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PubMed2003

Educating for social responsibility: changing the syllabus of developmental biology.

Developmental biology is deeply embedded in the social issues of our times. Such topics as cloning, stems cells, reproductive technologies, sex selection, environmental hormone mimics and gene therapy all converge on developmental biology. It is therefore critical that developmental biologists learn about the possible social consequences of their work and of the possible molding of their discipline by social forces. We present two models for integrating social issues into the developmental biology curriculum. One model seeks to place discussions of social issues into the laboratory portion of the curriculum; the other model seeks to restructure the course, such that developmental biology and its social contexts are synthesized directly.

Curriculum↗

PubMed2003

The glycolytic phenotype in carcinogenesis and tumor invasion: insights through mathematical models.

Malignant cells characteristically exhibit altered metabolic patterns when compared with normal mammalian cells with increased reliance on anaerobic metabolism of glucose to lactic acid even in the presence of abundant oxygen. The inefficiency of the anaerobic pathway is compensated by increased glucose flux, a phenomenon first noted by Otto Warburg approximately 80 years ago and currently exploited for 2-fluoro-2-deoxy-D-glucose-positron emission tomography imaging in clinical radiology. The latter has demonstrated the glycolytic phenotype is a near-universal phenomenon in human cancers. The potential role of the glycolytic phenotype in facilitating tumor invasion has been investigated through mathematical models of the tumor-host interface. Modified cellular automaton and diffusion reaction models demonstrate protons will diffuse from the tumor into peritumoral normal tissue subjecting nontransformed cells adjacent to the tumor edge to an extracellular pH significantly lower than normal. This leads to normal cell death via p53-dependent apoptosis pathways, as well as degradation of the interstitial matrix, loss of intercellular gap junctions, enhanced angiogenesis, and inhibition of the host immune response to tumor antigens. Transformed cells maintain their proliferative capacity in acidic extracellular pH because of mutations in p53 or some other component in the apoptosis pathways. This allows tumor cells to remain proliferative and migrate into the peritumoral normal tissue producing the invasive phenotype. Mathematical models of invasive cancer based on tumor-induced acidification are consistent with extant data on tumor microenvironment and results from clinical positron emission tomography imaging, including the observed correlation between tumor invasiveness and glucose utilization. Novel treatment approaches focused on perturbation of the tumor microenvironment are predicted from the mathematical models and are supported by recent clinical data demonstrating the benefits of azotemia and metabolic acidosis in survival of patients with metastatic renal cancer. The evolutionary basis for adoption of the glycolytic phenotype during carcinogenesis remains unclear because it appears to confer significant competitive disadvantages on the tumor cells due to of inefficient energy production and expenditure of resources to remove the acid byproducts. We propose that the glycolytic phenotype represents a successful adaptation to environmental selection parameters because it confers the ability to invade. That is, the glycolytic phenotype allows the cell to move from the microenvironment of a premalignant lesion to adjacent normal tissue. There it competes with normal cells that are less fit than the populations within the tumor in a microenvironment of relative substrate abundance. The consequent unrestrained proliferation allows the glycolytic phenotype to emerge simultaneous with the transition from a premalignant lesion to an invasive cancer.

Animals↗

PubMed1992

Emerging human B cell repertoire. Influence of developmental stage and interindividual variation.

