SEARCH · PubMed Health

Results for “functional inference”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 235 records · Page 13Linked to original sources

PubMed1986

Dental function and diet in the Carpolestidae (Primates, Plesiadapiformes).

Microwear analysis has long been used to infer dental function in primates; however, this is the first study to combine microwear and morphometric analyses to infer the dental function of the highly derived dentition of an early Tertiary primate. The Carpolestidae, a family of plesiadapiform primates, are characterized in part by a bladelike lower dentition (P4 and trigonid of M1). This study reveals a dual function of this dental complex. During the preparatory cycle, the tall, vertical enamel surfaces and broad basal lobes on P4 and trigonid of M1 probably functioned to wedge foods apart. This cycle is designated slicing-crushing and is uncommon among mammals, having been documented only for two extinct taxa: the multituberculates and the carpolestids. In addition to this special function, P4 and trigonid of M1 were used extensively with the molars in Phase I shearing. Facet analysis has revealed two new Phase I facets located on P3,4, whose formation is a result of normal Phase I movements and the derived morphology of these teeth. Slicing-crushing, used with Phase I shearing, would probably be most useful in processing food items of combined textures, particularly a soft interior covered by either a brittle or ductile coat, which are characteristic of an omnivorous diet composed of invertebrates, nuts, and seeds.

Animals↗

PubMed2004

Exploration of essential gene functions via titratable promoter alleles.

Nearly 20% of yeast genes are required for viability, hindering genetic analysis with knockouts. We created promoter-shutoff strains for over two-thirds of all essential yeast genes and subjected them to morphological analysis, size profiling, drug sensitivity screening, and microarray expression profiling. We then used this compendium of data to ask which phenotypic features characterized different functional classes and used these to infer potential functions for uncharacterized genes. We identified genes involved in ribosome biogenesis (HAS1, URB1, and URB2), protein secretion (SEC39), mitochondrial import (MIM1), and tRNA charging (GSN1). In addition, apparent negative feedback transcriptional regulation of both ribosome biogenesis and the proteasome was observed. We furthermore show that these strains are compatible with automated genetic analysis. This study underscores the importance of analyzing mutant phenotypes and provides a resource to complement the yeast knockout collection.

Alleles↗

PubMed2024

Predictions of rhizosphere microbiome dynamics with a genome-informed and trait-based energy budget model.

Soil microbiomes are highly diverse, and to improve their representation in biogeochemical models, microbial genome data can be leveraged to infer key functional traits. By integrating genome-inferred traits into a theory-based hierarchical framework, emergent behaviour arising from interactions of individual traits can be predicted. Here we combine theory-driven predictions of substrate uptake kinetics with a genome-informed trait-based dynamic energy budget model to predict emergent life-history traits and trade-offs in soil bacteria. When applied to a plant microbiome system, the model accurately predicted distinct substrate-acquisition strategies that aligned with observations, uncovering resource-dependent trade-offs between microbial growth rate and efficiency. For instance, inherently slower-growing microorganisms, favoured by organic acid exudation at later plant growth stages, exhibited enhanced carbon use efficiency (yield) without sacrificing growth rate (power). This insight has implications for retaining plant root-derived carbon in soils and highlights the power of data-driven, trait-based approaches for improving microbial representation in biogeochemical models.

Rhizosphere↗

PubMed1996

Discord between the phylogenies inferred from molecular versus functional data: uneven rates of functional evolution or low levels of gene flow?

According to measures of molecular divergence, the three species of the Drosophila simulans clade are closely related to and essentially equidistant from each other. We introgressed 10% of the D. sechellia X chromosome into a pure D. simulans genetic background and found that males carrying this introgressed region were consistently fertile; in contrast, males carrying the same segment from D. mauritiana are sterile and suffer from incompatibilities at a minimum of four loci. Together with other recent results, these data suggest that D. simulans and D. sechellia are much more closely related to each other than either is to D. mauritiana. How can we reconcile the phylogeny inferred from the density of hybrid sterility genes with that inferred from molecular divergence? If the molecular phylogeny is correct, the discrepancy might be explained by uneven rates of functional evolution, resulting in the uneven accumulation of substitutions with corresponding negative effects in hybrids. If the functional phylogeny is correct, then low levels of gene flow across nascent species boundaries, particularly for loci not tightly linked to a hybrid sterility gene, may have erased the original pattern of lineage splitting. We propose tests that will allow us to discriminate between these hypotheses.

