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Results for “variational inference”

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PubMed2004

Cyclin mRNA stability does not vary during the cell cycle.

The cyclins are tightly regulated elements governing eukaryotic cell cycle progression by means of sequential activation-inactivation of cyclin-dependent kinases. In one manifestation of this regulation, the mRNA levels of several cyclin genes oscillate during the cycle in mammalian cells. Such cycle-dependent fluctuations in transcript levels could result from changes not only in rates of transcription, but also in mRNA stability. Here we used a new, minimally-disturbing method for producing multi-cycle synchronous growth of human MOLT-4 cells, in combination with quantitative real-time RT-PCR, to compare cell cycle-dependent transcript levels and half-lives of cyclin A2, B1, D3, E and PCNA mRNAs. While all mRNA levels except cyclin D3 varied in the cycle, there were no apparent variations in message half-lives. This differs from several previous reports of dramatic fluctuations in the stabilities of cyclin mRNAs, and infers that fluctuations in cyclin mRNA transcript levels during the MOLT-4 cell cycle are not due to variations in half-lives. The discrepancy in mRNA stability determinations could be due to differences in cell types or synchronization methods, but our findings may be representative of mRNA processing in the cycle of cells in unstressed steady-state growth.

Cell Cycle↗

PubMed1997

Similarities inferred from the studies of long range correlations among mitochondrial DNA sequences.

Existence of long range correlations within the DNA sequences of living organism has immense importance in understanding the language of DNA sequences. Recently it has been reported that long range correlations occur in DNA sequences. Some investigators claimed that these type of correlations occur only on intron containing DNA sequences. Some observers, however, have the opinion that long range correlations do not distinguish between the intron containing DNA sequences and intronless DNA sequences. The biological origin of long range correlations in the DNA sequences is not clearly known. In this paper we have demonstrated that long range correlations also occur on intronless mitochondrial DNA sequences, indicating that these special type of correlations are not the unique features for intron containing DNA sequences. We have also demonstrated that long range correlations simply originate in the region around which there is a large variation of pyrimidine and purine ratios. The similarities among the mitochondrial DNA sequences can be inferred by computing the fractal exponents in the region where there is a large variation of pyrimidine and purine ratio, as well as in the region where the ratio of pyrimidine and purine fluctuates in a nearly constant manner. In other words the similarities among the mitochondrial DNA sequences cannot be inferred by calculating the fractral exponents for the whole sequence.

Animals↗

PubMed2004

Constrained linear basis sets for HRF modelling using Variational Bayes.

FMRI modelling requires flexible haemodynamic response function (HRF) modelling, with the HRF being allowed to vary spatially and between subjects. To achieve this flexibility, voxelwise parameterised HRFs have been proposed; however, inference on such models is very slow. An alternative approach is to use basis functions allowing inference to proceed in the more manageable General Linear Model (GLM) framework. However, a large amount of the subspace spanned by the basis functions produces nonsensical HRF shapes. In this work we propose a technique for choosing a basis set, and then the means to constrain the subspace spanned by the basis set to only include sensible HRF shapes. Penny et al. showed how Variational Bayes can be used to infer on the GLM for FMRI. Here we extend the work of Penny et al. to give inference on the GLM with constrained HRF basis functions and with spatial Markov Random Fields on the autoregressive noise parameters. Constraining the subspace spanned by the basis set allows for far superior separation of activating voxels from nonactivating voxels in FMRI data. We use spatial mixture modelling to produce final probabilities of activation and demonstrate increased sensitivity on an FMRI dataset.

Bayes Theorem↗

PubMed2004

Computational inference of scenarios for alpha-proteobacterial genome evolution.

