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PubMed1994

[Festival lecture. The position of microorganisms in the global phylogenetic system of three domains].

New insights into genealogic relations among organisms due to similarities of 16S rRNA sequences of more than 1000 representatives of the various groups led to a classification of the presently known living beings into three domains: Bacteria, Archaea (Archaebacteria) and Eucarya. All medical relevant prokaryotes belong to the domain Bacteria. The systematics of the eukaryote microorganisms (protista and fungi) and their numerous medically relevant representatives will be widely changed in the near future due to latest scientific findings on phylogenetic relations. The retrospective analysis of the 16S rRNA phylogenetic tree led to assuming a chemolithoautotrophic origin of life and an early splitting into three domains in an early precellular phase of evolution.

Bacteria↗

PubMed2005

Systematics and health effects of chemically distinct tannins in medicinal plants.

The research began with an investigation of tannins from traditional medicinal plants and resulted in isolation and structure determination of hundreds of ellagitannins and dehydroellagitannins, as well as their oligomers and oxidized derivatives with various structures specific to each plant species. These polyphenols have been classified according to the stage of oxidative structural transformation and oligomerization, into types I-IV and I+ to IV+, etc. Parallels were found between their oxidative transformations and plant evolution. They were also classified by the linkage units between the monomers, into DOG, GOD, GOG and DOGOD types (D=Diphenoyl, G=Galloyl, O=Oxygen), etc. Besides their fundamental activities, e.g., reduction and anti-peroxidation properties, remarkable biological and pharmacological activities of various potencies have also been found, including, amongst others, inhibition of lipid-peroxidation, mutagenicity of carcinogens and tumor promotion, host-mediated antitumor effects specific to particular tannin structures, antiviral activity and potentiation of antibacterial activity.

Plants, Medicinal↗

PubMed1995

[The importance of classifications in psychiatry].

The classifications currently used in psychiatry have different aims: to facilitate communication between researchers and clinicians at national and international levels through the use of a common language, or at least a clearly and precisely defined nomenclature; to provide a nosographical reference system which can be used in practice (diagnosis, prognosis, treatment); to optimize research by ensuring that sample cases are as homogeneous as possible; to facilitate statistical records for public health institutions. A classification is of practical interest only if it is reliable, valid and acceptable to all potential users. In recent decades, there has been a considerable systematic and coordinated effort to improve the methodological approach to classification and categorization in the field of psychiatry, including attempts to create operational definitions, field trials of inter-assessor reliability, attempts to validate the selected nosological categories by analysis of correlation between progression, treatment response, family history and additional examinations. The introduction of glossaries, and particularly of diagnostic criteria, marked a decisive step in this new approach. The key problem remains that of the validity of diagnostic criteria. Ideally, these should be based on demonstrable etiologic or pathogenic data, but such information is rarely available in psychiatry. Current classifications rely on the use of extremely diverse elements in differing degrees: descriptive criteria, evolutive criteria, etiopathogenic criteria, psychopathogenic criteria, etc. Certain syndrome-based classifications such as DSM III and its successors aim to be atheoretical and pragmatic. Others, such as ICD-10, while more eclectic than the different versions of DSM, follow suit by abandoning the terms "disease" and "illness" in favor of the more consensual "disorder". The legitimacy of classifications in the field of psychiatry has been fiercely contested, being variously dubbed "a reductive academic exercise of no relevance to patients", "a dehumanizing labelling system, and a potential source of social and political violence", "a destructive prognostic guide", and so on. Other critics point to various aspects of certain classifications: the abandonment of theoretical concepts, the arbitrary nature of certain categories, the selection of definitions and criteria, the privileged position systematically accorded to the notion of category over that of general dimension. Multiaxial systems such as those proposed in successive versions of DSM or the classifications used in child psychiatry go some way towards meeting these criticisms. They go beyond simple labelling and place the patient in an overall medicopsycho-social setting. Nosographical indicators do not constitute an obstacle to psychopathological understanding. No classifications are capable of satisfactorily fulfilling all needs, namely those of daily practice, research and health statistics. The has led to the development of specialized diagnostic criteria and instruments, as in research for example. It should also be noted in this context that different versions of ICD-10 exist for psychiatrists, general practitioners, researchers and healthcare managers. The greatest danger posed by classifications is the potential reification of hypothetical approaches, arbitrary categorization and the dulling of reflection, all of which have created a need for regular revisions underpinned by field trials.

