Acute and early life-stage toxicity of atrazine in sheepshead minnow (Cyprinodon variegatus).

Given the limited data available for estuarine/marine fish species and potential risk of being exposed to the herbicide atrazine, additional toxicity data regarding sensitive life-stages are needed. As such, this work sought to characterize: 1) the acute larval toxicity, and 2) early life-stage toxicity of technical atrazine in the model marine species sheepshead minnow (Cyprinodon variegatus). Atrazine was observed to be slightly to moderately toxic towards C. variegatus under acute conditions (as per U.S. EPA 2017 criteria). After 96 h exposure, mortality rates of 5%, 15%, 35%, and 90% were observed among fish exposed to atrazine at 4.6, 7.6, 13, and 22 mg a.i./L, respectively. Sub-lethal effects were observed among surviving fish exposed to > 3.2 mg a.i/L. The 96 h LC50 was 13 mg a.i./L and the NOEC was 3.2 mg a.i./L. In the 33 d early-life stage test, mean embryo survival rates in 0.15, 0.30, 0.57, 1.1, and 2.2 mg a.i./L treatments ranged from 71% to 79% and were not different from survival in the control (78%). Following 28 d post-hatch exposure (Day 33), mean larval survival ranged from 98% to 100% in all treatments and the control. Larval length and wet weight were the most sensitive indicators of the toxicity of atrazine to early life-stage sheepshead minnow. The NOEC for growth was 1.1 mg a.i./L and the LOEC was 2.2 mg a.i./L. Based on these, the MATC for atrazine to sheepshead minnow embryos and larvae was estimated to be 1.6 mg a.i./L. These results were consistent with previous investigations in sheepshead minnow and other marine fish species. Based on the results, atrazine would not be expected to pose unacceptable risks for sheepshead minnow early life-stages at environmentally relevant concentrations.

Human p53 directs DNA strand reassociation and is photolabelled by 8-azido ATP.

p53 is the most frequent known target for mutation in human cancer. Evidence suggests that p53 protein may be involved variously in transcription and cell cycle control, in DNA replication and in G1 checkpoint control following the cellular response to radiation induced DNA damage. p53 blocks DNA replication of the small DNA tumour virus, simian virus 40, by inhibiting unwinding of the viral origin of replication by the DNA helicase activity of the virally encoded large T antigen protein. Here we report the novel observation that human p53 protein can bind ATP and exhibits an intrinsic ATP stimulated DNA strand reassociation activity. Both activities map to the carboxyl terminal 128 amino acids of p53. Thus, in addition to any role in transcription, our results indicate that p53 is potentially capable of inhibiting mammalian replicative DNA synthesis by blocking the DNA strand separation step during replication origin recruitment. However, the ability of p53 to modulate the topological relationship between complementary nucleotide strands is also compatible with a direct role for p53 in other aspects of DNA synthesis, recombination or repair.

Mouse p53 blocks SV40 DNA replication in vitro and downregulates T antigen DNA helicase activity.

Immunopurified mouse p53 proteins were used to gain experimental access to the mechanisms underlying nonprimate p53 directed suppression of SV40 origin directed DNA replication in vivo. In replication competent HeLa cell extracts containing exogenous T antigen, mouse p53 blocks T antigen dependent DNA synthesis as in vivo. However, in transcription competent HeLa extracts, mouse p53 has no effect either on overall transcription or on the ability of immunopurified T antigen to downregulate SV40 early transcription. We show that although mouse p53 has no significant effect on T antigen encoded activities such as ATPase and DNA binding, helicase activity is somewhat reduced suggesting that the in vivo suppression by mouse p53 of SV40 replication may be due, at least in part, to direct modulation of T antigen function.

p53 interacts with p34cdc2 in mammalian cells: implications for cell cycle control and oncogenesis.

The p53 gene product has been implicated in both human and animal tumorigenesis. p53 complexes with the transforming proteins encoded by several different DNA tumour viruses. We demonstrate that human p53 is phosphorylated by the mammalian p34cdc2 kinase in vitro and coprecipitates with p34cdc2 in vivo. Our observations suggest that phosphorylation of p53 by p34cdc2 kinase may regulate the known activities of p53 in the initiation steps of DNA replication in mammalian cells.

A human tumour-derived mutant p53 protein induces a p34cdc2 reversible growth arrest in fission yeast.

We have expressed wild-type and human tumour-derived mutant p53 cDNA genes in the fission yeast Schizosaccharomyces pombe. In the case of one mutant this resulted in a growth arrest of recipient yeast cells. In contrast, wild-type p53 and three other mutant proteins tested did not block outgrowth of colonies. Human and yeast cdc2 acted as functionally equivalent extragenic suppressors of the mutant-induced growth arrest allowing the establishment of viable p53 expressor strains. In cotransformation assays the mutant allele was found to be dominant over wt p53. Our results provide the first evidence of a functional relationship between p53 and p34cdc2 in an in-vivo system and suggest that the wide variety of mutant proteins present in human tumours may fall into functionally distinct subclasses.

A C-terminal alpha-helix plus basic region motif is the major structural determinant of p53 tetramerization.

