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PubMed1985

Brain theory and cooperative computation.

"Top-down" brain theory, based upon functional analysis of cognitive processes in terms of interacting schemas, is distinguished from "bottom-up" brain theory based on analysis of the dynamics of neural nets. "Cooperative computation" is proposed as the style of interaction of neural subsystems at various levels. Perceptual schemas are introduced as the building blocks for the representation of the perceived environment, and motor schemas serve as control systems to be coordinated into programs for the control of movement. A cooperative computation view of the design of machine vision systems is exemplified both by an algorithm for computing optic flow which offers interesting insights into the evolution of hierarchical neural structures, and by an analysis of knowledge representation for machine interpretation of visual scenes. The interaction between top-down analysis and detailed neural modelling is illustrated by the study of visuomotor coordination in frogs and toads.

Animals↗
PubMed1986

[Progressive motor disability in spinal muscular atrophy. Psychosocial aspects and rehabilitation in adolescents and adults].

After a description of the principal clinical patterns of spinal muscular atrophies, the Authors discuss the aetiopathogenesis, diagnosis, articular, muscular, respiratory, whole functional and psychological evaluation, premises and aims of rehabilitation of patients with progressive motor disability. Rehabilitation techniques (postural education, prescription of braces, passive and active movements, respiratory physiotherapy) are described. The Authors assume that the role and effects of treatment vary a great deal, depending on the individual case and the moments of psychological crises. Rehabilitation may delay deterioration and achieve the prevention of evolutional complications: successful results are obtained if the patients and family are given detailed instructions for treatment at home and if a relationship and a close cooperation between the patient and the physiotherapist are established. Specific information and psychological support should be provided, which will cover not only the technical aspects of rehabilitation, but also the concrete problems of daily life and of adjustment in family and society.

Adolescent↗
PubMed2004

Characterization of evolutionary rates and constraints in three Mammalian genomes.

We present an analysis of rates and patterns of microevolutionary phenomena that have shaped the human, mouse, and rat genomes since their last common ancestor. We find evidence for a shift in the mutational spectrum between the mouse and rat lineages, with the net effect being a relative increase in GC content in the rat genome. Our estimate for the neutral point substitution rate separating the two rodents is 0.196 substitutions per site, and 0.65 substitutions per site for the tree relating all three mammals. Small insertions and deletions of 1-10 bp in length ("microindels") occur at approximately 5% of the point substitution rate. Inferred regional correlations in evolutionary rates between lineages and between types of sites support the idea that rates of evolution are influenced by local genomic or cell biological context. No substantial correlations between rates of point substitutions and rates of microindels are found, however, implying that the influences that affect these processes are distinct. Finally, we have identified those regions in the human genome that are evolving slowly, which are likely to include functional elements important to human biology. At least 5% of the human genome is under substantial constraint, most of which is noncoding.

Animals↗
PubMed1992

[Cardiology in general hospitals. A cooperative survey on medical teams, technical means and activity].

A national enquiry carried out in 1990 in the departments of cardiology of general and private non-profit making hospitals established the status of these departments and the evolution of their personnel and equipment since their creation. The enquiry involved two thirds of the cardiology departments of the general hospitals (119/180) and showed that most (66%) were established between 1974 and 1988. Implanted in fairly important cities with catchment areas of 100,000 to 400,000 people, they have an average of 32 beds (range 11 to 100) and 7.25 coronary care beds (range 4 to 19); 347 doctors work full (211) or part time (136) in these departments. These two types of work are allowed in the majority of these units (64/119). Specialist certified cardiologists practice in 62 departments (56%). The usual technical equipment is available in 80% of the units (Doppler echocardiography, exercise stress testing, Holter monitoring, right heart catheterisation). Permanent pacing is performed in 65% of these hospitals, more so in the provinces than in the Paris region. Coronary angiography is only available in 21%, radioisotopic investigations in 15% and coronary angioplasty in 12% of these centres. A prospective study performed in 1990 concerning 110 hospitals recruited 1,030 myocardial infarctions, which enabled the total number of infarcts hospitalised in the coronary care units of the general hospitals to be estimated at about 21,000 (60% of French myocardial infarctions).

