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PubMed2001

Advances in high-throughput mass spectrometry.

The evolution of high-throughput drug discovery is readily apparent as the pharmaceutical industry continues to stress the rapid progression of new chemical entities and biological agents through drug discovery and development pipelines. Mass spectrometry and high performance liquid chromatography-mass spectrometry have played an instrumental role in the support and advancement of all facets of high-throughput drug discovery. The introduction of new instrumentation has extended the breadth of mass spectrometric-based capabilities from the characterization of high-throughput organic synthesis products to early adsorption, distribution, metabolism and excretion profiling. Additionally, advances in the capacity and throughput of mass spectrometry systems have concurrently led to the introduction of data management tools to address automated data reduction, archival and mining, as well as analytical data integration to chemical and biological databases.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

[XY gonadal dysgenesis with female phenotype (author's transpl)].

In this paper, we are dealing with the study of a case of multiple somatic malformations, with external female genitals and 46 XY caryotype. The anatomical and histological study of the genital organs, allows us to verify the existence of internal genital organs; consisting essentially in tubes, bicornous uterus, a gonadal ligament in a normotopical position, Wolffian remains and the absence of a vagina. The external female genitals are completely normal. When we interpreted these findings, we paid special attention to the relation existing between the abnormal presence of the Wolffian remains, male genotype, and typical female genital structures. Taking account of the latest scientific advances concerning genital development, we considered the possibility of the existence of secretions of a "masculinizing" substance from the gonad, before its morphological differentiation, which was interrupted by an etiological undetermined noxa. When this evolution was arrested, together with the secretions of the masculinizing substance, the genital development continued normally for a female. The terminal teratogenic period for this malformation is situated from the 5th to the 6th week of gestation (human embryos from 11 to 14 mm., Streeter Horizon XVII).

Abnormalities, Multiple↗

PubMed2006

Compassionate caring.

Beginning with a concerned society, from individuals, to visiting nurse associations, and to publicly traded corporations, home care and hospice have been meaningful threads in the American fabric for over a hundred years. Today, advances in technology, a burgeoning regulatory environment, and universal health care cost concerns make continued change expected and certain. While external health care environmental pressures incessantly shape the evolution of home care and hospice, a central value lives on in the heart of what we do as caregivers, in what is nowtermed our "industry". It is a value we must safeguard from evolutionary extinction.

Community Health Nursing↗

PubMedDate not supplied

Preleukemic myelodysplastic syndromes (MDS): pathogenetical considerations based on retrospective clinicomorphological sequential studies.

Analysis of myelodysplastic syndromes (MDS) in 77 patients terminating in "overt" leukemia revealed sequential changes of marrow morphology with respect to cellularity and involvement of lineages, indicating that different "forms" of MDS represent in reality different phases. Three main phases were observed, which occurred in the following non-reversible sequence: (a) hypocellular dysplasia (H), (b) hypercellular dysplasia with predominance of erythropoiesis (E), and (c) with predominance of myelo(mono)poiesis (MM). Published studies suggest that these phases represent different manifestation stages of the stem cell lesion leading to MDS. Manifestation may probably be promoted by factors causing marrow aplasia. Transition to "overt" leukemia in several cases occurred locally, not throughout the whole marrow. In some patients a mature myelo(mono)-cytic cell population showed the capacity for widespread tissue infiltration, characteristic of leukemic cells. This argues against the theory that "overt" leukemia is the result of continuous dedifferentiation in MDS, but favours the concept of multiple initiating "events" leading to evolution of a leukemic subclone within a myelodysplastic clone. A connection between leukemia differentiation and MDS phase, from which leukemia developed, was also observed indicating that the risk of different stem cell subpopulations to become the target of the leukemia initiating "event" varies during the course of myelodysplasia.

Adult↗

PubMed1980

[Planktonic and bacterial population dynamics during experimental production of natural marine phytoplankton. II. Structure and physiology of populations and their interactions].

