RESUMEN

Satellite telemetry is an increasingly utilized technology in wildlife research, and current devices can track individual animal movements at unprecedented spatial and temporal resolutions. However, as we enter the golden age of satellite telemetry, we need an in-depth understanding of the main technological, species-specific and environmental factors that determine the success and failure of satellite tracking devices across species and habitats. Here, we assess the relative influence of such factors on the ability of satellite telemetry units to provide the expected amount and quality of data by analyzing data from over 3,000 devices deployed on 62 terrestrial species in 167 projects worldwide. We evaluate the success rate in obtaining GPS fixes as well as in transferring these fixes to the user and we evaluate failure rates. Average fix success and data transfer rates were high and were generally better predicted by species and unit characteristics, while environmental characteristics influenced the variability of performance. However, 48% of the unit deployments ended prematurely, half of them due to technical failure. Nonetheless, this study shows that the performance of satellite telemetry applications has shown improvements over time, and based on our findings, we provide further recommendations for both users and manufacturers.

Asunto(s)

RESUMEN

Werner syndrome is a segmental progeroid disorder with onset in adolescence or early adulthood. Typical symptoms contributing to patients' prematurely aged appearance include postpubertal development of short stature, cataracts, premature greying/thinning of scalp hair, scleroderma-like skin changes and regional atrophy of subcutaneous fat tissue. In addition, an increased rate and early onset of typical age-related diseases such as type 2 diabetes mellitus, osteoporosis, atherosclerosis, and various malignancies is observed. Werner syndrome is autosomal recessively inherited and caused by mutations in the Werner gene (WRN). To date, more than 70 WRN mutations have been identified. These are spread over the entire gene and typically represent loss of function mutations. WRN encodes a RecQ type helicase involved in DNA repair and the maintenance of DNA integrity, which is reflected by an increased genetic instability in patient cells. Despite the relative rarity of Werner syndrome, its analysis provides important general insights into the roles of DNA stability and integrity for the ageing process and the development of age-associated diseases.

RESUMEN

Dunnigan-type partial lipodystrophy (familial partial lipodystrophy, Dunnigan variety, FPLD2) can be caused by LMNA mutations. We identified a novel heterozygous LMNA mutation, P485R, in a patient referred to the International Registry of Werner Syndrome because of features consistent with that of progeroid disorder but who was wild type at the WRN locus. The novel mutation is located 2 amino acids away from the canonical FPLD mutations in exon 8 of the LMNA gene. Immunocytochemical analysis revealed abnormal nuclear morphology characteristic of laminopathies within primary fibroblast cultures, but not in a lymphoblastoid cell line, in keeping with previous observations. Our findings indicate that FPLD2 should be considered in the differential diagnosis of the Werner syndrome.

RESUMEN

The aim of the present study was to describe the characteristics of Guiana dolphins (S. guianensis) group size and composition in the Paranaguá Estuarine Complex (25 degrees 15'-25 degrees 36' S and 48 degrees 02'-48 degrees 45' W), Paraná State, as well as to verify the existence of relationships between a given environmental variable (water depth, salinity, transparency and temperature) and group size. An area of around 124 km(2) was surveyed by boat from April 2006 to February 2008 in the following subsets of the estuary: Canal do Superagui (approximately 28 km(2)), Pinheiros bay (approximately 34 km(2)), part of Laranjeiras bay, which included the Guaraqueçaba sub-estuary (approximately 38 km(2)), and part of the Mixture Section of the Paranaguá Estuarine Complex (approximately 24 km(2)). In 45 survey days, a total of 147 hours were spent observing 286 groups of S. guianensis. Groups varied from two individuals to aggregations of up to 90 individuals (mean +/- SD: 11.5 +/- 14.4 individuals). Solitary individuals were seen only on five occasions (1.7% of all observations). Groups with calves (n = 247) represented 86.4% overall and were more common in all sub-areas when compared to groups without calves. Groups without calves were found in all sub-areas and were usually smaller and composed of up to 12 individuals. A usual group composition of 70% of adults and 30% of calves was observed considering all sub-areas and seasons. No correlations were found between group size and water temperature (Spearman's rank test, r = 0.0059, p = 0.9338), transparency (Spearman's rank test, r = 0.0597, p = 0.9333), depth (Spearman's rank test, r = 0.1421, p = 0.4698), and salinity (Spearman's rank test, r = -0.1938, p = 0.0665). While Guiana dolphin groups were seen in the entire surveyed area, group size varied significantly among the three main surveyed sub-areas (Kruskal Wallis, H2,196 = 29.85, p = 0.0000). Groups were larger in Laranjeiras bay and smaller in Canal do Superagui. The physical environment, risk of predation, seasonal distribution and abundance of prey are the main possible factors driving larger groups in inner and protected waters.

