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PubMed2001

Private and collective interests; conflicts and solutions: the central theme of current thinking in evolutionary biology.

The statement made by the population geneticist Theodosius Dobzhansky (1973): "Nothing in Biology Makes Sense Except in the Light of Evolution", is often quoted as a crucially important generalization on the nature of biology. I am inclined to consider as equally important the statement: "Nothing in Evolutionary Biology Makes Sense Except in the Light of Conflicts between Parts and Systems." This generalization takes account of the dynamic nature of biological phenomena, but also of the fact that the study of transitions from autonomous units to cooperative systems has become one of the most exciting and scientifically rewarding enterprises in all of organismic biology. The problems encountered and the speculations generated in the course of this enterprise will be either of the more unit-centered or of the more system-centered type, most biologists tending to lean towards one or the other. This explains why evolutionary biology is fraught with so many antagonistic attitudes and polarizing points of view. In this essay I want specifically to draw attention to and discuss the following issues which in recent years have polarized biologists: the dual nature of genes; the logic of Hamilton's rule; the relationship between kin selection, signalling networks and systemic manipulation; the semantic problem of progress in evolution; and the evolutionary consequences of the vastly differing time scales over which genotypic and phenotypic information processing occurs in higher animals.

Journal Article↗
PubMed1994

Molecular evolution of alanine/glyoxylate aminotransferase 1 intracellular targeting. Analysis of the feline gene.

The subcellular distribution of hepatic alanine:glyoxylate aminotransferase 1 (AGT) has changed, under the influence of dietary selection pressure, on several o occasions during the evolution of mammals. In some species (e.g. human and rabbit) AGT is entirely peroxisomal; in other species (e.g. marmoset and rat) this enzyme is found in similar amounts in peroxisomes and mitochondria; in yet other species (e.g. cat) it is mainly mitochondrial. The molecular basis of the species-specific dual intracellular targeting of AGT has been partially elucidated in the human and rabbit (as examples of the first group), and in the rat and marmoset (as examples of the second group). As part of a wider study on the molecular evolution of AGT intracellular targeting, we report in the present paper the results of an investigation into the molecular basis of the subcellular distribution of AGT in the cat (as an example of the third group). Cat liver AGT cDNA has been cloned and sequenced, and shown to have a high degree of similarity to AGT from human, rabbit, marmoset and rat. Southern-blotting analysis showed that AGT in the cat is probably encoded by a single gene, as it is in other species. Transcript analysis by RNase protection indicated that almost all of the AGT mRNA would possess an open reading frame encoding a polypeptide of 414 amino acids and a molecular mass of 45,508 Da. The N-terminal 22 amino acids comprised the putative mitochondrial-targeting sequence (by analogy with the equivalent sequence in marmoset and rat pre-mitochondrial AGT). The very low level of peroxisomal AGT in cat liver is compatible with the absence of any RNase-protected transcripts initiating downstream of the first putative translation initiation codon (i.e. absence of any transcripts in which the mitochondrial-targeting sequence is excluded from the open reading frame). In vitro studies showed that the 45 kDa polypeptide was imported into rat liver mitochondria and processed to a mature protein of approximately 43 kDa, compatible with the cleavage of the N-terminal 22 amino acids, as is also the case in rat and marmoset. A polypeptide in which the N-terminal 22 amino acids was absent could not be imported into mitochondria in vitro.

Alanine Transaminase↗
PubMedDate not supplied

[The molecular mechanism of evolution of changes in the genetic code].

Alterations to the standard genetic code have been found in both prokaryotes and eukaryotes. This finding demolished the central dogma of molecular biology, postulated by Crick in 1968, of an immutable and universal genetic code and raised the question of how organisms survive genetic code alterations? Recent studies suggest that genetic code alterations are driven by selection using a mechanism that requires translational ambiguity. In C. albicans, the leucine CUG codon is decoded as serine through structural alterations of the translational machinery, in particular, of a Ser-tRNACAG which has dual identity and novel decoding properties. Here, we review the molecular mechanism of CUG reassignment focusing on the structural change of the translational machinery and on the impact that such alteration had on the evolution of the Candida albicans genome.

