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PubMed2000

Light-induced FTIR difference spectroscopy of the S(2)-to-S(3) state transition of the oxygen-evolving complex in Photosystem II.

We have applied flash-induced FTIR spectroscopy to study structural changes upon the S(2)-to-S(3) state transition of the oxygen-evolving complex (OEC) in Photosystem II (PSII). We found that several modes in the difference IR spectrum are associated with bond rearrangements induced by the second laser flash. Most of these IR modes are absent in spectra of S(2)/S(1), of the acceptor-side non-heme ion, of Yradical(D)/Y(D) and of S(3)'/S(2)' from Ca-depleted PSII preparations. Our results suggest that these IR modes most likely originate from structural changes in the oxygen-evolving complex itself upon the S(2)-to-S(3) state transition in PSII.

Lasers↗

PubMed1997

The curvature function evolved in scale-space as a representation of biological shapes.

A new and simple approach for calculating the curvature functions of arbitrary non-analytical (biological) contours of planar shapes is described. This approach does not require either parametrization or the evaluation of derivatives, which eliminates sources of error and noise amplification. It is shown that this method provides better results than the traditional procedure and the procedure employing polar coordinates. The paper describes how to evolve contours in scale-space, and it is discussed how, due to its invariant properties, curvature functions, evolved in scale-space, are suitable as representations of shapes. The techniques described are applied to the digitized contours of isolated corneal endothelial cells.

Cell Size↗

PubMed1997

Did cyclodextrin glycosyltransferases evolve from alpha-amylases?

The hydrolytic enzymes, alpha-amylases, and the cyclodextrin glycosyltransferases (CGTases) are key enzymes in the depolymerization of starch. These two groups of enzymes are evolutionarily related. We propose that the transferase activity is likely to have evolved from an ancestral hydrolase. Sequence analysis provides support for this hypothesis. Consequently, we have conducted an experimental study to test the possible adaptive value for evolving a CGTase. We found that when an alpha-amylase and a CGTase are combined more glucose is generated from starch than would be expected from the independent action of either of these enzymes. Thus, we propose that the biological role of CGTases is to work in concert with alpha-amylases for the efficient saccharification of starch. This observation can be useful in industrial processes aimed at producing syrups with high contents of glucose or maltose.

Bacteria↗

PubMed1998

Rapid and discrete isolation of oxygen-evolving His-tagged photosystem II core complex from Chlamydomonas reinhardtii by Ni2+ affinity column chromatography.

We have developed a simple and rapid procedure to isolate an oxygen-evolving photosystem II (PS II) core complex from Chlamydomonas reinhardtii. A His-tag made of six consecutive histidine residues was genetically attached at the carboxy terminus of D2 protein to create a metal binding site on the PS II supramolecular complex. The recombinant cells producing the His-tagged variant of D2 protein grew photoautotrophically as well as the wild-type cells. Characterization of the oxygen evolution and the thermoluminescence properties revealed that the His-tagging did not affect the functional integrity of the PS II reaction center. A PS II core complex was isolated from the detergent-solubilized thylakoids of the recombinant cells in 4 h by a single one-step Ni2+ affinity column chromatography. This preparation consists of D1, D2, CP43, CP47, 33 kDa, and a few low molecular weight proteins, and retains a high rate of oxygen-evolving activity (= 1000 micromol/mg Chl/h).

Animals↗

PubMed1999

Isolation and characterisation of oxygen evolving thylakoids from the marine prokaryote Prochloron didemni.

The present study describes the first successful attempt to isolate oxygen evolving thylakoids and thylakoid fragments from the marine prokaryote Prochloron didemni, a member of the recently discovered group of prochlorophytes. Oxygen evolving thylakoid membranes and fragments were isolated from seawater suspended cells of Prochloron didemni by passage of the cells through a Yeda press and subsequent differential centrifugation of the broken material. Three fractions were collected at 1000 x g, 5000 x g, and 3000 x g and identified by light microscopy as cells (and their fragments), thylakoids and membrane fragments, respectively. Pigment content, oxygen evolution rate and 77 K fluorescence spectra of these fractions were virtually identical. This finding indicates that the membrane fragments obtained are not enriched in photosystem II. The P680+* reduction kinetics of thylakoid membrane fragments were determined by monitoring flash induced absorption changes at 830 nm and analysing the time course of their decay. The multiphasic relaxation kinetics and their modification by NH2OH were found to be similar to those observed in cyanobacteria and plants. These findings provide an independent line of evidence for the idea of a high conservation of the basic structural and functional pattern of the water oxidising complex in all organisms that perform oxygenic photosynthesis.