The alpha-proteobacteria, from which mitochondria are thought to have originated, display a 10-fold genome size variation and provide an excellent model system for studies of genome size evolution in bacteria. Here, we use computational approaches to infer ancestral gene sets and to quantify the flux of genes along the branches of the alpha-proteobacterial species tree. Our study reveals massive gene expansions at branches diversifying plant-associated bacteria and extreme losses at branches separating intracellular bacteria of animals and humans. Alterations in gene numbers have mostly affected functional categories associated with regulation, transport, and small-molecule metabolism, many of which are encoded by paralogous gene families located on auxiliary chromosomes. The results suggest that the alpha-proteobacterial ancestor contained 3,000-5,000 genes and was a free-living, aerobic, and motile bacterium with pili and surface proteins for host cell and environmental interactions. Approximately one third of the ancestral gene set has no homologs among the eukaryotes. More than 40% of the genes without eukaryotic counterparts encode proteins that are conserved among the alpha-proteobacteria but for which no function has yet been identified. These genes that never made it into the eukaryotes but are widely distributed in bacteria may represent bacterial drug targets and should be prime candidates for future functional characterization.

Alphaproteobacteria↗

PubMed1992

Phylogenetic position of phylum Nemertini, inferred from 18S rRNA sequences: molecular data as a test of morphological character homology.

Partial 18S rRNA sequence of the nemertine Cerebratulus lacteus was obtained and compared with those of coelomate metazoans and acoelomate platyhelminths to test whether nemertines share a most recent common ancestor with the platyhelminths, as traditionally has been implied, or whether nemertines lie within a protostome coelomate clade, as suggested by more recent morphological analyses. Maximum-parsimony analysis supports the inclusion of the nemertine within a protostome-coelomate clade that falls within a more inclusive coelomate clade. Bootstrap analysis indicates strong support for a monophyletic Coelomata composed of a deuterostome and protostome-coelomate clade. Support for a monophyletic protostome Coelomata is weak. Inference by distance analysis is consistent with that of maximum parsimony. Analysis of down-weighted paired sites by maximum parsimony reveals variation in topology only within the protostome-coelomate clade. The relationships among the protostome coelomates cannot be reliably inferred from the partial sequences, suggesting that coelomate protostomes diversified rapidly. Results with evolutionary parsimony are consistent with the inclusion of the nemertine in a coelomate clade. The molecular inference corroborates recent morphological character analyses that reveal no synapomorphies of nemertines and flatworms but instead suggest that the circulatory system and rhynchocoel of nemertines are homologous to coelomic cavities of protostome coelomates, thus supporting the corresponding hypothesis that nemertines belong within a protostome-coelomate clade. The sequence data provide an independent test of morphological character homology.

Animals↗

PubMed2004

Changing the paradigm from 'race' to human genome variation.

Knowledge from the Human Genome Project and research on human genome variation increasingly challenges the applicability of the term 'race' to human population groups, raising questions about the validity of inferences made about 'race' in the biomedical and scientific literature. Despite the acknowledged contradictions in contemporary science, population-based genetic variation is continually used to explain differences in health between 'racial' and 'ethnic' groups. In this commentary we posit that resolution of apparent paradoxes in relating biology to 'race' and genetics requires thinking 'outside of the box'.

Genetic Variation↗

PubMed1986

A case study of physicians' use of liver-spleen scans. Are we doing what we think we're doing?

We evaluated physicians' perceptions of the performance capabilities of the liver-spleen scan (LSS) in detecting metastases and the inferences physicians draw from LSS results. Physicians' perceptions of the sensitivity and specificity of the LSS in detection of metastases, as well as their estimates of likelihood ratios for various scan results, varied broadly over a range that could result in clinically important variations in patient treatment. In addition, independent of any variations in estimates of test performance characteristics, physicians had difficulty drawing appropriate probabilistic inferences from LSS results. Our findings suggest that data regarding the performance capabilities of the LSS and other diagnostic tests within a particular hospital should be made available to physicians and that physicians should be given microcomputer assistance in estimating the impact of test results on the probability of disease.

Humans↗

PubMed1999

Genetic evidence for larger African population size during recent human evolution.

