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PubMed2004

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↗

PubMed1994

Role of mouse germ-cell mutagenesis in understanding genetic risk and in generating mutations that are prime tools for studies in modern biology.

Highlights are presented on (1) the role mouse germ-cell mutagenesis has played in assessing the genetic harm from radiations and chemicals, and (2) the contributions to the field of modern biology that are being made by the products of this research--the propagated mutations. Among the numerous findings in radiation mutagenesis were the humped dose-effect curve for spermatogonial stem cells, the major differences between the sexes and between germ-cell stages of each sex in both yield and nature of mutations, the dose-rate effect, which provided the first evidence for repair of mutational (or premutational) damage, the augmenting effect of certain regimes of dose fractionation, and many others. Chemical mutagenesis studies that followed revealed at least three patterns of mutation yield and demonstrated that germ-cell stage--much more than the nature of the chemical--governs the nature of the DNA lesions induced. Two "supermutagens," one for intragenic mutations and one for deletions and other rearrangements, have become very useful in the manufacture of mutations for specific purposes. The mutations propagated from radiation- and chemical-mutagenesis experiments are providing prime resources for basic studies in genome organization, gene structure, and function. DNA lesions that involve specific loci have made possible increasingly detailed characterization of extensive deletion complexes that facilitate high-intensity physical and functional mapping within them. Numerous loci associated with interesting developmental anomalies have been identified and have become accessible to positional cloning. Several of the genes accessed with the aid of induced mutations (deletions, other rearrangements, and point mutations) are furnishing prime reagents for elucidating human disease conditions.

Animals↗

PubMed2002

Cytotoxicity of modern dentin adhesives--in vitro testing on gingival fibroblasts.

The present investigation was designed to test cellular toxicity of modern dentin adhesives. With the use of the products Ariston Liner, Etch & Prime 3.0, Optibond Solo, Prime & Bond NT, Scotchbond 1, and Syntac Sprint, test specimens were prepared according to the manufacturers' instructions and transferred into a culture medium. Eluates were obtained and pipetted onto fibroblast cultures, incubated, and subsequently stained. The respective cell densities and the numbers of normal, altered, and dead cells were determined and compared with control cell cultures. Statistical analysis of the data showed that all materials caused cytotoxic effects. Scotchbond 1 displayed the highest number of dead cells. The difference was statistically significant compared to Etch" 3.0, Optibond Solo, Prime&Bond NT, and the control. The lowest cell density was found for Scotchbond 1 and Ariston Liner. The difference was also statistically significant in comparison with Etch" 3.0, Optibond Solo, Prime&Bond NT, and the control. To conclude, all tested dentin adhesives caused cytotoxic reactions. Taking the limitations of an in vitro experiment into consideration, Prime&Bond NT, Optibond Solo, and Etch" 3.0 appear to be the most recommendable products, and Scotchbond 1 and Ariston Liner the least.

Acrylates↗

PubMed2007

Electronic structure of CO--an exercise in modern chemical bonding theory.

This paper discusses recent progress that has been made in the understanding of the electronic structure and bonding situation of carbon monoxide which was analyzed using modern quantum chemical methods. The new results are compared with standard models of chemical bonding. The electronic charge distribution and the dipole moment, the nature of the HOMO and the bond dissociation energy are discussed in detail.

Journal Article↗

PubMed2006

From the "Modern Synthesis" to cybernetics: Ivan Ivanovich Schmalhausen (1884-1963) and his research program for a synthesis of evolutionary and developmental biology.

Ivan I. Schmalhausen was one of the central figures in the Russian development of the "Modern Synthesis" in evolutionary biology. He is widely cited internationally even today. Schmalhausen developed the main principles of his theory facing the danger of death in the totalitarian Soviet Union. His great services to evolutionary and theoretical biology are indisputable. However, the received view of Schmalhausen's contributions to evolutionary biology makes an unbiased reading of his texts difficult. Here we show that taking all of his works into consideration (including those only available in Russian) paints a much more dynamic and exciting picture of what he tried to achieve. Schmalhausen pioneered the integration of a developmental perspective into evolutionary thinking. A main tool for achieving this was his approach to living objects as complex multi-level self-regulating systems. Schmalhausen put enormous effort into bringing this idea into fruition during the final stages of his career by combining evolutionary theory with cybernetics. His results and ideas remain thought-provoking, and his texts are of more than just historical interest.