Chlorophyll↗

PubMed2002

[Antiphospholipid antibodies evolving into connective tissue disease: follow-up study of women with recurrent misscarriage].

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the clinical and immunologic profile, the rate of progression to connective tissue disease and the possible predictors of evolution in patients with antiphospholipid antibodies and abortions. PATIENTS AND METHOD: In a prospective follow-up study, we determined the prevalence of antiphospholipid antibodies as well as other autoimmune abnormalities and the evolution to connective tissue disease in 200 women with unexplained recurrent abortions. IgG and IgM anticardiolipin antibodies were determined by ELISA and the lupus anticoagulant was determined by means of coagulometric tests. RESULTS: Of 200 women with pregnancy losses, 69 (34.5%) had antiphospholipid antibodies. Thirty-one of 200 women (15.5%) had high or moderate positive anticardiolipin antibodies. During a mean follow-up of 32 months, 9 (13%) antiphospholipid-antibody-positive patients developed features of lupus- like disease or systemic lupus erythematosus. A low total hemolytic complement, increased circulating immune complexes and positive antinuclear antibodies (ANA) were more common in those patients evolving to a connective tissue disorder (p < 0.001, p = 0.003 and p < 0.001, respectively). Positive ANA in women with antiphospholipid antibodies predicted independently the evolution to a connective tissue disorder [Cox proportional hazard model; relative hazard = 4.92, p = 0.04]. CONCLUSIONS: A subgroup of patients with antiphospholipid antibodies and abortions may progress to a connective tissue disorder. A positive antinuclear antibody test result could be useful to identify those patients with antiphospholipid antibodies and abortions who are prone to evolve into a systemic autoimmune disease.

Abortion, Habitual↗

PubMed2003

Comparative study of the strategies evolved by two parasitoids of the genus Asobara to avoid the immune response of the host, Drosophila melanogaster.

Asobara tabida and Asobara citri are two braconid endoparasitoids of Drosophila melanogaster larvae. We studied and compared the strategies evolved by these two species to avoid the immune reaction of their host. A. tabida has no negative impact on host cellular defenses and its eggs avoid encapsulation by adhering to host tissues. At the opposite, we found that A. citri, whose eggs are devoid of adhesive properties, affects the host encapsulation abilities, hemolymph phenoloxidase activity and concentrations of circulating hemocytes. Some of these effects could directly rely on a severe disruption of the hematopoietic organ anterior lobes observed in parasitized larvae. This is the first report of the immune suppressive abilities of a parasitoid from the Asobara genus. Results are presented and discussed with respect to the strategies of virulence evolved by other parasitoids to counteract the D. melanogaster immune system.

Animals↗

PubMed2002

Evolving uses of hormonal agents for breast cancer therapy.

BACKGROUND: During the past decade, a number of new hormonal therapies (HTs) have been developed, including the selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), and estrogen receptor (ER) antagonists. Their uses in breast cancer are continually evolving as new clinical trial results become available. Although tamoxifen, the most widely used HT for breast cancer, was originally approved for and used in the treatment of metastatic breast cancer (MBC), its effectiveness as MBC therapy led to its subsequent assessment and use as adjuvant and risk-reduction therapy for breast cancer. However, tamoxifen is not universally effective in these settings and is associated with infrequent known toxicities such as increased risk of thromboembolism and endometrial cancer; therefore, a search for more effective and more tolerable HTs has evolved. OBJECTIVE: This article reviews the data supporting the use of newer HTs as initial treatment of MBC and their potential use as adjuvant, neoadjuvant, and chemopreventive therapies. METHODS: Articles for inclusion in this manuscript were identified through the following searches, limited to English-language publications: MEDLINE (mid 1960s to January 2002), American Society of Oncology abstracts (1997-2001), and San Antonio Breast Cancer Symposium abstracts (2001 and 2002). The following search terms were used: breast cancer, breast cancer guidelines, hormonal therapies, tamoxifen, toremifine, letrozole, anastrozole, exemestane, megestrol acetate, fulvestrant, and ICI 182,780. RESULTS: Recent studies have focused on newer agents as initial and subsequent treatment of MBC, adjuvant or neoadjuvant treatments of breast cancer, and chemopreventive agents in both healthy women and women with a history of ductal carcinoma in situ (DCIS). Results of clinical trials comparing AIs with tamoxifen as first-line MBC treatment show that AIs are as effective as, or more effective than, tamoxifen and are associated with fewer serious adverse events. Tamoxifen remains the gold standard for adjuvant therapy. However, preliminary results of ongoing clinical trials comparing tamoxifen with anastrozole suggest that anastrozole may be the superior agent. Both tamoxifen and the AIs have been shown to be active in the neoadjuvant treatment of breast cancer. Trial results have shown that tamoxifen is effective for breast cancer prevention in patients at high risk of developing breast cancer but who are otherwise healthy, patients with a history of DCIS, and patients with lobular carcinoma in situ. CONCLUSIONS: Although tamoxifen has been the gold standard of HT for breast cancer, results of ongoing trials assessing the newer HTs as initial, neoadjuvant, adjuvant, and chemopreventive therapies may substantially change our current clinical practice patterns.