Base Sequence↗
PubMed1994

[Morals, logic and ethics in reproductive medicine].

Human reproduction has always been a matter of philosophical interrogations and controversies. This situation has been reinforced by the technical evolution which has occurred during the past years. Both hopes and concerns have been raised at the same time. Two recent advancements deserve consideration and are given as demonstrative examples: intracytoplasmic injection of spermatozoon, preimplantatory diagnosis. Their consequences are very important for both the medical and the philosophical approach. One of the questions which arises at this occasion is to determine if research on pre embryos is legitimate or not. This evolution has provoked some reluctancy and several criticisms concerning the future of the children obtained by such techniques: the risk of slippery slope, possibly leading to a form of eugenics, and the fundamental and philosophical problem of the status of the embryo. However, behind these discussions a deeper and heavier controversial matter may be discovered; it deals with the role and the responsibilities of the governmental power. An opposition does exist between two different perceptions: on the one hand, the concept of a powerful governmental body, responsible for the respect of a statutory law, grounded on a sort of universal ethical rule, to be followed by all, a concept which bears the risk of totalitarianism; on the other hand, the concept of a law with a limited responsibility to protect public order, allowing a normal social life. Amongst the numerous responsibilities of the governmental power, one is often neglected, everywhere; its concerns the protection of the female life and health. Some examples are given. However the most frightening risk, much more dangerous than the frequently alleged risk of biological eugenics, is what can be called "economical eugenics". Again some examples are given, in all the systems of social protection. Submitted to ethical rules imposed by political and legal powers, and to the influence of economical forces, what will be the role and the responsibilities of the practitioner? Unfortunately the answer may be obvious: the only way is leading to a relinquishment of medical responsibility. Far away from the dialogue which was the rule of the "dual relationship" between the patient and the practitioner, away too from the more complicated situation of today, characterized by the intervention of "third parties", the evolution, probably unavoidable, appears to be towards the withdrawal of the psychological, moral, human and humanistic involvement of the practitioner, leading him or her to a technical role.(ABSTRACT TRUNCATED AT 400 WORDS)

Ethics, Medical↗
PubMed2006

Genomic organization and evolution of the 5S ribosomal DNA in Tilapiini fishes.

5S rDNA sequences present an intense dynamism and have proved to be valuable as genetic markers to distinguish closed related species and also in the understanding of the evolutionary dynamic of repetitive sequences in the genomes. In order to identify patterns of 5S rDNA organization and their evolution in the genome of fish species, such genomic segment was investigated in the tilapias Oreochromis niloticus and Tilapia rendalli, and in the hybrid O. urolepis hornorum x O. mossambicus. A dual 5S rDNA system was identified in the three analyzed tilapia samples. Although each 5S rDNA class was conserved among the three samples, a distinct 5S rDNA genome organization pattern could be evidenced for each sample. The presence of a dual 5S rDNA system seems to be a general trait among non-related teleost fish orders, suggesting that evolutionary events of duplication have occurred before the divergence of the main groups of teleost fishes.

Animals↗
PubMed1999

Factors contributing to the evolution and outcome of cirrhosis in hepatitis C.

A number of factors are important in the evolution of chronic hepatitis C to cirrhosis. These include the length of time that the patient has been infected, the age at exposure, dual infection with other viruses, alcohol use, and genotypes, especially in liver transplant recipients. The diagnosis of cirrhosis is made by clinical assessment of the patient, the use of imaging studies, a thoughtful laboratory evaluation, and histologic examination of liver tissue.

Alcoholism↗
PubMed1994

[Antidepressive agents: benefits/risks].

In 1994, the risk/benefit ratio when using antidepressant drugs for the treatment of mood disorders has become very difficult to assess. From the medical standpoint, frequent nosographical modifications generated new clinical entities (brief recurrent depression, subsyndromal depression, mixed anxiety and depression according to the ICD 10, dysthymia). Within these entities, mood appears modified in duration and severity and belongs to extremely different structures. The obvious link between antidepressants and typical depression has to be thoroughly assessed for these new forms of illness. But the evolution of medical and economical assessment techniques progressively turns the attributed risk into a global index based on group results far from the dual patient-physician relationship in which the risk/benefit ratio is assessed according to idiosyncratic criteria. The development of a dimensional clinical field could, if misused, be reduced to an addition of "target treatments". Finally, some antidepressants are no longer presented for their main antidepressive effects (for which their use is authorized) but for peripheral properties: treatment strategies (particularly duration) remain unclear for these latter effects. From a sociological point of view, consequences of consumerism, social and economical crisis and modifications of the image of the psychiatry, play a role in the evaluation of this risk/benefit ratio.