Biological Evolution↗

PubMed2006

Holmes tremor: Application of modern neuroimaging techniques.

Holmes tremor has a characteristic rest, intention, and postural component. The syndrome arises as a consequence of a lesion in the upper brainstem and cerebral peduncles, which, it is postulated, interrupts the cerebello-rubrothalamic pathway. Ataxia, ophthalmoplegia, and bradykinesia are associated features. We present a case of Holmes tremor secondary to a midbrain cavernoma. Modern neuroimaging techniques in this case confirm that a combination of damage to the cerebello-rubrothalamic pathway and the nigrostriatal pathway is required for the full Holmes tremor syndrome to occur.

Adult↗

PubMed1989

Microlaryngology: an update on its modern use in laryngology--malignant early and advanced glottic carcinoma.

The modern use of microlaryngology is improving the diagnosis and treatment of early and advanced glottic laryngeal lesions. Microlaryngology is a microscopic laryngoscopic technique that is used to carry out laryngeal tumor evaluation and biopsy. For early, small, and advanced laryngeal glottic lesions, a microscope is used to view the larynx through a laryngoscope that is placed transorally. This is a precise method of microsurgery to biopsy and stage early and advanced malignant tumors of the glottic area of the larynx. Recent advances using microscopic visualization, microsurgical instruments, and a CO2 laser as a tool to control bleeding and to debulk the tumors of patients with advanced lesions enable the operating surgeon to visualize accurately the involvement by tumor of the overlying mucosa or the underlying muscles and cartilages in this area and sometimes to restore the airway. Precise knowledge regarding the microscopic locational extent of these tumors is important in developing appropriate options for treatment of early and advanced malignant neoplasms of the glottic area of the larynx in order to cure the disease and save the voice of the patient.

Carcinoma↗

PubMed1997

Hydrogen exchange: the modern legacy of Linderstrøm-Lang.

This discussion, prepared for the Protein Society's symposium honoring the 100th anniversary of Kaj Linderstrøm-Lang, shows how hydrogen exchange approaches initially conceived and implemented by Lang and his colleagues some 50 years ago are contributing to current progress in structural biology. Examples are chosen from the active protein folding field. Hydrogen exchange methods now make it possible to define the structure of protein folding intermediates in various contexts: as tenuous molten globule forms at equilibrium under destabilizing conditions, in kinetic intermediates that exist for less than one second, and as infinitesimally populated excited state forms under native conditions. More generally, similar methods now find broad application in studies of protein structure, energetics, and interactions. This article considers the rise of these capabilities from their inception at the Carlsberg Labs to their contemporary role as a significant tool of modern structural biology.

Chemistry↗

PubMed1998

A note on the making of culinary tradition--an example of modern Japan.

This article deals with the transition of Japanese food culture in the late nineteenth and the first half of the twentieth century. It explains the three main stages of this transition, namely the adoption of Western haute cuisine by the Japanese élite, the diffusion of Western ingredients, dishes and cookery techniques among the urban middle class, and the popularization of the new Japanese-Western hybrid cuisine by the military. This new cuisine began to acquire the status of culinary "tradition" from the 1950s onwards. Dietary changes in modern Japan were to a large extent a consequence of deliberate policies of the government. In the early stage, Westernization of the élite's diet was regarded as necessary in order to achieve a status of a "civilized" nation. Later, deliberate dietary reforms were undertaken with the aim of improving physical conditions of the population. These deliberate actions were directly influenced by the political circumstances in which Japan found itself in the period discussed.

Cooking↗

PubMed1996

Bergson's "Matter and Memory" and modern selectionist theories of memory.

Bergson's reflections (in Matter and Memory, 1896) on memory anticipated development of modern selectionist theories of memory. Selectionist models offer new and potentially useful approaches to a theory of remembering. On the model of natural selection, these selectionist theories require at least two processing components: a device which generates a range of memory representations and a selection process which preserves a subset of those representations. Bergson shows how the subjective experience of remembering might be understood within a selectionist framework.

