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PubMed1984

Brain traits through phylogeny: evolution of neural characters.

We have previously derived a hypothetical tree of the lines of mammalian descent, based upon a comprehensive numerical taxonomic cross-analysis of primitive and derived states of 15 brain traits in 38 representative species. In this communication we use this tree to describe the probable sequence of changes that have taken place in phylogenetic history. 2 characters proved to be multiply convergent, occurring in parallel in several disparate lines of descent. The remaining 9 characters each appeared in ancestors of one or another of the lineages and characterize related progeny.

Animals↗

PubMed2002

[Phylogeny of Mammalian metabolism].

Mammals are at the end of a gradual metabolic evolution in the course of which the step from anaerobic to aerobic cellular metabolism and the transition from water to land life formed the basis for an increase in metabolic rate (from brady- to tachymetabolism). The increased metabolic rate and the resulting endogenous heat production were the preconditions for enhanced long-term performance as well as for homeothermy which allowed mammals and birds to invade temperate zones. However, the underlying increase in membrane permeability also results in an increased energy demand (for membrane pump activity) which leads to the reduced hypoxia tolerance of mammals and requires a permanent substrate supply. As an adaptation to a seasonal discrepancy between increased thermoregulatory energy demand and decreased food supply, some small mammals apparently extended the newly evolved non-REM-sleep into hibernation. Mammalian hibernation is characterized by a profound metabolic reduction which is influenced by acidosis and limited to a tolerable degree by maintained thermoregulation. The lower limit of cooling seems to be determined by a critical minimal metabolic rate which is common to all mammals. The higher the normothermic metabolic rate, the lower is the temperature at which this minimal metabolic rate is reached. Since specific (i. e., weight-corrected) basal metabolic rate increases with decreasing body mass, small mammals exhibit a higher hypothermia tolerance than larger ones. On the other hand, the metabolic decrease to a uniform minimal level reflects an inactivation of the overall metabolic size relationship and, thus, forms a counterpart to the metabolic increase from a lower fetomaternal to the higher size-related level, occurring after birth. The postnatal metabolic increase which favours the onset of thermoregulation, parallels the increase in oxygen tension at the transition from fetal to adult circulation and, thus, probably enables mammalian neonates to readjust their metabolic needs in response to hypoxia. There is increasing evidence that, similar to the step from anaerobiosis to aerobiosis, the increase in metabolic rate resulting from any increase in oxygen supply is a general principle of evolution that, apart from its further adaptive benefits, protects tissues from oxygen excess and subsequent oxidative stress.

Animals↗

PubMed2026

Two Paralogues as They Like It: Conserved and Divergent Evolution of Vertebrate Gcm Genes.

Gcm1 and Gcm2 are paralogous transcription factors in vertebrates that play key roles in the development of pharyngeal-derived epithelia, yet their deployment across vertebrate lineages remains incompletely understood. While Gcm2 shows deeply conserved pharyngeal expression across gnathostomes, Gcm1 has been mainly characterized in mammals, where it exhibits broader expression patterns. How Gcm1 is deployed in non-mammalian vertebrates has remained unexplored. Here, we performed a comparative analysis of Gcm1 expression in cartilaginous fishes, non-teleost actinopterygians, and amphibians. RNA in situ hybridization revealed conserved Gcm1 expression in gill epithelia across these taxa. Parallel analyses showed that Gcm2 is also expressed in gill epithelia, with overlapping but distinct spatial patterns. In addition, Gcm1 showed lineage-specific expression in bichir embryos, including strong expression in external gills and scattered epithelial cells in the yolk-sac membrane. In the external gills, Gcm1-positive cells possess vacuole-like cytoplasmic structures, suggesting a previously unrecognized epithelial cell population. Together, our findings indicate that Gcm1 and Gcm2 share ancestral expression in pharyngeal epithelia but have followed distinct evolutionary trajectories, with Gcm1 exhibiting greater lineage-specific diversification.

Animals↗

PubMed1988

Back muscle function during bipedal walking in chimpanzee and gibbon: implications for the evolution of human locomotion.