Humans↗

PubMed2001

T1 relaxation times for viability evaluation of the engrafted and the native liver in a rat model of heterotopic auxiliary liver transplantation: a pilot study.

Following a heterotopic auxiliary liver transplantation, commonly used measurements are either invasive or non-indicative of individual viability of the coexisting engrafted and native livers. Magnetic resonance imaging (MRI) was therefore tested for its potential to monitor the post-transplant hepatic viability in a rat model. Thirteen Wistar rats were systematically evaluated with MRI and serum biochemical liver parameters. Post-transplant complications and the causes of animal death were identified by autopsy and histo-pathological examinations. The data of the healthy survivors were compared with those of the rats that developed complications. On MRI, the hepatic complications could be depicted in the individual livers. A specific pattern of signal evolution was found in the livers of the healthy survivors: the mean T1 relaxation times of the engrafted livers increased immediately after transplantation (476 +/- 64 ms, mean +/- standard deviation, pre-operative; 730 +/- 48 ms, week 1) and then declined steadily to a 3 month value of 489 +/- 246 ms, while, following a transient first rise (476 +/- 64 ms, pre-operative; 589 +/- 28 ms, week 1), the mean T1 value of the native livers increased again 4 weeks after surgery and reached a 3 month value of 859 +/- 43 ms. However, in the rats with various complications, the mean T1 relaxation times of the engrafted livers continued to increase throughout the first post-operative month (760 +/- 48 ms, week 1; 922 +/- 76 ms, week 4), while that of the native liver only varied mildly (546 +/- 25 ms, week 1; 473 +/- 25 ms, week 4). After the first post-transplant week, the healthy engrafted livers could already be distinguished from those with complications by a significant decrease in T1 relaxation times. These data suggest that, besides demonstrating major complications, MRI may allow one to monitor the viability of each liver by analysing the relative signal intensity and T1 relaxation times after a heterotopic auxiliary liver transplantation.

Alanine Transaminase↗

PubMed2004

Self-cleaning in an estuarine area formerly affected by 226Ra anthropogenic enhancements.

The estuary of the Odiel River has been affected by both direct discharges of phosphogypsum (radium enriched industrial waste) and dissolution and weathering of the exposed piles where this radium enriched waste was stored. In 1998 the waste management policy for industries changed. The direct discharges stopped and the new phosphogypsum piles were well protected against dissolution processes, avoiding any transference of radium into the environment. This work presents a study of the evolution with time (1999-2002) of the levels of 226Ra in river water and sediment samples with the new waste management policy. A liquid scintillation technique was used to measure the 226Ra activity concentration in sediment samples. A gas-proportional counter was also used to measure the 226Ra activity concentration in river water samples. The main conclusion is that a systematic and continuous decrease of the activity concentration of 226Ra with time in the Odiel River estuary is occurring. Thus, a possible self-cleaning in the estuary, once the direct waste discharges were avoided, can be inferred.

Journal Article↗

PubMed2001

RISSC: a novel database for ribosomal 16S-23S RNA genes spacer regions.

A novel database, under the acronym RISSC (Ribosomal Intergenic Spacer Sequence Collection), has been created. It compiles more than 1600 entries of edited DNA sequence data from the 16S-23S ribosomal spacers present in most prokaryotes and organelles (e.g. mitochondria and chloroplasts) and is accessible through the Internet (http://ulises.umh.es/RISSC), where systematic searches for specific words can be conducted, as well as BLAST-type sequence searches. Additionally, a characteristic feature of this region, the presence/absence and nature of tRNA genes within the spacer, is included in all the entries, even when not previously indicated in the original database. All these combined features could provide a useful documentation tool for studies on evolution, identification, typing and strain characterization, among others.

