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What happened in the origin of human consciousness?

At some point in its evolutionary history, our species Homo sapiens ceased to be a nonlinguistic, nonsymbolic organism, living in the world as presented to it by Nature, and instead began to exist in a world that it reconstructs in its own mind. Most scientists since Darwin have been content to explain this extraordinary transformation in human consciousness by the operation of natural selection. However, the human fossil and archaeological records indicate that modern human symbolic consciousness is not the culmination of the long trend that natural selection would predict. Instead, it shows that major change in the human past has been episodic and rare and that, as far as can be determined from the archaeological record, the passage from nonsymbolic to symbolic cognition is a recent event as well as an unprecedented one. So recent, indeed, that it significantly postdates the acquisition of modern human anatomy as expressed in skeletal structure. It, thus, appears most likely that the biological (neural) capacity underwriting the radically new behavioral mode arose as an incidental exaptation in the same process that produced the new skeletal structure of Homo sapiens, but that it lay unexpressed until it was "discovered" by means of a cultural innovation, plausibly the invention of language. As in the case of the modern anatomical structure, it appears that the new capacity was initially expressed in Africa and that its various behavioral potentials were sequentially discovered in a drawn-out process that is continuing today. An "accidental" origin of the human capacity helps understand why so many human behaviors have proven self-destructive and contradictory, a feature of our species that reductionist, selection-based scenarios are hard-put to explain.

Animals↗

Effect of corazonin and crustacean cardioactive peptide on heartbeat in the adult American cockroach (Periplaneta americana).

Changes in the frequency of cardiac pulsations have been monitored in the decapitated body of adult P. americana before and 5 h after the injections of [Arg(7)]-corazonin and CCAP, using newly invented touch-free, noninvasive optocardiographic methods. Relatively large dosages of these peptides (10(-6) M concentrations in the body) had no effect on the rate of the heartbeat beyond the Ringer control limits. It has been concluded, therefore, that Corazonin and CCAP, which are currently cited in the literature as "the most potent cardiostimulating peptides" in insects, have no effect on the physiological regulation of cardiac functions in the living body.

Animals↗

Gleanings of a chemiosmotic eye.

In 1961, an inventive Englishman, named Peter Mitchell, proposed a radically novel hypothesis to explain how energy is conserved during respiration and photosynthesis, and applied to the generation of ATP and other kinds of functional work. The chemiosmotic hypothesis sparked an intense controversy that lasted for 15 years. Today, Mitchell's conception of proton currents and their role in phosphorylation and active transport is generally accepted, and has ramified into many corners of cellular physiology. His most profound contribution may have been to introduce spatial direction into biochemistry, and thereby transform our perception of the relationship between molecules and cells.

Bacteria↗

The transcriptome: malariologists ride the wave.

The Plasmodium falciparum genome-sequencing project has provided malariologists with vast amounts of new information pertinent to a multitude of cellular processes that previously were only guessed about. In exploring this morass of predicted genes and proteins, there is now a danger of simply re-inventing the cell. Fortunately, new global transcriptional analyses reassure malariologists that they are not dealing with just "any old cell." The informative papers on the plasmodial transcriptome by Le Roch et al. (2003)1 and Bozdech et al. (2003)2 discussed below forge a bridge between the genomics and proteomics of P. falciparum. They are likely to act as a fulcrum upon which much future research will turn: for example, the study of regulation and feed-back loops.

Animals↗

Harnessing the potential of chemical defenses from antimicrobial activities.

Resistance to the drugs used in the treatment of many infectious diseases is increasing, while microbial infections are being found to be responsible for more life-threatening diseases than previously thought. Despite a large investment in the invention and application of high-throughput screening techniques involving miniaturization and automation, and a diverse array of strategies for designing and constructing various chemical libraries, relatively few new drugs have resulted. Natural products, however, have been a major source of drugs for centuries. Since some of them are produced by organisms as a result of selection in favour of improved defense against competing deleterious microorganisms, in principle they would be less likely to incur resistance. Furthermore, the production of those defensive secondary metabolites is inducible because their original function is a response to environmental challenges. Moreover, symbioses, co-habitation associations between two or more different species of organisms, are universal in nature, and the production of secondary metabolites by symbiotic microbes may be an important adaptation allowing microbes to affect their hosts. Therefore, co-culture strategies, using combinations of plant cell-pathogenic microbes, plant cell-endophytes (or symbionts), and symbiont-pathogenic microbes, based on the principles of chemical defense and the known mechanisms of organism interactions, may be an efficient general approach in the search for new anti-microbial drugs.

