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PubMedDate not supplied

Neuronal differentiation of mouse embryonic stem cells: lineage selection and forced differentiation paradigms.

Primitive embryonic stem cells are an ideal starting cell population for studies of gene expression and lineage segregation during development. Despite their potential, it has been difficult to determine culture conditions that cause single-lineage differentiation of these pluripotent cells. Both genetic and epigenetic approaches have been taken to promote neuronal differentiation of embryonic stem cells, including aggregation, exposure to the nonspecific teratogen/morphogen retinoic acid, low-density culture, exposure to growth/differentiation factors, and forced differentiation following expression of lineage-restricted "developmental control" genes. In the current investigation, a hybrid approach involving genetic techniques of "lineage selection" or "forced differentiation" has been employed to develop primitive neural progenitor cell lines. These lines form an important starting point to examine the cascades of gene expression (and inhibition) during neuronal and glial lineage segregation, to study growth factor effects on neural differentiation, and ultimately to provide a source of cells for transplantation to a damaged nervous system.

Animals↗

PubMed1992

Strains and forces in selected carpal ligaments during in vitro flexion and deviation movements of the hand.

The forces induced in tiny wrist joint ligaments must be estimated in order to understand their role in the mechanism of the joint. We estimated forces in a number of selected ligaments in seven human wrist joint specimens, using a noninvasive method. The method is based on the rationale that the force generated in a ligament depends on its change of length with the joint under load. In vitro length changes of the ligaments were determined during flexion and deviation movements of the hand, using a roentgenstereophotogrammetric analysis technique. Subsequently, bone-ligament-bone (BLB) preparations were dissected from the specimens. From these BLB preparations the zero-force length and the force-elongation relationship were determined in a material testing machine. The forces generated in the ligaments during flexion and deviation were calculated by combining results on the in vitro ligament length changes, the zero-force length, and the force-elongation relationship. Large interspecimen variations of the force patterns were found. Due to this variability, it is not possible to obtain quantitative models for the kinetic behavior of the ligaments. However, qualitative trends could be distilled from the strain and force patterns. It is clear that for most ligaments, the zero-force lengths were not equal to the lengths they possessed in the neutral position of the hand. Furthermore, it could be shown which motions of the hand would most likely strain a particular ligament. It could be shown that the variations in the force patterns originate mainly from variations in the zero-force lengths, and from variations in the force-strain relationship between specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1980

Serum cholesterol levels in selected air force cadets compared with levels in the West Point study.

In the USAFSAM Cardiovascular Disease Followup Study, the surprising rise in average cholesterol levels in West Point cadets during the 6 years following their entry into the U.S. Military Academy in 1952 implied a significant increase in risk of heart disease in later years. To ascertain whether that pattern of change suggested increased risk is characteristic of cadets at military academies, a similar study on a smaller scale was conducted on U.S. Air Force Academy cadets beginning in 1972. Randomly selected cadets were monitored throughout their 4-year training at the U.S. Air Force Academy. Mean levels of serum cholesterol were similar at the beginning and end of the study; values between those times were generally somewhat lower. Average body fat never exceeded 12.6%; the average remained close to 12% during the last 3 years. Possible reasons for the differences between the pattern of change in serum cholesterol in the West Point cadets in earlier years (1952-56) and in the U.S. Air Force Academy cadets are discussed. Differences in exercise or stress levels were ruled out as likely explanations. Changes in dietary fat intakes may account for the differences, while unidentified changes in the social environment are possible contributory factors.

Adolescent↗

PubMed2006

'SOSORT consensus paper on brace action: TLSO biomechanics of correction (investigating the rationale for force vector selection)'.

