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The origin of vertebrate limbs.

The earliest tetrapod limbs are polydactylous, morphologically varied and do not conform to an archetypal pattern. These discoveries, combined with the unravelling of limb developmental morphogenetic and regulatory mechanisms, have prompted a re-examination of vertebrate limb evolution. The rich fossil record of vertebrate fins/limbs, although restricted to skeletal tissues, exceeds the morphological diversity of the extant biota, and a systematic approach to limb evolution produces an informative picture of evolutionary change. A composite framework of several phylogenetic hypotheses is presented incorporating living and fossil taxa, including the first report of an acanthodian metapterygium and a new reconstruction of the axial skeleton and caudal fin of Acanthostega gunnari. Although significant nodes in vertebrate phylogeny remain poorly resolved, clear patterns of morphogenetic evolution emerge: median fin origination and elaboration initially precedes that of paired fins; pectoral fins initially precede pelvic fin development; evolving patterns of fin distribution, skeletal tissue diversity and structural complexity become decoupled with increased taxonomic divergence. Transformational sequences apparent from the fish-tetrapod transition are reiterated among extant lungfishes, indicating further directions for comparative experimental research. The evolutionary diversification of vertebrate fin and limb patterns challenges a simple linkage between Hox gene conservation, expression and morphology. A phylogenetic framework is necessary in order to distinguish shared from derived characters in experimental model regulatory systems. Hox and related genomic evolution may include convergent patterns underlying functional and morphological diversification. Brachydanio is suggested as an example where tail-drive patterning demands may have converged with the regulation of highly differentiated limbs in tetrapods.

Animals↗

[Portal hypertension and percutaneous transjugular portasystemic stent shunt].

This paper reports 1) the historic development of TIPSS, the transjugular intrahepatic portosystemic stent shunt from experimental evaluation to clinical realization. 2) The evolution of the instrumental technique during a period of 6 years of clinical applications is described in detail. 3) Results based on 204 consecutive procedures are demonstrated: e.g. the early technical success defined as successful completion of the procedure and 30-day survival was 95%; the clinical success defined as technically successful procedure and no rebleeding during the first 30 days was 83%, the 30-day mortality rate was 6.3%; the 30-day encephalopathy rate was 14.1%; the one-year re-bleeding rate was 11%; the one-year survival rate was 74%, the 3-year survival rate was 41%. 4) Problems of the TIPSS procedure are discussed including a 3-months re-stenosis rate of 46% and a cumulative one-year re-stenosis rate of 84% which requires correction by interventional procedures such as shunt dilatation or additional vascular stent placement. 5) Limitations and indications of TIPSS are elucidated based on hemodynamic and functional aspects of liver cirrhosis.

Esophageal and Gastric Varices↗

[Kinetics of the humoral immune response in mice immunized against and inoculated with Trypanosoma cruzi].

Evolution of the immune humoral response against experimentally induced Chagas disease was followed in three groups of white mice CD-1; one group without any previous treatment; a second group that had been immunized with membranes from cultured epimastigotes, and a third group treated only with Freund's adjuvant. The response was observed through immunotransference (Western Blot) against membrane antigens from cultured epimastigotes. As early as 11 days after inoculation, the sera of animals previously immunized showed a great number of recognition bands between 22 and 115 kDa; on the other hand, the animals treated only with adjuvant or those inoculated without any previous treatment, showed antibodies on the 18th day. These reacted against 52 and 62 kDa proteins. Antibodies against 68 and 72 kDa proteins were found on the 32nd day in mice treated with adjuvant and on the 39th day, in mice with no treatment. The antibodies could be relevant in the healing of the animals because they appear at the same time that parasites start disappearing from the blood.

Animals↗

[Is in depth diagnosis important in renal artery stenosis?].

The experimental discovery of the pathophysiological relationship between renal artery stenosis and arterial hypertension was historically reported (1934) before the clinical description of the disease in human patients (1950). The experimental model explains the relation between renal ischemia, renal endocrine activation, and morphological alterations of the homo and contralateral kidneys. In particular, the experimental model improves the understanding of the evolution of renovascular disease. In human patients, renal artery stenosis does not always lead to clinical disease. Because of the frequency of arterial hypertension, there is not always a clear relationship between hypertension and renal insufficiency or renal artery stenosis. Therefore a complete diagnosis of renal endocrine and exocrine function is needed to understand this relation before deciding on the therapeutic approach. This diagnosis is made by exploration of the renal renin-angiotensin axis, its pharmacological blockade and the response of the excretory function. This approach corresponds to the clinical description of the evolution of the disease; the peripheral and renal vein renin assays; the pressure and scintigraphic response to converting enzyme inhibition and renal morphological definition by echography and CT scan. This pathological approach permits a rational choice of the therapeutic indication: non-intervention, specific medical treatment, endovascular or surgical revascularization or nephrectomy.

