Biosynthesis and molecular genetics of cephamycins

Cephamycin C is produced in a nine steps pathway by the actinomycetes S. clavuligerus and N. lactamdurans. The genes encoding the biosynthesis enzymes are clustered in both microorganisms as well as in the cephabacin producer Lysobacter lactamgenus, a Gram negative bacterium. The clusters of genes include genes encoding enzymes common to the biosynthesis of penicillin and cephalosporin C by the eukaryotic producers Penicillium chrysogenum and Cephalosporiun acremonium and genes for steps specific for the formation of the precursor -aminoadipic acid as well as for the enzymes involved in the late modification of the cephalosporin intermediates of the pathway. Present are also genes for proteins involved in the export and/or resistance to cephamycin C. In S. clavuligerus a gene encoding a regulatory protein controlling the formation of cephamycin C and clavulanic acid is also present in the cluster.     

Multivariate analysis of anthropometric data and classifications of British Columbian natives

Anthropometric data collected in native populations of British Columbia in the late 19th century by Franz Boas were analyzed by two multivariate techniques. Multivariate analysis of variance was used to test physical classificatory units devised by Boas and an ad hoc classification based on local cultural units. Both were found to have some empirical validity. Mahalanobis' D (Mahalanobis, '30) was computed between pairs of local groups, for both sexes. From these a matrix of differences was prepared and diagrams drawn to illustrate phenetic relationships among samples. By this means one cluster of groups, Interior B.C. peoples, could be distinguished and other local samples appeared distinctly different from each other. It was concluded that in the absence of genealogical data by which to identify local populations, local cultural units are preferable to more inclusive units for making empirical comparisons and classifications.     

Quantifying Agreement between Anatomical and Functional Interhemispheric Correspondences in the Resting Brain

The human brain is composed of two broadly symmetric cerebral hemispheres, with an abundance of reciprocal anatomical connections between homotopic locations. However, to date, studies of hemispheric symmetries have not identified correspondency precisely due to variable cortical folding patterns. Here we present a method to establish accurate correspondency using position on the unfolded cortical surface relative to gyral and sulcal landmarks. The landmark method is shown to outperform the method of reversing standard volume coordinates, and it is used to quantify the functional symmetry in resting fMRI data throughout the cortex. Resting brain activity was found to be maximally correlated with locations less than 1 cm away on the cortical surface from the corresponding anatomical location in nearly half of the cortex. While select locations exhibited asymmetric patterns, precise symmetric relationships were found to be the norm, with fine-grained symmetric functional maps demonstrated in motor, occipital, and inferior frontal cortex.     

Congenital cataracts and their molecular genetics

Cataract can be defined as any opacity of the crystalline lens. Congenital cataract is particularly serious because it has the potential for inhibiting visual development, resulting in permanent blindness. Inherited cataracts represent a major contribution to congenital cataracts, especially in developed countries. While cataract represents a common end stage of mutations in a potentially large number of genes acting through varied mechanisms in practice most inherited cataracts have been associated with a subgroup of genes encoding proteins of particular importance for the maintenance of lens transparency and homeostasis. The increasing availability of more detailed information about these proteins and their functions and is making it possible to understand the pathophysiology of cataracts and the biology of the lens in general.     

Recent advances in molecular genetics of glaucoma

Glaucoma represents a heterogeneous group of optic neuropathies, with different genetic bases. It can affect all ages generally with a rise in intra-ocular pressure. Three major types of glaucoma have been reported: primary open angle glaucoma (POAG), primary acute closed angle glaucoma (PACG) and primary congenital glaucoma (PCG), as well as a few others associated with developmental abnormalities. In recent years impressive progress has been made in the molecular genetic studies of POAG and PCG. These include the discovery of three genes – Myocilin, Optineurin and CYP1B1 – defects in which results in Mendelian transmission of glaucoma. Identification of single nucleotide polymorphisms in multiple other genes that are associated with glaucoma and alteration of drug sensitivity are enriching our knowledge regarding the complex nature of the disease. This review attempts to present the recent progress made in the molecular genetics of glaucoma.     