Animals↗

PubMed2003

Language systems in normal and aphasic human subjects: functional imaging studies and inferences from animal studies.

The old neurological model of language, based on the writings of Broca, Wernicke and Lichtheim in the 19th century, is now undergoing major modifications. Observations on the anatomy and physiology of auditory processing in non-human primates are giving strong indicators as to how speech perception is organised in the human brain. In the light of this knowledge, functional activation studies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are achieving a new level of precision in the investigation of language organisation in the human brain, in a manner not possible with observations on patients with aphasic stroke. Although the use of functional imaging to inform methods of improving aphasia rehabilitation remains underdeveloped, there are strong indicators that this methodology will provide the means to research a very imperfectly developed area of therapy.

Animal Communication↗

PubMed1994

Neurophysiologic monitoring during cranial base surgery.

The last decade has seen a rapid growth in surgical techniques directed at resection of skull base tumors. Lesions that were previously inoperable can now be resected either partially or in some cases completely. The morbidity in these procedures has diminished with increased surgical experience. Additional aids to successful surgical resection include intraoperative neurophysiologic monitoring techniques. The following text outlines methods of monitoring cranial nerve and brain function in a manner that is directly relevant to cranial base surgery in which so many structures are potentially at risk. These techniques permit the identification of nerves obscured by tumor before they may be inadvertently damaged, the repeated confirmation during tumor resection that a nerve is still functional, and infer the state of brain and brainstem function during the course of long surgical procedures to help signal vascular compromise, or the effects of brain retraction. These techniques can only help to enhance the safety of the long and complex procedures required for successful resection of tumors of the cranial base.

Anesthesia, General↗

PubMed2004

Short interfering RNAs can induce unexpected and divergent changes in the levels of untargeted proteins in mammalian cells.

RNA interference (RNAi) mediated by short interfering RNAs (siRNAs) is a widely used method to analyze gene function. To use RNAi knockdown accurately to infer gene function, it is essential to determine the specificity of siRNA-mediated RNAi. We have assessed the specificity of 10 different siRNAs corresponding to the MEN1 gene by examining the expression of two additional genes, TP53 (p53) and CDKN1A (p21), which are considered functionally unrelated to menin but are sensitive markers of cell state. MEN1 RNA and corresponding protein levels were all reduced after siRNA transfection of HeLa cells, although the degree of inhibition mediated by individual siRNAs varied. Unexpectedly, we observed dramatic and significant changes in protein levels of p53 and p21 that were unrelated to silencing of the target gene. The modulations in p53 and p21 levels were not abolished on titration of the siRNAs, and similar results were obtained in three other cell lines; in none of the cell lines tested did we see an effect on the protein levels of actin. These data suggest that siRNAs can induce nonspecific effects on protein levels that are siRNA sequence dependent but that these effects may be difficult to detect until genes central to a pivotal cellular response, such as p53 and p21, are studied. We find no evidence that activation of the double-stranded RNA-triggered IFN-associated antiviral pathways accounts for these effects, but we speculate that partial complementary sequence matches to off-target genes may result in a micro-RNA-like inhibition of translation.

2',5'-Oligoadenylate Synthetase↗

PubMed1998

Neuropsychological evidence of the functional integration of visual, auditory and proprioceptive spatial maps.