Genetic evidence suggests that the long-term average effective size of sub-Saharan Africa is larger than other geographic regions. A method is described that allows estimation of relative long-term regional population sizes. This method is applied to 60 microsatellite DNA loci from a sample of 72 sub-Saharan Africans, 63 East Asians, and 120 Europeans. Average heterozygosity is significantly higher in the sub-Saharan African sample. Expected heterozygosity was computed for each region and locus using a population genetic model based on the null hypothesis of equal long-term population sizes. Average residual heterozygosity is significantly higher in the sub-Saharan African sample, indicating that African population size was larger than other regions during recent human evolution. The best fit of the model is with relative population weights of 0.73 for sub-Saharan Africa, 0.09 for East Asia, and 0.18 for Europe. These results are similar to those obtained using craniometric variation for these three geographic regions. These results, combined with inferences from other genetic studies, support a major role of Africa in the origin of modern humans. It is less clear, however, whether complete African replacement is the most appropriate model. An alternative is an African origin with non-African gene flow. While Africa is an important region in recent human evolution, it is not clear whether the gene pool of our species is completely out of Africa or predominately out of Africa.

Africa↗

PubMed1998

Direct fluorometry of phase-extracted tryptamine-based fast quantitative assay of L-tryptophan decarboxylase from Catharanthus roseus leaf.

An assay for the enzyme L-tryptophan decarboxylase (TDC; EC 4.1.1.28) is described. It is based on direct fluorometry of the enzymatic reaction product (tryptamine) selectively recovered in ethyl acetate from the reaction mixture. Catalytically formed tryptamine from tryptophan in the incubation mixture is selectively (free from tryptophan) physically separated as ethyl acetate solution under basic (pH > or = 11) conditions and subjected to direct fluorescence measurement in the organic solvent using a spectrofluorometer with excitation and emission wavelengths of 280 and 350 nm, respectively. Tryptamine production rate was quantitated from the luminescence response curve of tryptamine drawn under similar extraction and measurement conditions. Luminescence calibration curves were drawn for tryptamine in aqueous (water or buffer system) as well as in organic solvent as recovered from the varied aqueous solution conditions including those similar to the enzyme incubation mixture. The luminescence calibration graphs were linear for at least 0.5 to 10 microM tryptamine. The examination of interassay variations and the comparative magnitude of fluorescence response allowed to infer that a satisfactory and sufficient sample luminescence response was retained under the varied conditions including those akin to the enzymatic assay mixture, allowing adaptation of the fluorometry for the TDC activity quantitation. The assay was found to follow the proportionality principle of product formation with respect to catalytic reaction time as well as protein concentration in the assay mixture using Catharanthus roseus leaf crude homogenate as well as the enzyme preparation at different states of purity. The rate of tryptamine formation under the catalytic conditions was linear for at least 1 h at 30 degrees C. Though the assay has been demonstrated to use the C. roseus leaf as the enzyme source, it should be equally applicable to other plant and nonplant sources. The merits and precautions of the protocol have been discussed.

Alkalies↗

PubMed1999

Discrepancies between normative and descriptive models of decision making and the understanding/acceptance principle.

Several tasks from the heuristics and biases literature were examined in light of Slovic and Tversky's (1974) understanding/acceptance principle-that the deeper the understanding of a normative principle, the greater the tendency to respond in accord with it. The principle was instantiated both correlationally and experimentally. An individual differences version was used to examine whether individuals higher in tendencies toward reflective thought and in cognitive ability would be more likely to behave normatively. In a second application of the understanding/acceptance principle, subjects were presented with arguments both for and against normative choices and it was observed whether, on a readministration of the task, performance was more likely to move in a normative direction. Several discrepancies between performance and normative models could be explained by the understanding/acceptance principle. However, several gaps between descriptive and normative models (particularly those deriving from some noncausal base rate problems) were not clarified by the understanding/acceptance principle-they could not be explained in terms of varying task understanding or tendencies toward reflective thought. The results demonstrate how the variation and instability in responses can be analyzed to yield inferences about why descriptive and normative models of human reasoning and decision making sometimes do not coincide.

Adolescent↗

PubMed2004

Do avian mitochondria recombine?