In B cell precursors developing in fetal lymphopoietic tissue, the selection of VH, DH, and JH gene segments for initial H chain gene assembly is biased. The present study was designed to determine whether these biases persist in fully developed human fetal B cells and to examine specificities encoded by the favored elements. B cells were prepared from two sites representing different stages of development, i.e., fetal liver as a source of cells newly generated in that lymphopoietic environment and fetal spleen as a source of more mature cells, potentially subject to selective environmental factors. The expressed repertoires were sampled by two methods. EBV transformation so binding and structure could be examined simultaneously and generation of cDNA from individual, sorted, unstimulated B cells. We found that mature B cells in liver and secondary lymphoid tissue exhibit the same degree of bias in VH use we previously reported in lymphopoietic tissue of the same gestational age. However, the pattern of DH and JH use more nearly resembled that of the adult, suggesting that some constraints imposed by the rearrangement process are normalized rapidly. Sequences recovered from EBV-transformed clones were not distinguishable from transcripts recovered from single cells by direct amplification. Among antibodies expressed by the EBV clones, binding to self-Ag was common, binding profiles varied, and, in contrast to mice, there was little relationship between specificity and VH element. Interestingly, the two individuals studied differed in the VH element most commonly used. One resembled previously studied fetal repertoires in that VH56p1 encoded about 20% of expressed antibodies, whereas the other did not express VH56p1 and used VH26 in 25% of expressed antibodies. This was found to reflect a lack of the genomic VH56p1 allele, suggesting that genetic variation at the VH locus may significantly influence the emerging human antibody repertoire.

Antibody Diversity↗

PubMed2004

Bacteriophages and insertion sequences of Chromobacterium violaceum ATCC 12472.

A fluid genome is a great advantage to prokaryotes, enabling quick adaptation to various types of ecological niches and to diverse environmental selective pressures. A substantial portion of these sudden changes is mediated by lateral gene transfer (LGT), through genetic recombination mechanisms, such as transformation, conjugation and transduction. The recent sequencing of several organisms has offered a new approach to the study of LGT, using comparison and analysis of nucleotide sequences dispersed throughout the genome of these species. This analysis in Choromobacterium violaceum has revealed four prophage and 12 insertion sequences, suggesting genetic exchange with several other bacterial species, including Salmonella enterica, Ralstonia and Xanthomonas. An Rhs (recombination hot spot) element (containing a vgr-like gene) was also observed, the function of which remains unknown, but it has a sequence related to species of Acinetobacter and Sphingomonas. These results support the role of LGT in the acquisition of new traits by C. violaceum.

Bacteriophages↗

PubMed2005

Use of Geographic Information Systems in the development of prediction models for onchocerciasis control in Ethiopia.

A risk assessment model was developed for onchocerciasis distribution and its control in Ethiopia using Geographic Information System (GIS) methods. GIS data analysis was done to generate 3 separate risk models using selected environmental features of (1) earth observing satellite data on Normalized Difference Vegetation Index (NDVI) and midday Land Surface Temperature (LST) prepared from AVHRR sensor data of the Global land 1-km project for the years 1992 and 1995, (2) FAO agroclimatic databases from the Crop Production System Zone (CPSZ) of the Intergovernmental Authority on Development (IGAD) sub-region of East Africa, and (3) a climate-based forecast index based on the growing degree days (GDD) and water budget concepts. Parasitological data used for the analysis were published and unpublished reports of onchocerciasis surveillance made between 1969 and 2000 in various parts of the country. Analysis of queries based on 1992 and 1995 annual wet and dry season data of the Global land 1-km project resulted in a predictive value of 95.1%, 94.0% and 96.3%, respectively, using data values extracted from buffers centered on sites above 5% prevalence. The model based on CPSZ data predicted an endemic area that best fit the distribution of sites over 5% prevalence; the query was based on CPSZ values of average altitude (442-2134 m), annual mean temperature (18-28 degrees C), annual rainfall (822-1980 mm), annual potential evapotranspiration (1264-1938 mm), rain minus potential evapotranspiration (-124 - 792 mm), average NDVI x 100 (2000-5000) and average terrain percent slope (9-34). The climate-based model based on GDD and water-budget predicted high risk to severe risk areas in the western and southwestern parts of the country. All three of the models predicted suitable areas for the transmission of onchocerciasis outside known endemic areas, suggesting the need for ground-based validation and potential application to current community-directed treatment programs with ivermectin (CDTI) for control of onchocerciasis in Ethiopia.

Agriculture↗

PubMed2006

Genetic population structure and call variation in a passerine bird, the satin bowerbird, Ptilonorhynchus violaceus.