Animals↗

recA mutants of E. coli K12: a personal turning point.

A first year graduate student, Ann Dee Margulies, changed my research career in 1962 by challenging me to direct her in the isolation of recombination-deficient mutants of Escherichia coli K-12. She succeeded in isolating two mutants, which conjugated with donor strains and received the donor DNA, but could not recombine that DNA with their own chromosomes. Ann Dee showed that both mutants were much more sensitive to UV radiation than was the wild type. Furthermore, she showed that one of these mutants carried a single mutation affecting both recombination and resistance. This work, published in 1965, was the first demonstration of the recA gene of E. coli. Subsequent work led to the discovery of many more recombination genes, the phenomenon of post replication-recombination repair, the invention of the SOS hypothesis and the discovery of genes encoding proteins with similar primary structure and function in all major groups of organisms. This article honors the memory of Ann Dee.

Escherichia coli↗

Striving for atomic resolution in biomolecular topography: the scanning force microscope (SFM).

The invention in 1986 of scanning force microscopy (SFM) provided a new and powerful tool for the investigation of biological structures. SFM yields a three-dimensional view at nanometer resolution of the surface topography associated with biological objects. The potential for imaging either macromolecules or biomolecules and cells under native (physiological) conditions is currently being exploited to obtain functional information at the molecular level. In addition, the forces involved in individual bimolecular interactions are being assessed under static and dynamic conditions. In this report we focus on the imaging capability of the SFM. The rather broad spectrum of applications represented is intended to orient the prospective user of biological SFM.

Animals↗

The unique role of fluorine in the design of active ingredients for modern crop protection.

The task of inventing and developing active ingredients with useful biological activities requires a search for novel chemical substructures. This process may trigger the discovery of whole classes of chemicals of potential commercial interest. Similar biological effects can often be achieved by completely different compounds. However, compounds within a given structural family may exhibit quite different biological activities depending on their interactions with different intracellular proteins like enzymes or receptors. By varying the functional groups and structural elements of a lead compound, its interaction with the active site of the target protein, as well as its physicochemical, pharmacokinetic, and dynamic properties can be improved. In this context, the introduction of fluorine into active ingredients has become an important concept in the quest for a modern crop protection product with optimal efficacy, environmental safety, user friendliness, and economic viability. Fluorinated organic compounds represent an important and growing family of commercial agrochemicals. A number of recently developed agrochemical candidates represent novel classes of chemical compounds with new modes of action; several of these compounds contain new fluorinated substituents. However, the complex structure-activity relationships associated with biologically active molecules mean that the introduction of fluorine can lead to either an increase or a decrease in the efficacy of a compound depending on its changed mode of action, physicochemical properties, target interaction, or metabolic susceptibility and transformation. Therefore, it is still difficult to predict the sites in a molecule at which fluorine substitution will result in optimal desired effects.

Animals↗

Palladium-catalyzed cross-coupling reactions of silanolates: a paradigm shift in silicon-based cross-coupling reactions.

This paper chronicles the conceptual development, proof of principle experiments, and recent advances in the palladium-catalyzed cross-coupling reactions of the conjugate bases of organosilanols. The discovery that led to the design and refinement of this process represents a classical illustration of how mechanistic studies can provide a fertile ground for the invention of new reactions. On the basis of a working hypothesis (which ultimately proved to be incorrect) and the desire to effect silicon-based cross-coupling without the agency of fluoride activation, a mild and practical palladium-catalyzed cross-coupling of alkenyl-, aryl-, and heteroaryl silanolates has been developed. The mechanistic underpinnings, methodological extensions, and the successful applications of this technology to the synthesis of complex molecules are described.

Butanols↗

The interactive videodisc.

Dynamic audiovisual presentations that are interactive due to the use of videodisc systems provide more efficient and effective communication of those elements of medicine best learned by seeing them, than is possible via traditional modes. This is particularly true when externally interfaced electronic data processors are used to automate the process. While magnetic and stylus-type videodisc players can serve in education, it is the optical videodisc that has the greatest educational potential. The AMA has been exploring the capabilities of optical videodisc systems and demonstrating pilot programs that use good principles of audiovisual and computer-assisted instruction in tutorial formats or presented as patient management problems. We are on the threshold of a revolution in communication potentially as significant to education as the one which followed the invention of movable type. Using interactive videodisc programs, designed and produced with skill and care, we can solve some of medical education's most pressing problems.