Antidepressive Agents↗
PubMed2005

Patterns of protein evolution in Tetrahymena thermophila: implications for estimates of effective population size.

High levels of synonymous substitutions among alleles of the surface antigen SerH led to the hypothesis that Tetrahymena thermophila has a tremendously large effective population size, one that is greater than estimated for many prokaryotes (Lynch, M., and J. S. Conery. 2003. Science 302:1401-1404.). Here we show that SerH is unusual as there are substantially lower levels of synonymous variation at five additional loci (four nuclear and one mitochondrial) characterized from T. thermophila populations. Hence, the effective population size of T. thermophila, a model single-celled eukaryote, is lower and more consistent with estimates from other microbial eukaryotes. Moreover, reanalysis of SerH polymorphism data indicates that this protein evolves through a combination of vertical transmission of alleles and concerted evolution of repeat units within alleles. SerH may be under balancing selection due to a mechanism analogous to the maintenance of antigenic variation in vertebrate immune systems. Finally, the dual nature of ciliate genomes and particularly the amitotic divisions of processed macronuclear genomes may make it difficult to estimate accurately effective population size from synonymous polymorphisms. This is because selection and drift operate on processed chromosomes in macronuclei, where assortment of alleles, disruption of linkage groups, and recombination can alter the genetic landscape relative to more canonical eukaryotic genomes.

Alleles↗
PubMed2004

Deletion 6p23 and add(11)(p15) leading to NUP98 translocation in a case of therapy-related atypical chronic myelocytic leukemia transforming to acute myelocytic leukemia.

A NUP98 gene translocation occurring with a del(6p23) and an add(11)(p15) was determined in a 61-year-old patient with therapy-related atypical chronic myelocytic leukemia after complete remission from acute promyelocytic leukemia that eventually underwent clonal evolution and transformed to CD56-positive acute myelocytic leukemia (French-American-British classification M0). Precise chromosome analysis by G-banding, spectral karyotyping analysis, and dual-color fluorescence in situ hybridization showed this abnormality as 46,XY,del(6)(p23),add(p15). ish del(6)(NUP98-,D6Z1+),der(7)(NUP98+,D7Z1+),der(11)(NUP98+,D11Z1). A split signal of NUP98 was observed in 68.4% of the 117 cells analyzed, which clearly indicated that the NUP98 partially translocated to chromosome 7. However, the potential fusion partner of the NUP98 was not HOX family or DEK. The fusion gene has not been found by a differential display method. The significance of simultaneously combined del(6)(p23), which also has been reported with secondary leukemogenesis, has not been elucidated. Additional karyotype abnormalities evolved increasingly, and leukocytosis with blasts with more complex karyotypic abnormalities appeared 5 months later. Careful and continuous analysis of karyotype change clarified the process of the clonal evolution after NUP98 translocation. Further investigation of molecular characterization of this NUP98 translocation and interaction with 6p23 abnormalities might be worthwhile for understanding leukemogenesis.

Chromosome Deletion↗
PubMed2006

Functionality of unspliced XBP1 is required to explain evolution of overlapping reading frames.

Eukaryotic genes with overlapping reading frames exemplify some of the most striking biological phenomena. Transcript of one such gene, the gene encoding X-box protein (XBP1), has evolved a mechanism for "on-demand" switching of translation between two overlapping reading frames. Despite the existence of this elaborate system, only one reading frame was believed to be functional. Here, we show that XBP1 evolves in a fashion that is only consistent with functionality of both reading frames. Our study provides a novel evolutionary framework for the analysis of loci with overlapping reading frames, which can be used for identification and analyses of novel dual-coding genes.

Animals↗
PubMed1999

Evolution of the vertebrate cardio-pulmonary system.