Geographic variation in vocalizations is widespread in passerine birds, but its origins and maintenance remain unclear. One hypothesis to explain this variation is that it is associated with geographic isolation among populations and therefore should follow a vicariant pattern similar to that typically found in neutral genetic markers. Alternatively, if environmental selection strongly influences vocalizations, then genetic divergence and vocal divergence may be disassociated. This study compared genetic divergence derived from 11 microsatellite markers with a metric of phenotypic divergence derived from male bower advertisement calls. Data were obtained from 16 populations throughout the entire distribution of the satin bowerbird, an Australian wet-forest-restricted passerine. There was no relationship between call divergence and genetic divergence, similar to most other studies on birds with learned vocalizations. Genetic divergence followed a vicariant model of evolution, with the differentiation of isolated populations and isolation-by-distance among continuous populations. Previous work on Ptilonorhynchus violaceus has shown that advertisement call structure is strongly influenced by the acoustic environment of different habitats. Divergence in vocalizations among genetically related populations in different habitats indicates that satin bowerbirds match their vocalizations to the environment in which they live, despite the homogenizing influence of gene flow. In combination with convergence of vocalizations among genetically divergent populations occurring in the same habitat, this shows the overriding importance that habitat-related selection can have on the establishment and maintenance of variation in vocalizations.

Animals↗

PubMed1990

Multigenic human hypertension: evidence for subtypes and hope for haplotypes.

Hypertension that occurs before the age of 60 years is strongly aggregated in families, mostly due to genetic factors with weaker contributions from a shared family environment. Hypertension is probably a heterogeneous collection of overlapping subsets of pathophysiological mechanisms, such as dyslipidemia, obesity, hyperinsulinemia and cation metabolism. Highly heritable traits such as sodium-lithium countertransport, urinary kallikrein excretion and a body fat pattern index show evidence of major gene segregation in families with hypertension. They are thought to be intermediate phenotypes in the chain of pathophysiological events leading from specific genes to the distant phenotype of hypertension. They provide evidence of measurable contributions from single gene traits to the susceptibility to hypertension. Genetic linkage studies have suggested that other specific loci (e.g. histocompatibility leukocyte antigen, blood group MN and the haptoglobin protein) contribute to the susceptibility to hypertension. DNA sequencing has shown a point mutation for lipoprotein lipase that conveys susceptibility to lipid abnormalities, and possibly also hypertension, as seen in families with dyslipidemic hypertension. Further application of these approaches, especially in families that include multiple siblings with hypertension, shows promise of a true understanding of how the combined effects of a few specific genes, the polygenic background and selected environmental factors can lead to essential hypertension. This understanding should foster better tailored and more effective approaches to the prevention, diagnosis and treatment of hypertension.

Blood Pressure↗

PubMed1990

Limnological and botanical characterization of larval habitats for two primary malarial vectors, Anopheles albimanus and Anopheles pseudopunctipennis, in coastal areas of Chiapas State, Mexico.

Field surveys of mosquito breeding sites on the Pacific coastal plain and foothill regions of southern Chiapas, Mexico, were carried out in the dry and wet seasons of 1988. At each site, selected environmental variables were measured or estimated, presence and percent cover of aquatic plants recorded, a water sample collected for subsequent analyses, and 10-30 dips made for mosquito larvae. Logistic regression and discriminant analyses revealed that the occurrence of Anopheles albimanus larvae in both the wet and dry seasons was positively associated with planktonic algae and negatively associated with altitude. In the dry season, An. albimanus larvae were largely restricted to the margins of permanent water bodies and were associated with the presence of floating plants, particularly Eichhornia crassipes. During the wet season An. albimanus larvae were positively associated with emergent plants, particularly seasonally flooded Cyperaceae, and phosphorus (PO4) concentrations, and were negatively associated with abundant filamentous algae, high levels of total suspended solids (TSS) and Salvinia. In the dry season, An. pseudopunctipennis larvae were positively associated with filamentous algae, altitude and the presence of Heteranthera if encountered in a riverine setting, and were negatively associated with water depth. During the wet season, flooding eliminated typical flood plain An. pseudopunctipennis habitats, and larvae were rarely encountered.