We infer the functional integration of the visual, auditory and proprioceptive spatial maps from the behaviour of a patient (G.A.) with left visual neglect, i.e. a derangement of visual space representation. G.A. was required to point manually to left, centre or right acoustic stimuli, under visual control or blindfolded, with the responding hand (left or right) located either on the left, centre or right space. G.A.'s manual pointing responses to left auditory stimuli were strongly influenced by the visual spatial information and by the proprioceptive spatial information related to the position of the responding effector. In the visual control condition, when the patient performed the task with the left effector located on the left, pointing responses to left auditory stimuli were shifted towards the right intact visual space. In contrast, when the visual spatial information was rendered less salient, i.e. in the blindfolded condition, and the effector was again located on the left, manual pointing responses were confined to the previously ignored left space. These findings are consistent with the view that the acoustic representation is modulated by the impaired visual representation and by the proprioceptive spatial map related to the position of the responding effector.

Acoustic Stimulation↗

PubMed1993

Design of a functional calcium channel protein: inferences about an ion channel-forming motif derived from the primary structure of voltage-gated calcium channels.

To identify sequence-specific motifs associated with the formation of an ionic pore, we systematically evaluated the channel-forming activity of synthetic peptides with sequence of predicted transmembrane segments of the voltage-gated calcium channel. The amino acid sequence of voltage-gated, dihydropyridine (DHP)-sensitive calcium channels suggests the presence in each of four homologous repeats (I-IV) of six segments (S1-S6) predicted to form membrane-spanning, alpha-helical structures. Only peptides representing amphipathic segments S2 or S3 form channels in lipid bilayers. To generate a functional calcium channel based on a four-helix bundle motif, four-helix bundle proteins representing IVS2 (T4CaIVS2) or IVS3 (T4CaIVS3) were synthesized. Both proteins form cation-selective channels, but with distinct characteristics: the single-channel conductance in 50 mM BaCl2 is 3 pS and 10 pS. For T4CaIVS3, the conductance saturates with increasing concentration of divalent cation. The dissociation constants for Ba2+, Ca2+, and Sr2+ are 13.6 mM, 17.7 mM, and 15.0 mM, respectively. The conductance of T4CaIVS2 does not saturate up to 150 mM salt. Whereas T4CaIVS3 is blocked by microM Ca2+ and Cd2+, T4CaIVS2 is not blocked by divalent cations. Only T4CaIVS3 is modulated by enantiomers of the DHP derivative BayK 8644, demonstrating sequence requirement for specific drug action. Thus, only T4CaIVS3 exhibits pore properties characteristic also of authentic calcium channels. The designed functional calcium channel may provide insights into fundamental mechanisms of ionic permeation and drug action, information that may in turn further our understanding of molecular determinants underlying authentic pore structures.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2002

Genomic functional annotation using co-evolution profiles of gene clusters.

BACKGROUND: The current speed of sequencing already exceeds the capability of annotation, creating a potential bottleneck. A large proportion of the genes in microbial genomes remains uncharacterized. Here we propose a new method for functional annotation using the conservation patterns of gene clusters. If several gene clusters show the same coevolution pattern across different genomes it is reasonable to infer they are functionally related. The gene cluster phylogenetic profile integrates chromosomal proximity information and phylogenetic profile information and allows us to infer functional dependences between the gene clusters even at great distance on the chromosome. RESULTS: As a proof of concept, we applied our method to the genome of Escherichia coli K12 strain. Our method establishes functional relationships among 176 gene clusters, comprising 738 E. coli genes. The accuracy of pair phylogenetic profiles was compared with the single-gene phylogenetic profile and was shown to be higher. As a result, we are able to suggest functional roles for several previously unknown genes or unknown genomic regions in E. coli. We also examined the robustness of coevolution signals across a larger set of genomes and suggest a possible upper limit of accuracy for the phylogenetic profile methods. CONCLUSIONS: The higher-order phylogenetic profiles, such as the gene-pair phylogenetic profiles, can detect functional dependences that are missed by using conventional single-gene phylogenetic profile or the chromosomal proximity method only. We show that the gene-pair phylogenetic profile is more accurate than the single-gene phylogenetic profiles.

Alleles↗

PubMed1995

Spatial field advantages for tactile line bisection as a function of hemispheric specialisation inferred from dichotic listening.