During the spring, an experiment was conducted on the production of natural phytoplankton in a continuous flow layout of large capacity, and an analysis was made of the simultaneous evolution of microplanktonic populations (taxonomic composition, diversity, class ranges, and energetic charge) and of bacterial populations (structure, diversity, dominances, and cetabolic potentialities). Oligotrophic initial conditions were charcterized by a poor (0.22 umg of chlorphyll a/L) and diversified (pigment diversity = 4.5) phytoplankton with nanoplanktonic dominance associated with several benthic type diatoms. Bacterial flora, in which pseudomonads were dominant (54.5%), were also diversified (Shannon index H = 3.57). Metabolic potentialities of these bacterial communities were several. Enrichment of the milieu caused the selection and development of a small number of algal species dominated by the diatoms skeletonema costatum (64 x 106/L) and Chaetoceros (3.2 x 106/L) leading to a paucispecific population with a large biomass, a pigment diversity of 1.97, and a chlorophyll a concentration of 25.08 mu/L. The bacterial community then because diversified (H = 4.12) and, although pseudomonads remained dominant (62%), a larger use of organic micromolecules was noted. The establishment of this phytoplanktonic community was followed by a zooplanktonic development in which larger species succeeded smaller ones (ciliates, tintinnides, rotifers, and copepods) corresponding to the global increase of the phytobiomass. Although this system appeared to be in a phase of relative stability, a decease in the energetic charge showed a disturbance in the physiological state of the planktonic populations. These phenomena led to the vanishing of the diatom's dominance (Chaetoceros, and then S. costatum) and its replacement by nanoplankton (123 x 106 cells/L) and dinoflagellates (300000 cells/L). A modification in the organic wealth of the milieu with the addition of particular complex material that was not or little degraded caused deep disturbances in the bacterial populations. Their diversity reached a very low level (H = 1.56 to 2.25) with a proliferation of vibrions (up to 74%) well equipped with exoenzymes, but more restricted in their nutritional versatility (marked preference for organic macromolecules). During the final phase of experimentation, despite a change in qualitative composition and a more important biomass, microplanktonic and bacterial populations returned to a diversified state nearing that of the initial conditions (pigment diversity = 3.2; H = 3.37).

Adenosine Triphosphate↗

PubMed1994

Progressive bleeding in spontaneous thalamic hemorrhage.

Progressive bleeding is uncommon in spontaneous intracerebral hemorrhage. We describe two cases of spontaneous thalamic hemorrhage with evidence of active bleeding or rebleeding detected by noncontrast CT. The first patient was a 47-year-old man with a history of hypertension and cocaine abuse. The second patient, a 73-year-old man, had no valuable risk factors. It is noteworthy that most well-documented instances of continued bleeding or rebleeding in spontaneous intracerebral hemorrhage occur in the thalamus. The natural evolution of spontaneous intracerebral hemorrhage after the first hours of stroke remains to be elucidated.

Aged↗

PubMed1976

[Homoplastic transplantation of crayfish testes (Pontastacus leptodactylus leptodactylus (Eschscholtz, 1823)) in sexual rest into normal and destalked males and females: preliminary results].

Implantation of Crayfish testes in sexual rest into females leads to a new onset of spermatogenetic activity characterized by a precocious appearance of spermatocytes. However, these cells degenerate: their evolution never goes further than the pachytene stage of meiosis prophase. Abortive prophases appear continuously; this also takes place in acini which develop secondarily. Implantation of testes in sexual rest into males in the same physiological shape also leads to the precocious appearance of primary spermatocytes blocked in prophase of meiosis. However, the transplant tends to reacquire a structure similar to the one of a normal resting testis. The delay of appearance of the first spermatocytes is always shortened--less than a month instead of one month and a half--if the receptive female is destalked at the time of the implantation or if the donor male has been destalked one month before the transplantation. The interpretation of the observed phenomena is discussed.

Animals↗

PubMed1996

Structuring cardiology services for the 21st century.