Anastrozole↗

PubMed2003

Functional and structural study on chelator-induced suppression of S2/S1 FTIR spectrum in photosynthetic oxygen-evolving complex.

Chelating agents have been shown to induce characteristic changes in the light-minus-dark Fourier transform infrared (FTIR) difference spectrum for the S(2)/S(1) difference in the oxygen-evolving complex (OEC). Addition of various ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA)-type chelators, such as EDTA, O,O'-bis(2-aminoethyl)ethyleneglycol-N,N,N',N'-tetraacetic acid (EGTA), trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (CyDTA), or N-(2-hydroxyethyl)ethylenediamine-N,N',N'-triacetic acid (HEDTA), to Ca(2+)-depleted PS II membranes resulted in the suppression of typical S(2)/S(1) vibrational features, including the symmetric (1365(+)/1404(-) cm(-1)) and the asymmetric (1587(+)/1566(-) cm(-1)) carboxylate stretching vibrations, as well as the amide I and II modes of the backbone polypeptides. In contrast, the addition of ethylenediamine-N,N'-diacetic acid (EDDA) showed less inhibitory effects. The effects of the chelators depended on the number of the carboxylate groups; chelators with more than two carboxymethyl groups were effective in altering the FTIR spectrum. The bridging structure that connects the two nitrogen atoms also influenced the inhibitory effects. However, the effects were not necessarily correlated with the stability constants of the chelators to Mn(2+). The vibrational modes that were suppressed by EDTA were almost completely restored by subsequent washing with Chelex-treated Ca(2+)-free buffer medium, indicating that the spectral changes are attributable to the reversible association of chelators with the Ca(2+)-depleted OEC. Nevertheless, prolonged incubation with chelators led to the impairment of the O(2)-evolving capability, with differences in the effectiveness, in the order that is consistent with that for the suppression effects on FTIR spectra. Chelators with carboxylate and/or carboxymethyl groups bound to a single nitrogen [nitrilotriacetic acid (NTA) and iminodiacetic acid (IDA)] or carbon (citric acid) were relatively ineffective for the suppression. A chelator that includes four phosphate groups, ethylenediamine-N,N,N',N'-tetrakis(methylenephosphonic) acid (EDTPO), also showed suppression effects on both the carboxylate and amide modes. Based on these findings, a possible mode of interaction between the chelators and the Mn cluster is discussed.

Calcium↗

PubMed2002

Quantitative structure-activity relationships by evolved neural networks for the inhibition of dihydrofolate reductase by pyrimidines.

Evolutionary computation provides a useful method for training neural networks in the face of multiple local optima. This paper begins with a description of methods for quantitative structure activity relationships (QSAR). An overview of artificial neural networks for pattern recognition problems such as QSAR is presented and extended with the description of how evolutionary computation can be used to evolve neural networks. Experiments are conducted to examine QSAR for the inhibition of dihydrofolate reductase by pyrimidines using evolved neural networks. Results indicate the utility of evolutionary algorithms and neural networks for the predictive task at hand. Furthermore, results that are comparable or perhaps better than those published previously were obtained using only a small fraction of the previously required degrees of freedom.

Biological Evolution↗

PubMed2003

The evolution of evolvability in genetic linkage patterns.