Angioplasty↗
PubMed2004

Long-term excretion of vaccine-derived poliovirus by a healthy child.

A child was found to be excreting type 1 vaccine-derived poliovirus (VDPV) with a 1.1% sequence drift from Sabin type 1 vaccine strain in the VP1 coding region 6 months after he was immunized with oral live polio vaccine. Seventeen type 1 poliovirus isolates were recovered from stools taken from this child during the following 4 months. Contrary to expectation, the child was not deficient in humoral immunity and showed high levels of serum neutralization against poliovirus. Selected virus isolates were characterized in terms of their antigenic properties, virulence in transgenic mice, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin type 1 strain. The VDPV isolates showed mutations at key nucleotide positions that correlated with the observed reversion to biological properties typical of wild polioviruses. A number of capsid mutations mapped at known antigenic sites leading to changes in the viral antigenic structure. Estimates of sequence evolution based on the accumulation of nucleotide changes in the VP1 coding region detected a "defective" molecular clock running at an apparent faster speed of 2.05% nucleotide changes per year versus 1% shown in previous studies. Remarkably, when compared to several type 1 VDPV strains of different origins, isolates from this child showed a much higher proportion of nonsynonymous versus synonymous nucleotide changes in the capsid coding region. This anomaly could explain the high VP1 sequence drift found and the ability of these virus strains to replicate in the gut for a longer period than expected.

Animals↗
PubMed2000

The evolution of happiness.

An evolutionary perspective offers novel insights into some major obstacles to achieving happiness. Impediments include large discrepancies between modern and ancestral environments, the existence of evolved mechanisms "designed" to produce subjective distress, and the fact that evolution by selection has produced competitive mechanisms that function to benefit one person at the expense of others. On the positive side, people also possess evolved mechanisms that produce deep sources of happiness: those for mating bonds, deep friendship, close kinship, and cooperative coalitions. Understanding these psychological mechanisms--the selective processes that designed them, their evolved functions, and the contexts governing their activation--offers the best hope for holding some evolved mechanisms in check and selectively activating others to produce an overall increment in human happiness.

Adaptation, Psychological↗
PubMed1996

A zinc finger-like domain of the molecular chaperone DnaJ is involved in binding to denatured protein substrates.

The Escherichia coli heat-shock protein DnaJ cooperates with the Hsp70 homolog DnaK in protein folding in vitro and in vivo. Little is known about the structural features of DnaJ that mediate its interaction with DnaK and unfolded polypeptide. DnaJ contains at least four blocks of sequence representing potential functional domains which have been conserved throughout evolution. In order to understand the role of each of these regions, we have analyzed DnaJ fragments in reactions corresponding to known functions of the intact protein. Both the N-terminal 70 amino acid 'J-domain' and a 35 amino acid glycine-phenylalanine region following it are required for interactions with DnaK. However, only complete DnaJ can cooperate with DnaK and a third protein, GrpE, in refolding denatured firefly luciferase. As demonstrated by atomic absorption and extended X-ray absorption fine structure spectroscopy (EXAFS), the 90 amino acid cysteine-rich region of DnaJ contains two Zn atoms tetrahedrally coordinated to four cysteine residues, resembling their arrangement in the C4 Zn binding domains of certain DNA binding proteins. Interestingly, binding experiments and cross-linking studies indicate that this Zn finger-like domain is required for the DnaJ molecular chaperone to specifically recognize and bind to proteins in their denatured state.

Absorptiometry, Photon↗
PubMed2000

Heat shock proteins in human cancer.

The heat shock proteins (hsp) are ubiquitous molecules induced in cells exposed to sublethal heat shock, present in all living cells, and highly conserved during evolution. Their function is to protect cells from environmental stress damage by binding to partially denatured proteins, dissociating protein aggregates, to regulate the correct folding, and to cooperate in transporting newly synthesized polypeptides to the target organelles. The molecular chaperones are involved in numerous diseases, including cancer, revealing changes of expression. In this review, we mainly describe the relationship of hsp expression with human cancer, and discuss what is known about their post-translational modifications according to malignancies.

Animals↗
PubMed2001

Heterogeneity stabilizes reciprocal altruism interactions.