American Medical Association↗

A high-speed atomic force microscope for studying biological macromolecules in action.

The atomic force microscope (AFM), which was invented by Binnig et al. in 1986, can image at nanometer resolution individual biological macromolecules on a substrate in solution. This unique capability awoke an expectation of imaging processes occurring in biological macromolecules at work. However, this expectation was not met, because the imaging rate with available AFMs was too low to capture biological processes. This expectation has at last been realized by the high-speed AFM developed by our research group at Kanazawa University. In this article, after a brief review of the development of our apparatus, its recent advancement and imaging data obtained with motor proteins are presented.

Journal Article↗

Multimodal imaging of mouse development: tools for the postgenomic era.

With the sequence of the mouse genome known, it is now possible to create or identify mutations in every gene to determine the molecules necessary for normal development. Consequently, there is a growing need for advanced phenotyping tools to best understand defects produced by altering gene function. Perhaps nothing is more satisfying than to directly observe a process in action; to disturb it and see for ourselves how the process changes before our very eyes. No doubt, this desire is what drove the invention of the very first microscopes and continues to this day to fuel progress in the field of biological imaging. Because mouse embryos are small and develop embedded within many tissue layers within the nurturing environment of the mother, directly observing the dynamic, micro- and nanoscopic events of early mammalian development has proven to be one of the greater challenges for imaging scientists. Here, I will review some of the imaging methods being used to study mouse development, highlighting the results obtained from imaging.

Animals↗

The use of ultrathin-layer polyacrylamide gel isoelectric focusing in two-dimensional analysis of plant and fungal proteins.

Although use of ultrathin polyacrylamide gel isoelectric focusing in the first dimension of two-dimensional analysis bestows a number of advantages, it has been little used by the plant science community. Nonstandardization along with problems unique to the format have probably delayed wider adoption. Relevant parameters were therefore tested in order to optimize resolution, reproducibility, economy and ease of use. Ultrathin-layer gels (200 microns in this study) used in the first dimension require a semirigid backing for support. Widely available matte-finished thin polyester film without chemical pretreatment was found to bind the gel adequately. The gel adheres to the film through all processing steps, yet, if desired, can be easily transferred to Whatman 3MM paper for special applications such as Western blotting. The ultrathin first-dimensional gels can be quickly dried on the polyester backing for convenient handling and long term storage. Strips cut from the dried gel for use in the second dimension are more easily manipulated than their tube format counterparts. The difficulty of disrupting and recovering microsamples of labeled leaf and root tissue prompted the invention of an efficient and simple communition device. An economical and efficient silver stain process is also described. This analytical technique was applied in an attempt to detect resistance gene products in different genetic backgrounds of maize. Although the ultrathin flatbed format provides as good as or better resolution than the tube gel system, the level of sensitivity was still inadequate to reveal the apparently rare resistance gene product.

Electrophoresis, Polyacrylamide Gel↗

Some reminiscences of the history of electrophoresis.

Dole's and Longsworth's solution of the whole set of moving boundary equations by using the dimensionless transference numbers is reviewed. Longsworth's teachings on the nature of transference numbers and his pondering over transference numbers of proteins led the author to inquire why transference numbers of ampholytes were never measured. Logical reasoning on this subject led to the invention of isoelectric focusing.

Electrochemistry↗

Intramolecular controls for the generation of clinical-quality SNP genotypes and the assessment of normal heterozygote imbalance.

We present an inventive method that generates intramolecular controls for SNP analysis, termed Mirror SNPs. Using the ovine diseases of callipyge and scrapie as examples, we describe the PCR-driven production of balanced heterozygote copies of the various SNPs implicated in these diseases. In the absence of a callipyge-positive control DNA, we generated a balanced heterozygote Mirror SNP that represents both the wild-type and mutant forms of the causal polymorphism. Simultaneous analysis of this artificial Mirror SNP and the Real (target) SNP was used to prove the absence of the mutant form of the nucleotide at the Real SNP position in tested samples. Scrapie susceptibility was assessed using a PCR-driven system which generated four separate Mirror SNPs, and these enabled the confirmation of an apparent departure from 'balanced' heterozygote appearance at Real SNPs tested. Mirror SNP technology is generic and will enable the accurate assessment of rare and medically important SNP variants, more accurate frequency determinations, and the potential assessment of SNPs in 'mixed template' samples common in forensic analyses.