Vertebrate lungs have long been thought to have evolved in fishes largely as an adaptation for life in hypoxic water. This view overlooks the possibility that lungs may have functioned to supply the heart with oxygen and may continue to serve this function in extant fishes. The myocardium of most vertebrates is avascular and obtains oxygen from luminal blood. Because oxygen-rich pulmonary blood mixes with oxygen-poor systemic blood before entering the heart of air-breathing fishes, lung ventilation may supply the myocardium with oxygen and expand aerobic exercise capabilities. Although sustained exercise in tetrapods is facilitated by septation of the heart and the formation of a dual pressure system, a divided cardio-pulmonary system may conflict with myocardial oxygenation because the right side of the heart is isolated from pulmonary oxygen. This may have contributed to the evolution of the coronary circulation.

Animals↗
PubMed2004

Molecular basis of exopeptidase activity in the C-terminal domain of human angiotensin I-converting enzyme: insights into the origins of its exopeptidase activity.

Proteolytic processing is a primary means of biological control. Exopeptidases use terminal anchoring interactions to restrict cleavage at peptide substrate N or C termini. In contrast, internal peptide bond targeting by endopeptidases is through context-driven recognition. Angiotensin I-converting enzyme (ACE), a zinc metalloproteinase, has tandem duplicate catalytic domains, N- and C-terminal, each of which is a dual specificity enzyme with exo- and endocarboxypeptidase activities. The mechanisms by which ACE evolved from its endopeptidase ancestors as a dual specificity enzyme have not been defined. Based on kinetic studies of wild-type and mutant forms of the C-terminal catalytic domain of human ACE and of the ACE substrates angiotensin I, substance P, and bradykinin, as well as considerations of the ACE x-ray structure, we provide evidence that the acquisition of its exopeptidase activity is due to novel evolutionary specializations. These involve not only interactions between the S(2)' subsite cognate for the C-terminal substrate P(2)' side chain, acting in concert with carboxylate-docking interactions with Lys(1087) and Tyr(1096), but also electrostatic selection against a cationic C-terminal substrate carboxylate. With a blocked C terminus, substrate side chain interactions are dominant in cleavage site selection. In the evolution of obligate exopeptidases from endopeptidase ancestors, mutations that destroy context-driven peptide bond targeting are likely to have followed the acquisition of terminal docking interactions. Evolutionary intermediates between endopeptidases and obligate exopeptidases could therefore have been dual specificity proteinases like ACE.

Angiotensin I↗
PubMed2003

Conventional and magnetization transfer MRI predictors of clinical multiple sclerosis evolution: a medium-term follow-up study.

The correlation between conventional MRI lesion load accumulation and multiple sclerosis clinical evolution is only modest. The assessment of brain parenchymal volume and of its changes over time may provide adjunctive MRI markers reflecting the more disabling aspects of multiple sclerosis pathology. Magnetization transfer (MT) MRI is sensitive to 'occult' multiple sclerosis-related brain damage and might also contribute to overcome the clinical/MRI paradox. In this study, we assessed the value of conventional and MT MRI-derived metrics in predicting the medium-term clinical evolution of patients with different multiple sclerosis phenotypes. We studied 73 patients, with relapsing-remitting multiple sclerosis (n = 34), secondary progressive multiple sclerosis (n = 19) and clinically isolated syndromes suggestive of multiple sclerosis (n = 20), and 16 healthy subjects. Brain dual-echo, T1-weighted (only in patients) and MT MRI scans were obtained at baseline and after 12 months. T2-hyperintense and T1-hypointense lesion volumes, normalized brain volume and average lesion MT ratio (MTR) were measured. MTR histograms from the whole brain tissue were also obtained. Clinical multiple sclerosis evolution and neurological disability were re-assessed in all patients after a median follow-up of 4.5 years. A multivariate analysis was performed to establish which clinical and MRI-derived variables were significant predictors of neurological deterioration at the end of the study period. At the end of follow-up, 34 patients showed significant neurological deterioration. The final multivariable model included average brain MTR percentage change after one year [P = 0.02, odds ratio (OR) = 0.86] and baseline T2-hyperintense lesion volume (P = 0.04, OR=1.04) as independent predictors of medium-term disability accumulation (r2 = 0.23). In this cohort of patients, abnormal values of average brain MTR changes showed a relatively high specificity (76.9%) and positive predictive value (59.1%) for Expanded Disability Status Scale score deterioration in individual cases. In patients with multiple sclerosis, a comprehensive estimation of the short-term changes of both conventional and MT MRI-detectable lesion burden might provide useful prognostic information for the medium-term clinical disease evolution.