DNA, Ribosomal Spacer↗

PubMed2006

Stepping stones towards a new prokaryotic taxonomy.

Technological developments provide new insights into prokaryotic evolution and diversity and provoke a continuous need to update taxonomy and revise classification schemes. Our present species concept and definition are being challenged by the growing amount of whole genomic information, which should allow improvements in the natural species definition. The continuous quest for an objective and stable method for sorting strains into coherent homogeneous groups is inherent to prokaryotic systematics and nomenclature. Morphological, biochemical, physiological, phenotypic and chemotaxonomic criteria have been complemented by molecular data and pragmatic, purpose built, species definitions are being replaced by more natural ones based on evolutionary insights. It is imperative to give due consideration to both fundamental and applied aspects of future species concepts and definitions. The present paper discusses the present practice in prokaryotic taxonomy of how this system developed and how it may evolve in the future.

Archaea↗

PubMed2000

Diffusional mechanism of strong selection in ostwald ripening

The purpose of this paper is to show through a systematic asymptotic analysis that fluctuations, accounted for as a diffusional perturbation in the Lifshitz-Slyozov-Wagner (LSW) model of Ostwald ripening, provides, as conjectured previously by Meerson [Phys. Rev. E 60, 3072 (1999)], a "strong" selection of the limiting solution, out of a one-parameter family of similarity solutions with a finite support, as the sole attractor of time evolution. Throughout the latter, the previously described weak selection of other similarity solutions of that family, by the initial conditions with finite supports, occurs as intermediate time asymptotics. The respective mechanism is traced first for a simple instance of the LSW model with linear characteristic equations (integer power in the particle growth rate law equals -1), beginning with the analysis of steady states in the perturbed problem in similarity variables and weak selection in the unperturbed problem, followed by a detailed asymptotic analysis of the time-dependent perturbed problem, and generalized next for an arbitrary integer power in the range [-1,2]. The approximate asymptotic solutions obtained are compared with the exact numerical ones.

Journal Article↗

PubMed2001

Is there a future for renin inhibitors?

Pharmacological interruption of the renin-angiotensin system is possible at three major sites, the angiotensin-converting enzyme (ACE), the AT1 receptor and at the interaction of renin with its substrate, angiotensinogen. Skeggs and his associates in 1957 argued logically but without prognostic accuracy that 'since renin is the initial and rate-limiting substance in the renin-angiotensin system, it would seem that the renin inhibition approach would be the most likely to succeed'. In fact, the development of agents that act at all three levels has enjoyed substantial success, yet renin inhibition, which showed early progress in studies in humans, has languished. Our task in this essay is to review the reasons for the slow evolution of renin inhibition and to discuss the potential of such agents in modern pharmacotherapy. All of the structure-action relationships have involved variation on the original peptide structure. The possibility that alternative approaches based on x-ray crystallography and reconstruction of the structure of the active site would lead to novel agents, appears not to have been explored systematically. This opportunity is all the more attractive because renin is one of the few targets that is actually soluble and amenable to x-ray crystallographic studies. At the moment, it appears that all renin inhibitor development programs have been closed, although hints periodically reappear to indicate that one company or another is pursuing a novel agent. The decision to close programs seems to have reflected not the therapeutic potential of renin inhibitors, but rather the cost of their synthesis, continuing problems with bioavailability and the remarkable success of the competitor class--the AngII antagonists. We believe that the potential of renin inhibition in human therapy has been under estimated and still shows substantial promise.

Angiotensin Receptor Antagonists↗

PubMed2004

Ablation of atrial fibrillation: localizing triggers, mapping systems and ablation techniques.

