Habitat- and sex-related differences in a small carnivore’s diet in a competitor-free environment

The alien invasive American mink Neovison vison is fully established in the low species richness and competitor-free environment of Iceland. This study documents the diversity as well as seasonal and sexual variation in the diet of mink in Iceland based on stomach contents. Seasonal changes mainly reflected variation in abundance of migratory birds and wood mice Apodemus sylvaticus. In comparison with mink elsewhere in similar habitats, the mink in Iceland consumed more fish and birds and fewer mammals, which is in accordance with local availability. This reinforces evidence of opportunistic foraging. Females generally ate more fish and fewer birds than males and this might be explained by their smaller body size and possible limitation in catching larger birds. Mink in coastal habitats showed greater sexual differences in diet than mink in riparian habitats, probably reflecting less prey diversity in riparian habitats than coastal ones. This study is an input towards explaining the ecological consequences of sexual size dimorphism and supports the hypothesis that generalist species might be successful invaders due to their capability in utilising new and diverse resources. The mink in Iceland can be regarded as a model for a small-bodied semi-aquatic carnivore away from the confounding effects of inter-specific competition.     

Functional Traits in a Species-Rich Grassland and a Short-Term Change in Management: Is There a Competition-Colonization Trade-Off?

The species richness of grasslands generally cannot be fully restored after changes in management. Some species with small statures and basal leaf rosettes can be lost forever. The same species, however, seem to possess the traits necessary for successful re-colonization – they produce small, easily dispersable seeds, numerous seedlings and have lasting seed banks. We tested the hypothesis that plants in species-rich grasslands can be characterized by a negative correlation between their competitive ability and potential for generative regeneration, i.e. by a competition-colonization trade-off. An analysis of the traits of 95 grassland species supported this hypothesis. We then conducted a manipulative experiment in three different meadow communities in the Bílé Karpaty Mts. The experiment involved characterizing species traits during periods of different grassland management regimes in the years 1997–2000 and comparing these with the original management regime, which was restored between 2000 and 2003. We found out that the hypothesis only holds true for the pooled dataset for all three communities. When the individual meadow communities were analyzed separately, plant traits other than those responsible for the competition-colonization trade-off appear to be characteristic of responsive species, e.g. shoot lifespan or phenology. Our results imply that despite the general trade-offs found in large comparative studies, the plant response in a specific community is constrained by the local species pool.     

Evidence-based hydro- and balneotherapy in Hungary—a systematic review and meta-analysis

Balneotherapy is appreciated as a traditional treatment modality in medicine. Hungary is rich in thermal mineral waters. Balneotherapy has been in extensive use for centuries and its effects have been studied in detail. Here, we present a systematic review and meta-analysis of clinical trials conducted with Hungarian thermal mineral waters, the findings of which have been published by Hungarian authors in English. The 122 studies identified in different databases include 18 clinical trials. Five of these evaluated the effect of hydro- and balneotherapy on chronic low back pain, four on osteoarthritis of the knee, and two on osteoarthritis of the hand. One of the remaining seven trials evaluated balneotherapy in chronic inflammatory pelvic diseases, while six studies explored its effect on various laboratory parameters. Out of the 18 studies, 9 met the predefined criteria for meta-analysis. The results confirmed the beneficial effect of balneotherapy on pain with weight bearing and at rest in patients with degenerative joint and spinal diseases. A similar effect has been found in chronic pelvic inflammatory disease. The review also revealed that balneotherapy has some beneficial effects on antioxidant status, and on metabolic and inflammatory parameters. Based on the results, we conclude that balneotherapy with Hungarian thermal-mineral waters is an effective remedy for lower back pain, as well as for knee and hand osteoarthritis.     

Encystment Processes and the “Matrioshka-like Stage” in a Moss-dwelling and in a Limnic Species of Eutardigrades (Tardigrada)

Tardigrades have two forms of dormancy, namely cryptobiosis and encystment. The encystment is a form of diapause known for a limited number of species of tardigrades and still little studied. To increase the knowledge on encystment, two species of eutardigrades from Italy have been considered: the moss-dwelling Amphibolus volubilis (Eohypsibiidae), and the limnic Dactylobiotus parthenogeneticus (Murrayidae). Cysts have been collected in nature, or induced under laboratory conditions. In the latter case, it was possible to follow the several steps of encystment processes. Two different types of cyst (“type 1” and “type 2”) have been found in A. volubilis, while in D. parthenogeneticus only one type has been found. In general, the ovoid-shaped cysts are constituted by a series of cuticles surrounding the animals and resemble an onion or a Matrioshka Russian doll. In all three types of cyst, the encystment processes show both common and peculiar traits. Encystment begins with the discharging of the sclerified parts of the buccal-pharyngeal apparatus, as in the molting process, but without the loss of the old cuticle. Then, two or three new cuticles are serially synthesized, according to cyst type. In A. volubilis, the ultrastructure of these new cuticular involucra is similar to that of non-encysted animal cuticles, while in D. parthenogeneticus the ultrastructure of the new cuticular involucra differs from that of non-encysted animal cuticle. A modified buccal-pharyngeal apparatus has been observed both in “type 2” cyst of A. volubilis and in the D. parthenogeneticus cyst.     