Asunto(s)

RESUMEN

The main objective of the present study was to describe the characteristics regarding interactions between Guiana dolphins, Sotalia guianensis and seabirds in feeding associations in two distinct areas of the Lagamar estuary, Brazil. Boat-based surveys directed towards photo-identification studies of S. guianensis were conducted in the Cananéia Estuary (CE) (25 degrees 01' S and 47 degrees 55' W) from July 2004 to March 2008, as well as in the Paranaguá Estuarine Complex (PEC) (25 degrees 24' S and 48 degrees 24' W) from April 2006 to February 2008. On all occasions when seabirds were observed engaging in multi-species feeding associations with S. guianensis, data on species involved and their numbers were gathered. From 435 observed groups of S. guianensis in the CE, 38 (8.7%) involved interactions with seabirds. In the PEC, from the 286 observed groups, 32 (11.2%) involved the mentioned interactions. The following seabirds were observed in feeding associations with S. guianensis: Fregata magnificens, Sula leucogaster, Phalacrocorax brasilianus, and Sterna sp. In the CE, S. leucogaster was more commonly observed in feeding associations with Guiana dolphins (chi2 = 22.84; d.f. = 3, p < 0.05), while in the PEC no differences were reported when comparing seabird species (chi2 = 5.78; d.f.=3, p = 0.1223). In the CE, feeding associations were significantly more frequent in inner waters (subset A0; chi2 = 9.52; d.f. = 2, p < 0.05), and in winter (chi2 = 12.46; d.f. = 1, p < 0.05). Within these events, 44.7% of the association groups were composed by more than one seabird species. Seasonality in feeding associations was also observed in the PEC (chi2 = 4.76; d.f. = 1, p < 0.05), with same patterns observed in the CE. Interactions were more frequent in inner waters of the Laranjeiras bay, PEC (chi2 = 11.65; d.f. = 2, p < 0.05). Within these events, 74.2% of the association groups were composed by more than one seabird species. Water transparency, prey and seabird abundance and distribution, cetacean group size, and the life cycle of prey and seabirds are listed as the main factors addressing multi-species feeding associations in the Lagamar estuary.

Asunto(s)

RESUMEN

Impaired wound healing is a feature of Werner's syndrome. Treatment of one such patient with painful chronic leg ulcers included topical application of PDGF-BB. Granulation increased slightly, enabling full-thickness skin grafting to take place.

Asunto(s)

RESUMEN

In mammalian cells, DNA double-strand breaks are repaired by non-homologous end-joining and homologous recombination, both pathways being essential for the maintenance of genome integrity. We determined the effect of mutations in Ku86 and DNA-PK on the efficiency and the accuracy of double-strand break repair by non-homologous end-joining and homologous recombination in mammalian cells. We used an assay, based on the transient transfection of a linearized plasmid DNA, designed to simultaneously detect transfection and recombination markers. In agreement with previous results non-homologous end-joining was largely compromised in Ku86 deficient cells, and returned to normal in the Ku86-complemented isogenic cell line. In addition, analysis of DNA plasmids recovered from Ku86 mutant cells showed an increased use of microhomologies at the nonhomologous end joining junctions, and displayed a significantly higher frequency of DNA insertions compared to control cells. On the other hand, the DNA-PKcs deficient cell lines showed efficient double-strand break repair by both mechanisms.

Asunto(s)

RESUMEN

Problems associated with long-term treatment of advanced Parkinson's disease (PD) include motor complications and psychotic and autonomic symptoms. We switched patients from bromocriptine (BR) or pergolide (PER) to cabergoline (CB) therapy and investigated CB's usefulness in alleviating such problems. Subjects were 30 patients (mean age 68.2 years; 13 receiving BR, 17 PER) with PD complicated by effects of long-term treatment but in whom their dose of dopamine (DA) agonist was contraindicated due to adverse reactions. Patients were switched to CB over a 2-4-week period. Hoehn-Yahr and Unified Parkinson Disease Rating Scale (UPDRS) I-IV "on" and "off" scores improved in both the BR and PER groups. CB was not discontinued due to adverse reactions in any patient. In conclusion, switching to CB is useful in patients in whom it is problematic to increase their dose of DA agonist due to motor complications or psychotic symptoms of advanced PD.

Asunto(s)

RESUMEN

We describe a boy with chromosomal breakage syndrome, who died of hepatocellular carcinoma at the age of 17 years. Other findings included growth retardation, bilateral cataracts, premature graying of hair and elevated levels of urinary hyaluronic acid. Intellectual functions were normal. Although some manifestations were suggestive of Werner syndrome, the diagnosis could not be confirmed by molecular investigations. Therefore, this patient probably represents a provisionally unique syndrome, perhaps due to a mutation in a related (helicase) gene.