Animals↗

An update on uremic toxins.

The author reviews trends and evolution in biochemical methodology, clinical symptomatology description, experimental models and definitions of uremic toxins. The assumption is made of one specific toxic effect for one specific toxin.

Animals↗

The evolution of multiple male traits in the yellow-browed leaf warbler

I examined how male competition and female choice influence the evolution of multiple male traits in the yellow-browed leaf warbler, Phylloscopus inornatus, by investigating the roles of colour patches, territory size, body weight and song rate in sexual selection. Comparison of 3 years of observational studies and 3 years of experimental studies, in which the colour patches on the wings of males were experimentally altered, suggest several mechanisms that may explain the evolution of multiple characters in males. First, females based their choice of mates on several male characters, not a single character. Second, the male characters preferred by females were different in observational and experimental studies. Females apparently preferred high-quality males as mates, and were able to vary the characters used in mate choice to distinguish these individuals under both experimental and observational conditions. Third, the characters important in male competition differed from those that formed the basis of female choice: the manipulation of colour patch size directly affected male territory size but was not associated with female choice. These results may provide an explanation for the diversity of sexual ornaments shown by males of many species.Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

Nonlinear theory of void formation in colloidal plasmas.

A nonlinear time-dependent model for void formation in colloidal plasmas is proposed. For experimentally relevant initial conditions, the model describes the nonlinear evolution of a zero-frequency linear instability that grows rapidly in the nonlinear regime and subsequently saturates to form a void. A number of features of the model are consistent with experimental observations under laboratory and microgravity conditions.

Journal Article↗

Laboratory selection for the comparative physiologist.

An increasingly popular experimental approach in comparative physiology is to study the evolution of physiological traits in the laboratory, using microbial, invertebrate and vertebrate models. Because selective conditions are well-defined, selected populations can be replicated and unselected control populations are available for direct comparison, strong conclusions regarding the adaptive value of an evolved response can be drawn. These studies have shown that physiological systems evolve rapidly in the laboratory, but not always as one would expect from comparative studies of different species. Laboratory environments are often not as simple as one thinks, so that the evolution of behavioral differences or selection acting on different life stages can lead to unanticipated results. In some cases, unexpected responses to laboratory selection may suggest new insights into physiological mechanisms, which might not be available using other experimental approaches. I outline here recent results (including success stories and caveats for the unwary investigator) and potential directions for selection experiments in comparative physiology.

Adaptation, Physiological↗

Comparison between coated vs. uncoated suture middle cerebral artery occlusion in the rat as assessed by perfusion/diffusion weighted imaging.

Differences among models in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental treatment studies. Using diffusion and perfusion imaging, we compared the spatiotemporal evolution of ischemia in Sprague-Dawley rats after permanent MCAO (pMCAO) with different types of sutures. Male Sprague-Dawley rats were randomly assigned to pMCAO produced with either 4-0 silicone coated (n=8), or 3-0 uncoated monofilaments (n=8). Serial determination of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps were performed up to 3 h after pMCAO. Lesion volumes were calculated by using previously validated thresholds and correlated with infarct volume corrected for edema defined by 2,3,5-triphenyltetrazolium chloride (TTC) staining at 24 h after MCAO. The ADC/CBF-defined mismatch volume in the 4-0 coated suture model was present significantly longer (up to 120 min) compared to the uncoated 3-0 suture model (30 min). The TTC-derived infarct volume was significantly larger in the coated model (290.3+/-32.8 mm(3)) relative to the uncoated model (252.3+/-34.6 mm(3)). This study demonstrates that the type of suture may significantly influence the spatiotemporal evolution of the ADC/CBF-mismatch as well as the final infarct volume. These inter-model variations must be taken into account when assessing new therapeutic approaches on ischemic lesion evolution in the rat MCAO model.

Animals↗

Comparison of ischemic lesion evolution in embolic versus mechanical middle cerebral artery occlusion in Sprague Dawley rats using diffusion and perfusion imaging.