Brain↗

PubMedDate not supplied

Radiographic and histological methodologies in estimating the chronology of crown development in modern humans and great apes: a review, with some applications for studies on juvenile hominids.

There has been a burgeoning of interest in the last decade on growth studies in hominids. These studies have relied heavily on dental development, and have compared juvenile hominids to modern human and ape standards, which are usually established using radiographic data. There has been considerable discussion on the most appropriate methods of deriving population standards from radiographs, but very little on the accuracy of the radiographic image itself. Previous histological and dissection studies have shown that age at onset of mineralization is overestimated, and age at crown completion is underestimated using radiographs. This study considers the process of X-ray absorbence by mineralized tissues and the formation of radiographic images of developing teeth. Following tooth initiation a critical mass of mineral is required for the tooth to register superimposed on the absorbence of alveolar crypt bone, which accounts for the late identification of tooth initiation. Determination of completion of crown growth depends upon the identification of the last formed enamel at the cervix. Recognition of this key stage is difficult as crown growth slows towards the cervix, and the last secreted enamel may take months to attain full mineralization levels due to the prolonged maturation process. Morphological and geometric factors have a significant influence on the imaging of the completed crown. The last formed enamel is located on the buccal face, where enamel thins progressively to nothing. X-ray absorption by enamel at the cervix becomes insignificant, and may be counterbalanced by increased dentine absorption. Approximal enamel in contrast is clearly visualized once maturation is complete. However, developmentally this enamel face initiates later, and is completed much earlier than buccal enamel. All of the radiographic estimates of crown completion times are based upon interpretations of approximal enamel completion. These considerations suggest that the human population standards in current usage may not represent true anatomical and chronological stages of crown development, and care should be taken in referring juvenile hominids to these radiological standards.

Animals↗

PubMed2001

A study of carnivore competition in riparian and open habitats of modern savannas and its implications for hominid behavioral modelling.

Some of the models proposed to explain Plio-Pleistocene hominid behavior and the formation of early East African archaeological sites are based on the assumption that the riparian habitats in which most of them occur were places of low interspecific competition. Competition is expressed here in terms of carnivore and hominid interactions. In this paper, a study of carnivore interaction in open and closed habitats is presented. The results indicate that riparian woodland shows the lowest degree of competition in savanna ecosystems. This suggests that if Plio-Pleistocene carnivores were adapted like their modern counterparts, the paleoecological settings of early sites could have provided hominids with enough safety to process carcasses and behave as shown in "central-place", "near-kill location" and "refuge" foraging models.

Animals↗

PubMed1995

Divergence time and population size in the lineage leading to modern humans.

We have developed maximum likelihood (ML) methods for comparisons of nucleotide sequences from unlinked genomic regions. In the case of a single species, the ML method primarily estimates the effective population size (Ne) under both constant size and abrupt expansion conditions. In the case of two or three species, the ML method simultaneously estimates the species divergence time and the effective size of ancestral populations. This allows us to trace the evolutionary history of the human population over the past several million years (my). Available sequences at human autosomal loci indicate Ne = 10,000 in the Late Pleistocene, a figure concordant with the results obtained from mitochondrial DNA sequence and allele-frequency data analysis, and there is no indication of population expansion. The ML analysis of two species shows that humans diverged from chimpanzees 4.6 my ago and that the human and chimpanzee clade diverged from the gorilla 7.2 my ago. Furthermore, the effective population size of humans more than 4.6 my ago is nearly 10 times larger than Ne of modern humans. The effective population size in the human lineage does not seem to have remained constant over the past several million years. The ML model for three species predicts slightly different, but consistent results to those obtained by the two-species analysis.

Animals↗

PubMed2002

History of modern genetics in Germany.