The evolution of erect posture and locomotion continues to be a major focus of interest among paleoanthropologists and functional morphologists. To date, virtually all of our knowledge about the functional role of the back muscles in the evolution of bipedalism is based on human experimental data. In order to broaden our evolutionary perspective on the vertebral region, we have undertaken an electromyographic (EMG) analysis of three deep back muscles (multifidus, longissimus thoracis, iliocostalis lumborum) in the chimpanzee (Pan troglodytes) and gibbon (Hylobates lar) during bipedal walking. The recruitment patterns of these three muscles seen in the chimpanzee closely parallel those observed in the gibbon. The activity patterns of multifidus and longissimus are more similar to each other than either is to iliocostalis. Iliocostalis recruitment is clearly related to contact by the contralateral limb during bipedal walking in both species. It is suggested that in both the chimpanzee and gibbon, multifidus controls trunk movement primarily in the sagittal plane, iliocostalis responds to and adjusts movement in the frontal plane, while longissimus contributes to both of these functions. In many respects, the activity patterns shared by the chimpanzee and gibbon are quite consistent with recent human experimental data. This suggests a basic similarity in the mechanical constraints placed on the back during bipedalism among these three hominoids. Thus, the acquisition of habitual bipedalism in humans probably involved not so much a major change in back muscle action or function, but rather an improvement in the mechanical advantages and architecture of these muscles.

Animals↗

PubMed2004

Long-term suppression of plasma viremia with highly active antiretroviral therapy despite virus evolution and very limited selection of drug-resistant genotypes.

HIV-1 evolution and the possible emergence of mutations associated with resistance to antiretroviral inhibitors have been evaluated in a cohort of sixty-three patients successfully treated with highly active antiretroviral therapy (HAART). The patients under effective HAART were recruited in three different hospitals in Spain, and none of them had been treated (naïve) before entering this study. HIV-1 RNA levels, CD4+, and CD8+ T-cell counts were determined, and nucleotide sequences of proviral regions encoding protease and reverse transcriptase (RT) were obtained for longitudinal blood samples spanning a mean follow-up period of 88 weeks. Phylogenetic reconstructions and calculations of genetic distances among the different sequences of each patient were performed. All except one of the patients under study showed an early and sustained decrease in plasma HIV-1 RNA to levels that were below 200 copies/ml. The plasma viral decline paralleled a significant increase in the CD4+ T-lymphocyte counts. Amino acid sequence analyses revealed the occurrence of mutations associated with antiretroviral resistance in nine patients (14.3%) during HAART treatment, that in some cases could be attributed to excess G to A transitions. In six of the nine patients, the mutations conferred resistance to inhibitors administered in the treatment regime, although the mutations did not result in treatment failure. Sequence comparisons revealed viral evolution during the period of treatment in 47.5% of the patients. The results indicate successful suppression of HIV-1 under HAART for extended time periods, indistinguishable for patients in which evidence of virus evolution could or could not be documented.

Adult↗

PubMed2002

Circular dichroism spectroscopy reveals invariant conformation of guanine runs in DNA.

We demonstrate that the characteristic circular dichroism (CD) features of the parallel-stranded DNA tetraplex of d(G4), especially the strong band at 260 nm, are characteristic for the B and A forms of the antiparallel duplex of d(C4G4). Hence, this band evidently originates from intrastrand guanine-guanine stacking, which is therefore very similar in the duplex and tetraplex DNA. In addition, the same type of the CD spectrum is provided by the ordered single strand of d(GA)10. This observation suggests that the ordered single strand of d(GA)10 is stabilized by a core of guanines stacked like in the parallel tetraplex. This view is used to start the modeling of the molecular structure of the ordered d(GA)10 single strand. Our studies suggest that guanine itself is strong enough to stabilize various secondary structures of DNA, which is a property relevant to thinking about the origin and evolution of molecular replicators.

Circular Dichroism↗

PubMed2004

Morphological description of combined variation of distal attachments of fibulares in a foot.