BACKGROUND AND PURPOSE: Differences among models in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental stroke research. Using diffusion and perfusion imaging, we compared the spatiotemporal evolution of ischemia in Sprague Dawley rats after permanent suture MCAO (sMCAO; n=8) and embolic MCAO (eMCAO; n=8). METHODS: Serial measurements of quantitative cerebral blood flow (CBF) and the apparent diffusion coefficient (ADC) were performed up to 180 minutes after MCAO. ADC and CBF values within 5 different brain regions were analyzed. ADC and CBF lesion volumes were calculated by using previously established viability thresholds and correlated with infarct volume defined by 2,3,5-triphenyltetrazolium chloride staining 24 hours after MCAO. RESULTS: Compared with sMCAO animals, the threshold-derived CBF lesion volume was significantly larger in eMCAO at all time points (P<0.01), remained relatively constant over time, and was highly correlated with the 2,3,5-triphenyltetrazolium chloride-defined infarct size. The ADC lesion volume did not differ between models at any time point. A diffusion/perfusion mismatch was present significantly longer in eMCAO animals (P<0.05), and these rats demonstrated larger absolute mismatch volumes that were statistically significant at 30, 60, and 90 minutes (P<0.05). In both models, CBF and ADC declines were highly correlated. CONCLUSIONS: This study demonstrated substantial differences in acute ischemic lesion evolution between the eMCAO and sMCAO models.

Animals↗

Acute inflammation and loss of retinal architecture and function during experimental Bacillus endophthalmitis.

Rapid vision loss and explosive inflammation are devastating consequences of Bacillus endophthalmitis that have not been well defined. We therefore analyzed the evolution of intraocular inflammation and loss of retinal architecture and function during experimental Bacillus endophthalmitis. Mice were intravitreally injected with 100 CFU of B. cereus, and eyes were analyzed for bacterial growth, retinal function, architectural changes and retinal cellular stress, inflammatory cytokines, and infiltrating cells. Retinal electrophysiologic and structural changes began as early as 4 to 6 hr postinfection. Significant declines in retinal function paralleled the loss of retinal architecture. Glial fibrillary acidic protein (GFAP) was detected in retina, indicating potential stress. Polymorphonuclear leukocyte (PMN) infiltration into the vitreous began as early as 4 hr postinfection, coinciding with a significant increase in TNF-alpha in the eye. These results indicated that acute inflammation and detrimental architectural and electrophysiologic changes in the retina began earlier than once thought, suggesting that therapeutic intervention should be given at the earliest possible time to avoid vision loss during Bacillus endophthalmitis.

Acute Disease↗

Development of specific antibodies mediating antibody-dependent cell-mediated cytotoxicity following experimental infection of cattle with bovine herpesvirus 1 and subsequent viral reactivation.

Evolution of sensitizing antibodies involved in antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-complement cell lysis and complement-facilitated ADCC was followed in bulls after primary infection by a wild strain of infectious bovine rhinotracheitis virus (bovine herpesvirus 1; BHV-1) and after experimental reactivation of the virus. These antibodies were detected between the 4th and the 7th day after primary infection, reached a maximum level after 2 weeks and rose slightly after reactivation of the virus following dexamethasone treatment. The presence of endogenous complement slightly enhanced the ADCC reaction.

Animals↗

Compositional complementarity and prebiotic ecology in the origin of life.

We hypothesize that life began not with the first self-reproducing molecule or metabolic network, but as a prebiotic ecology of co-evolving populations of macromolecular aggregates (composomes). Each composome species had a particular molecular composition resulting from molecular complementarity among environmentally available prebiotic compounds. Natural selection acted on composomal species that varied in properties and functions such as stability, catalysis, fission, fusion and selective accumulation of molecules from solution. Fission permitted molecular replication based on composition rather than linear structure, while fusion created composomal variability. Catalytic functions provided additional chemical novelty resulting eventually in autocatalytic and mutually catalytic networks within composomal species. Composomal autocatalysis and interdependence allowed the Darwinian co-evolution of content and control (metabolism). The existence of chemical interfaces within complex composomes created linear templates upon which self-reproducing molecules (such as RNA) could be synthesized, permitting the evolution of informational replication by molecular templating. Mathematical and experimental tests are proposed.

Biological Evolution↗

Embryological evidence for developmental lability during early angiosperm evolution.