Thirty left-ear advantaged (LEA) and 30 right-ear advantaged (REA) right-handed subjects performed tactile line bisection (TLB) in left and right spatial fields, and at midline. REA subjects were found to perform significantly better in the right spatial field than in the left and LEA subjects significantly better in the left than in the right. Significant directional deviations were found only at midline with the left hand deviating to the right and the right hand to the left. These findings suggest that TLB is primarily a spatial task subserved by feedforward motor processes and that directional deviations are due to the differential scaling of egocentric space.

Adolescent↗

PubMed2003

Multivariate autoregressive modeling of fMRI time series.

We propose the use of multivariate autoregressive (MAR) models of functional magnetic resonance imaging time series to make inferences about functional integration within the human brain. The method is demonstrated with synthetic and real data showing how such models are able to characterize interregional dependence. We extend linear MAR models to accommodate nonlinear interactions to model top-down modulatory processes with bilinear terms. MAR models are time series models and thereby model temporal order within measured brain activity. A further benefit of the MAR approach is that connectivity maps may contain loops, yet exact inference can proceed within a linear framework. Model order selection and parameter estimation are implemented by using Bayesian methods.

Algorithms↗

PubMed1997

Non-parametric inference for cumulative incidence functions in competing risks studies.

In the competing risks problem, a useful quantity is the cumulative incidence function, which is the probability of occurrence by time t for a particular type of failure in the presence of other risks. The estimator of this function as given by Kalbfleisch and Prentice is consistent, and, properly normalized, converges weakly to a zero-mean Gaussian process with a covariance function for which a consistent estimator is provided. A resampling technique is developed to approximate the distribution of this process, which enables one to construct confidence bands for the cumulative incidence curve over the entire time span of interest and to perform Kolmogorov-Smirnov type tests for comparing two such curves. An AIDS example is provided.

AIDS-Related Opportunistic Infections↗

PubMed1990

Functional elements and domains inferred from sequence comparisons of a heat shock gene in two nematodes.

Caenorhabditis elegans and Caenorhabditis briggsae are two closely related nematode species that are nearly identical morphologically. Interspecific cross-hybridizing DNA appears to be restricted primarily to coding regions. We compared portions of the hsp-3 homologs, two grp 78-like genes, from C. elegans and C. briggsae and detected regions of DNA identity in the coding region, the 5' flanking DNAs, and the introns. The hsp-3 homologs share approximately 98% and 93% identity at the amino acid and nucleotide levels, respectively. Using the nucleotide substitution rate at the silent third position of the codons, we have estimated a lower limit for the date of divergence between C. elegans and C. briggsae to be approximately 23-32 million years ago. The 5' flanking DNAs and one of the introns contain elements that are highly conserved between C. elegans and C. briggsae. Some of the regions of nucleotide identity in the 5' flanking DNAs correspond to previously detected identities including viral enhancer sequences, a heat shock element, and an element present in the regulatory regions of mammalian grp78 and grp94 genes. We propose that a comparison of C. elegans and C. briggsae sequences will be useful in the detection of potential regulatory and structural elements.

Amino Acid Sequence↗

PubMed2002

Structure and function of human fibrinogen inferred from dysfibrinogens.