Asunto(s)

RESUMEN

Werner syndrome (WS) is a human premature aging syndrome, which is associated with high frequencies of neoplasia and genetic instability. We have examined the occurrence of microsatellite instability, which may result from defective mismatch repair, in lymphoblastoid cell lines derived from nine WS patients. Instability was measured at the D2S123 locus by gel analysis of PCR products. Three WS cell lines had 4-13% altered alleles, compared with 0% in the other six lines. The increased frequency of microsatellite instability could not readily be associated with overt cancer or any other known clinical condition in the three patients. To examine whether the WS defect affected the humoral immune system, we measured the hypermutation of immunoglobulin variable genes in peripheral blood cells from the WS patient who donated the cell line with the highest frequency of microsatellite instability. The frequency and pattern of mutation was similar to that from normal individuals, suggesting that the Werner protein is not involved in generating hypermutation.

Asunto(s)

RESUMEN

Reduced replicative capacity is a consistent characteristic of cells derived from patients with Werner syndrome. This premature senescence is phenotypically similar to replicative senescence observed in normal cell strains and includes altered cell morphology and gene expression patterns. Telomeres shorten with in vitro passaging of both WRN and normal cell strains; however, the rate of shortening has been reported to be faster in WRN cell strains, and the length of telomeres in senescent WRN cells appears to be longer than that observed in normal strains, leading to the suggestion that senescence in WRN cell strains may not be exclusively associated with telomere effects. We report here that the telomere restriction fragment length in senescent WRN fibroblasts cultures is within the size range observed for normal fibroblasts strains and that the expression of a telomerase transgene in WRN cell strains results in lengthened telomeres and replicative immortalization, thus indicating that telomere effects are the predominant trigger of premature senescence in WRN cells. Microarray analyses showed that mRNA expression patterns induced in senescent WRN cells appeared similar to those in normal strains and that hTERT expression could prevent the induction of most of these genes. However, substantial differences in expression were seen in comparisons of early-passage and telomerase-immortalized derivative lines, indicating that telomerase expression does not prevent the phenotypic drift, or destabilized genotype, resulting from the WRN defect.

Asunto(s)

RESUMEN

A number of human genes have been identified in which mutations can lead to the accelerated emergence of features of senescence. Studies of these genes, and of the functions of their protein products, may lead to a clearer understanding of the nature of senescence, and could provide clues for ways in which ageing might be retarded.

Asunto(s)

RESUMEN

Werner syndrome is a Mendelian disorder of man that produces a number of manifestations resembling human aging. This disorder is caused by inactivation of the wrn gene, a member of the RecQ family of DNA helicases. The helicase and exonuclease activities of the Werner protein (WRN) suggest that it functions in DNA transactions, but the physiological function of WRN remains elusive. We present several lines of evidence that WRN interacts specifically with the p50 subunit of polymerase delta, the major DNA polymerase required for chromosomal DNA replication. P50, identified by yeast two-hybrid screening, interacts physically with the C terminus of WRN. Native WRN protein coimmunoprecipitates with p50 in a cellular fraction enriched in nucleolar proteins, and this immunocomplex also includes p125, the catalytic subunit of polymerase delta. In subcellular localization studies of cells transfected with WRN, p50 and p125 redistribute to the nucleolus and colocalize with WRN. These results suggest that one of the functions of WRN protein is to directly modify DNA replication via its interaction with p50 and abet dynamic relocalization of the DNA polymerase delta complexes within the nucleus.

Asunto(s)

RESUMEN

Progeria and progeroid syndromes are characterized by the earlier onset of complex senescent phenotypes. WRN was originally identified as a gene responsible for Werner syndrome (WS; "Progeria of Adults"). The WRN gene product has RecQ-type helicase domains in the central region of the protein. Subsequent studies also revealed that the WRN protein displays exonuclease activity and acts as a transcriptional activation factor. These biochemical studies, combined with cell biological studies, suggested that this protein is likely to be involved in the response to DNA damage during replication, as well as recombination and transcription processes. However, the precise molecular mechanisms by which mutations in WRN cause the WS phenotype remain unknown. Recent progress in the understanding of the WRN protein and its implication in the normal aging process are discussed.

Asunto(s)

RESUMEN

Although maladaptive coping strategies in eating disorder patients have been reported, the relationship between impulsivity and coping strategy has not previously been studied. Subjects consisted of 43 patients with anorexia nervosa restricting type (AN-R), 42 patients with anorexia nervosa binge eating/purging type (AN-BP), 71 patients with bulimia nervosa purging type (BN), and 97 controls. The Coping Inventory for Stressful Situations was used to evaluate coping strategies. Only AN-BP patients had a significantly lower task oriented-coping score than controls, and AN-R and BN patient groups used significantly less social diversion-avoidance coping strategies than controls. Emotion-oriented coping scores of AN-BP and BN patients were significantly higher than those of controls. In addition, impulsive BN patients had significantly higher emotional coping scores than less impulsive BN patients. These results suggest that maladaptive coping strategies may be a perpetuating factor even for impulsive patients and emphasizing a change in maladaptive coping strategies may be a useful treatment strategy even for highly impulsive patients.