In considering the phenomena of reciprocal altruism few would dispute that there are differences in individual quality-in particular, that for some individuals, at least on occasion, the cost of doing favors will exceed the potential of future benefits. That is, at any given time, a typical population is heterogeneous with respect to the affordability of reciprocal altruism. However, methodological limitations of the traditional analytical framework-Single Type (symmetric) Evolutionary Game Theory-have restricted previous analytical efforts to addressing populations idealized in terms of their averages. Here we use the methods of Multitype Evolutionary Game Theory to analyse the role of individual differences in direct reciprocity interactions. Multitype analysis shows that non-idealized populations possess an ESS profile wherein individuals who cannot afford reciprocity (low-quality) defect, while individuals who derive net benefits from reciprocity (high-quality) cooperate. Furthermore, this cooperation is implemented via unmodified tit-for-tat (TfT) strategy. Hence, our results may help resolve a long-standing problem concerning the evolutionary stability of TfT in direct reciprocal altruism. Finally, this difference between idealized and real populations is not restricted to direct reciprocal cooperation. Previously (Lotem et al., 1999) we have demonstrated evolutionarily stable indirect reciprocal cooperation among high-quality individuals in heterogeneous populations.

Altruism↗
PubMedDate not supplied

An odyssey in search of a cure: the evolution of treatment of childhood acute lymphoblastic leukemia in the United Kingdom.

This review charts the evolution of therapy for childhood acute lymphoblastic leukaemia (ALL) in the United Kingdom. The present chemotherapeutic regimen is the result of experience gained from carefully planned randomised cooperative studies carried out during the last two decades. In common with the experience of the West German and American groups, the best results have been in those treated with post remission intensification blocks. With current chemotherapy protocols, almost 70% of children with ALL in U.K. can be cured but there may be a medical cost of such a cure, in terms of both acute and long term toxicity. This was especially true when central nervous system (CNS) therapy with cranial irradiation was used. Therefore present regimens are examining chemotherapeutic options for CNS disease control and the efficacy of additional post remission intensification. Failure of chemotherapy is most often seen in those children with a presenting white cell count of more than 50 x 10(9)/l, very young children and/or the presence of certain chromosomal rearrangements (e.g. t4: 11, t9: 22). At present the optimum therapeutic option for such high risk patients and for the majority of those in second remission, is an allogenic bone marrow transplant if an HLA-matched sibling is available. Modern day therapy is both complicated and costly and will be beyond the resources available for most children with ALL in developing countries. A significant decrease in worldwide mortality due to ALL will only occur if either the disease can be prevented or a simpler cure devised.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Inhibition of SK cell activity in frogs by certain drugs and sugars.

We present similarities between mammalian natural killer (NK) cells and (anuran amphibian) frog spontaneous killer (SK) cells. A cytotoxic assay utilizing allogeneic erythrocytes as target cells was used and lysis assessed by measuring release of hemoglobin. SK effector cells, just as mammalian NK cells, are not sensitive to cycloheximide nor most simple sugars (50 mM glucose, glucose-6-phosphate, galactose, fucose, mannose). However, SK activity is inhibited by chloroquine, colchicine and mannose-6-phosphate. When SK cells were co-incubated with mammalian tumor cells, they were able to lyse only the NK-sensitive target YAC-1, but not other mammalian tumor cell targets including K562, Molt-4, Raji, P815 and EL4. Lysis of YAC-1 cells was also inhibited by colchicine and chloroquine. These results allow speculation on the evolution of cell mediated cytotoxicity since natural cytotoxic cells are present in ectothermic vertebrates.

Animals↗
PubMedDate not supplied

Evolving public perceptions of spaceflight in American culture.

There is a belief that exists in the United States about public support for NASA's activities. The belief is almost universally held that NASA and the cause of space exploration enjoyed outstanding public support and confidence in the 1960s during the era of Apollo and that public support waned in the post-Apollo era, only to sink to quite low depths in the decade of the 1990s. These beliefs are predicated on anecdotal evidence that should not be discounted, but empirical evidence gleaned from public opinion polling data suggest that some of these conceptions are totally incorrect and others are either incomplete or more nuanced than previously believed. This paper explores evolution of public support for space exploration since the 1960s. Using polling data from a variety of sources it presents trends over time and offers comments on the meaning of public perceptions for the evolution of space policy and the development of space exploration in the United States.