The history of modern genetics in Germany during the 20th century is a story of missed chances. In the USA the genetic revolution opened a fascinating new field for ambitious scientists and created a rapidly growing new industry. Meanwhile Germany stood aside, combating with political and social restrictions. Promising young scientists who wanted to work in the field left Germany for the US, and big companies moved their facilities out of the country. Up until the middle of the 1990s molecular biology in Germany remained a "sleeping beauty" even though many brilliant scientists did their jobs very well. Then a somewhat funny idea changed everything: the German minister for education and science proclaimed the BioRegio contest in order to award the most powerful biotechnology region in Germany concerning academia and especially industry. Since then Germany's biotechnology industry has grown constantly and rapidly due to the foundation of a number of small biotech companies; big companies have returned their interests and their investments to Germany, paralleled by an improvement in academic research because of more funding and better support especially for younger scientists. In respect to biotechnology and molecular biology, Germany is still a developing country, but it has started to move and to take its chances in an exciting global competition.

Agriculture↗

PubMed2000

Development of applied microbiology to modern biotechnology in Japan.

Development of modern biotechnology in Japan is characterized by unique contributions from applied microbiology and bioindustry. This review tries to summarize these original contributions with special emphasis on industrial production of useful substances by microorganisms. In the first part, development of applied microbiology and bioindustry in the last half of the twentieth century is summarized with a brief overview of the traditional background. In the second part, recent progress is reviewed with citation of typical achievements in biotechnology, applied enzymology, secondary metabolites, genetic engineering, and screening of microbial diversity, respectively.

Amino Acids↗

PubMed1989

Modern coding sequences are in the periodic-to-chaotic transition.

Modern coding sequences are in the periodic-to-chaotic transition. In the case of alpha A-crystallin coding sequence of the chicken, the initial tetrameric periodicity of the primordial tetramer C C T G has been decaying by the golden mean: the 4, 7, 11 rule. Thus, the tetramer has become parts of recurring heptamers, and some heptamers have become parts of the 11-base-long repeating units.

Amino Acid Sequence↗

PubMed2004

Modern multimodal neuroimaging for radiosurgery: the example of PET scan integration.

Radiosurgery relies critically on medical imaging modalities. Leksell Gamma Knife (LGK) radiosurgery presents the highest requirements in terms of imaging accuracy as the treatment is applied in a single high-dose session with no other spatial control than medical imaging. The advent of new imaging modalities opens challenges for LGK planning strategies. The integration of stereotactic PET in LGK represents an example of such application of modern multimodality imaging in radiosurgery. Our experience consists of 80 patients treated with the combination of MR/CT and PET guidance. In order to analyze the specific contribution of PET findings, we developed a classification reflecting the strategy used to define the target volume. When combining PET and MR information, 102 target volumes were defined, because some patients presented with multiple lesions or multifocal tumor areas. Abnormal PET uptake was found in 86% of the lesions, and this information altered significantly the MR-defined tumor in 73%. In conclusion, integration of PET in radiosurgery provides additional information opening new perspectives for the treatment of brain tumors. The use of a standardized classification allows to assess the relative role of PET. A similar approach could be useful and may serve as a template for the evaluation of the integration of other new imaging modalities in radiosurgery.

Adenoma↗

PubMed2003

Cécile & Oskar Vogt: the significance of their contributions in modern neuroscience.

A) By introducing and propagating the use of multidisciplinary approaches, Cécile and Okar Vogt played a decisive role in establishing brain research as a distinct branch of science, and thus laid the foundations for modern Neuroscience. B) The Vogts' and Brodmann's monumental work on brain cytoarchitectonics, supplemented with electrical stimulation of the exposed cerebral cortex, demonstrated correlations between evoked functional responses and the topography of brain regions endowed with distinct cytoarchitectonic structure (topistic units). This opened the field of functional brain mapping, a subject hotly pursued at the present time. C) One of the most important aspects of Pathoclisis is that the Vogts based their theory on molecular genetics. They envisaged that in any topistic unit the neurons had a different specific, molecular ("physico-chemical") composition, accounting for differences observed in the dynamics of neuronal development and involution. In sublethal injury, the induced genomic reactivity varies according to the selective vulnerability of various topistic units. Thus, in cerebral ischemia, the fluctuating genomic reactivity may play a significant role in designing therapeutic strategies, which would include enhancing regenerative expressions and suppressing harmful ones. D) The pathoclisis theory may be of assistance in analyzing the nature of various genetic disorders, which could be considered for the application of gene therapy.

Germany↗