Asunto(s)

RESUMEN

Werner's syndrome (WS) is an autosomal recessive disorder in humans characterized by the premature development of a partial array of age-associated pathologies. WRN, the gene defective in WS, encodes a 1432 amino acid protein (hWRN) with intrinsic 3'-->5' DNA helicase activity. We recently showed that hWRN is also a 3'-->5' exonuclease. Here, we further characterize the hWRN exonuclease. hWRN efficiently degraded the 3' recessed strands of double-stranded DNA or a DNA-RNA heteroduplex. It had little or no activity on blunt-ended DNA, DNA with a 3' protruding strand, or single-stranded DNA. The hWRN exonuclease efficiently removed a mismatched nucleotide at a 3' recessed terminus, and was capable of initiating DNA degradation from a 12-nt gap, or a nick. We further show that the mouse WRN (mWRN) is also a 3'-->5' exonuclease, with substrate specificity similar to that of hWRN. Finally, we show that hWRN forms a trimer and interacts with the proliferating cell nuclear antigen in vitro. These findings provide new data on the biochemical activities of WRN that may help elucidate its role(s) in DNA metabolism.

Asunto(s)

RESUMEN

WRN encodes a RecQ helicase, which is mutated in Werner syndrome. Werner syndrome is a genetic condition of young adults characterized by premature aging, limited replicative capacity of cells in vitro, and increased cancer risk. Telomerase is a reverse transcriptase that extends the G-rich strand of telomeric DNA. Primary cells in vitro typically lack telomerase activity and undergo senescence, whereas telomerase is reactivated in many, but not all, tumors. The roles of the two genes are not known to be related. Here we report the development of an effective colony-forming assay in which a SV40-transformed Werner fibroblast cell line is 6-18-fold more sensitive to 4-nitroquinoline 1-oxide than SV40-transformed normal cell lines. The sensitivity can be partially reversed by transfecting a normal WRN gene but not a mutated WRN gene into the cells. Curiously, the sensitivity can be reversed equally well by transfecting a telomerase gene (TERT) into the cells. These data indicate the possibility of an interdependent function of these two genes.

Asunto(s)

RESUMEN

Werner syndrome (WRN) is an uncommon autosomal recessive disease in which progeroid features are associated with genetic instability and an elevated risk of neoplasia. We have used the glycophorin A (GPA) somatic cell mutation assay to analyze genetic instability in vivo in WRN patients and heterozygotes. GPA variant frequencies were determined for 11 WRN patients and for 10 heterozygous family members who collectively carry 10 different WRN mutations. Genetic instability as measured by GPA O/N allele loss variant frequency was significantly increased, and this increase was strongly age-dependent in WRN patients. GPA O/N allele loss variants were also significantly elevated in heterozygous family members, thus providing the first evidence for in vivo genetic instability in heterozygous carriers in an autosomal recessive genetic instability syndrome. Our results and comparable data on other human genetic instability syndromes allow an estimate of the level of genetic instability that increases the risk of human bone marrow dysfunction or neoplasia.

Asunto(s)

RESUMEN

Werner syndrome (WS) ("Progeria of the adult"; entry *27770 (1)) was originally defined by Dr. Otto Werner in 1904 on the basis of "scleroderma-like" thin, tight skin and bilateral cataracts in a sibship (2). Among the many systemic clinical features of WS, the various progeroid features have drawn special attention. WS is caused by a mutation at the Werner syndrome gene (WRN) locus, which belongs to the family of RecQ helicases (GenBank accession number L76937)(3). This review focuses on the comparative aspects of WRN, including differential gene action within humans and the potential differences between species, particularly the mouse and human.

Asunto(s)

RESUMEN

Mutations at the Werner helicase locus (WRN) are responsible for the Werner syndrome (WS). WS patients prematurely develop an aged appearance and various age-related disorders. We have generated transgenic mice expressing human WRN with a putative dominant-negative mutation (K577M-WRN). Primary tail fibroblast cultures from K577M-WRN mice showed three characteristics of WS cells: hypersensitivity to 4-nitroquinoline-1-oxide (4NQO), reduced replicative potential, and reduced expression of the endogenous WRN protein. These data suggest that K577M-WRN mice may provide a novel mouse model for the WS.

Asunto(s)