HIV and malaria: a lesson in immunology?

HIV is now common in many areas of Africa that are also highly endemic for malaria. In this article, Geoff Butcher summarizes the available data on the possible interaction o f HIV and malaria, and shows that the course of falciparum malaria is virtually unaffected by the presence of HIV. This raises significant questions for our understanding of immunity to the asexual blood stages of human malaria and the use of animal models in malaria research.     

Coactivators and corepressors: what's in a name?

Nuclear receptor coregulators are molecules required for efficient function of nuclear receptors. The field of nuclear receptor coregulators has experienced remarkably rapid growth since its inception in the mid-1990s. With this growth has emerged a complex and often redundant nomenclature, which, although relatively familiar to those within the immediate field, has the potential to generate confusion as coactivators and corepressors come under increasing scrutiny in other, less familiar disciplines. We discuss this issue with reference to some specific examples and proffer some guidelines to the community for identifying these molecules.     

ROCs and SOCs: what's in a name?

There is currently a great deal of interest in the relative contributions of external and internally sequestered Ca(2+) in various physiological responses. However, this field is losing clarity due to inattentive use of terms. In particular, the terms "receptor-operated channels" and "store-operated channels" (ROCs and SOCs, respectively) are becoming ambiguous through over-use. In this paper, we will first consider basic principles of channel gating in order to set the stage for defining criteria which can be used to distinguish precisely between different channel-related functions. We will then focus on recurring examples of adventurous use of terminology, or of blurring of the distinctions between channel types, and propose solutions to this quandary.     

Challenges and complexities in estimating both the functional impact and the disease risk associated with the extensive genetic variation in human DNA repair genes

Individual risk and the population incidence of disease result from the interaction of genetic susceptibility and exposure. DNA repair is an example of a cellular process where genetic variation in families with extreme predisposition is documented to be associated with high disease likelihood, including syndromes of premature aging and cancer. Although the identification and characterization of new genes or variants in cancer families continues to be important, the focus of this paper is the current status of efforts to define the impact of polymorphic amino acid substitutions in DNA repair genes on individual and population cancer risk. There is increasing evidence that mild reductions in DNA repair capacity, assumed to be the consequence of common genetic variation, affect cancer predisposition. The extensive variation being found in the coding regions of DNA repair genes and the large number of genes in each of the major repair pathways results in complex genotypes with potential to impact cancer risk in the general population. The implications of this complexity for molecular epidemiology studies, as well as concepts that may make these challenges more manageable, are discussed. The concepts include both experimental and computational approaches that could be employed to develop predictors of disease susceptibility based on DNA repair genotype, focusing initially on studies to assess functional impact on individual proteins and pathways and then on molecular epidemiology studies to assess exposure-dependent health risk. In closing, we raise some of the non-technical challenges to the utilization of the full richness of the genetic variation to reduce disease occurrence and ultimately improve health care.     

ARLTS1, MDM2 and RAD51 gene variations are associated with familial breast cancer

Genetic factors that contribute to the risk of breast cancer are largely not known and association studies have revealed several genes with low penetrance risk alleles for breast cancer. Analysis of these genes may provide important information on the risk factors affecting carcinogenesis. Variations in the ARLTS1, RAD51 and MDM2 genes have been associated with increased risk of different cancer types but for breast cancer the results are not consistent. In this study we investigated the role of the allelic variants in candidate genes acting in the tumor suppressor, DNA repair and p53 pathways as risk factors for familial breast cancer in 147 patients displaying characteristics of familial disease. Presence of the polymorphic variants were investigated by amplification of the corresponding regions and restriction fragment length polymorphism analysis. Genotype and allele frequencies in the patients were significantly different for all three variants. Our results indicate that the polymorphic variants might affect individual susceptibility towards breast cancer.     

Polymorphisms in DNA repair and environmental interactions

The repair of damage to DNA is critical to the survival of a cell. However, not all organisms nor all individuals express a similar response to challenges to their genetic material. Numerous polymorphisms in genes involved in DNA repair have been found in individuals with DNA repair-related disease as well as in the general population. Studies of these variants are critical in understanding the response of the cell to DNA damage. In some cases, these changes predispose the carrier to a greatly increased risk of cancer. In other cases, the effects are subtler and depend on interactions between the alleles of several genes, or with environmental factors. Consequently, the health effects of exposure to genotoxic or carcinogenic compounds or agents can depend on the variations in these genes. This review will highlight some of the effects that variants, found in many of the genes involved in human DNA repair pathways, have on the response to damage, and their role in susceptibility of the cell and organism to environmental genotoxins. This review will concentrate on the mismatch repair, nucleotide repair, base excision repair, strand break repair, and direct alkyl repair pathways.     