The p53 gene product has been implicated in both human and animal tumorigenesis. p53 forms heterologous complexes with the transforming proteins encoded by several different DNA tumor viruses. p53 also assembles into stable homo-oligomers. We demonstrate that the major structural determinant for the tetramerization of p53 is an alpha-helical plus basic region motif near the C-terminus of the protein. A monomeric p53 mutant adopts a conformation distinct from both 'wild-type' and 'mutant' form as defined by PAb1620 and PAb240 monoclonal antibody recognition. Nevertheless, monomeric and dimeric mutant p53 proteins retain the ability to suppress SV40 origin-directed DNA replication in vivo. Thus, p53-p53 interaction and expression of the PAb1620 epitope is not a prerequisite for such activity. We present data suggesting that suppression of replication by p53 may occur by a mechanism that is independent of detectable p53-T antigen association.

Assessing pesticide risks to threatened and endangered species using population models: Findings and recommendations from a CropLife America Science Forum.

This brief communication reports on the main findings and recommendations from the 2014 Science Forum organized by CropLife America. The aim of the Forum was to gain a better understanding of the current status of population models and how they could be used in ecological risk assessments for threatened and endangered species potentially exposed to pesticides in the United States. The Forum panelists' recommendations are intended to assist the relevant government agencies with implementation of population modeling in future endangered species risk assessments for pesticides. The Forum included keynote presentations that provided an overview of current practices, highlighted the findings of a recent National Academy of Sciences report and its implications, reviewed the main categories of existing population models and the types of risk expressions that can be produced as model outputs, and provided examples of how population models are currently being used in different legislative contexts. The panel concluded that models developed for listed species assessments should provide quantitative risk estimates, incorporate realistic variability in environmental and demographic factors, integrate complex patterns of exposure and effects, and use baseline conditions that include present factors that have caused the species to be listed (e.g., habitat loss, invasive species) or have resulted in positive management action. Furthermore, the panel advocates for the formation of a multipartite advisory committee to provide best available knowledge and guidance related to model implementation and use, to address such needs as more systematic collection, digitization, and dissemination of data for listed species; consideration of the newest developments in good modeling practice; comprehensive review of existing population models and their applicability for listed species assessments; and development of case studies using a few well-tested models for particular species to demonstrate proof of concept. To advance our common goals, the panel recommends the following as important areas for further research and development: quantitative analysis of the causes of species listings to guide model development; systematic assessment of the relative role of toxicity versus other factors in driving pesticide risk; additional study of how interactions between density dependence and pesticides influence risk; and development of pragmatic approaches to assessing indirect effects of pesticides on listed species.

The ontology of the questionnaire: Max Weber on measurement and mass investigation.

Although contemporary sociologists of science have sometimes claimed Max Weber as a methodological precursor, they have not examined Weber's own writings about science. Between 1908 and 1912 Weber published a series of critical studies of the extension of scientific authority into public life. The most notable of these concerned attempts to implement the experimental psychology or psycho-physics laboratory in factories and other real-world settings. Weber's critique centered on the problem of social measurement. He emphasized the discontinuities between the space of the laboratory and that of the factory, showing how several qualitative and historically conditioned differences between the two settings rendered the transfer of instruments and methods between them highly problematic. Weber's critical arguments prepared the ground for his greatest foray into empirical sociology, a survey he directed for the Verein für Sozialpolitik investigating the conditions and attitudes affecting the lives and performance of industrial workers. Using a different measuring instrument - the questionnaire - Weber tried to implement a concept of social measurement which implied a different ontology, drawn not from natural sciences but from the historical sciences.

Impact of treadmill running and sex on hippocampal neurogenesis in the mouse model of amyotrophic lateral sclerosis.

Hippocampal neurogenesis in the subgranular zone (SGZ) of dentate gyrus (DG) occurs throughout life and is regulated by pathological and physiological processes. The role of oxidative stress in hippocampal neurogenesis and its response to exercise or neurodegenerative diseases remains controversial. The present study was designed to investigate the impact of oxidative stress, treadmill exercise and sex on hippocampal neurogenesis in a murine model of heightened oxidative stress (G93A mice). G93A and wild type (WT) mice were randomized to a treadmill running (EX) or a sedentary (SED) group for 1 or 4 wk. Immunohistochemistry was used to detect bromodeoxyuridine (BrdU) labeled proliferating cells, surviving cells, and their phenotype, as well as for determination of oxidative stress (3-NT; 8-OHdG). BDNF and IGF1 mRNA expression was assessed by in situ hybridization. Results showed that: (1) G93A-SED mice had greater hippocampal neurogenesis, BDNF mRNA, and 3-NT, as compared to WT-SED mice. (2) Treadmill running promoted hippocampal neurogenesis and BDNF mRNA content and lowered DNA oxidative damage (8-OHdG) in WT mice. (3) Male G93A mice showed significantly higher cell proliferation but a lower level of survival vs. female G93A mice. We conclude that G93A mice show higher hippocampal neurogenesis, in association with higher BDNF expression, yet running did not further enhance these phenomena in G93A mice, probably due to a 'ceiling effect' of an already heightened basal levels of hippocampal neurogenesis and BDNF expression.