BACKGROUND: The effectiveness of orthotic treatment continues to be controversial in international medical literature due to differences in the reported results and conclusions of various studies. Heterogeneity of the samples has been suggested as a reason for conflicting results. Besides the obvious theoretical differences between the brace concepts, the variability in the technical factors can also explain the contradictory results between same brace types. This paper will investigate the degree of variability among responses of scoliosis specialists from the Brace Study Ground of the International Society on Scoliosis Orthopedic and Rehabilitation Treatment SOSORT. Ultimately, this information could be a foundation for establishing a consensus and framework for future prospective controlled studies. METHODS: A preliminary questionnaire on the topic of 'brace action' relative to the theory of three-dimensional scoliosis correction and brace treatment was developed and circulated to specialists interested in the conservative treatment of adolescent idiopathic scoliosis. A particular case was presented (main thoracic curve with minor lumbar). Several key points emerged and were used to develop a second questionnaire which was discussed and full filed after the SOSORT consensus meeting (Milano, Italy, January 2005). RESULTS: Twenty-one questionnaires were completed. The Chêneau brace was the most frequently recommended. The importance of the three point system mechanism was stressed. Options about proper pad placement on the thoracic convexity were divided 50% for the pad reaching or involving the apical vertebra and 50% for the pad acting caudal to the apical vertebra. There was agreement about the direction of the vector force, 85% selecting a 'dorso lateral to ventro medial' direction but about the shape of the pad to produce such a force. Principles related to three-dimensional correction achieved high consensus (80%-85%), but suggested methods of correction were quite diverse. CONCLUSION: This study reveals that among participating SOSORT specialists there continues to be a strongly held and conflicting if not a contentious opinion regarding brace design and treatment. If the goal of a 'treatment consensus' is realistic and achievable, significantly more effort will be required to reconcile these differences.

Journal Article↗

PubMed1994

Envelope sequence variation, neutralizing antibodies, and primate lentivirus persistence.

Studies in ungulate lentivirus systems clearly indicate that neutralization escape variants emerge over time in chronically infected animals. Studies in the EIAV system, in particular, have provided strong evidence that the humoral branch of the immune system is at least one selective force acting on an array of viral variants. In previous studies with the ungulate lentiviruses, molecularly cloned virus was never used, and plaque-purified virus was only sometimes used; the genetic determinants responsible for antigenic variation and immune selection were not determined. While molecular clones are available for HIV-1, immune selection studies have been hampered in this system by the fact that HIV-1 is infectious only for chimpanzees, which do not develop disease and are available in only limited numbers. Experiments on immune selection in humans are generally complicated by lack of knowledge on the time of infection and the genetic make-up of the infecting virus. Our studies on SIV immune selection summarized in this review provide definitive evidence that neutralization-resistant variants emerge in an individual during persistent infection by primate lentiviruses. By cloning viral envelope genes from rhesus monkeys over time and obtaining sequential serum samples from them, we have been able to study not only the evolution of envelope sequences but also the emergence of neutralization-resistant variants. Reciprocal neutralization studies were performed using parental and variant specific sera, and immune selection was demonstrated using molecularly cloned virus of defined sequence. During the course of persistent infection with SIV and HIV, there is clear selective pressure for change in discrete variable regions of envelope. The host neutralizing antibody response appears to be at least one of the selective forces driving sequence change in envelope since one result of the sequence variation is the emergence of neutralization escape mutants. This indicates that neutralizing antibodies do serve to limit HIV and SIV replication during the lengthy asymptomatic stage of infection. The coincidence of neutralization domains of HIV and/or SIV with variable regions V1, V2, V3, V4, V5, and V6 suggests a direct relationship between neutralization domains and the emergence of sequence variants. However, different selective forces may be responsible all or in part for driving sequence changes in some variable domains (summarized in Table 2). For example, alterations in cell and/or tissue tropism may be responsible at least in part for driving change in V3 and the cytotoxic T-lymphocyte response may be responsible for driving change in the signal peptide (V0; Henderson et al. 1992; Wei and Cresswell 1992).(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed1996

U.S. Air Force pilot selection tests: what is measured and what is predictive?

Selection of military pilots has long included the use of multiple aptitude test batteries. Although the names and appearances of the tests used in pilot selection vary, most are to a large extent measures of general cognitive ability, or g. This is consistent with the central role played by cognitive ability measures in the prediction of numerous job training (r = 0.43) and performance (r = 0.34) criteria. Measures of specific cognitive abilities (e.g., verbal, quantitative, spatial, perceptual speed) have shown little incremental validity beyond g (increase in correlation of about 0.02). The incremental validity, beyond g, of measures of pilot job knowledge (e.g., aviation concepts, instruments, principles and terms; increase in correlation beyond g of about 0.08), psychomotor abilities, and personality scores (increase in correlation beyond g between 0.02 and 0.04) also has been small, but significant. The unavoidable requirement to reason in responding to test material causes g to be measured. In broad-ability-range samples, the positive correlations of the measures demonstrate that general cognitive ability is always present as a higher-order factor. Future measures of pilot aptitude may include tests based on cognitive components, chronometric methods, neural conductive velocity, or other methods. These measures, despite their appearance, have been shown to mostly measure g. Subsequently, we expect that future U.S. Air Force pilot selection tests will mostly be measures of g and will, therefore, continue to be predictive of performance.