Segregating patients into small coronary care units began in the 1960s. This step was deemed necessary for two reasons: (1) the high mortality and often profound morbidity of patients who had acute myocardial infarction and (2) the boom in treatment technologies, with the introduction of bedside oscilloscopes, defibrillation, and mechanical and pharmacological means of resuscitation and pacing. Another series of technology booms in cardiology has occurred in the 1990s. This new technology and other associated factors may signal the need for reviewing the cardiac care environment. This article presents the evolution of acute care in cardiology from the 1960s to 1996 and questions the continuing need for small, highly staffed cardiac care units. In the current climate of technological refinements, improved nursing education, and a large and diverse population of cardiovascular patients, these units may be redundant.

Australia↗

PubMed1998

Adult participation in youth sports. A developmental perspective.

Societal and familial forces of enormous emotional intensity have contributed to the growth of youth sports during the twentieth century, and continue to affect adult participation in children's athletics. This article addresses the historical evolution of youth sport programs, then identifies opportunities for adults to facilitate developmental progress and surmount emotional obstacles as they interact in sport activities with children ranging from preschool ages through adolescence. Youth sports are viewed as offering tremendous opportunities to teach not only physical skills and playing strategies, but also psychological skills and coping strategies that have applicability throughout life. A developmental rationale is provided to support recommendations for parents and coaches. Child and adolescent psychiatrists are faced with the challenge of collaborating with other professionals and making their knowledge base available to the volunteers who coach in and support youth sport programs.

Adolescent↗

PubMed2002

Evolution of phenotypic drug susceptibility and viral replication capacity during long-term virologic failure of protease inhibitor therapy in human immunodeficiency virus-infected adults.

Continued use of antiretroviral therapy despite the emergence of drug-resistant human immunodeficiency virus (HIV) has been associated with the durable maintenance of plasma HIV RNA levels below pretherapy levels. The factors that may account for this partial control of viral replication were assessed in a longitudinal observational study of 20 HIV-infected adults who remained on a stable protease inhibitor-based regimen despite ongoing viral replication (plasma HIV RNA levels consistently >500 copies/ml). Longitudinal plasma samples (n = 248) were assayed for drug susceptibility and viral replication capacity (measured by using a single-cycle recombinant-virus assay). The initial treatment-mediated decrease in plasma viremia was directly proportional to the reduction in replicative capacity (P = 0.01). Early virologic rebound was associated the emergence of a virus population exhibiting increased protease inhibitor phenotypic resistance, while replicative capacity remained low. During long-term virologic failure, plasma HIV RNA levels often remained stable or increased slowly, while phenotypic resistance continued to increase and replicative capacity decreased slowly. The emergence of primary genotypic mutations within protease (particularly V82A, I84V, and L90M) was temporally associated with increasing phenotypic resistance and decreasing replicative capacity, while the emergence of secondary mutations within protease was associated with more-gradual changes in both phenotypic resistance and replicative capacity. We conclude that HIV may be constrained in its ability to become both highly resistant and highly fit and that this may contribute to the continued partial suppression of plasma HIV RNA levels that is observed in some patients with drug-resistant viremia.

Adult↗

PubMed2006

The road from Santa Rosalia: a faster tempo of evolution in tropical climates.

Using an appropriately designed and replicated study of a latitudinal influence on rates of evolution, we test the prediction by K. Rohde [(1992) Oikos 65, 514-527] that the tempo of molecular evolution in the tropics is greater than at higher latitudes. Consistent with this prediction we found tropical plant species had more than twice the rate of molecular evolution as closely related temperate congeners. Rohde's climate-speciation hypothesis constitutes one explanation for the cause of that relationship. This hypothesis suggests that mutagenesis occurs more frequently as productivity and metabolic rates increase toward the equator. More rapid mutagenesis was then proposed as the mechanism that increases evolutionary tempo and rates of speciation. A second possible explanation is that faster rates of molecular evolution result from higher tropical speciation rates [e.g., Bromham, L. & Cardillo, M. (2003) J. Evol. Biol. 16, 200-207]. However, we found the relationship continued to hold for genera with the same number of, or more, species in temperate latitudes. This finding suggests that greater rates of speciation in the tropics do not cause higher rates of molecular evolution. A third explanation is that more rapid genetic drift might have occurred in smaller tropical species populations [Stevens, G. C. (1989) Am. Nat. 133, 240-256]. However, we targeted common species to limit the influence of genetic drift, and many of the tropical species we used, despite occurring in abundant populations, had much higher rates of molecular evolution. Nonetheless, this issue is not completely resolved by that precaution and requires further examination.

