesterol and ovarian functions in layer poultry birds (Rhode Island Red: Gallus domesticus) fed a diet containing various concentrations of furazolidone (FZ). A total of 40 birds were randomly assigned to receive FZ 0, 200, 400 or 800 mg/kg feed (ppm) daily during the pre-laying age, i.e. 13-18 weeks (for 5 weeks). Blood samples were collected at weekly intervals. Concentrations of LH and oestradiol in serum were estimated at alternate weeks using radioimmunoassays. Serum cholesterol levels were analysed by an enzymatic calorimetric method. Furazolidone administration was terminated at the 18th week of age. The birds were sacrificed at 22nd week of age and ovarian tissues were processed for morphometric studies. Serum LH, oestradiol and cholesterol levels were affected by age (p < 0.001) and FZ dose (p < 0.001). Serum LH and oestradiol levels were lower (p < 0.05) in birds receiving FZ 800 mg/kg feed daily compared with the controls, whereas serum cholesterol profiles were lower (p < 0.05) in all FZ-administered groups than in the control group. The mean weight of ovaries having no yolky follicles observed in the group receiving FZ 400 or 800 mg/kg feed per day was reduced (p < 0.05) compared with the control group. Dosing FZ at 800 mg/kg feed per day reduced (p < 0.05) the mean volume of ovaries having no yolky follicles compared with the control group. In birds receiving FZ 800 mg/kg feed per day, the mean length of the oviduct was reduced (p < 0.05) as compared with the control group. Morphometric studies revealed that the mean number of oocytes with diameter in the range 401-800 microm decreased (p < 0.05) in birds fed FZ 400 or 800 mg/kg feed per day. Initial egg production was affected by age (p < 0.001) and dose (p < 0.001) of FZ. The mean number of eggs laid by different groups revealed that egg production was reduced (p < 0.05) in birds receiving FZ 800 mg/kg feed per day as compared with the controls. The present data suggest that FZ causes suppression in serum profiles of LH, oestradiol, cholesterol and ovarian functions in Rhode Island Red layer poultry birds. Therefore, great care must be taken with use of FZ in layer poultry birds (Gallius domesticus) with regard to dosage and duration of administration.

Animals↗
PubMed2005

Bilinear model for the prediction of drug solubility in ethanol/water mixtures.

A new bilinear function that accounts for the disparity between the log-linear and parabolic models for cosolvent solubilization is presented, where ethanol was used as the model cosolvent. This accounts for both the initial and terminal slopes in the ethanol/water solubility profiles of semi-polar solutes. The proposed model has only two fitted parameters sigmaA and sigmaB, which represent the initial and terminal asymptotes in the solubility profiles. The bilinear function can also model the ethanol/water solubility profile more accurately than the log-linear model and a general parabolic model.

Ethanol↗
PubMed2002

Bone mass, gonadal function and biochemical assessment in young men with trisomy 21.

OBJECTIVE: The objective of the study was to find out whether biochemical and hormonal profile of sexual function and mineral metabolism are related to low bone mass in young men with Down syndrome. STUDY DESIGN: Eleven young men with trisomy 21 (mean age 26.45 years) and 12 healthy university students of similar age, participated in the study. The bone mineral density (BMD) of the lumbar vertebrae was measured in posteroanterior (PA) projection. Sexual development was assessed by clinical examination. The levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone sulfate (DHEA-S), 17-OH progesterone and parathormone (PTH) were measured accordingly by radioimmunoassay. Serum calcium (Ca) and phosphate (P) as well as fasting urinary Ca and hydroxyproline (OHP) were also measured. RESULTS: BMD in DS patients was significantly lower (P<0.001) compared to their control counterparts. No significant differences were observed in mean concentrations of FSH, testosterone and DHEA-S, while LH and 17-OH progesterone levels were significantly higher in DS compared to control group (P<0.01 and <0.05, respectively). Serum Ca and P and urine Ca/Creat ratio did not differ between groups. OHP/Creat ratio was significantly higher in DS patients. PTH levels were extremely low (1pmol/l) in two patients. CONCLUSIONS: The findings of this study show decreased bone mass in subjects with DS. Factors, possibly related to low bone mass, are some degree of hypogonadim, hypotonia, low muscular strength and immobility. The findings suggest further research on the biochemistry and endocrinology of bone metabolism in patients with trisomy 21.

17-alpha-Hydroxyprogesterone↗