Cognition↗

PubMed1992

A stochastic evolutionary model of molecular sequences.

A stochastic evolutionary model of molecular sequences is proposed. The basic forces in evolution are supposed to be mutation and selection. The concept is somewhat similar to Kauffman-Levin's concept of adaptive walks and corresponding analytical expressions have been developed. The selective force is divided into two parts: a slowly-varying part and a rapidly-changing fluctuation. The latter influences the distribution of sequences and results in an equation of motion along the flow line. The former plays a more important role in the emergence of evolutionary order. It is demonstrated that the asymmetry of selective forces would lead to a definite order of the system.

Animals↗

PubMed1999

The evolution of viruses, the emergence of viral diseases: a synthesis that Martinus Beijerinck might enjoy.

The relentless production of viral variants and their selection for improved "fit" are seen from the perspective of the infectious disease sciences as ever-changing viral phenotypes and emerging disease risks. In the Darwinian cause:effect equation, we can characterize very well the effects of mutation and selection--these are catalogued as new viral phenotypes or pathotypes. However, the selective forces themselves driving such changes remain rather mysterious. Many selective forces must be at work, acting on the virus, the host, the host population and the environment. In some instances the virus seems to test new unoccupied niches in the absence of any apparent environmental change, but usually it is clear that changes are driven by human activity. Most important must be the ever increasing density of human, domestic animal and crop plant populations and the consequent increased opportunities for transmission of viral variants. Also important must be the great changes affecting all ecosystems--these especially favor the emergence of new zoonotic viruses and viral "species jumpers." The great increase in human travel and transport carries exotic viruses, vectors and hosts around the world, again favoring viral occupation of new niches. The rise of bioterrorism adds yet another threat. Increasing numbers of emerging viral disease episodes seem to be linked to a decline in global resources for proven public health programs, agricultural extension programs, and the like, programs that have stood in the way of the spread and evolution of viral pathogens. If the relationship between viral evolution and the emergence of new viral diseases is rooted firstly in the host and the host population, then more research and resources must be directed to intervention at these levels rather than at the level of the viruses themselves.

Animals↗

PubMed1983

Correlation of myoelectric activity and muscle force during selected cat treadmill locomotion.

The purpose of this investigation was to associate the force produced by the cat medial gastrocnemius (MG) during unrestrained treadmill locomotion with the corresponding myoelectric signals (MES's). An intervention analysis based on the autoregressive-integrated moving average (ARIMA) process was performed on records obtained at treadmill speeds of 0.67 ms-1 and 2.24 ms-1. Results indicate that the pattern of MG myoelectric activity during a single step cycle may be divided into two parts. The primary burst (E1 burst) of activity occurs before foot contact and represents an energy build up which is related to a major part of the MG force monitored at the tendon. During stance, a second burst of activity is depicted by an almost critically damped second order system, and is responsible for the residual tension observed. Thus in vivo forces can be linked to MES's provided that phase differences between electrical and mechanical responses are taken into account.

Animals↗

PubMed2005

The effect of selected macro forces on the contemporary social construction of American Indian ethnic identity.

This article explains selected historical acts and events that continue to impact comtemporary Native American ethnic identity, social policy, and social services delivery. Although cultural competence is increasingly encouraged in social work education, the events of history usually do not appear as partial explanations for current phenomena. For those who work with Native American populations, understanding this history is a critical piece in the process of acquiring cultural competence. These selected historical events provide at least partial understanding of some contemporary issues which are sometimes presented to social workers and other social services professionals who work with Native populations.

Acculturation↗

PubMed2002

Evolution of ageing.

Explaining why ageing occurs is a solution to the longstanding enigma of the role of senescence in nature. Even after half a century of progress, this solution continues to unfold. Evolution theory argues strongly against programmed ageing, suggesting instead that organisms are programmed for survival, not death. In the current view, ageing results from the twin principles that (i) the force of natural selection declines with age, and (ii) longevity requires investments in somatic maintenance and repair that must compete against investments in growth, reproduction and activities that might enhance fitness. In addition to explaining why ageing occurs, the evolutionary theory also provides insight into the mechanisms underlying the complex cellular and molecular changes that contribute to senescence, as well as an array of testable predictions. Some of the most interesting current problems are to understand how the genetic factors influencing ageing and longevity are predicted to respond to fluctuating environments, such as temporary periods of famine, as well as to other kinds of spatial and/or temporal heterogeneity. Rapid progress in human genomics raises the prospect of greatly increasing our knowledge of the determinants of human longevity. To make progress in understanding the role and evolution of genetic and non-genetic factors in human longevity, we need more detailed theoretical studies of how intra-population variables, such as socio-economic status, influence the selection forces that shape the life history.