The dogma of strict maternal inheritance of mitochondria is now being tested with population genetics methods on sequence data from many species. In this study we investigated whether recombination occurs in the mitochondria of the blue tit ( Parus caeruleus) by studying polymorphisms in the mitochondrial control region and in a recently identified (A)(n) microsatellite on the W chromosome. The female heterogamety of avian sex chromosomes allows a test of whether mitochondrial recombination affects genealogical inference by comparison of mitochondrial and W-linked sequence variation. There is no discrepancy between mitochondrial and W-linked genealogies in blue tits, consistent with no recombination. We also analyzed mitochondrial sequence variation in both blue tits and peregrine falcons ( Falco peregrinus) using a coalescent-based approach which accounts for recurrent mutation; in neither bird species did we find evidence of recombination. We conclude that it is unlikely that mitochondrial recombination has large effects on mitochondrial genetic variability in birds.

Animals↗

PubMed1996

ERG measurements of the spectral sensitivity of common chimpanzee (Pan troglodytes).

The spectral sensitivity of the common chimpanzee (Pan troglodytes) was measured with electroretinogram (ERG) flicker photometry. Chromatic adaptation conditions were used to establish the presence of S-, M- and L-cone pigments. Each of 26 chimpanzees showed substantial and approximately equivalent adaptational changes over the middle and long wavelengths implying an absence of any significant polymorphic variations in the M- and L-cone pigments. As inferred from ERG measurements, the S-cone pigment of the chimpanzee has a spectral peak of about 430 nm. Chimpanzee spectral sensitivity measurements were compared to those obtained from equivalently tested normal human trichromats. The spectral sensitivity of the two species is very similar, chimpanzees being slightly more sensitive to short wavelength lights and slightly less sensitive to long wavelength lights than human subjects. Curve-fitting analyses suggest that spectral filtering may be lower in the chimpanzee lens than it is in the human lens, and that the L/M cone ratio is lower in the chimpanzee.

Adaptation, Ocular↗

PubMed2006

The predictive value of routine semen evaluation and IVF technology for determining relative boar fertility.

Practical techniques for assessing semen quality in order to predict male fertility are still needed. The principal objective of this experiment was to evaluate routine laboratory evaluation and in vitro fertilization (IVF) techniques as predictors of relative boar fertility using a low-dose AI protocol. Nine boars were evaluated during a 6.5+/-1 mo period, beginning at 29-32 wk of age. Ejaculates were evaluated for motility, morphology and concentration, diluted to 1.5 billion sperm in 50 mL extender, and used to breed 50+/-5 gilts over the same period. On nine occasions, a specific aliquot of the ejaculate's first sperm-rich fraction was evaluated using IVF procedures. Boars differed (P<0.001) consistently for pregnancy rate (from 73 to 98%), farrowing rate (71-98%) and total born (8.8-12.0). Routine semen evaluation and IVF parameters that presented significant differences between boars, but no differences in time and no boar by time interaction, were used to correlate in vivo fertility. A multiple regression model based on routine semen evaluation parameters accounted for up to 27 and 22% of the variation of fertility index and total piglets born, respectively, whereas male pronuclear formation rate was the IVF variable that accounted for 17 and 12% of the variation in farrowing rate and fertility index, respectively. Collectively, we inferred that the use of low sperm numbers for AI, determination of pregnancy rate at Day 30, motility of extended semen after 7 and 10d, and specific IVF parameters may be useful for identifying relatively infertile boars that are not currently excluded from use in existing commercial boar studs.

Algorithms↗

PubMed2002

Temporal relationship of hippocampal liquor- and plasma-cortisol-concentrations in the domestic pig challenged with synthetical adreno-corticotrophic hormone.

