Genotoxic and cytotoxic effect of exposure to thallium on mature spermatozoa of mice

Introduction. The adverse effects of chemicals on male reproduction is an area of growing concern. Currently, Thallium (Tl) is used mainly in the manufacture of electronic devices, switches and closures, as well as in power plants, cement factories and foundries. Aim. To evaluate sperm quality and genetic damage of sperm in mice exposed orally to Tl. Materials and methods. Male mice were treated with Tl doses of 5, 15 and 25 mg/kg/5d, sperm quality parameters and DNA damage were evaluated by the Sperm Chromatin Structure Assay (SCSA) technique. Results. Exposure to Tl affected sperm motility, viability and morphology. Alterations in the DNA structure (%DFI and %HSD) of the spermatozoa were observed. Tl could be considered reprotoxic, since it alters reproductive capacity.Introducción. Los efectos adversos de los químicos en la reproducción masculina es un área de preocupación creciente, actualmente el Tl es utilizado principalmente en la fabricación de dispositivos electrónicos, interruptores y cierres; así como en plantas generadoras de energía, fábricas de cemento y fundiciones. Objetivo.  Evaluar la calidad espermática y el daño genético de los espermatozoides en ratones expuestos oralmente a Tl. Materiales y métodos. Se utilizaron ratones macho y dosis de Tl de 5, 15 y 25 mg/kg/5d, se evaluaron los parámetros de calidad espermática y el daño al ADN por la técnica de SCSA. Resultados. La exposición a Tl afecto la motilidad, la viabilidad y la morfología espermática. Se observaron alteraciones en la estructura del ADN (%DFI y %HSD) de los espermatozoides. El Tl  se podría considerar reprotóxico, ya que altera capacidad reproductiva.&nbsp

Inhibition of Acetylcholinesterase in Wild Bird Populations Exposure to Pesticides

El uso generalizado de plaguicidas en los campos agrícolas ha resultado en la exposición de especies de vida silvestre. Las especies de aves han mostrado una disminución sustancial de su población y una contracción de su distribución en los agroecosistemas, lo que se ha relacionado con la intensificación de la agricultura. En este estudio se evalúa la AChE en sangre en diferentes especies de aves (Turdus rufopalliatus, Icterus pustulatus, Melanerpes chrysogenys, Crotophaga sulcirostris; ambos géneros) en tierras agrícolas del estado de Guerrero, sur de México. Los resultados muestran una tendencia a ser sensibles en las hembras a la inhibición de AChE. Nuestros resultados también sugieren que la inhibición de la AChE por plaguicidas podría tener repercusiones en la población de especies de aves.The widespread use of pesticides in agricultural fields has resulted in the exposure of wildlife species. Bird species have shown substantial population decline and range contraction in agroecosystems, which have been linked to the intensification of agriculture. In this study AChE evaluation in blood in different species of birds (Turdus rufopalliatus, Icterus pustulatus, Melanerpes chrysogenys, Crotophaga sulcirostris; both genders) in agricultural lands of the state of Guerrero, southern Mexico. The result show a tendency to susceptible the female birds at inhibition AChE. Our results also suggest that inhibition of AChE due to pesticides could have repercussions in the population of bird species

Binding of hnRNP H and U2AF65 to Respective G-codes and a Poly-Uridine Tract Collaborate in the N50-5'ss Selection of the REST N Exon in H69 Cells

The splicing of the N exon in the pre-mRNA coding for the RE1-silencing transcription factor (REST) results in a truncated protein that modifies the expression pattern of some of its target genes. A weak 3’ss, three alternative 5’ss (N4-, N50-, and N62-5’ss) and a variety of putative target sites for splicing regulatory proteins are found around the N exon; two GGGG codes (G2-G3) and a poly-Uridine tract (N-PU) are found in front of the N50-5’ss. In this work we analyzed some of the regulatory factors and elements involved in the preferred selection of the N50-5’ss (N50 activation) in the small cell lung cancer cell line H69. Wild type and mutant N exon/b-globin minigenes recapitulated N50 exon splicing in H69 cells, and showed that the N-PU and the G2-G3 elements are required for N50 exon splicing. Biochemical and knockdown experiments identified these elements as U2AF65 and hnRNP H targets, respectively, and that they are also required for N50 exon activation. Compared to normal MRC5 cells, and in keeping with N50 exon activation, U2AF65, hnRNP H and other splicing factors were highly expressed in H69 cells. CLIP experiments revealed that hnRNP H RNA-binding occurs first and is a prerequisite for U2AF65 RNA binding, and EMSA and CLIP experiments suggest that U2AF65-RNA recognition displaces hnRNP H and helps to recruit other splicing factors (at least U1 70K) to the N50-5’ss. Our results evidenced novel hnRNP H and U2AF65 functions: respectively, U2AF65-recruiting to a 5’ss in humans and the hnRNP H-displacing function from two juxtaposed GGGG codes