Recent advances in angiosperm phylogeny reconstruction, palaeobotany and comparative organismic biology have provided the impetus for a major re-evaluation of the earliest phases of the diversification of flowering plants. We now know that within the first fifteen million years of angiosperm history, three major lineages of flowering plants-monocotyledons, eumagnoliids and eudicotyledons-were established, and that within this window of time, tremendous variation in vegetative and floral characteristics evolved. Here I report on a novel type of embryo sac (angiosperm female gametophyte or haploid egg-producing structure) in Amborella trichopoda, the sole member of the most ancient extant angiosperm lineage. This is the first new pattern of embryo sac structure to be discovered among angiosperms in well over half a century. This discovery also supports the emerging view that the earliest phases of angiosperm evolution were characterized by an extensive degree of developmental experimentation and structural lability, and may provide evidence of a critical link to the gymnospermous ancestors of flowering plants.

Biological Evolution↗

Mineral substance of bone tissue and of experimental cutaneous calcinosis in rats: chemical analysis and ESR study.

The evolution of the mineral constituents of subcutaneous calcinosis induced in rats by topical calciphylaxis was studied by the method of quantitative chemical analysis, and after treatment with excited gases by electron spin resonance (ESR) analysis. Chemical data show that the genesis of the subcutaneous calcinosis does not significantly alter the concentration of Ca, P, F, CO3, Mg, and Fe in the mineral phase of the femoral bone of calciphylactic rats. In the calcinosis an important increase of the fluoride concentration is noticed in function of the time after challenging. There is also a high concentration of Mg2+ ions in the early stages of the experimental calcification. Iron injected for the challenging is continuously present in the calciphylactic tissue after this treatment. This suggests that subcutaneous calcinosis might be a means of fixing certain heavy metal ions. After treatment with excited gases, the proportions of the trapped CO33- and O3- radicals are of the same order of magnitude in calciphylactic tissue after 12 days and observations in bone mineral. These suggest that after 12 days the mineral of the calciphylactic tissue has a crystalline state close to that of bone.

Animals↗

Hormonal influences on the muscle-bone feedback system: a perspective.

Hormones, muscle and bone tissues have co-existed virtually during the whole evolution of vertebrates, and it is obvious that they constitute a complex system able to cope with needs and challenges arising from a variety of physiological and locomotive needs. All body movements are produced by co-ordinated contractions of skeletal muscles, while consequent dynamic muscle work provides the fundamental source of mechanical loading to the skeleton. Mechanical competence of the skeleton is principally maintained by a mechanosensory feedback system that senses the loading-induced deformations within the bones and maintains the skeletal rigidity through structural adaptation. In contrast to the prevalent view suggesting a modulatory effect of hormones on the sensitivity of the mechanosensory system, a new conceptual scheme is proposed. In particular, it is argued that the mechanical and hormonal functions in the skeleton are fundamentally independent but can be seemingly interactive through hormonally-induced modifications in the bone structure, those basically forming a mineral reservoir for maintenance of physiological homeostasis. Whenever needed, utilization of this strategically placed reservoir would not essentially compromise the mechanical competence and locomotive capability of the skeleton. Although plausible, the present view is necessarily speculative and awaits corroborative experimental evidence.

Biological Evolution↗

Immunopathogenesis of experimental Chagas' disease in mice: damage to the autonomic nervous system.

Infection of mice with Trypanosoma cruzi produces pathological change which in many ways parallels the evolution of Chagas' disease in human patients. An essential element in this experimental pathology is the intense denervation observed during the resolution of acute-stage parasitaemia. Host cells, from a variety of tissues, have been shown to absorb parasite antigens and thus to become targets for the hosts' own anti-parasite immune response. The definition of common antigenic determinants, shared by T. cruzi and human neuronal cells, might explain why the electrical conduction systems and the autonomic nervous system are especially vulnerable to the postulated autoimmune process. We have the models, the tools and the hypotheses, and now we await the proof.

Animals↗

A vertebrate model of extreme physiological regulation.

Investigation of vertebrate regulatory biology is restricted by the modest response amplitudes in mammalian model species that derive from a lifestyle of frequent small meals. By contrast, ambush-hunting snakes eat huge meals after long intervals. In juvenile pythons during feeding, there are large and rapid increases in metabolism and secretion, in the activation of enzymes and transporter proteins, and in tissue growth. These responses enable an economic hypothesis concerning the evolution of regulation to be tested. Combined with other experimental advantages, these features recommend juvenile pythons as the equivalent of a squid axon in vertebrate regulatory biology.

Animals↗