Variation in base excision repair capacity

The major DNA repair pathway for coping with spontaneous forms of DNA damage, such as natural hydrolytic products or oxidative lesions, is base excision repair (BER). In particular, BER processes mutagenic and cytotoxic DNA lesions such as non-bulky base modifications, abasic sites, and a range of chemically distinct single-strand breaks. Defects in BER have been linked to cancer predisposition, neurodegenerative disorders, and immunodeficiency. Recent data indicate a large degree of sequence variability in DNA repair genes and several studies have associated BER gene polymorphisms with disease risk, including cancer of several sites. The intent of this review is to describe the range of BER capacity among individuals and the functional consequences of BER genetic variants. We also discuss studies that associate BER deficiency with disease risk and the current state of BER capacity measurement assays.     

NBN Gene Polymorphisms and Cancer Susceptibility: A Systemic Review

The relationship between DNA repair failure and cancer is well established as in the case of rare, high penetrant genes in high cancer risk families. Beside this, in the last two decades, several studies have investigated a possible association between low penetrant polymorphic variants in genes devoted to DNA repair pathways and risk for developing cancer. This relationship would be also supported by the observation that DNA repair processes may be modulated by sequence variants in DNA repair genes, leading to susceptibility to environmental carcinogens. In this framework, the aim of this review is to provide the reader with the state of the art on the association between common genetic variants and cancer risk, limiting the attention to single nucleotide polymorphisms (SNPs) of the NBN gene and providing the various odd ratios (ORs). In this respect, the NBN protein, together with MRE11 and RAD50, is part of the MRN complex which is a central player in the very early steps of sensing and processing of DNA double-strand breaks (DSBs), in telomere maintenance, in cell cycle control, and in genomic integrity in general. So far, many papers were devoted to ascertain possible association between common synonymous and non-synonymous NBN gene polymorphisms and increased cancer risk. However, the results still remain inconsistent and inconclusive also in meta-analysis studies for the most investigated E185Q NBN miscoding variant.     

Interaction between APC and Fen1 during breast carcinogenesis

Aberrant DNA base excision repair (BER) contributes to malignant transformation. However, inter-individual variations in DNA repair capacity plays a key role in modifying breast cancer risk. We review here emerging evidence that two proteins involved in BER – adenomatous polyposis coli (APC) and flap endonuclease 1 (Fen1) – promote the development of breast cancer through novel mechanisms. APC and Fen1 expression and interaction is increased in breast tumors versus normal cells, APC interacts with and blocks Fen1 activity in Pol-β-directed LP-BER, and abrogation of LP-BER is linked with cigarette smoke condensate-induced transformation of normal breast epithelial cells. Carcinogens increase expression of APC and Fen1 in spontaneously immortalized human breast epithelial cells, human colon cancer cells, and mouse embryonic fibroblasts. Since APC and Fen1 are tumor suppressors, an increase in their levels could protect against carcinogenesis; however, this does not seem to be the case. Elevated Fen1 levels in breast and lung cancer cells may reflect the enhanced proliferation of cancer cells or increased DNA damage in cancer cells compared to normal cells. Inactivation of the tumor suppressor functions of APC and Fen1 is due to their interaction, which may act as a susceptibility factor for breast cancer. The increased interaction of APC and Fen1 may occur due to polypmorphic and/or mutational variation in these genes. Screening of APC and Fen1 polymorphic and/or mutational variations and APC/Fen1 interaction may permit assessment of individual DNA repair capability and the risk for breast cancer development. Such individuals might lower their breast cancer risk by reducing exposure to carcinogens. Stratifying individuals according to susceptibility would greatly assist epidemiologic studies of the impact of suspected environmental carcinogens. Additionally, a mechanistic understanding of the interaction of APC and Fen1 may provide the basis for developing new and effective targeted chemopreventive and chemotherapeutic agents.     

Trichothiodystrophy and the relationship between DNA repair and cancer

The identification of cellular deficiencies in the ability to repair damage in DNA in individuals with several cancer-prone genetic disorders, has led to the idea that defective DNA repair results in cancer. In patients with trichothiodystrophy, however, a recently discovered defect in the repair of ultraviolet damage in DNA is not associated with cancer-proneness. Thus our previous ideas about the connections between DNA repair capacity and cancer susceptibility need to be reevaluated.     