Diet overlaps and feeding relationships between the year classes in the yellow perch (Perca flavescens)

Synopsis A comparative study of the diets of five year classes of perch in Lake Opinicon showed Year class 0 to be mainly Cladocera feeders, the Year class 11 to take a diversified range of insect larvae, whereas from Year class V onwards Anisoptera nymphs, decapods, and fish dominated the diet. Sizes of the dominant food items changed strikingly with growth, prey weights of 0.1, 0.5–1.0, and 100–250 mg predominating in these three age groupings. There were marked month to month changes in types and proportions of different prey consumed.Overall and month to month feeding overlaps between consecutive year classes were considerable, most values ranging from 0.68–1.0 by the Levins formula. However, diet overlap dropped sharply with increasing age gap.Month to month dietary changes and year class differences were interpreted relative to benthic invertebrate abundance cycles. Months of increased diet overlap were characteristically those when favored prey types peaked, thereby simultaneously attracting several year classes to them. Hence increased diet. overlap is not necessarily an indicator of increased intraspecific competition.Habitat differences between the year classes of perch in Lake Opinicon were partial and concerned mainly the smaller, and larger, fish relative to those in the middle size range.     

Integrating evolutionary and molecular genetics of aging

Aging or senescence is an age-dependent decline in physiological function, demographically manifest as decreased survival and fecundity with increasing age. Since aging is disadvantageous it should not evolve by natural selection. So why do organisms age and die? In the 1940s and 1950s evolutionary geneticists resolved this paradox by positing that aging evolves because selection is inefficient at maintaining function late in life. By the 1980s and 1990s this evolutionary theory of aging had received firm empirical support, but little was known about the mechanisms of aging. Around the same time biologists began to apply the tools of molecular genetics to aging and successfully identified mutations that affect longevity. Today, the molecular genetics of aging is a burgeoning field, but progress in evolutionary genetics of aging has largely stalled. Here we argue that some of the most exciting and unresolved questions about aging require an integration of molecular and evolutionary approaches. Is aging a universal process? Why do species age at different rates? Are the mechanisms of aging conserved or lineage-specific? Are longevity genes identified in the laboratory under selection in natural populations? What is the genetic basis of plasticity in aging in response to environmental cues and is this plasticity adaptive? What are the mechanisms underlying trade-offs between early fitness traits and life span? To answer these questions evolutionary biologists must adopt the tools of molecular biology, while molecular biologists must put their experiments into an evolutionary framework. The time is ripe for a synthesis of molecular biogerontology and the evolutionary biology of aging.     

Predicting local biological characteristics in streams: a comparison of landscape classifications

1. Landscape classifications group tracts of land based on similar physico‐chemical attributes that may affect the biological characteristics of streams at local scales. We tested the ability of five landscape models to account for variation in algal and macroinvertebrate biomass, brook trout (Salvelinus fontinalis) growth and macroinvertebrate community composition from 132 riffles in 15 catchments in the Big Horn Mountains, Wyoming. 2. A model created by the U.S. Forest Service (FS) combined catchment and ecoregion approaches to classify the landscape. Our model used digital elevations to create a landscape classification for streams (DEM). The last three models were based on: (1) standard ecoregions (Ecoregion), (2) the type of underlying bedrock (Geology) and (3) the geographical distance between sites (Site Proximity model). 3. Overall, the Ecoregion and Geology models performed better than the two catchment models (FS and DEM) in predicting local biological characteristics. The Geology model was best at predicting differences in algal and macroinvertebrate biomass, the Site Proximity and Ecoregion models were best at predicting patterns of similarity in macroinvertebrate community composition, and the Site Proximity, Ecoregion, Geology, and FS models, in order from best to worst, accounted for significant variation in brook trout growth. The Site Proximity model performed well because of the effects of spatial autocorrelation. The DEM was consistently one of the worst models at predicting local biological characteristics because it failed to include important attributes (e.g. dominant geology). Calcareous geology was positively associated with greater macroinvertebrate biomass and faster brook trout growth, but it was inversely related to algal biomass. 4. None of the models accounted for a large amount of variation in local biological characteristics. Single‐scale, landscape classifications may never accurately predict variation in local biological characteristics because: (1) landscapes show a high degree of spatial heterogeneity, (2) local effects are stronger than landscape attributes and (3) there are too many intervening levels between landscape and local scales in the nested hierarchy of streams. However, landscape classifications did account for significant variation in biological characteristics. Thus, they would be a valuable management tool as part of a multi‐scale, hierarchical technique for classifying stream ecosystems.     

