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High level of cryptic species diversity revealed by sympatric lineages of Southeast Asian forest frogs.

Amphibians tend to exhibit conservative morphological evolution, and the application of molecular and bioacoustic tools in systematic studies have been effective at revealing morphologically 'cryptic' species within taxa that were previously considered to be a single species. We report molecular genetic findings on two forest-dwelling ranid frogs from localities across Southeast Asia, and show that sympatric evolutionary lineages of morphologically cryptic frogs are a common pattern. These findings imply that species diversity of Southeast Asian frogs remains significantly underestimated, and taken in concert with other molecular investigations, suggest there may not be any geographically widespread, forest-dwelling frog species in the region. Accurate assessments of diversity and distributions are needed to mitigate extinctions of evolutionary lineages in these threatened vertebrates.

Amphibians↗

Posterior urethral valves in Eastern Ontario - a 30 year perspective.

INTRODUCTION: Posterior urethral valves (PUV) are the most common cause of male pediatric obstructive uropathy. Recent advancements in antenatal ultrasound and endoscopy have altered the presentation and management of PUV. Herein we describe the presentation, management and outcome of PUV patients in Eastern Ontario/Western Quebec over the last 3 decades. A comparison analysis of those cases identified pre and post widespread utilization of antenatal ultrasound diagnosis was performed to discern the clinical evolution of PUV with respect to long-term outcome. METHODS: Retrospective systematic chart review of all PUV cases diagnosed and treated at the Children's Hospital of Eastern Ontario over the last 3 decades. Charts were reviewed for initial presentation, method of diagnosis, radiological and clinical findings at diagnosis, initial management, and long-term clinical outcome. The evolution of PUV was interpreted by dividing the cohort into two groups chronologically delineated by the first case detected by antenatal ultrasound in the mid-1980s. These pre- and post- antenatal ultrasound eras were compared with respect to the parameters outlined above. RESULTS: Fifty-three cases were reviewed - 21 prior to widespread antenatal ultrasound screening in the mid-1980s and 32 after. There were 13/53 cases (32%) discovered by prenatal ultrasound evidence of hydronephrosis, none prior to 1985. VCUG confirmed the diagnosis in all cases. Mean age at presentation in the remaining post-natally diagnosed patients was 33 months. Of the cases diagnosed post-natally, ultrasound investigation complemented VCUG findings in 19/40 cases (47%), whereas IVP was utilized in 14/40 (35%). IVP has not been utilized for this purpose since 1987. Overall, 26/53 cases (49%) had documented VUR - 16/26 (62%) bilateral; 42/53 (79%) had hydronephrosis on ultrasound - 37/42 (88%) bilateral; 26/53 (49%) had radiological evidence of renal parenchymal damage at diagnosis; 41/53 (77%) cases had a thickened bladder wall on ultrasound at diagnosis, and 23/53 (43%) had at least one bladder diverticulum. Techniques of initial management comprised: valve ablation 32/53, vesicostomy 11/53, and high diversion 10/53. Clinically significant bladder dysfunction was found in 31% of cases, ranging from bladder instability to myogenic failure. Globally impaired renal function, as determined by significantly elevated serum creatinine levels, reduced GFR, or both, was found in 12/53 (23%). 6/53 (11%) progressed to ESRD, of which 4 received transplants. Two patients died - one from complications related to renal failure. Of the six cases of myogenic bladder failure identified, three (50%) had concurrently significant renal impairment. Average length of follow-up was 8.3 years, varying between 1 month and 18 years. CONCLUSIONS: The presentation of PUV is variable, and currently antenatal detection is the most common mode. Despite this, it still does not make up the majority of diagnoses. Complete radiological work up should include abdominal and pelvic U/S in conjunction with VCUG. Concurrent VUR in 50% of boys mandates suppressive antibiotic use. Primary valve ablation remains the gold standard for treatment of PUV, with vesicostomy reserved for selected cases. Long-term bladder and renal dysfunction is common in this population, and mandates long-term urological and nephrological follow-up.

Child↗

[The relevance of ethology for psychiatry].