International Cooperation↗
PubMed2000

Cooperative thermal denaturation of proteins designed by binary patterning of polar and nonpolar amino acids.

We previously reported a combinatorial strategy for designing alpha-helical proteins by assigning only the binary patterning of polar or nonpolar residues [Kamtekar, S., Schiffer, J. M., Xiong, H. Y., Babik, J. M., and Hecht, M. H. (1993) Science 262, 1680-1685]. Here we describe the finding that approximately half of the proteins in the original collection display some level of cooperativity in their thermal denaturation profiles. Many are monomeric in solution, demonstrating that the observed cooperativity is not merely a consequence of oligomerization. These findings demonstrate that although the combinatorial nature of the design strategy precludes explicit design of side-chain packing, binary patterning incorporates sufficient sequence information to generate de novo proteins with cooperatively folded structures. As binary partitioning of polar and nonpolar amino acids is an intrinsic part of the genetic code, these findings may bear on the early evolution of native proteins.

Allosteric Regulation↗
PubMed2001

Intergroup collaboration in ovarian cancer: the Gynecologic Cancer Intergroup (GCIG).

Randomized clinical trials are considered the definitive source of evidence for guiding decisions in clinical practise. In patients with ovarian cancer many of the randomized trials from the 1970s and 1980s did not have the statistical power to detect realistic and clinically important differences. Therefore, evolution of so-called "optimal therapy" has been rather slow and some important questions have gone unanswered. In order to overcome this challenge, representatives of different Cooperative Groups started an Ovarian Cancer Trials Intergroup Network in the mid 1990s, as a vehicle to develop future trial collaboration and as a mechanism for communication about strategic directions of phase I/II trials within individual Groups. In 1997 this network became more formalized, going beyond ovarian cancer as a single focus, and the Gynecologic Cancer Intergroup (GCIG) was created. At present GCIG includes representatives of 12 Cooperative Groups and the NCI-US, and functions as a forum for development of global trial collaborations, which hopefully will answer important questions in a more timely fashion and make them more rapidly available for the oncologic community.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[Phylogenetics of the immunosystem].

The human immune system is composed of two closely cooperating entities: innate, "unspecific" immune defense on one hand and adaptive, "specific" immunity on the other. Innate immune defense mechanisms were already developed very early in the evolution of the animal kingdom. By contrast, adaptive immunity exclusively evolved in jawed vertebrates within a surprisingly short time span. New data especially from genome sequencing projects now allow first glimpses on those events that resulted in the formation of adaptive immunity.

Animals↗
PubMed2001

Theory for normal and impaired experience-dependent plasticity in neocortex of adult rats.

We model experience-dependent plasticity in the cortical representation of whiskers (the barrel cortex) in normal adult rats, and in adult rats that were prenatally exposed to alcohol. Prenatal exposure to alcohol (PAE) caused marked deficits in experience-dependent plasticity in a cortical barrel-column. Cortical plasticity was induced by trimming all whiskers on one side of the face except two. This manipulation produces high activity from the intact whiskers that contrasts with low activity from the cut whiskers while avoiding any nerve damage. By a computational model, we show that the evolution of neuronal responses in a single barrel-column after this sensory bias is consistent with the synaptic modifications that follow the rules of the Bienenstock, Cooper, and Munro (BCM) theory. The BCM theory postulates that a neuron possesses a moving synaptic modification threshold, theta(M), that dictates whether the neuron's activity at any given instant will lead to strengthening or weakening of its input synapses. The current value of theta(M) changes proportionally to the square of the neuron's activity averaged over some recent past. In the model of alcohol impaired cortex, the effective theta(M) has been set to a level unattainable by the depressed levels of cortical activity leading to "impaired" synaptic plasticity that is consistent with experimental findings. Based on experimental and computational results, we discuss how elevated theta(M) may be related to (i) reduced levels of neurotransmitters modulating plasticity, (ii) abnormally low expression of N-methyl-d-aspartate receptors (NMDARs), and (iii) the membrane translocation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in adult rat cortex subjected to prenatal alcohol exposure.

Action Potentials↗