Fibrinogen is a 340-kDa plasma protein that is composed of two identical molecular halves, each consisting of three non-identical subunit polypeptides designated as A alpha, B beta- and gamma-chains held together by multiple disulfide bonds. Fibrinogen has a trinodular structure, i.e., one central E domain comprizing the amino-terminal regions of paired individual three polypeptides, and two identical outer D domains. These three nodules are linked by two coiled-coil regions [1,2]. After activation with thrombin, a tripeptide segment consisting of Gly-Pro-Arg is exposed at the amino-terminus of each alpha-chain residing at the center of the E domain and combines with its complementary binding site, called the 'a' site, residing in the carboxyl-terminal region of the gamma-chain in the outer D domain of another molecule. By crystallographic analysis [3], the alpha-amino group of alpha Gly-1 is shown to be juxtaposed between the carboxyl group of gamma Asp-364 and the carboxyamide of Gln-329 in the 'a' site. Half molecule-staggered, double-stranded fibrin protofibrils are thus formed [4,5]. Upon abutment of two adjacent D domains on the same strand, D-D self association takes place involving Arg-275, Tyr-280 and Ser-300 of the gamma-chain on the surface of the abutting two D domains [3]. Thereafter, carboxyl-terminal regions of the fibrin a-chains are thought to be untethered and interact with those of other protofibrils leading to the formation of thick fibrin bundles and interwoven networks after appropriate branching [6-9]. Although many enigmas still remain regarding the mechanisms of these molecular interactions, fibrin assembly proceeds in a highly ordered fashion. In my talk, I would like to discuss these molecular interactions of fibrinogen and fibrin based on the up-date data provided by analyses of normal as well as hereditary dysfibrinogens, particularly in the latter by introducing representative molecules at each step of fibrin clot formation.

Binding Sites↗

PubMed1997

Sequence alignments of the H(+)-dependent oligopeptide transporter family PTR: inferences on structure and function of the intestinal PET1 transporter.

PURPOSE: To study the structure and function of the intestinal H+/ peptide transporter PET1, we compared its amino acid sequence with those of related transporters belonging to the oligopeptide transporter family PTR, and with more distant transporter families. METHODS: We have developed a new approach to the sequence analysis of proteins with multiple transmembrane domains (TMDs) which takes into account the repeated TMD-loop topology. In addition to conventional analyses of the entire sequence, each TMD and its adjacent loop residues (= TMD segments) were analyzed separately as independent structural units. In combination with hydropathy analysis, this approach reveals any changes in the order of the TMD segments in the primary structure and permits TMD alignments among divergent structures even if rearrangements of the order of TMD segments have occurred in the course of evolution. RESULTS: Alignments of TMD segments indicate that the TMD order in PTR transporters may have changed in the process of evolution. Consideration of such changes permits the alignment of homologous TMD segments from PTR transporters belonging to distant akaryotic and eukaryotic phyla. Multiple alignments of TMDs reveal several highly conserved regions that may play a role in transporter function. In comparing the PTR transporters with other transporter gene families, alignment scores using the entire primary structure are too low to support a finding of probable homology. However, statistically significant alignments were observed among individual TMD segments if one disregards the order in which they occur in the primary structure. CONCLUSIONS: Our results support the hypothesis that the PTR transporters may have evolved by rearrangement, duplication, or insertions and deletions of TMD segments as independent modules. This modular structure suggests new alignment strategies for determining functional domains and testing relationship among distant transporter families.

Amino Acid Sequence↗

PubMed2002

Statistical inference for a linear function of medians: confidence intervals, hypothesis testing, and sample size requirements.

When the distribution of the response variable is skewed, the population median may be a more meaningful measure of centrality than the population mean, and when the population distribution of the response variable has heavy tails, the sample median may be a more efficient estimator of centrality than the sample mean. The authors propose a confidence interval for a general linear function of population medians. Linear functions have many important special cases including pairwise comparisons, main effects, interaction effects, simple main effects, curvature, and slope. The confidence interval can be used to test 2-sided directional hypotheses and finite interval hypotheses. Sample size formulas are given for both interval estimation and hypothesis testing problems.

Humans↗

PubMed1994

Sequence similarity scores and the inference of structure-function relationships.

Improved methods are described for the interpretation of two or more aligned protein or nucleic acid sequences. These methods can be used to interpret the possible biological importance of regions within a known three-dimensional structure, or, even without a structure, to correlate sequence similarity with the known function of particular amino acids and to associate sequence similarity with properties predicted from the sequences. Improvements include the calculation of a position-dependent, gap-penalized similarity score; computer-assisted graphical association of sequence similarity with structural, functional or chemical properties of the sequences; and statistical comparisons of the sequence conservation or variability of different groups of residues. An application is described to analyze the sequences of piconarviral capsid proteins.

Algorithms↗