Darwin's evolutionary theory was the starting point for ethology, associated with an impact on scientific psychiatry. Psychiatry and ethology have common scientific and methodological prerequisites: inductive and deductive methods and "gestalt theory" as a basis for observing and describing behaviour patterns with subsequent causal analysis. There have been early endeavours to anchor ethological thinking in psychiatry but this tendency did not prevail for the following reasons: on the one hand, the methodology of ethology was immature or not applicable to man, whereas on the other hand the dominating experiential phenomenological school of Karl Jaspers and Kurt Schneider stressed the privileged position of human thinking, perception, and feeling. These fundamental categories of human existence did not appear amenable to any causal ethological analysis. Psychiatry and evolutionary biology were linked in an atrocious manner during the Nazi regime, both being abused for propaganda purposes and genocide. More recently, there is a "reconciliation" of both disciplines. In psychiatric nosology, operational, behaviour-oriented diagnostic systems have been introduced; ethology has opened up for theories of learning; new subsections like human ethology and sociobiology have evolved. The seeming incompatibility of (behavioural) biological psychiatry and experiential phenomenological psychopathology may be overcome on the basis of Konrad Lorenz' evolutionary epistemology. The functional analysis of human feeling and behaviour in psychotic disorders on the basis of Jackson's theory of the evolution and dissolution of the nervous system may serve as an example. The significance of an "ethological psychiatry" for diagnostic and therapeutical processes of psychiatric disorders derive from prognostic possibilities and the analysis of non-verbal communication in therapist-patient-interactions, but have not yet been systematically investigated.

Animals↗

Phylogenetics and evolution of nematode-trapping fungi (Orbiliales) estimated from nuclear and protein coding genes.

The systematic classification of nematode-trapping fungi is redefined based on phylogenies inferred from sequence analyses of 28S rDNA, 5.8S rDNA and beta-tubulin genes. Molecular data were analyzed with maximum parsimony, maximum likelihood and Bayesian analysis. An emended generic concept of nematode-trapping fungi is provided. Arthrobotrys is characterized by adhesive networks, Dactylellina by adhesive knobs, and Drechslerella by constricting-rings. Phylogenetic placement of taxa characterized by stalked adhesive knobs and non-constricting rings also is confirmed in Dactylellina. Species that produce unstalked adhesive knobs that grow out to form loops are transferred from Gamsylella to Dactylellina, and those that produce unstalked adhesive knobs that grow out to form networks are transferred from Gamsylella to Arthrobotrys. Gamsylella as currently circumscribed cannot be treated as a valid genus. A hypothesis for the evolution of trapping-devices is presented based on multiple gene data and morphological studies. Predatory and nonpredatory fungi appear to have been derived from nonpredatory members of Orbilia. The adhesive knob is considered to be the ancestral type of trapping device from which constricting rings and networks were derived via two pathways. In the first pathway adhesive knobs retained their adhesive material forming simple two-dimension networks, eventually forming complex three-dimension networks. In the second pathway adhesive knobs lost their adhesive materials, with their ends meeting to form nonconstricting rings and they in turn formed constricting rings with three inflated-cells.

Animals↗

Systematic variation of amino acid substitutions for stringent assessment of pairwise covariation.

During protein evolution, amino acids change due to a combination of functional constraints and genetic drift. Proteins frequently contain pairs of amino acids that appear to change together (covariation). Analysis of covariation from naturally occurring sets of orthologs cannot distinguish between residue pairs retained by functional requirements of the protein and those pairs existing due to changes along a common evolutionary path. Here, we have separated the two types of covariation by independently recombining every naturally occurring amino acid variant within a set of 15 subtilisin orthologs. Our analysis shows that in this family of subtilisin orthologs, almost all possible pairwise combinations of amino acids can coexist. This suggests that amino acid covariation found in the subtilisin orthologs is almost entirely due to common ancestral origin of the changes rather than functional constraints. We conclude that naturally occurring sequence diversity can be used to identify positions that can vary independently without destroying protein function.

Amino Acid Sequence↗

Dephasing of spin echoes by multiple heteronuclear dipolar interactions in rotational echo double resonance NMR experiments.

The application of rotational echo double resonance (REDOR) nuclear magnetic resonance (NMR) for accurate distance measurements has thus far been largely restricted to isolated heteronuclear two-spin systems. In the present paper, the informational content of REDOR curves is explored for systems characterized by multi-spin interactions. To this end, numerical REDOR simulations are presented for cases in which single observe spins S are dipolarly coupled to groups of spins I in distinct geometries. To develop the utility of REDOR for characterizing dipolar couplings in unknown and/or ill-defined geometries, the validity ranges and systematic errors of certain analytical approximations are studied. In the limit of short dipolar evolution times where 0 < deltaS/S0 < or = 0.2 to 0.3, the REDOR difference signal intensity increases approximately proportional to the square of the dipolar evolution time. Here, the curvature depends simply on the second moment M2 characterizing the overall strength of the heterodipolar coupling, irrespective of specific molecular geometries. Fitting experimental REDOR data in this manner produces slight systematic underestimates of M2. However, these errors tend to be counterbalanced by additional systematic errors made by neglecting weak couplings to more remote spins and distribution effects caused by disorder. Based on these findings, the results suggest a convenient method of obtaining site-resolved second moment information in disordered materials.