An interesting case of peculiarity of the distal attachment of the three fibular muscles is reported in the left foot of a male adult cadaver of Indian origin. The fibularis brevis, just inferior to the fibular malleolus, gave off an additional slender tendon anteromedial to its main tendon. This was attached to the dorsal digital expansion of the little toe while its main tendon was inserted to the customary bone. The tendon of fibularis longus on the plantar aspect just medial to the cuboid tunnel received a prominent slip of attachment of the tendon of tibialis posterior. The fibularis tertius had two parallel-running tendons attached to the bases of the fourth metatarsal and the fourth and fifth metatarsals respectively. The combined variation of the three fibulares in a single foot has not been reported previously. The more distal attachment of the fibularis brevis in this case is a regression in evolution. Weakness of both the fibularis brevis and fibularis longus is found in pes cavovarus. The former can be used as a rotational graft in soft tissue loss of the leg.

Adult↗

PubMed2000

Artificial neural networks: fundamentals, computing, design, and application.

Artificial neural networks (ANNs) are relatively new computational tools that have found extensive utilization in solving many complex real-world problems. The attractiveness of ANNs comes from their remarkable information processing characteristics pertinent mainly to nonlinearity, high parallelism, fault and noise tolerance, and learning and generalization capabilities. This paper aims to familiarize the reader with ANN-based computing (neurocomputing) and to serve as a useful companion practical guide and toolkit for the ANNs modeler along the course of ANN project development. The history of the evolution of neurocomputing and its relation to the field of neurobiology is briefly discussed. ANNs are compared to both expert systems and statistical regression and their advantages and limitations are outlined. A bird's eye review of the various types of ANNs and the related learning rules is presented, with special emphasis on backpropagation (BP) ANNs theory and design. A generalized methodology for developing successful ANNs projects from conceptualization, to design, to implementation, is described. The most common problems that BPANNs developers face during training are summarized in conjunction with possible causes and remedies. Finally, as a practical application, BPANNs were used to model the microbial growth curves of S. flexneri. The developed model was reasonably accurate in simulating both training and test time-dependent growth curves as affected by temperature and pH.

Humans↗

PubMed2000

Evolution of changes in neuronal activity in the subthalamic nucleus of rats with unilateral lesion of the substantia nigra assessed by metabolic and electrophysiological measurements.

Cellular expression of cytochrome oxidase subunit I (COI) mRNA has recently been used as a metabolic marker for neuronal activity to study the functional changes in the subthalamic nucleus (STN) in parkinsonism. The previous experimental studies have been performed when the pathological state was stabilized at a maximal level. In order to determine the evolution of changes in neuronal activity in the STN after nigrostriatal denervation, we analysed by in situ hybridization the cellular expression of COI mRNA in the subthalamic neurons at different times, from 6 h to 14 days, after unilateral intranigral microinjection of 6-hydroxydopamine (6-OHDA) in rats. In parallel, the time-dependent changes of the unit neuronal activity of subthalamic neurons have been recorded. Levels of COI mRNA increased by 41% in subthalamic neurons from 24 h after 6-OHDA intoxication, to 14 days (+26%). Similarly, electrical activity started to increase slightly 24 h after lesion (+20%) and remained significantly higher at 14 days after the lesion (+189%). Changes in neuronal mean discharge rate were associated with changes in the pattern of spiking activity, from a regular firing pattern to an irregular one with a high bursting activity. These results show that: (i) the hyperactivity of the STN represents a very early phenomenon in the physiopathology of parkinsonian syndromes; and (ii) that changes in COI mRNA expression slightly precede changes in electrical neuronal activity.

Animals↗

PubMed1977

Root and nodule respiration in relation to acetylene reduction in intact nodulated peas.

Inoculated pea plants (Pisum sativum L.) were grown with N-free nutrients in a controlled environment room and rates of respiratory CO(2) evolution and C(2)H(2) reduction by the intact nodulated roots were determined. Experiments followed changes related to diurnal cycles, light and dark treatments, partial defoliation, aging of plants and NH(4)NO(3) addition. In all experiments, changes in C(2)H(2) reduction were associated with parallel changes in the respiration rate, although in all but the defoliation experiment there was a basal level of respiration which was independent of the rate of C(2)H(2) reduction. In conditions which affected growth or plant size as well as C(2)H(2) reduction, respiration changed by an average of 0.42 mg CO(2) (mumol C(2)H(2) reduced)(-1). However, some treatments decreased C(2)H(2) reduction without greatly changing the growth and in these conditions respiration was decreased by an average of 0.27 mg CO(2) (mumol C(2)H(2) reduced)(-1). While this value may also include some respiration associated with other processes, it is proposed that it more closely estimates respiration directly associated with energy utilization for acetylene reduction; whereas the higher value includes respiration related to maintenance and growth processes as well.