Aged↗

PubMed2002

Potassium-selective atomic force microscopy on ion-releasing substrates and living cells.

A new method for simultaneous mapping of cell topography and ion fluxes was developed. A highly sensitive ion sensor system was generated by coating atomic force microscopy tips with a PVC layer containing valinomycin, an ionophore for potassium. The activity of specific ions was traced on artificial ion-releasing PVC substrates. A boundary potential was generated owing to the selective exchange of a specific ion between coated tip and ion-releasing substrate. The boundary potential was detectable as a force induced by ion-selective electrostatic interactions. The selectivity coefficient of valinomycin for potassium against sodium (K(K,Na)f) was -2.5 +/- 0.5. Potassium efflux was measured on living MDCK-F1 cells expressing BK(Ca) channels. We could demonstrate localized areas of high potassium concentrations at the cell surface. The potassium efflux could be reversibly inhibited by thapsigargin, which is known to inhibit the efflux of potassium from BK(Ca) channels by suppression of calcium ATPase.

Biosensing Techniques↗

PubMed2005

Homogeneity of common cosmopolitan inversion frequencies in Southeast Asian Drosophila melanogaster.

East Asian Drosophila melanogaster are known for great variation in morphological and physiological characters among populations, variation that is believed to be maintained by genetic drift. To understand the genetic properties of Asian D. melanogaster populations, we initiated a population genetic study of chromosome inversion polymorphisms in hitherto unanalysed population samples from Southeast (SE) Asia. We generally found a high frequency of each of the four common cosmopolitan inversions in comparison to populations from Africa, Asia, and Australia. In contrast to the great phenotypic variation among Asian populations, however, we could not detect differences in inversion frequencies among populations. Furthermore, we observed neither correlations of inversion frequencies with population latitude and longitude, nor evidence for linkage disequilibrium between different inversion loci. We propose two explanations for the observed genetic homogeneity among these SE Asian D. melanogaster populations: (i) the observed pattern simply reflects the retention of ancestral polymorphisms originating from a panmictic population that was once present on a large single landmass (Sundaland), and/or is a consequence of high recent gene flow between populations; and (ii) it is caused by selective forces (e.g. balancing selection).

Animals↗

PubMed2006

The biology and evolution of music: a comparative perspective.

Studies of the biology of music (as of language) are highly interdisciplinary and demand the integration of diverse strands of evidence. In this paper, I present a comparative perspective on the biology and evolution of music, stressing the value of comparisons both with human language, and with those animal communication systems traditionally termed "song". A comparison of the "design features" of music with those of language reveals substantial overlap, along with some important differences. Most of these differences appear to stem from semantic, rather than structural, factors, suggesting a shared formal core of music and language. I next review various animal communication systems that appear related to human music, either by analogy (bird and whale "song") or potential homology (great ape bimanual drumming). A crucial comparative distinction is between learned, complex signals (like language, music and birdsong) and unlearned signals (like laughter, ape calls, or bird calls). While human vocalizations clearly build upon an acoustic and emotional foundation shared with other primates and mammals, vocal learning has evolved independently in our species since our divergence with chimpanzees. The convergent evolution of vocal learning in other species offers a powerful window into psychological and neural constraints influencing the evolution of complex signaling systems (including both song and speech), while ape drumming presents a fascinating potential homology with human instrumental music. I next discuss the archeological data relevant to music evolution, concluding on the basis of prehistoric bone flutes that instrumental music is at least 40,000 years old, and perhaps much older. I end with a brief review of adaptive functions proposed for music, concluding that no one selective force (e.g., sexual selection) is adequate to explaining all aspects of human music. I suggest that questions about the past function of music are unlikely to be answered definitively and are thus a poor choice as a research focus for biomusicology. In contrast, a comparative approach to music promises rich dividends for our future understanding of the biology and evolution of music.

Animal Communication↗

PubMed2005

Thermodynamics and information in aging: why aging is not a mystery and how we will be able to make rational interventions.