The concentration of plasma and intracerebral cortisol in pigs challenged with 0.5 IU adrenocorticotrophic hormone/kg body weight was simultaneously measured at a 30 min rate. The pigs (n=5) were provided with indwelling jugular vein catheters and guide canullas for insertion of a hippocampal microdialysis probe. Every five blood samples taken at 6 min intervals were pooled to simulate the 30 min collection time of the microdialysis. Stimulation resulted in an increment of cortisol of roughly 200% in plasma and 190% in the dialysate compared to basal value. The average time lag of hippocampal to plasma peak was 48.75 min. Considering the temporal resolution of the protocol it is inferred that delays of at least 30 min occur between variations of peripheral and central nervous cortisol.

Adrenocorticotropic Hormone↗

PubMed2000

Phylogenetic analysis of mitochondrial LSU rRNA in oniscids.

The phylogenetic relationships among oniscids (Crustacea, Isodopa) remain contradictory despite numerous morphological studies. We have investigated them using molecular data. Partial sequences of the mitochondrial LSU rRNA gene were obtained from 42 species of aquatic and terrestrial crustaceans from 31 genera. This gene provided well-supported information, notwithstanding the high taxonomic level of this study, indicating a useful amount of variation despite the noise due to multiple substitutions. The phylogenetic inferences demonstrated that a) Crinocheta and Synocheta sections are monophyletic and sister-groups, b) Ligiidae and Tylidae representatives are in a basal position compared to other oniscids, c) Helleria brevicornis, the only representative of the Helleriinae subfamily, has undergone different evolution, d) the relationships between aquatic isopods and ancient groups of Oniscidea are not resolved, probably due to fast radiation not discriminated by the molecular phylogeny.

Animals↗

PubMed2001

Do human and JC virus genes show evidence of host-parasite codemography?

Information about similarities and differences in the demographic history of host and parasite populations is potentially useful for making inferences about a variety of evolutionary processes. However, it is difficult to observe the historical demographic properties of natural populations directly. Here, the extent of demographic similarity in a host and its parasite was examined indirectly by inferring long-term population history from patterns of genetic variation. Nucleotide sequence diversity in human and JC virus (JCV) DNA is consistent with a long-term demographic connection between the two species: both show evidence of large-scale population expansion. However, genetic data also suggest that the two species have different patterns of population substructuring. These similarities and differences have implications for adaptive evolution in JCV that are not evident when the two species are considered separately.

Africa↗

PubMed2003

Haplotypic relationship between SNP and microsatellite markers at the NOS2A locus in two populations.

The density of genetic markers required for successful association mapping of complex diseases depends on linkage disequilibrium (LD) between non-functional markers and functional variants. The haplotypic relationship between stable markers and potentially unstable but highly informative markers (e.g. microsatellites) indicates that LD might be maintained over considerable genetic distance in non-African populations, supporting the use of such 'mixed marker haplotypes' in LD-based mapping, and allowing inferences to be drawn about human origins. We investigated sequence variation in the proximal 2.6 kb of the inducible nitric oxide synthase (NOS2A) promoter and the relationship between SNP haplotypes and a pentanucleotide microsatellite (the 'NOS2A(-2.6) microsatellite') in Gambians and UK Caucasians. UK Caucasians exhibited a subset of sequence diversity observed in Gambians, sharing four of 11 SNPs and a similar haplotypic structure. Five SNPs were found in the sequence of interspersed repetitive DNA elements. In both populations, there was dramatic loss of LD between SNP haplotypes and microsatellite alleles across a very short physical distance, suggesting a high intrinsic mutation rate of the NOS2A(-2.6) microsatellite, the SNP haplotypes are relatively ancient, or that this was a region of frequent recombination. Understanding locus- and population-specific LD is essential when designing and interpreting genetic association studies.

Gambia↗

PubMed1979

Comparison of radioactive peptides obtained from specifically labelled human renal and placental alkaline phosphatases.

Peptides with different chromatographic and electrophoretic properties were obtained from human placental and renal alkaline phosphatases by tryptic digestion of the enzymes labelled with radioactive orthophosphate at their active centres. These results provide structural evidence for the distinct genetic origins of the two isoenzymes that had previously been inferred from their different properties and from the observed phenotypic variation of placental phosphatase.

Alkaline Phosphatase↗