Ablation to eliminate atrial fibrillation (AF) is a therapy in evolution. Approaches to the ablation appear to be currently divided into 2 major strategies anatomic versus electrically guided. In addition in using an electrically guided techniques debate remains whether a targeted approach should be used, whether exit block should be documented, and whether all non pulmonary vein triggers should be targeted. This review highlights the different ablation strategies and identifies a systematic approach to ablation of pulmonary and non pulmonary vein triggers that we have adapted at our institution. The role of intracardiac echo, trigger provocation and localization and the use of 3-D mapping systems in AF ablation are defined.

Adrenergic beta-Agonists↗

PubMed2000

Phylogenetic information in inter-SINE and inter-SSR fingerprints of the artiodactyla and evolution of the bov-tA SINE.

Various interspersed repeated sequences and elements (IRSs) can be utilized to generate PCR-based multilocus fingerprint profiles by amplifying the interelement segments, using primers matching the elements themselves. We assessed the utility of inter-IRS fingerprinting in phylogenetic comparisons among six artiodactyl species using several primers derived from two abundant genomic components: the Bov-tA short interspersed nuclear elements (SINEs) and simple sequence repeats or microsatellites (SSRs). Character- and distance-based analyses of the fingerprint data produced trees conforming to the established phylogenetic relationships of species. The strength of phylogenetic signal from different primers varied; combining data from different experiments resulted in robust trees. Within the Cervidae, the hierarchical relationship [(Odocoileus, Rangifer) Alces] was strongly supported. Both methods appear useful tools for systematic studies at time scales <30 Myr. To elucidate the material basis of inter-SINE fingerprints, we obtained the first sequences of the 'bovid' Bov-tA element also from two cervids (reindeer and white-tailed deer) and analysed their relationship to a number of paralogous bovid elements. The differences among sequences, both intra- and interspecific, were relatively high (mean 18.5%); the sequences showed no clear clustering with the species from which they had been isolated. Most individual elements probably date back to the cervid-bovid ancestor >25 Myr ago, which is in line with the observed fingerprint distributions.

Animals↗

PubMed2005

Molecular phylogenetics of the siphonophora (Cnidaria), with implications for the evolution of functional specialization.

Siphonophores are a group of pelagic colonial hydrozoans (Cnidaria) that have long been of general interest because of the division of labor between the polyps and medusae that make up these "superorganisms." These polyps and medusae are each homologous to free living animals but are generated by an incomplete asexual budding process that leaves them physiologically integrated. They are functionally specialized for different tasks and are precisely organized within each colony. The number of functional types of polyps and medusae varies across taxa, and different authors have used this character to construct phylogenies polarized in opposite directions, depending on whether they thought siphonophore evolution proceeded by a reduction or an increase in functional specialization. We have collected taxa across all major groups of siphonophores, many of which are found exclusively in the deep sea, using remotely operated underwater vehicles (ROVs) and by SCUBA diving from ships in the open ocean. We have used 52 siphonophores and four outgroup taxa to estimate the siphonophore phylogeny with molecular data from the nuclear small subunit ribosomal RNA gene (18S) and the mitochondrial large subunit ribosomal RNA gene (16S). Parsimony reconstructions indicate that functionally specialized polyps and medusae have been gained and lost across the phylogeny. Maximum likelihood and Bayesian analyses of morphological data suggest that the transition rate for decreased functional specialization is greater than the transition rate for increased functional specialization for three out of the four investigated categories of polyps and medusae. The present analysis also bears on several long-standing questions about siphonophore systematics. It indicates that the cystonects are sister to all other siphonophores, a group that we call the Codonophora. We also find that the Calycophorae are nested within the Physonectae, and that the Brachystelia, a historically recognized grouping of short-stemmed taxa, are polyphyletic. [Cnidaria; colonial animals; deep sea; division of labor; functional specialization; Hydrozoa; phylogenetics; Siphonophores.].