Adult↗
PubMed2001

Shared dynamics of attentional cost and pattern stability.

This paper examines the informational activity devoted by the CNS to couple oscillating limbs in order to sustain and stabilize bimanual coordination patterns. Through a double-task paradigm associating a bimanual coordination task and a reaction time (RT) task, we investigated the relation between the stability of preferred bimanual coordination patterns and the central cost expended by the CNS for their stabilization. Ten participants performed in-phase and anti-phase coordination patterns in a dual task condition (coordination + RT) at several frequencies (0.5, 0.75, 1.0, 1.5, and 2.0 Hz), thereby decreasing the stability of the bimanual patterns. Results showed a U-shaped evolution of pattern stability and attentional cost, as a function of oscillation frequency, exhibiting a minimum value at the same frequency. These findings indicate that central cost and pattern stability covary and may share common, high order dynamics. Moreover, the attentional focus given to the bimanual coordination and the RT task was also manipulated by requiring either shared attention or priority to the coordination task. Such a manipulation led to a tradeoff between pattern stability and RT performance: The more stable the pattern, the more costly it is to stabilize. This suggests that stabilizing a coordination pattern incurs a central cost that depends on its intrinsic stability. Conceptual consequences of these results for understanding the relationship between attention and coordination are drawn, and the mechanisms putatively at work in dual tasks are discussed.

Adult↗
PubMed2006

The dual role of Fas-ligand as an injury effector and defense strategy in diabetes and islet transplantation.

The exact process that leads to the eruption of autoimmune reactions against beta cells and the evolution of diabetes is not fully understood. Macrophages and T cells may launch an initial immune reaction against the pancreatic islets of Langerhans, provoking inflammation and destructive insulitis. The information on the molecular mechanisms of the emergence of beta cell injury is controversial and points to possibly important roles for the perforin-granzyme, Fas-Fas-ligand (FasL) and tumor-necrosis-factor-mediated apoptotic pathways. FasL has several unique features that make it a potentially ideal immunomodulatory tool. Most important, FasL is selectively toxic to cytotoxic T cells and less harmful to regulatory T cells. This review discusses the intrinsic sensitivity of beta cells to FasL-mediated apoptosis, the conditions that underlie this beta cell sensitivity, and the feasibility of using FasL to arrest autoimmunity and prevent islet allograft rejection. In both the autoimmune and transplant settings, it is imperative to progress from the administration of nonspecific immunosuppressive therapy to the concept of beta-cell-specific immunomodulation. FasL evolves as a prime candidate for antigen-specific immunomodulation.

Animals↗
PubMed2003

Evolution of fibrin glue applicators.

Fibrin glue (FG) is used worldwide as a potent surgical tool, which establishes hemostasis in wounds and also bonds tissue. The standard FG applicator is based on a dual-syringe system. This review, based mainly on the patent literature, describes the development of the quasi-standard dual syringe system as well as the rise of other FG applicator designs based on mechanical force (ratchet systems), Bernoulli gas flow, positive gas pressure, or electro-servo devices. The packaging of commercial FG components is reviewed within the context of "loading" the FG applicators and the need to minimize the number of needles required to access the packaged (vials) components. Parameters such as internal clogging, homogeneity of spray, the requirement for gas or vacuum house lines, the number of parts that must be handled, and the time required to assemble the applicator, load it, and have it ready for use are also discussed. A rating system is proposed that permits one to use such parameters to rank the various applicator designs, relative to the dual-syringe system. Hopefully, this review will stimulate the design of better FG applicators and packaging required for elective surgery, emergency treatments, and tissue engineering in the 21st century.