A number of factors have been proposed that may affect the capacity for an evolutionary system to generate adaptation. One that has received little recent attention among biologists is linkage patterns, or the ordering of genes on chromosomes. In this study, a simple model of genetic interactions, implemented in an evolutionary simulation, demonstrates that clustering of epistatically interacting genes increases the rate of adaptation. Moreover, long-term evolution with inversion can reorganize linkage patterns from random gene ordering into this more modular organization, thereby facilitating adaptation. These results are consistent with a large body of biological observations and some mathematical theory. Although linkage patterns are neutral with respect to individual fitness in this model, they are subject to lineage level selection for evolvability. At least two candidate mechanisms may contribute to improved evolvability under epistatic clustering: clustering may reduce interference between selection on different traits, and it may allow the simultaneous optimization of different recombination rates for gene pairs with additive and epistatic fitness effects.

Adaptation, Physiological↗

PubMed2003

Evolving significance of prognostic markers associated with new treatment strategies in neuroblastoma.

The striking differences in the natural history of clinical subgroups of neuroblastoma (NB), and the evolving therapeutic approaches for each, makes it imperative for prognostic markers to be reevaluated within individual clinical categories. At least one third of NB cases present without distant metastasis and cytotoxic therapy does not alter the natural history. We carried out a retrospective analysis of archived tumor samples. Fifty-seven of these patients had local-regional (LR) NB and were managed conservatively, initially treated with surgery alone. Among the biologic and clinical features analyzed including age, stage, histology, ploidy, MYCN, and 1p36, 1p22, 11q, 14q, 9p and 19q loss of heterozygosity (LOH) in multivariate analysis, diploidy was one of the most significant factors associated with progression-free survival and stage 4 progression. Clonal ploidy heterogeneity was common in LR NB. A predominant near-triploid clonal population was found in most cases of non-progressing LR NB tumors whereas progressing LR NB cases had a predominant diploid clone. We also reviewed the prognostic factors among 84 stage 4 NB cases treated with the N5, N6 or N7 protocols at MSKCC from 1987 to 1999. Traditional markers such as lactate dehydrogenase (LDH), ferritin, age and MYCN status were not prognostic in the univariate analysis. 11q23 and 1p22 LOH were correlated with better survival. These results highlight the evolving significance of prognostic analysis in homogeneous clinical groups undergoing similar treatments. To further characterize the gene expression profile between local-regional and metastatic NB, we carried out Microarray analysis of 41 NB tumors and 12 NB cell lines, using the Affymetrix Genechip Human Genome U95 Set. Distinct gene expression patterns between metastatic and non-metastatic NB tumors have been identified. Validation of these results and further mechanistic studies may shed new light on the biology of metastasis in human NB.

Biomarkers, Tumor↗

PubMed2001

Differential and age-dependent expression of hyperpolarization-activated, cyclic nucleotide-gated cation channel isoforms 1-4 suggests evolving roles in the developing rat hippocampus.

Hyperpolarization-activated cation currents (I(h)) are found in several brain regions including thalamus and hippocampus. Important functions of these currents in promoting synchronized network activity and in determining neuronal membrane properties have been progressively recognized, but the molecular underpinnings of these currents are only emerging. I(h) currents are generated by hyperpolarization-activated, cyclic nucleotide-gated cation channels (HCNs). These channel proteins are encoded by at least four HCN genes, that govern the kinetic and functional properties of the resulting channels. Because of the potential impact of I(h)-mediated coordinated neuronal activity on the maturation of the functional hippocampal network, this study focused on determining the expression of the four members of the HCN gene family throughout postnatal hippocampal development at both the regional and single cell level.The results of these experiments demonstrated that HCNs 1, 2 and 4 are differentially expressed in interneuronal and principal cell populations of the rat hippocampal formation. Expression profiles of each HCN isoform evolve during postnatal development, and patterns observed during early postnatal ages differ significantly from those in mature hippocampus. The onset of HCN expression in interneurons of the hippocampus proper precedes that in the dentate gyrus, suggesting that HCN-mediated pacing activity may be generated in hippocampal interneurons prior to those in the hilus. Taken together, these findings indicate an age-dependent spatiotemporal evolution of specific HCN expression in distinct hippocampal cell populations, and suggest that these channels serve differing and evolving functions in the maturation of coordinated hippocampal activity.

Aging↗

PubMed2004

Aging as an evolved characteristic - Weismann's theory reconsidered.