Computer Simulation↗

Expanding the substrate scope of enzymes: combining mutations obtained by CASTing.

In a previous paper, the combinatorial active-site saturation test (CAST) was introduced as an effective strategy for the directed evolution of enzymes toward broader substrate acceptance. CASTing comprises the systematic design and screening of focused libraries around the complete binding pocket, but it is only the first step of an evolutionary process because only the initial libraries of mutants are considered. In the present study, a simple method is presented for further optimization of initial hits by combining the mutational changes obtained from two different libraries. Combined lipase mutants were screened for hydrolytic activity against six notoriously difficult substrates (bulky carboxylic acid esters) and improved mutants showing significantly higher activity were identified. The enantioselectivity of the mutants in the hydrolytic kinetic resolution of two substrates was also studied, with the best mutant-substrate combination resulting in a selectivity factor of E=49. Finally, the catalytic profile of the evolved mutants in the hydrolysis of simple nonbranched carboxylic acid esters, ranging from acetate to palmitate, was studied for theoretical reasons.

Catalysis↗

[Sleep study of progressive supranuclear paralysis].

From a group of 9 patients suffering from progressive supranuclear palsy 11 polygraphic records and 6 tests with probenecid have been made. The changes in sleep can be correlated with the severity of the clinical picture and the stage of evolution of the disease. They support the hypothesis of a systematic progression of the lesions in the hypnogenic structures of the brain stem.

Aged↗

[Current treatment of acute type A aortic dissection. Surgical treatment and treatment of malperfusion syndrome].

Acute type A aortic dissection is a surgical emergency. Treatment is based on dissected ascending aortic replacement and correction of an associated aortic insufficiency. Catheterization of the axillary artery, open distal anastomosis and systematic resection of the intimal tear are the main surgical evolutions of the last years. They allowed to significantly reduce intraoperative mortality rate particularly due to bleeding. Thirty days mortality rate of operated aortic dissection is about 20 to 30%. Visceral malperfusion syndromes induced by aortic dissection represent an important cause of postoperative death. An early diagnosis and treatment appears necessary. Thoracoabdominal CT scan allows understanding mechanisms inducing malperfusion. Aortography and an emergency endovascular procedure allow restoring arterial blood flow before renal or mesenteric irreversible ischemia. Collaboration between radiologist, anesthesiologist and surgeon is necessary to optimize survival of acute type A aortic dissection.

Acute Disease↗

Mutational analysis of gene families in human cancer.

The completion of the human genome project has marked a new beginning in biomedical sciences. Human cancer is a genetic disease and, accordingly, the field of oncology has been one of the first to be impacted by this historic revolution. Knowledge of the sequence and organization of the human genome facilitates the systematic analysis of the genetic alterations underlying the origin and evolution of tumors. Recent mutational analyses in colorectal and other cancers have focused on examination of gene families involved in signal transduction, such as kinases and phosphatases. This approach has been successful in identifying mutations in a variety of different genes, including the identification of PI3KCA as one of the most commonly mutated oncogenes in human cancer. Such genomic analyses have already demonstrated their utility in basic and clinical cancer research, and are expected to have an important impact on future diagnostic and therapeutic strategies.

Colorectal Neoplasms↗

An evidence-based estimate of appropriate radiotherapy utilization rate for breast cancer.

PURPOSE: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. We sought to use an evidence-based approach to estimate the proportion of incident cases of breast cancer that will require RT at any point in the evolution of the illness. METHODS AND MATERIALS: We undertook a systematic review of the literature to identify indications for RT for breast cancer and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of breast cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error was estimated by sensitivity analysis. RESULTS: It was estimated that 66.4% +/- 4.8% of breast cancer patients develop one or more indications for RT at some point in the course of the illness. The plausible range for this rate was 56.3%-72.4% on sensitivity analysis. Of all breast cancer patients, 57.3% +/- 4.7% require RT in their initial treatment and 9.1% +/- 1.0% do so later for recurrence or progression. The proportion of patients who ever require RT is stage dependent: 39.8% +/- 1.1% in ductal carcinoma in situ; 68.6% +/- 4.1% in Stage I invasive carcinoma; 81.5% +/- 2.3% in Stage II; 95.3% +/- 0.3% in Stage III; and 63.7% +/- 0.3% in Stage IV. CONCLUSION: This method provides a rational starting point for the long-term planning of RT services and for the audit of access to RT at the population level. By completing such evaluations in the major cancer sites, it will be possible to estimate the appropriate RT treatment rate for the cancer population as a whole.