Altitude↗

PubMed1995

[Peptic ulcer among workers in the engineering and chemical industries].

Incidence of peptic ulcer among workers employed in the engineering and chemical industries is presented in view of selected environmental factors. The study covered 157 workers with peptic ulcer who reported themselves to outpatient clinics at the Nitrogenous Fertilizers Plant in Pulawy and the Automobile Works in Lublin (5000 and 3252 employees, respectively). The study was conducted over a period of one year. It included: medical examinations, supplementary tests and a questionnaire survey. The questionnaire asked, among others, about working conditions, type of occupation performed and lifestyle. Peptic ulcer was diagnosed in 2.03% of workers engaged in the engineering industry and 1.82% of those working at the chemical plant. The incidence of peptic ulcer was higher among manual workers (2.18%) than in office workers (1.16%). The patients had been exposed to the following environmental factors: excessive noise--21%, vibration--17.2%, commuting--11.5%, extra work--14.5%, conflicts at work--13.5%, conflicts at home--15.3%, irregular meals--21.6%, alcohol intake--22.4%, cigarette smoking--62.4%. The study indicates that peptic ulcer is more often diagnosed in manual than in office workers and its incidence can be associated with working conditions and lifestyle. However, no significant variation in annual morbidity caused by peptic ulcer was observed among workers of the plants under study.

Chemical Industry↗

PubMed2002

The assessment of peer selection and peer environmental influences on behavior using pairs of siblings or twins.

Many studies have found strong peer correlations for a variety of problem behaviors that begin in adolescence (e.g. substance use). Such correlations are commonly attributed to peer influences, but could also be explained by selective ('assortative') friendship: the tendency for those with similar patterns of behavior to become friends. Here we show how, under certain assumptions, cross-sectional data from pairs of siblings or twins and their peers may be used to resolve the contributions of peer selection and reciprocal peer environmental influences to peer resemblance. We performed power calculations to determine necessary sample sizes for rejecting with 80% power, at the 5% significance level, the hypothesis of only peer selection effects, or only reciprocal peer environmental effects. A false hypothesis of only selective friendship effects was always easier to reject than a false hypothesis of only reciprocal peer environmental influences. Limitations of these simulations, including uncertainty about the most appropriate way to model peer selection, are discussed.

Adolescent↗

PubMed1994

The relationship of self-esteem to selected personal and environmental resources of adolescents.

This study examined the relationship of selected variables to self-esteem among 648 high school and college students. Multiple regression analyses, with self-esteem as the dependent variable, were computed separately for both males and females from small and large schools. Predictor variables were sex role orientation (masculinity/femininity); attitudes toward women's roles in society; high school activity participation; high school athletic participation; employment practices of students; and parents' education, occupational, and marital status. For all four groups, higher masculinity scores and greater levels of activity participation were significantly related to self-esteem. As predicted, however, there were differences in the regression equations as a function of school size. For males in small schools, but not in large schools, athletic participation was a significant predictor of self-esteem. For females in small schools, but not in large schools, more nontraditional or egalitarian attitudes toward women were related to higher self-esteem scores. Only masculinity and activity participation were significant predictors of self-esteem for both males and females in large schools. The implications of these results for the understanding of adolescent development are discussed.

Adolescent↗

PubMed2006

Environmental coupling of selection and heritability limits evolution.