Animals↗

PubMed2026

Genomic surveillance of enterovirus D68 circulating in 2025 reveals the emergence of a novel A2/B3 recombinant lineage.

Enterovirus D68 (EV-D68) has re-emerged over the past decade as a significant respiratory pathogen associated with severe respiratory disease and acute flaccid myelitis. Its circulation has typically followed a biennial pattern, with predominance in late summer and early fall, a pattern that was temporarily disrupted during the COVID-19 pandemic. Surveillance in 2025 revealed off-season circulation of EV-D68. This study describes the genomic characteristics of the 2025 EV-D68 viruses and the clinical features of affected patients. Between May and December 2025, remnant respiratory specimens positive for rhinovirus/enterovirus were screened for EV-D68 and subjected to whole-genome sequencing. Phylogenetic analyses were performed using maximum-likelihood methods. Recombination was assessed using subgenomic phylogenies, SimPlot similarity and BootScan analyses, and read-level inspection. Among 1,321 patients tested, 147 (11.1%) were EV-D68-positive, and 119 (81.0%) yielded complete genomes. EV-D68 positivity increased in July 2025, peaked in August (~21%), and remained elevated through September and October, exceeding levels observed in 2024. Patients had a median age of 36 years, with infections disproportionately affecting older adults. Phylogenetic analysis demonstrated exclusive circulation of subclade A2. Five genomes formed a distinct recombinant lineage (A2-Re). Subgenomic phylogenies showed clustering with A2 viruses in the P1 region and with B3 viruses in the P2-P3 regions. SimPlot and BootScan analyses identified a recombination breakpoint near the 2A/2B junction (~nt 3,700). The recombinant lineage was associated with temporally clustered cases in September-October. These findings demonstrate recombination between distinct EV-D68 subclades and underscore the importance of whole-genome surveillance for accurate viral characterization. Continued genomic monitoring is essential for detecting emerging variants with potential implications for transmissibility, pathogenicity, and public health preparedness.IMPORTANCEThis study highlights an increased off-season circulation of Enterovirus D68 (EV-D68) and a higher burden of disease in adults in 2025. The identification of a novel A2-B3 recombinant lineage provides evidence of ongoing viral evolution through recombination, a mechanism that may alter transmissibility, virulence, or immune responses. Detection of this lineage in temporally clustered cases suggests local transmission and underscores the potential for rapid spread of newly emerged variants. These findings emphasize the limitations of partial genomic approaches and the critical role of whole-genome sequencing in accurately characterizing circulating strains and identifying recombination events. Enhanced genomic surveillance is essential to detect emerging variants in real time, inform diagnostic assay performance, and support public health responses. Continued monitoring of EV-D68 evolution will be important for anticipating changes in disease burden, guiding clinical awareness, and strengthening preparedness for future outbreaks.

Humans↗

PubMed2005

Genome analysis of Coxiella burnetii species: insights into pathogenesis and evolution and implications for biodefense.

Coxiella burnetii, the etiological agent of Q fever, is a class B biodefense agent. We are continuing the momentum of discovery generated by the first Coxiella genome sequences by extending the breadth of genomics to include four additional heterogeneous C. burnetii strains. We are also sequencing the genome of Rickettsiella grylli, an intracellular parasite of grasshoppers and the closest known phylogenetic relative to the Coxiella group. These data will enable the investigation of fundamental questions about Coxiella pathogenicity and virulence as well as broader evolutionary questions about the transition to obligate intracellular life. Specifically, sequence comparisons will permit examination of genetic differences, allowing us to address key questions: What core genes are necessary for an obligate intracellular lifestyle and developmental cycle of the genus? What specific genetic determinants can be linked to virulence properties such as host preference, disease severity, and pathology (i.e., acute vs. chronic disease)? What are the frequencies of mutation and intragenomic recombination, and levels of genome reduction? What specific factors are relevant to colonization and virulence in human hosts (based on comparisons with R. grylli)? From a public health and biodefense perspective, exposure to different strains, either natural or due to illegitimate release, may have different outcomes. With extensive genomic-level information from diverse strains, investigators can determine effective drug and vaccine targets and design methods to accurately type Coxiella based on a subset of genes, opening the way for cost-effective targeted PCR- or antibody-based tests.