Journal Article↗

PubMed2006

The role of perioperative chemotherapy in the treatment of urothelial cancer.

Cancer of the urothelium is the fourth most common malignancy in men in the U.S. and the ninth most common in women. More than 63,000 Americans will be diagnosed with bladder cancer this year (47,010 men and 16,200 women), and more than 13,000 (8,970 men and 4,210 women) can expect to die of their disease. The approximate 5:1 ratio of incidence to mortality roughly parallels the frequency of superficial to invasive disease. Efforts to improve this ratio have generated a potential paradigm shift in the treatment of urothelial cancer, incorporating increasingly active chemotherapy into treatment regimens for high-risk tumors in both the pre-and postoperative settings. This review summarizes the evolution of chemotherapeutic treatment of urothelial cancer and the rationale for its perioperative administration and addresses the future directions of clinical research in this field.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

[Comparative study, using a placebo, of the frequency of micturition after repeated administration of piretanide SR 6 mg/day (Eurelix) to healthy volunteers].

Thirty healthy volunteers received piretanide SR 6 mg/day (n = 15) or placebo (n = 15) in a 10-day double-blind parallel-group comparative trial. 24-h urine output was significantly greater with piretanide than with placebo on D1 (1919 +/- 434 ml and 1160 +/- 335 ml respectively, p = 0.001 one-sided) as on D10 (1563 +/- 538 ml and 1236 +/- 435 ml respectively, p = 0.04 one-sided). Nevertheless the evolution of urinary output from D1 to D10 was significantly different (p = 0.008): it remained stable with placebo but diminished with piretanide. The diuretic effect of piretanide was apparent with a supplementary miction between 8 a.m. and 4 p.m. both on D1 and D10. Between 4 p.m. and 8 a.m., the number of mictions was the same in both groups. Thus piretanide SR 6 mg has a mild effect on the number of mictions; it should not alter patients' well-being.

Adult↗

PubMed1996

[The detection of antibodies against HIV-1 24-kd protein. A clinico-serological correlation].

The presence of antibodies against the HIV protein of 24 kd was studies by the parallel use of the DAVIH BLOT western blot and of the DAVIH AC P24 ELISA in serum samples from 176 patients at different HIV-1 infection stages. The results were correlated with the clinical classification of the patient at the moment of taking the sample and with the further evolution during 6 months. 57% of the patients with opportunistic minor infections and 96% of AIDS patients had low antibodies titres. Dead patients showed no reactivity or presented very low titres in samples taken before dying. Different titrations were observed in serum groups with an apparently uniform reactivity in the western blot. The results show and adequate clinical and serological correlation. Therefore, the DAVIH AC P24 ELISA could be useful in the clinical follow-up of HIV-1 infected persons.

Acquired Immunodeficiency Syndrome↗

PubMed2003

The evolution of cell death programs as prerequisites of multicellularity.

One of the hallmarks of multicellularity is that the individual cellular fate is sacrificed for the benefit of a higher order of life-the organism. The accidental death of cells in a multicellular organism results in swelling and membrane-rupture and inevitably spills cell contents into the surrounding tissue with deleterious effects for the organism. To avoid this form of necrotic death the cells of metazoans have developed complex self-destruction mechanisms, collectively called programmed cell death, which see to an orderly removal of superfluous cells. Since evolution never invents new genes but plays variations on old themes by DNA mutations, it is not surprising, that some of the genes involved in metazoan death pathways apparently have evolved from homologues in unicellular organisms, where they originally had different functions. Interestingly some unicellular protozoans have developed a primitive form of non-necrotic cell death themselves, which could mean that the idea of an altruistic death for the benefit of genetically identical cells predated the invention of multicellularity. The cell death pathways of protozoans, however, show no homology to those in metazoans, where several death pathways seem to have evolved in parallel. Mitochondria stands at the beginning of several death pathways and also determines, whether a cell has sufficient energy to complete a death program. However, the endosymbiotic bacterial ancestors of mitochondria are unlikely to have contributed to the recent mitochondrial death machinery and therefore, these components may derive from mutated eukaryotic precursors and might have invaded the respective mitochondrial compartments. Although there is no direct evidence, it seems that the prokaryotic-eukaryotic symbiosis created the space necessary for sophisticated death mechanisms on command, which in their distinct forms are major factors for the evolution of multicellular organisms.