There has recently been great interest in applying theoretical quantitative genetic models to empirical studies of evolution in wild populations. However, while classical models assume environmental constancy, most natural populations exist in variable environments. Here, we applied a novel analytical technique to a long-term study of birthweight in wild sheep and examined, for the first time, how variation in environmental quality simultaneously influences the strength of natural selection and the genetic basis of trait variability. In addition to demonstrating that selection and genetic variance vary dramatically across environments, our results show that environmental heterogeneity induces a negative correlation between these two parameters. Harsh environmental conditions were associated with strong selection for increased birthweight but low genetic variance, and vice versa. Consequently, the potential for microevolution in this population is constrained by either a lack of heritable variation (in poor environments) or by a reduced strength of selection (in good environments). More generally, environmental dependence of this nature may act to limit rates of evolution, maintain genetic variance, and favour phenotypic stasis in many natural systems. Assumptions of environmental constancy are likely to be violated in natural systems, and failure to acknowledge this may generate highly misleading expectations for phenotypic microevolution.

Animals↗

PubMed2004

Selecting agri-environmental indicators to facilitate monitoring and assessment of EU agri-environmental measures effectiveness.

Since its introduction in the early 1960s, the EU Common Agricultural Policy (CAP) has demonstrated a capacity to adapt and change in the face of new challenges. The reformed CAP, under AGENDA 2000, encourages more environmentally friendly farming practices. In the context of their rural development plans, Member States are required to link policies on agriculture with protection of the environment and to ensure that farmers meet environmental standards. Additionally, Member States should maintain and restore the quality of both their aquatic and adjacent terrestrial ecosystems according to the Directive 2000/60/EU, 'Establishing a framework for Community Action in the field of Water Policy'. Within this framework, agri-environmental indicators play an important role in planning and implementing CAP guidelines. However, selection and use of the proper indicators remains unresolved, considering that ecosystem processes are complex and interactions in most cases not obvious. This paper proposes a methodology for assessing the environmental state and impacts of current land use and management when implementing agri-environmental measures of CAP. The proposed methodology includes a modified Driving forces-Pressures-Impacts-Responses (DPSIR) framework, identification of Zones of Specific Functional Interest (ZSFI), and criteria for selecting agri-environmental indicators, which assess the functional performance of each zone and meet existing legislation. The Mygdonia Watershed (Greece) is an example where through use of both the appropriate Minimum Data Set of agri-environmental indicators at the identified zones and the proposed modified DPSIR, the functioning performance of each ZSFI can be assessed to evaluate the applied agri-environmental measures.

Agriculture↗

PubMed2004

Evolutionary potential of Chamaecrista fasciculata in relation to climate change. I. Clinal patterns of selection along an environmental gradient in the great plains.

Climate change will alter natural selection on native plant populations. Little information is available to predict how selection will change in the future and how populations will respond. Insight can be obtained by comparing selection regimes in current environments to selection regimes in environments similar to those predicted for the future. To mimic predicted temporal change in climate, three natural populations of the annual legume Chamaecrista fasciculata were sampled from a climate gradient in the Great Plains and progeny of formal crosses were reciprocally planted back into common gardens across this climate gradient. In each garden, native populations produced significantly more seed than the other populations, providing strong evidence of local adaptation. Phenotypic selection analysis conducted by site showed that plants with slower reproductive development, more leaves, and thicker leaves were favored in the most southern garden. Evidence of clinal variation in selection regimes was also found; selection coefficients were ordered according to the latitude of the common gardens. The adaptive value of native traits was indicated by selection toward the mean of local populations. Repeated clinal patterns in linear and nonlinear selection coefficients among populations and within and between sites were found. To the extent that temporal change in climate into the future will parallel the differences in selection across this spatial gradient, this study suggests that selection regimes will be displaced northward and different trait values will be favored in natural populations.

Adaptation, Physiological↗

PubMed2006

Developing an environmental indicator system for sustainable development in China: Two case studies of selected indicators.