Animals↗

Intensity-modulated radiation therapy in head and neck cancers: an update.

Intensity-modulated radiation therapy (IMRT), an advent of three-dimensional conformal radiotherapy (3D CRT), has excited the profession of radiation oncology more than any other new invention since the introduction of the linear accelerator. Approximately 1000 articles have been published on this topic to date, more than 200 of which focus on head and neck cancer. IMRT is based on computer-optimized treatment planning and a computer-controlled treatment delivery system. The computer-driven technology generates dose distributions that sharply conform to the tumor target while minimizing the dose delivered to the surrounding normal tissues. The high dose volume that tailors to the 3D configuration of the tumor along with the ability to spare the nearby normal tissues allows the option of tumor dose escalation. The head and neck region is an ideal target for this new technology for several reasons. First, IMRT offers the potential for improved tumor control through delivery of high doses to the target volume. Second, because of sharp dose gradients, IMRT results in the relative sparing of normal structures, such as the parotid glands, in the head and neck region. Third, organ motion is virtually absent in the head and neck region so, with proper immobilization, treatment can be accurately delivered. Although this is a relatively new technology, single-institution retrospective studies show better dosimetric profiles compared with conventional radiation techniques, as well as excellent clinical results. Salivary gland sparing using IMRT has also resulted in reduced incidence and severity of xerostomia, and this has been tested in a randomized trial against conventional radiotherapy for early-stage nasopharyngeal cancer. The results do confirm that IMRT does decrease xerostomia compared with conventional radiotherapy.

Head and Neck Neoplasms↗

A review of vascular anastomosis with mechanical aids and nonsuture techniques.

Devices and techniques for nonsuture vascular anastomosis and for suture anastomosis with minimum blood flow interruption are reviewed from their beginnings in the late 19th century through the development of microvascular surgery in the 20th century. The various devices that have been invented fall into 3 basic categories: butt, flanged, and lapped joints. Although the development of microsurgical instruments and the improvement of suture materials have diminished the use of such mechanical aids in recent years, it is hoped that this historical overview will be of interest to investigators involved in the surgery of vessels of various calibers.

Absorption↗

Experimental methods of ethanol administration.

Techniques are reviewed for the experimental feeding of alcohol, including a liquid diet procedure invented 25 years ago. This technique results in much higher ethanol intake than with other approaches. As a consequence, various complications observed in alcoholics can be reproduced in animal models. These include fatty liver, hyperlipemia, various metabolic and endocrine disorders, tolerance to ethanol and other drugs, physical dependence and withdrawal and, in the baboon, liver fibrosis and cirrhosis. Variations of the liquid diet formulation are compared, and adequacy of nutrition in terms of minerals, vitamins, lipotropes, carbohydrates and proteins is discussed. The importance of selecting proper controls is emphasized. The respective advantages of three standardized basic rat formulas are reviewed: (i) an all-purpose (35% fat) diet, comparable to the diet previously referred to as the "Lieber-DeCarli formula" and suitable for most experimental applications, particularly those intended to mimic the clinical situation in which the various effects of alcohol occur in the setting of hepatic changes characterized by a fatty liver; (ii) a low-fat diet comparable in all respects to the preceding diet but with a lower fat content, intended to minimize the hepatic changes, and (iii) a high-protein formula particularly useful in those circumstances in which an oversupply of dietary protein might be recommended (i.e. pregnancy). Variations of this technique, including continuous intragastric infusion, are also discussed. It is concluded that, for most experimental studies of chronic alcohol consumption, the liquid diet technique provides one of the most efficient tools to study the effects of ethanol under controlled nutritional conditions because it allows for alcohol consumption of clinical relevance and offers flexibility to adjust to special experimental or physiologic needs by allowing for various substitutions required for a particular experimental design, including changes in lipids, proteins or other dietary constituents. The technique also facilitates the comparison with controls by simplifying the pair feeding and is the best procedure available for the study of the toxic effects of alcohol and their interactions with deficiency or excess of various nutrients.

Administration, Inhalation↗