Algorithms↗

[Alveolar hypoventilation during sleep and domiciliary assisted ventilation].

INTRODUCTION: An alveolar hypoventilation physiologically occurs during sleep and more specifically during REM sleep. STATE OF THE ART: During obstructive chronic respiratory failures, increases in PaCO2 that are associated with REM sleep can participate to the severity of daytime hypercapnia and in a subgroup of patients lead to an indication of nocturnal non-invasive ventilation (NIV) in association with the long-term oxygen therapy. A REM sleep hypoventilation generally appears during the early course of restrictive chronic respiratory failures. This REM sleep hypoventilation represents one of the most frequent reasons for initiating NIV in restrictive respiratory insufficiencies. Obesity-hypoventilation syndrome (OHS) refers to a hypercapnic chronic respiratory failure in which REM sleep hypoventilation is one of the main determinants. In France, in 2004, OHS is the primary chronic respiratory failure leading to at home NIV. NIV on OHS aims to maintain upper airway patency as sleep apnoea is frequently associated and to allow sufficient alveolar ventilation during REM sleep. PERSPECTIVES: Thus, sleep alveolar hypoventilation should be systematically assessed in obese patients and during the time curse evolution of all the chronic respiratory failures. This can be done relatively easily by using nocturnal oximetry concurrently with a transcutaneous PCO2 measurement. CONCLUSION: The understanding of exact mechanisms underlying abnormal respiratory events occurring during sleep allows optimising adjustments in NIV parameters.

Chronic Disease↗

Phylogenetic analyses of diplomonad genes reveal frequent lateral gene transfers affecting eukaryotes.

BACKGROUND: Lateral gene transfer (LGT) is an important evolutionary mechanism among prokaryotes. The situation in eukaryotes is less clear; the human genome sequence failed to give strong support for any recent transfers from prokaryotes to vertebrates, yet a number of LGTs from prokaryotes to protists (unicellular eukaryotes) have been documented. Here, we perform a systematic analysis to investigate the impact of LGT on the evolution of diplomonads, a group of anaerobic protists. RESULTS: Phylogenetic analyses of 15 genes present in the genome of the Atlantic Salmon parasite Spironucleus barkhanus and/or the intestinal parasite Giardia lamblia show that most of these genes originated via LGT. Half of the genes are putatively involved in processes related to an anaerobic lifestyle, and this finding suggests that a common ancestor, which most probably was aerobic, of Spironucleus and Giardia adapted to an anaerobic environment in part by acquiring genes via LGT from prokaryotes. The sources of the transferred diplomonad genes are found among all three domains of life, including other eukaryotes. Many of the phylogenetic reconstructions show eukaryotes emerging in several distinct regions of the tree, strongly suggesting that LGT not only involved diplomonads, but also involved other eukaryotic groups. CONCLUSIONS: Our study shows that LGT is a significant evolutionary mechanism among diplomonads in particular and protists in general. These findings provide insights into the evolution of biochemical pathways in early eukaryote evolution and have important implications for studies of eukaryotic genome evolution and organismal relationships. Furthermore, "fusion" hypotheses for the origin of eukaryotes need to be rigorously reexamined in the light of these results.

Adaptation, Physiological↗

Comparative studies of bile salts. Bile salts of sturgeons (Acipenseridae) and of the paddlefish Polyodon spathula: a new partial synthesis of 5 beta-cyprinol.

1. Bile salts of the sturgeons Acipenser guldenstaedti Brandt, Acipenser stellatus Pall and Huso huso L. and of the paddlefish Polyodon spathula Walbaum are shown to be closely similar, consisting mainly of taurocholate with minor amounts of tauroallocholate and the monosulphates of bile alcohols. The bile alcohols, comprising less than 10% of the bile salts, are mixtures with high proportions of substances resembling C(27) tetrols and of C(27) pentols, including 5beta-cyprinol and (probably) 5alpha-cyprinol. 2. 5beta-Cyprinol (3alpha,7alpha,12alpha,26,27-pentahydroxy-5beta-cholestane) was made from cholic acid via 3alpha,7alpha,12alpha-triacetoxy-5beta-cholan-24-ol in an overall yield of about 0.8%. 3. The chemical nature of chondrostean bile salts agrees with the systematic position of the fishes and suggests further correspondence between evolution at the morphological and molecular levels.

Animals↗