Environmental indicator systems are a fundamental tool in quantifying the environmental component of sustainable development. They are useful because they quantify the status and trends of key environmental parameters and provide information on the environment that allows authorities and communities to make informed decisions. This article analyzes the basic framework for Chinese environmental indicator systems and presents a "core" set of environmental indicators. In our research, we used a theme approach to develop the environmental indicator systems. We performed two case studies of selected indicators. In the first, we used an urban ambient air pollution composite index and an urban ambient air pollution indicator for three main pollutants to examine trends in urban air pollution in China from 1990 to 2000 at regional and national levels. The results indicate that China has made some progress towards controlling urban air pollution, but must do more in order to reach acceptable pollution levels. We think that an aggregated index and disaggregated indicators have important complementary roles in the policy-making processes. In the second case study, we developed and constructed a grassland degradation index that aggregates information on the extent and severity of grassland degradation. Taking the Xilinhaote region of Inner Mongolia as the study area, we calculated this index by combining remote-sensing data, a geographical information system (GIS), and field investigation. Based on these results, we provide recommendations regarding further development and measurement of environmental indicators in China.

Air Pollutants↗

PubMed1998

The influence of sex and selected paragenetic and environmental factors on the basic anthropometric measurements of newborns in Bialystok.

On the basis of retrospective analysis of 1913 deliveries (40-weeks, single, from healthy mothers) that took place in Bialystok hospitals from 1 January to 31 December 1997, the influence of sex and selected paragenetic and environmental factors on the somatic development of newborns was assessed. Mathematical description of the material was based on the following statistical methods: arithmetic mean (x), standard deviation (SD). In the assessment of significance of the obtained differences Student T test was used. The layout of empirical distribution curves of the examined parameters formed centile nets for the first-born newborns. The analyses revealed that the influence of the genetic factor manifested by sexual dimorphism is the highest in case of body mass at birth. The pathogenic factors of the strongest influence included pregnancy and delivery. Age of parents had smaller effect on the somatic development of the foetus. The influence of the mother's puberty time on the somatic development of the foetus is an interesting phenomenon. Women who mature earlier give birth to bigger newborns compared to those with late puberty time. As far as the environmental factors are concerned, no influence of education level or place of residence of the parents on somatic condition of the foetus was observed.

Anthropometry↗

PubMed2005

Are pharmaceuticals potent environmental pollutants? Part II: environmental risk assessments of selected pharmaceutical excipients.

As part of achieving national environmental goals, the Swedish Government commissioned a report from the Swedish Medical Products Agency on environmental effects of pharmaceuticals and cosmetics and hygiene products. Five excipients used in pharmaceutical products were selected for environmental risk assessments, applying the computer-based model EUSES. Docusate sodium was identified as a possible risk for sediment-dwelling organisms when taking the total amount used into account. Although, experimental toxicity data on sediment-dwelling organism and data on concentrations in sediments are still required before firm conclusions regarding the environmental risk can be made. The environmental risks posed by excipients used in pharmaceutical products are likely to be negligible. This study identifies that knowledge gaps regarding environmental risks posed by pharmaceutical excipients are evident.

Drug Industry↗

PubMed2005

Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder that displays both sporadic and inherited forms. Exposure to several common environmental toxins acting through oxidative stress has been shown to be associated with PD. One recently identified inherited PD gene, DJ-1, may have a role in protection from oxidative stress, thus potentially linking a genetic cause with critical environmental risk factors. To develop an animal model that would allow integrative study of genetic and environmental influences, we have generated Drosophila lacking DJ-1 function. Fly DJ-1 homologs exhibit differential expression: DJ-1beta is ubiquitous, while DJ-1alpha is predominantly expressed in the male germline. DJ-1alpha and DJ-1beta double knockout flies are viable, fertile, and have a normal lifespan; however, they display a striking selective sensitivity to those environmental agents, including paraquat and rotenone, linked to PD in humans. This sensitivity results primarily from loss of DJ-1beta protein, which also becomes modified upon oxidative stress. These studies demonstrate that fly DJ-1 activity is selectively involved in protection from environmental oxidative insult in vivo and that the DJ-1beta protein is biochemically responsive to oxidative stress. Study of these flies will provide insight into the critical interplay of genetics and environment in PD.

Amino Acid Sequence↗