Biological Warfare↗

PubMed1982

Criteria for the emergence and evolution of life in the solar system.

During the past years we have explored most of the bodies of the solar system by means of the Apollo, Venera, Viking, Voyager, and other space missions. We are now in a better position to be able to compare the conditions of other planets and satellites with those of the Earth in order to determine what is unique about our planet which permitted the emergence and evolution of life on it. On the basis of this and other available scientific information we have arrived at the conclusion that there are at least some twentyfive specific conditions or requirements which have to be fulfilled in order for life as we know it to appear and evolve in a planetary system such as ours. Most of these necessary conditions or requirements are mutually interdependent, but in order to discuss their role in depth they have been divided into five major general areas which are discussed in some detail herein. Planetary criteria, which relate to the physical properties of the planet as it is formed and as it becomes a differentiated cosmic body and potential abode of life. The mass, orbital characteristics and energetic relationships with the central star as well as the discrete separation of gas, liquid and solid phases of the planet are of utmost importance. Chemical criteria, which are concerned with the composition, availability of effective energy sources, and chemical constraints (solvent, pH range, redox potential) of the environment(s) where reactions take place for the prebiological formation of biochemical compounds. Protobiological criteria, which relate to the prebiologically synthesized oligomeric and polymeric biomolecules, how they interact cooperatively to form protobiological structures and functions (replication, catalysis, information transfer, etc.) and self-assemble to give rise to a living system. Evolutionary criteria, which are concerned with the processes responsible for the increase in complexity of organisms by genomic multiplication, symbiotic integration and cellular differentiation, as well as with the negentropic ability of organisms to continuously recycle all the volatile biogenic elements. Altogether these processes made possible the development and evolution of life from the simplest prokaryotic cell ancestor to a cognitive and manipulative multicellular organism (man). In order to extend this inquiry to other systems beyond our solar system a fifth set of requirements based on astronomical observations is also discussed, namely, the Stellar criteria, which relate to the elemental composition mass, lifetime, and other features of Main Sequence stars which may be surrounded by planetary systems similar to our own. Finally, a brief review is made on the probability of the existence of extraterrestrial life as well as of civilizations capable of interstellar communication in our Galaxy.

Biological Evolution↗

PubMed2004

Development and evaluation of an online CO(2) evolution test and a multicomponent biodegradation test system.

Well-established biodegradation tests use biogenously evolved carbon dioxide (CO(2)) as an analytical parameter to determine the ultimate biodegradability of substances. A newly developed analytical technique based on the continuous online measurement of conductivity showed its suitability over other techniques. It could be demonstrated that the method met all criteria of established biodegradation tests, gave continuous biodegradation curves, and was more reliable than other tests. In parallel experiments, only small variations in the biodegradation pattern occurred. When comparing the new online CO(2) method with existing CO(2) evolution tests, growth rates and lag periods were similar and only the final degree of biodegradation of aniline was slightly lower. A further test development was the unification and parallel measurement of all three important summary parameters for biodegradation--i.e., CO(2) evolution, determination of the biochemical oxygen demand (BOD), and removal of dissolved organic carbon (DOC)--in a multicomponent biodegradation test system (MCBTS). The practicability of this test method was demonstrated with aniline. This test system had advantages for poorly water-soluble and highly volatile compounds and allowed the determination of the carbon fraction integrated into biomass (heterotrophic yield). The integrated online measurements of CO(2) and BOD systems produced continuous degradation curves, which better met the stringent criteria of ready biodegradability (60% biodegradation in a 10-day window). Furthermore the data could be used to calculate maximal growth rates for the modeling of biodegradation processes.