Theories of aging have become significantly more important because of discoveries which indicate that aging is not universal or inevitable and which therefore indicate that major medical intervention in aging is possible. Directions of anti-aging research could be significantly influenced by basic theories of aging. Weismann proposed in 1882 that aging was an evolved genetically programmed adaptation that had a species benefit. Since then this idea has been largely replaced by various theories in which aging is not an adaptation but results from accumulated adverse mutations or is an adverse side effect of some essential process. Arguments are presented to the effect that aging is an evolved beneficial characteristic and is therefore likely to result from a more complex and structured mechanism than if it resulted from more random processes such as mutation accumulation. Further, aging appears to be one of a number of related and interactive life-cycle characteristics including age-at-puberty suggesting that it might be controlled by similar biological mechanisms.

Adaptation, Biological↗

PubMedDate not supplied

A large left ventricular thrombus evolving towards canalization and mimicking a left ventricular pseudoaneurysm: an echocardiographic study.

We describe a case of a large apical left ventricular thrombus evolving towards canalization and showing echocardiographic features mimicking a left ventricular pseudoaneurysm. Only serial echocardiographic studies allowed an appreciation of the changing morphologic features of the apical structure, permitting differential diagnosis between a canalization of an evolving thrombus and a myocardial free-wall rupture with pseudoaneurysm formation.

Aged↗

PubMed2003

Evolving connectionist systems for knowledge discovery from gene expression data of cancer tissue.

Microarray techniques have made it possible to observe the expression of thousands of genes simultaneously. They have recently been applied to study gene expression patterns in tissue samples. This may lead to highly desirable improvements in the diagnosis and treatment of human diseases. Statistical and machine learning methods have recently been used to classify cancer tissue based on gene expression data. Although some of these methods have achieved a high degree of accuracy, they generally lack transparency in their classification process. This, however, is crucial for the application in the medical field. In order to overcome this obstacle, we used knowledge-based neurocomputing (KBN), since KBN seeks to gain knowledge that is comprehensible to humans. In particular, we applied evolving fuzzy neural networks (EFuNNs) to classify cancer tissue, which is illustrated on the case studies of leukaemia and colon cancer. EFuNNs belong to the evolving connectionist system paradigm (ECOS) that has been recently introduced. They are well suited for adaptive learning and knowledge discovery. Fuzzy logic rules can be extracted from the trained networks and offer knowledge about the classification process in an easily accessible form. These rules point to genes that are strongly associated with specific types of cancer and may be used for the development of new tests and treatment discoveries.

Algorithms↗

PubMed1998

Evolving artificial neural networks for screening features from mammograms.

Disagreement or inconsistencies in mammographic interpretation motivates utilizing computerized pattern recognition algorithms to aid the assessment of radiographic features. We have studied the potential for using artificial neural networks (ANNs) to analyze interpreted radiographic features from film screen mammograms. Attention was given to 216 cases (mammogram series) that presented suspicious characteristics. The domain expert (Wasson) quantified up to 12 radiographic features for each case based on guidelines from previous literature. Patient age was also included. The existence or absence of malignancy was confirmed in each case via open surgical biopsy (111 malignant, 105 benign). ANNs of various complexity were trained via evolutionary programming to indicate whether or not a malignancy was present given a vector of scored input features in a statistical cross validation procedure. For suspicious masses, the best evolved ANNs generated a mean area under the receiver operating characteristic curve (AZ) of 0.9196 +/- 0.0040 (1 S.E.), with a mean specificity of 0.6269 +/- 0.0272 at 0.95 sensitivity. Results when microcalcifications were included were not quite as good (AZ = 0.8464), however, ANNs with only two hidden nodes performed as well as more complex ANNs and better than ANNs with only one hidden node. The performance of the evolved ANNs was comparable to prior literature, but with an order of magnitude less complexity. The success of small ANNs in diagnosing breast cancer offers the promise that suitable explanations for the ANN's behavior can be induced, leading to a greater acceptance by physicians.

Artificial Intelligence↗

PubMed2002

Giardia: highly evolved parasite or early branching eukaryote?

The phylogeny of the commonest protozoal agent of intestinal disease, Giardia, is unclear. Although recent intensive research suggests this important human parasite is an early branching eukaryote that evolved before the endosymbiotic origin of mitochondria, there is also evidence to suggest that, as a highly evolved parasite, it has lost many of its ancestral characteristics. In this case, these organisms might have arisen much more recently from aerobic free-living flagellates.

Animals↗