Animals↗

PubMed1994

Bone and cartilage differentiation.

Recent progress in the study of regulation of bone and cartilage differentiation has come from the isolation, cloning, and expression of genes encoding bone morphogenetic proteins (BMPs). BMPs initiate cartilage and bone formation in a sequential cascade. Their pleiotropic effects on chemotaxis, mitosis, and differentiation are based on concentration-dependent thresholds. The existence of multiple members of the BMP family raises issues concerning functional redundancy. Current work in progress in different laboratories has revealed that BMP-2 or BMP-4 gene knockout by homologous recombination results, surprisingly, in embryonic lethality. Cartilage and bone differentiation during endochondral development involves a continuum of steps: initiation, promotion, maintenance, modeling, and termination. The signaling factors for initiation and maintenance are being defined at the molecular level, and future studies will focus on the gene regulation of initial signaling molecules such as BMPs. Critical progress in the determination of the role of BMPs in bone development has been accomplished by systematic study of skeletal mutations such as short ear and brachypodism in mice. The accelerating pace of advance in this area augurs well for the resolution of the molecular basis of morphogenesis of bone and cartilage.

Animals↗

PubMed2000

Is the Gibraltar strait a barrier to gene flow for the bat Myotis myotis (Chiroptera: Vespertilionidae)?

Because of their role in limiting gene flow, geographical barriers like mountains or seas often coincide with intraspecific genetic discontinuities. Although the Strait of Gibraltar represents such a potential barrier for both plants and animals, few studies have been conducted on its impact on gene flow. Here we test this effect on a bat species (Myotis myotis) which is apparently distributed on both sides of the strait. Six colonies of 20 Myotis myotis each were sampled in southern Spain and northern Morocco along a linear transect of 1350 km. Results based on six nuclear microsatellite loci reveal no significant population structure within regions, but a complete isolation between bats sampled on each side of the strait. Variability at 600 bp of a mitochondrial gene (cytochrome b) confirms the existence of two genetically distinct and perfectly segregating clades, which diverged several million years ago. Despite the narrowness of the Gibraltar Strait (14 km), these molecular data suggest that neither males, nor females from either region have ever reproduced on the opposite side of the strait. Comparisons of molecular divergence with bats from a closely related species (M. blythii) suggest that the North African clade is possibly a distinct taxon warranting full species rank. We provisionally refer to it as Myotis cf punicus Felten 1977, but a definitive systematic understanding of the whole Mouse-eared bat species complex awaits further genetic sampling, especially in the Eastern Mediterranean areas.

Animals↗

PubMed2002

Basic limb kinematics of small therian mammals.

A comparative study of quantitative kinematic data of fore- and hindlimb movements of eight different mammalian species leads to the recognition of basic principles in the locomotion of small therians. The description of kinematics comprises fore- and hindlimb movements as well as sagittal spine movements including displacement patterns of limb segments, their contribution to step length, and joint movements. The comparison of the contributions of different segments to step length clearly shows the proximal parts (scapula, femur) to produce more than half of the propulsive movement of the whole limb at symmetrical gaits. Basically, a three-segmented limb with zigzag configuration of segments is mainly displaced at the scapular pivot or hip joint, both of which have the same vertical distance to the ground. Two segments operate in matched motion during retraction of the limb. While kinematic parameters of forelimbs are independent of speed and gait (with the scapula as the dominant element), fundamental changes occur in hindlimb kinematics with the change from symmetrical to in-phase gaits. Forward motion of the hindlimbs is now mainly due to sagittal lumbar spine movements contributing to half of the step length. Kinematics of small therian mammals are independent of their systematic position, their natural habitat, and also of specific anatomical dispositions (e.g. reduction of fingers, toes, or clavicle). In contrast, the possession of a tail influences 'pelvic movements'.

Animals↗

PubMed1993

The anatomy of a consultation: a teaching method.