Molecular epidemiology in cancer research

The use of molecular biomarkers in epidemiological investigations brings clear advantages of economy, speed and precision. Epidemiology--the study of the factors that control the patterns of incidence of disease--normally requires large numbers of subjects and/or long periods of time, because what is measured (the occurrence of disease) is a rare event. Biomarkers are measurable biological parameters that reflect, in some way, an individual's risk of disease-because they indicate exposure to a causative (or protective) agent, or because they represent an early stage in development of the disease, or because they allow an assessment of individual susceptibility. Biomarkers must be usable on one of the few materials available for biomonitoring of humans, i.e. blood, urine, exfoliated epithelial cells and, with some difficulty, biopsies. The approach of molecular epidemiology has a great potential is several areas of cancer research: investigating the aetiology of the disease; monitoring cancer risk in people exposed to occupational or environmental carcinogens; studying factors that protect from cancer; and assessing intrinsic factors that might predispose to cancer. The biomarkers most commonly employed in cancer epidemiology include: measurements of DNA damage--DNA breaks, altered bases, bulky adducts--in lymphocytes; the surrogate marker of chemical modifications to blood proteins, caused by agents that also damage DNA; the presence of metabolites of DNA-damaging agents (or the products of DNA damage themselves) in urine; chromosome alterations, including translocations, micronuclei and sister chromatid exchange, resulting from DNA damage; mutations in marker genes; DNA repair; and the differential expression of a variety of enzymes, involved in both activation and detoxification of carcinogens, that help to determine individual susceptibility. The molecular approach has been enthusiastically employed in several studies of occupational/environmental exposure to carcinogens. While the estimation of biological markers of exposure has certainly shown the expected effects in terms of DNA damage and adducts, the detection of the biological effects of exposure (e.g. at the level of chromosome alterations) has not been so clear-cut. This is true also when smokers are examined as a group compared with non-smokers. Several markers (especially of chromosome damage and mutation) show a strong correlation with age-indicating either an increasing susceptibility to damage with age, or an accumulation of long-lived changes. DNA repair--a crucial player in the removal of damage before it can cause mutation--may vary between individuals, and may be modulated by intrinsic or extrinsic factors, but limited data are available because of the lack of a reliable assay. Information on other enzymes determining individual susceptibility does exist, and some significant effects of phenotypic or genotypic polymorphisms have emerged, although the interactions between various enzymes make the situation very complex. The important question of whether oxidative DNA damage in normal cells is decreased by dietary antioxidants (vitamin C, carotenoids etc., from fruit and vegetables) has been tackled in antioxidant supplementation experiments. The use of poorly validated assays for base oxidation has not helped us to reach a definitive answer; it seems that, in any case, the level of oxidative damage has been greatly exaggerated. DNA-damaging agents lead to characteristic kinds of base changes (transitions, transversions, deletions). The investigation of the spectrum of mutations in cancer-related genes studied in tumour tissue should lead to a better understanding of the agents ultimately responsible for inducing the tumour. Similarly, studying mutations in a neutral marker gene (not involved in tumorigenesis) can tell us about the origins of the 'background' level of mutations. So far, interpretation of the growing databases is largely speculative. (ABSTRACT     

Molecular epidemiology, biomarkers and cancer prevention.

Molecular epidemiological studies within the field of cancer research provide the potential for elucidating the carcinogenic cascade at the molecular level. Identification of susceptible subsets of the population, based on polymorphisms in genes involved in carcinogenesis, has the potential to delineate more clearly those factors that might increase cancer risk among some, but not all, individuals. Rapid advances in human genomics are making it possible to develop detailed profiles of susceptible subgroups based upon genetic variants in multiple pathways. Here we discuss examples of recent susceptibility studies involving genes, such as those involved in carcinogen metabolism, DNA repair, cell cycle and immune status, that hold the promise of increasing our understanding of cancer etiology and possible prevention strategies.     

Coding variants in human double-strand break DNA repair genes

DNA repair is essential for the maintenance of genomic integrity. Consequently, altered repair capacity may impact individual health in such areas as aging and susceptibility to certain diseases. Defects in some DNA repair genes, for example, have been shown to increase cancer risk, accelerate aging and impair neurological functions. Now that over 115 genes directly involved in human DNA repair have been characterized at the DNA sequence level, the identification of single nucleotide polymorphisms (SNPs) in DNA repair genes is becoming a reality. This information will likely lead to the identification of alleles, or combinations of alleles that affect disease predisposition. This communication summarizes SNPs identified to date in the coding region of 24 human double-strand break repair (DSBR) genes. SNP data for four of these genes were obtained by screening at least 100 individuals in our laboratory. For each SNP, the codon number, amino acid substitution, allele frequency and population information is supplied.