Nivel de dolor en pacientes amigdalectomizados / Level of pain in tonsilectomy patients

Obtener datos epidemiológicos de lasamigdalectomías realizadas durante dos años quirúrgicos en el Hospital Nacional de Clínicas. Valorar la incidencia entre la técnica quirúrgica empleada y el gradode dolor postoperatorio. Relacionar la técnica quirúrgica con el dolor postoperatorio y la incorporación de ladieta.Material y método: Se realizó un estudioprospectivo, utilzando el método estadístico, que incluyó a 10 pacientes de ambos sexos, de 14 a 56 años deedad, amigdalectomizados en el Hospital Nacional de Clínicas de Córdoba -Argentina -con técnica de Danielso decolación y utilzación de Ansa, en el periodo comprendido entre marzo del 2010 y abril del 2012.

Get epidemiological data oftonsilectomy surgery performed for two years in theNational Clinical Hospital.Ases whether there is arelationship betwen surgical technique and the degreof postoperative pain. Relate surgical technique with thereturn of the diet.Materials and methods A prospective study wasperformed using the statistical method, which included10 patients of both sexes aged 14 to 56 years old,tonsilectomy in the National Clinical Hospital of Cordoba- Argentina, with Daniels technique, or parietal peritoneumand using Ansa ,in the period betwen March 2010 and April 2012.

Microcosm evaluation of the toxicity and risk to aquatic macrophytes from perfluorooctane sulfonic acid.

Perfluorooctane sulfonic acid (PFOS) is an anthropogenic contaminant detected in various environmental and biologic matrices. This compound is a fluorinated surfactant, a class of molecules renowned for their persistence and their global distribution but for which few ecotoxicological data are currently available, especially under field conditions. The toxicity of PFOS to the aquatic macrophytes Myriophyllum sibiricum and M. spicatum was investigated using 12,000 L outdoor microcosms. Replicate microcosms (n = 3) were treated with 0.3, 3, 10, and 30 mg/L PFOS as the potassium salt and assessed at regular intervals during a period of 42 days. M. sibiricum was more sensitive to PFOS under these simulated field conditions than M. spicatum. Toxicity was observed in the evaluated end points at > 3 mg/L PFOS for EC10s and > 12 mg/L PFOS for EC50s for M. spicatum and in M. sibiricum at > 0.1 mg/L PFOS for EC10s and > 1.6 mg/L PFOS for EC50s. The no observed-effect concentration (NOEC) for M. spicatum was consistently > or = 11.4 mg/L PFOS, whereas the NOEC for M. sibiricum was > or = 0.3 mg/L PFOS. A risk assessment for these plants estimated a negligible probability of toxicity being observed in these plants from PFOS exposure at current environmental concentrations.

Ganglion cells in achalasia of the cardia.

The histopathology of 40 cases of achalasia of the cardia, 6 cases of oesophageal spasm-incoordination and 4 cases of scleroderma was examined. Three cases of carcinoma and 6 cases of reflux oesophagitis were used as a control group. A nearly complete loss of myenteric ganglion cells was found in the upper thickened segment in achalasia. Some surviving ganglion cells were found in the lower segments in half the cases of achalasia; in two cases counts were normal in this segment. The occurrence of neuronal chromatolysis in 9 biopsies of achalasia supports the view that an active disease process was involved. The preganglionic parasympathetic fibres in two cases of achalasia were normal in appearance and number; this somewhat limited evidence tends to count against a primary disorder of the preganglionic neurone in this condition. The 6 cases of oesophageal spasm-incoordination showed similar neuronal loss to that in the lower segment in achalasia. Possibly "oesophageal spasm" represent an early stage or incomplete expression of achalasia. One cases of scleroderma showed loss of ganglion cells, but the myenteric plexus was here involved by the disease process. None of the 9 cases in the control group showed any loss of ganglion cells or chromatolysis. Acute and chronic inflammation was not convincingly associated with loss of ganglion cells in either achalasia or oesophageal spasm.

The E2 binding sites determine the efficiency of replication for the origin of human papillomavirus type 18.

Human papillomaviruses (HPV-s) have been shown to possess transforming and immortalizing activity for many different, mainly keratinocyte cell lines and they have been detected in 90% of anogenital cancer tissues, which suggests a causative role in the induction of anogenital and other tumours. We have exploited a quantitative assay to identify and characterize the origin of replication of the human papillomavirus type 18 (HPV-18), one of the most prevalent types in the high-risk HPV group. Replication of HPV origin fragments was studied transiently by cotransfection with a protein expression vector providing replication proteins E1 and E2. We have localized the HPV-18 origin to nucleotides 7767-119. This region contains three E2 binding sites and an essential A/T rich DNA region (nucleotides 9-35) that is partly homologous to the E1 binding site found in bovine papillomavirus type 1 (BPV-1) genome. At least one of the three E2 binding sites was absolutely required for origin function; addition of other E2 sites had cooperative stimulating effect. This is the first quantitative analysis of the E2 binding sites for papillomavirus replication.