Currently, the aging research field lacks consensus in its focus and methodology. Foundational principles, such as the evolutionary origins and physiological definition of aging, remain controversial. The aim of this paper is to resolve these issues. By applying the concepts of thermodynamics and information in an evolutionary context, the aging phenotype can be derived from first principles. Life uses information storage to maintain its distance from thermodynamic equilibrium. Since it is impossible to make any process 100% efficient, a selective force (i.e., natural selection) is needed to maintain the information's viability. Natural selection operates upon generations, and for reasons discussed subsequently, the somatic body cannot implement an analogous selective process. The aging phenotype we see can be derived from this model along with a number of insights that will enhance our ability to make intelligent and rational interventions.

Aging↗

PubMed2025

Recurrent Evolutionary Innovations in Rodent and Primate Schlafen Genes.

SCHLAFEN proteins are a large family of RNase-related enzymes carrying essential immune and developmental functions. Despite these important roles, Schlafen genes display varying degrees of evolutionary conservation in mammals. While this appears to influence their molecular activities, a detailed understanding of these evolutionary innovations is still lacking. Here, we used in-depth phylogenomic approaches to characterize the evolutionary trajectories and selective forces shaping mammalian Schlafen genes. We traced lineage-specific Schlafen amplifications and found that recent duplicates evolved under distinct selective forces, supporting repeated subfunctionalization cycles. Codon-level natural selection analyses in primates and rodents identified recurrent positive selection over Schlafen protein domains engaged in viral interactions. Combining known crystal structures and predicted protein structures, we discovered a novel class of rapidly evolving residues enriched at the contact interface of SCHLAFEN protein dimers. Our results suggest that inter-SCHLAFEN compatibilities are under strong selective pressures and are likely to impact their molecular functions. We posit that cycles of genetic conflicts with pathogens and between paralogs drove Schlafens' recurrent evolutionary innovations in mammals.

Animals↗

PubMed2004

Coadsorption and surface forces for selective surfaces in contact with aqueous mixtures of oppositely charged surfactants and low charge density polyelectrolytes.

The coadsorption of a positively charged polyelectrolyte (with 10% of the segments carrying a permanent positive charge, AM-MAPTAC-10) and an anionic surfactant (sodium dodecyl sulfate, SDS) on silica and glass surfaces has been investigated using optical reflectometry and a noninterferometric surface force technique. This is a selective coadsorption system in the sense that the polyelectrolyte does adsorb to the surface in the absence of surfactant, whereas the surfactant does not adsorb in the absence ofpolyelectrolyte. It is found that the total adsorbed amount goes through a maximum when the SDS concentration is increased. Maximum adsorption is found when the polyelectrolyte/surfactant complexes formed in bulk solution are close to the charge neutralization point. Some adsorption does occur also when SDS is present in significant excess. The force measured between AM-MAPTAC-10-coated surfaces on approach in the absence of SDS is dominated at long range by an electrostatic double-layer force. Yet, layers formed by coadsorption from solutions containing both polyelectrolyte and surfactant generate long-range forces of an electrosteric nature. On separation, adhesive interactions are found only when the adsorbed amount is low, i.e., in the absence of SDS and in a large excess of SDS. The final state of the adsorbed layer is found to be nonhysteretic, i.e., independent of the history of the system. The conditions for formation of long-lived trapped adsorption states from mixed polymer-surfactant solutions are discussed.

Journal Article↗

PubMed1999

The role of interelement selection in Saccharomyces cerevisiae Ty element evolution.

Retrotransposons are mobile genetic elements that are ubiquitous components of eukaryotic genomes. The evolutionary success of retrotransposons is explained by their ability to replicate faster than the host genomes in which they reside. Elements with higher rates of genomic replication possess a selective advantage over less active elements. Retrotransposon populations, therefore, are shaped largely by selective forces acting at the genomic level between elements. To evaluate rigorously the effects of selective forces acting on retrotransposons, detailed information on the patterns of molecular variation within and between retrotransposon families is needed. The sequencing of the Saccharomyces cerevisiae genome, which includes the entire genomic complement of yeast retrotransposons, provides an unprecedented opportunity to access and analyze such data. In this study, we analyzed in detail the patterns of nucleotide variation within the open reading frames of two parental (Ty1 and Ty2) and one hybrid (Ty1/2) family of yeast retrotransposons. The pattern and distribution of nucleotide changes on the phylogenetic reconstructions of the three families of Ty elements reveal evidence of negative selection on both internal and external branches of the Ty phylogenies. These results indicate that most, if not all, Ty elements examined represent active or recently active retrotransposon lineages. We discuss the relevance of these findings with respect to the coevolutionary dynamic operating between genomic element populations and the host organisms in which they reside.

Databases, Factual↗