Equipment Design↗
PubMed2005

Poisson, Poisson-gamma and zero-inflated regression models of motor vehicle crashes: balancing statistical fit and theory.

There has been considerable research conducted over the last 20 years focused on predicting motor vehicle crashes on transportation facilities. The range of statistical models commonly applied includes binomial, Poisson, Poisson-gamma (or negative binomial), zero-inflated Poisson and negative binomial models (ZIP and ZINB), and multinomial probability models. Given the range of possible modeling approaches and the host of assumptions with each modeling approach, making an intelligent choice for modeling motor vehicle crash data is difficult. There is little discussion in the literature comparing different statistical modeling approaches, identifying which statistical models are most appropriate for modeling crash data, and providing a strong justification from basic crash principles. In the recent literature, it has been suggested that the motor vehicle crash process can successfully be modeled by assuming a dual-state data-generating process, which implies that entities (e.g., intersections, road segments, pedestrian crossings, etc.) exist in one of two states-perfectly safe and unsafe. As a result, the ZIP and ZINB are two models that have been applied to account for the preponderance of "excess" zeros frequently observed in crash count data. The objective of this study is to provide defensible guidance on how to appropriate model crash data. We first examine the motor vehicle crash process using theoretical principles and a basic understanding of the crash process. It is shown that the fundamental crash process follows a Bernoulli trial with unequal probability of independent events, also known as Poisson trials. We examine the evolution of statistical models as they apply to the motor vehicle crash process, and indicate how well they statistically approximate the crash process. We also present the theory behind dual-state process count models, and note why they have become popular for modeling crash data. A simulation experiment is then conducted to demonstrate how crash data give rise to "excess" zeros frequently observed in crash data. It is shown that the Poisson and other mixed probabilistic structures are approximations assumed for modeling the motor vehicle crash process. Furthermore, it is demonstrated that under certain (fairly common) circumstances excess zeros are observed-and that these circumstances arise from low exposure and/or inappropriate selection of time/space scales and not an underlying dual state process. In conclusion, carefully selecting the time/space scales for analysis, including an improved set of explanatory variables and/or unobserved heterogeneity effects in count regression models, or applying small-area statistical methods (observations with low exposure) represent the most defensible modeling approaches for datasets with a preponderance of zeros.

Accidents, Traffic↗
PubMed2004

Reductive titration of photosystem I and differential extinction coefficient of P700+ at 810-950 nm in leaves.

We describe a method of reductive titration of photosystem I (PSI) density in leaves by generating a known amount of electrons (e-) in photosystem II (PSII) and measuring the resulting change in optical signal as these electrons arrive at pre-oxidized PSI. The method complements a recently published method of oxidative titration of PSI donor side e- carriers P700, plastocyanin (PC) and cytochrome f by illuminating a darkened leaf with far-red light (FRL) [V. Oja, H. Eichelmann, R.B. Peterson, B. Rasulov, A. Laisk, Decyphering the 820 nm signal: redox state of donor side and quantum yield of photosystem I in leaves, Photosynth. Res. 78 (2003) 1-15], presenting a nondestructive way for the determination of PSI density in intact leaves. Experiments were carried out on leaves of birch (Betula pendula Roth) and several other species grown outdoors. Single-turnover flashes of different quantum dose were applied to leaves illuminated with FRL, and the FRL was shuttered off immediately after the flash. The number of e- generated in PSII by the flash was measured as four times O2 evolution following the flash. Reduction of the pre-oxidized P700 and PC was followed as a change in leaf transmittance using a dual-wavelength detector ED P700DW (810 minus 950 nm, H. Walz, Effeltrich, Germany). The ED P700DW signal was deconvoluted into P700+ and PC+ components using the abovementioned oxidative titration method. The P700+ component was related to the absolute number of e- that reduced the P700+ to calculate the extinction coefficient. The effective differential extinction coefficient of P700+ at 810-950 nm was 0.40+/-0.06 (S.D.)% of transmittance change per micromol P700+ m(-2) or 17.6+/-2.4 mM(-1) cm(-1). The result shows that the scattering medium of the leaf effectively increases the extinction coefficient by about two times and its variation (+/-14% S.D.) is mainly caused by light-scattering properties of the leaf.

Light↗