Animals↗

PubMed1991

IgG allotypes of the domestic mink: genetics, expression and evolution.

A brief review summarized the results we obtained with the identification, analysis of population distribution, genetics, expression, and evolution of 12 IgG allotypes in the American mink and several closely related mustelids. The American mink is a unique species with respect to expressed allotypic polymorphism of Ig lambda chains. In contrast to the rabbit, human, mouse and rat, the phenotypic expression of IgC gamma allotypes shows unusual variations which mask their true genetic relationships (linkage of C gamma genes; C gamma = constant region of IgG chains). The allotypic IgG polymorphism in the American mink during mustelid phylogenesis underwent saltatory change. A parallelism between the data on changes in IgG allotype frequencies in man and mink in disease is emphasized. In mink, these changes are provided by allotype-specific activation of the expression of the 2 CH genes (CH = constant region of the Ig heavy chains). The results make apparent the need of including more taxa in investigations of Ig genetics. In addition, the Aleutian disease of the mink is presented as a model of human disease.

Animals↗

PubMed2003

Reducing the time complexity of the derandomized evolution strategy with covariance matrix adaptation (CMA-ES).

This paper presents a novel evolutionary optimization strategy based on the derandomized evolution strategy with covariance matrix adaptation (CMA-ES). This new approach is intended to reduce the number of generations required for convergence to the optimum. Reducing the number of generations, i.e., the time complexity of the algorithm, is important if a large population size is desired: (1) to reduce the effect of noise; (2) to improve global search properties; and (3) to implement the algorithm on (highly) parallel machines. Our method results in a highly parallel algorithm which scales favorably with large numbers of processors. This is accomplished by efficiently incorporating the available information from a large population, thus significantly reducing the number of generations needed to adapt the covariance matrix. The original version of the CMA-ES was designed to reliably adapt the covariance matrix in small populations but it cannot exploit large populations efficiently. Our modifications scale up the efficiency to population sizes of up to 10n, where n is the problem dimension. This method has been applied to a large number of test problems, demonstrating that in many cases the CMA-ES can be advanced from quadratic to linear time complexity.

Algorithms↗

PubMed1995

CpG islands in human ZFX and ZFY and mouse Zfx genes: sequence similarities and methylation differences.

The human ZFX, human ZFY, and mouse Zfx genes have CpG islands near their 5; ends. These islands are typical in that they span about 1.5 kb, contain transcription initiation sites, and encompass some 5' untranslated exons and introns. However, comparitive nucleotide sequencing of these human and mouse islands provided evidence of evolutionary conservation to a degree unprecedented among mammalian 5' CpG islands. In one stretch of 165 nucleotides containing 19 CpGs, mouse Zfx and human ZFX are identical to each other and differ from human ZFY at only 9 nucleotides. In contrast, we found no evidence of homologous CpG islands in the mouse Zfy genes, whose transcription is more circumscribed than that of human ZFX, human ZFY, and mouse Zfx. Using the isoschizomers HpaII and MspI to examine a highly conserved segment of the ZFX CpG island, we detected methylation on inactive mouse X chromosomes but not on inactive human X chromosomes. These observations parallel the previous findings that mouse Zfx undergoes X inactivation while human ZFX escapes it.

Animals↗

PubMed1975

Variation in spotting among the close relatives of the butterfly, Maniola jurtina.

A study of spotting in seven related butterfly species in the genera Maniola and Pyronia has been initiated, in the hope of complementing previous work on Maniola jurtina. Marked individual variability has been found in six of the species. Stability of spotting over large areas has not been prominent, but a high degree of apparent geographical variability has been found in four species. Sometimes this has taken the form of clines and sometimes of quantal steps. Some of the quantal changes coincide with the appearance of different "subspecies". Among the incomplete data presented, parallel geographical variation in different species has not been an obvious feature. There have not been enough samples to test for temporal variation in spotting.

Animals↗