The Anatomy of a Consultation is a teaching method useful in introducing residents to Consultation-Liaison psychiatry. It is designed to stimulate them to think actively about the process of consultation in its broadest implications, including interaction with staff. The residents are encouraged to observe, make inferences, establish hypotheses about the evolution of the consultation, and to test these hypotheses by obtaining new information. The analogy of an unfolding detective story is used. A resident is asked to present the evolution of a consultation chronologically for ongoing group discussion. A vertical and a horizontal approach to the examination of the material are used. The vertical proceeds with clarification of the consultation as it evolves toward closure. The horizontal takes as its point of departure various topics that emerge to illustrate general principles and applications in different situations. These topics are approached more systematically and in greater detail in later teaching. Emphasis is placed upon coping and adaptation and the principles of active interventions useful for people in crisis. Patient data is organized within two broad categories: 1) the diagnostic, phenomenologic, and psychopathologic; and 2) the psychodynamic, conflictual, and life historical. An illustrative example is presented.

Adaptation, Psychological↗

PubMed2004

The transition to a sulphidic ocean approximately 1.84 billion years ago.

The Proterozoic aeon (2.5 to 0.54 billion years (Gyr) ago) marks the time between the largely anoxic world of the Archean (> 2.5 Gyr ago) and the dominantly oxic world of the Phanerozoic (< 0.54 Gyr ago). The course of ocean chemistry through the Proterozoic has traditionally been explained by progressive oxygenation of the deep ocean in response to an increase in atmospheric oxygen around 2.3 Gyr ago. This postulated rise in the oxygen content of the ocean is in turn thought to have led to the oxidation of dissolved iron, Fe(II), thus ending the deposition of banded iron formations (BIF) around 1.8 Gyr ago. An alternative interpretation suggests that the increasing atmospheric oxygen levels enhanced sulphide weathering on land and the flux of sulphate to the oceans. This increased rates of sulphate reduction, resulting in Fe(II) removal in the form of pyrite as the oceans became sulphidic. Here we investigate sediments from the approximately 1.8-Gyr-old Animikie group, Canada, which were deposited during the final stages of the main global period of BIF deposition. This allows us to evaluate the two competing hypotheses for the termination of BIF deposition. We use iron-sulphur-carbon (Fe-S-C) systematics to demonstrate continued ocean anoxia after the final global deposition of BIF and show that a transition to sulphidic bottom waters was ultimately responsible for the termination of BIF deposition. Sulphidic conditions may have persisted until a second major rise in oxygen between 0.8 to 0.58 Gyr ago, possibly reducing global rates of primary production and arresting the pace of algal evolution.

Atmosphere↗

PubMed2001

Philosophical conjectures and their refutation.

Sir Karl Popper is well known for explicating science in falsificationist terms, for which his degree of corroboration formalism, C(h,e,b), has become little more than a symbol. For example, de Queiroz and Poe in this issue argue that C(h,e,b) reduces to a single relative (conditional) probability, p(e,hb), the likelihood of evidence e, given both hypothesis h and background knowledge b, and in reaching that conclusion, without stating or expressing it, they render Popper a verificationist. The contradiction they impose is easily explained--de Queiroz and Poe fail to take account of the fact that Popper derived C(h,e,b) from absolute (logical) probability and severity of test, S(e,h,b), where critical evidence, p(e,b), is fundamental. Thus, de Queiroz and Poe's conjecture that p(e,hb) = C(h,e,b) is refuted. Falsificationism, not verificationism, remains a fair description of the parsimony method of inference used in phylogenetic systematics, not withstanding de Queiroz and Poe's mistaken understanding that "statistical" probability justifies that method. Although de Queiroz and Poe assert that maximum likelihood has the power "to explain data", they do not successfully demonstrate how causal explanation is achieved or what it is that is being explained. This is not surprising, bearing in mind that what is assumed about character evolution in the accompanying likelihood model M cannot then be explained by the results of a maximum likelihood analysis.

Likelihood Functions↗