Mouse aortic ring assay: A new approach of the molecular genetics of angiogenesis

Angiogenesis, a key step in many physiological and pathological processes, involves proteolysis of the extracellular matrix. To study the role of two enzymatic families, serine-proteases and matrix metalloproteases in angiogenesis, we have adapted to the mouse, the aortic ring assay initially developed in the rat. The use of deficient mice allowed us to demonstrate that PAI-1 is essential for angiogenesis while the absence of an MMP, MMP-11, did not affect vessel sprouting. We report here that this model is attractive to elucidate the cellular and molecular mechanisms of angiogenesis, to identify, characterise or screen “pro- or anti-angiogenic agents that could be used for the treatment of angiogenesis-dependent diseases. Approaches include using recombinant proteins, synthetic molecules and adenovirus-mediated gene transfer. Published: October 28, 2002     

Determination and differentiation in the light of molecular genetics

A review of the data obtained by the author and his collaborators in studying tissue specific esterase of Drosophila males. Patterns were established for molecular-genetic regulation of synthesis of this isozyme.     

Use of computer simulations in microbial and molecular genetics

The development of five computer programs in microbial and molecular genetics is described. Four of these are simulations of genetic and physical mapping experiments, designed to give students experience in generating and analysing meaningful data, and to help in the consolidation of the concepts underlying the simulation. They should be used after the experiment proper has been performed, rather than as a substitute for it. The fifth is an interactive learning program on the genetic coding mechanism.     

An overview of clinical molecular genetics

Clinical molecular genetics has recently become recognized as a diagnostic discipline. This article covers the evolution, structure, and possible forward development of clinical molecular genetics. Topics covered include general test categories, introducing new tests, laboratory facilities, staffing and training, and overview of quality issues.     

The molecular genetics of Alzheimer's disease

The major pathological characteristic of Alzheimer's disease (AD) is the abnormal deposition of β-amyloid peptide (Aβ) in the brain. In some early onset cases, the disease develops because of mutations in the gene coding for β-amyloid precursor protein (βAPP). However, the majority of AD families in the early onset subgroup are linked to a locus on chromosome 14. The genetic analysis and age of onset correlates of both the βAPP gene and the chromosome 14 locus are discussed. We speculate on the mechanisms by which the βAPP mutations cause the disease and discuss recent advances in βAPP processing that may be relevant to the pathogenesis of the late-onset (common) form of the disease. In addition, we review the association of theAPOE locus with late-onset familial and nonfamilial disease. Further work is required to establish the effects of this locus on disease occurrence, age of onset, and progression. The molecular pathology of ApoE in relation to AD development and the identification of the chromosome 14 gene will greatly contribute to a general pathogenic model of AD, and will clarify the role of βAPP and its derivatives.     

Cyanobacterial metallothioneins: Biochemistry and molecular genetics

Summary Metallothioneins have been extensively studied in many different eukaryotes where they sequester, and hence detoxify, excess amounts of certain metal ions. However, the precise functions of many of these molecules are not fully understood. This article reviews literature concerning their namesakes in prokaryotes.Abbreviations MT metallothionein - MRE metal regulatory element