Aniline Compounds↗

PubMed2004

Evolution of cross-feeding in microbial populations.

Although limited by a single resource, microbial populations that grow for long periods in continuous culture (chemostat) frequently evolve stable polymorphisms. These polymorphisms may be maintained by cross-feeding, where one strain partially degrades the primary energy resource and excretes an intermediate that is used as an energy resource by a second strain. It is unclear what selective advantage cross-feeding strains have over a single competitor that completely degrades the primary resource. Here we show that cross-feeding may evolve in microbial populations as a consequence of the following optimization principles: the rate of ATP production is maximized, the concentration of enzymes of the pathway is minimized, and the concentration of intermediates of the pathway is minimized.

Adaptation, Physiological↗

PubMed2004

Effects of brood manipulation costs on optimal sex allocation in social hymenoptera.

In eusocial Hymenoptera, queens and workers are in conflict over optimal sex allocation. Sex ratio theory, while generating predictions on the extent of this conflict under a wide range of conditions, has largely neglected the fact that worker control of investment almost certainly requires the manipulation of brood sex ratio. This manipulation is likely to incur costs, for example, if workers eliminate male larvae or rear more females as sexuals rather than workers. In this article, we present a model of sex ratio evolution under worker control that incorporates costs of brood manipulation. We assume cost to be a continuous, increasing function of the magnitude of sex ratio manipulation. We demonstrate that costs counterselect sex ratio biasing, which leads to less female-biased population sex ratios than expected on the basis of relatedness asymmetry. Furthermore, differently shaped cost functions lead to different equilibria of manipulation at the colony level. While linear and accelerating cost functions generate monomorphic equilibria, decelerating costs lead to a process of evolutionary branching and hence split sex ratios.

Animals↗

PubMed1994

Role of the epidermal growth factor receptor and transforming growth factor alpha in mouse skin carcinogenesis.

The mouse skin model of multistage carcinogenesis continues to serve as a major in vivo model for studying the sequential and stepwise evolution of the cancer process by chemical and physical carcinogens. The initiation stage of mouse skin carcinogenesis involves genetic damage in the form of DNA adducts or initiator-induced DNA base changes. These changes ultimately lead to mutations in critical target genes of epidermal stem cells. The rasHa gene, and to a limited extent the N-ras gene, have been identified as target genes for certain tumor initiators in this model system (reviewed in DiGiovanni 1992). The promotion stage of mouse skin carcinogenesis involves the production and maintenance of a chronic state of hyperplasia and cell proliferation and ultimately the selective clonal expansion of initiated cells. The hallmark of all tumor promoters that have been adequately tested is their ability to induce a potentiated hyperplasia after several treatments that is greater than that observed after a single application. Tumor promoters produce many effects when applied topically to mouse skin. Many of the effects that occur after a single application of phorbol esters such as TPA appear to be mediated by its interaction with PKC (Nishizuka 1989). An important question is whether the activation of PKC per se is responsible for tumor promotion by TPA. Because repetitive treatments with TPA lead to a sustained loss of PKC, it is possible that other effects not mediated by PKC but produced by phorbol esters and related compounds may play an important role in the production and maintenance of chronic hyperplasia and cell proliferation in the skin and for skin tumor promotion. More attention should be placed on studying the promoting actions of other compounds outside of the most commonly studied phorbol esters. Investigations of some of these compounds already have and will continue to provide important clues regarding possible common pathways shared by diverse promoting agents. One such pathway may involve the EGFr and its ligand TGF alpha. As discussed in this review, it is now evident that many different types of promoting agents increase production of TGF alpha (Ellem et al. 1988, Pittelkow et al. 1989, Choi et al. 1991, Imamoto et al. 1991, J. DiGiovanni unpublished studies). Although many tumor promoters initially decrease the binding of 125I-EGF to EGFr in specific cell types, including mouse epidermal cells, the long-term effects of tumor promoters, especially after repetitive treatments, may be considerably different.+4

9,10-Dimethyl-1,2-benzanthracene↗