Efecto del cloruro de cadmio sobre la expresión del represor transcripcional REST/NRSF y su gen blanco CDH1 en tejido pulmonar de ratones ICR-CD1

REST (RE1-Silencing Transcription factor) is a transcription factor with zinc fingers that represses its transcriptional targets through its interaction with the RE1 (Restrictive Element 1) sequence. Although some metals such as cadmium can alter protein function by competing with zinc, studies at the molecular level have not been performed to determine this effect on REST. The CDH1 gene is a transcriptional target of REST that codes for the cell adhesion glycoprotein E-cadherin and the deregulation of its expression has been associated with the cancerous process. The objective of this work was to evaluate the effect of exposure to 1.3 µM/3 days with CdCl2 in ICR-CD1 mice on the levels of REST and its target gene CDH1 in lung tissue. CDH1 mRNA levels were determined by RT-PCR, while E-cadherin and REST protein levels were assessed by Western blot. After CdCl2 treatment, the levels of CDH1 and its product E-cadherin increased in relation to the loss of REST expression. In conclusion, cadmium promotes a decrease in REST at the protein level, as well as an increase in the levels of CDH1 messenger RNA and its E-cadherin product. The increase in E-cadherin is probably due to CDH1 transcriptional relaxation mediated by loss of REST expression.REST (RE1-Silencing Transcription factor) es un factor de transcripción con dedos de zinc que reprime a sus blancos transcripcionales a través de su interacción con la secuencia RE1 (Restrictive Element 1). Aunque algunos metales como el cadmio pueden alterar la función de proteínas al competir con el zinc, no se han realizado estudios a nivel molecular para para determinar dicho efecto sobre REST. El gen CDH1 es un blanco transcripcional de REST que codifica para la glicoproteína de adhesión celular E-cadherina y la desregulación de su expresión ha sido asociada al proceso canceroso. El objetivo de este trabajo fue evaluar el efecto de la exposición a 1.3 µM/3 días con CdCl2 en ratones ICR-CD1 sobre los niveles de REST y de su gen blanco CDH1 en tejido pulmonar. Los niveles del mRNA de CDH1 se determinaron por RT-PCR, mientras que los niveles de las proteínas E-cadherina y REST se evaluaron mediante Western blot. Después del tratamiento con CdCl2 los niveles de CDH1 y de su producto E-cadherina se incrementaron en relación con la pérdida de la expresión de REST. En conclusión, el cadmio promueve la disminución de REST a nivel de proteína, así como el incremento de los niveles de ARN mensajero de CDH1 y de su producto E-cadherina. El incremento de E-cadherina probablemente se debe a la relajación transcripcional de CDH1 mediado por la pérdida de la expresión de REST

Principal component analysis as an efficient method for capturing multivariate brain signatures of complex disorders—ENIGMA study in people with bipolar disorders and obesity

Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. Practitioner Points: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.</p

Principal component analysis as an efficient method for capturing multivariate brain signatures of complex disorders—ENIGMA study in people with bipolar disorders and obesity

Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. Practitioner Points: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.</p

Principal component analysis as an efficient method for capturing multivariate brain signatures of complex disorders—ENIGMA study in people with bipolar disorders and obesity

Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. Practitioner Points: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables

Deering House Seniors, Westbrook Junior College, Class of 1957

Twenty-five of the twenty-nine Class of 1957 Deering House seniors have their photos glued to the windows of a paper assembled replica of Deering House in this black and white photograph by the Wendell White Studio, Portland, Maine. This photo was used as an introductory page in The Tower yearbook to those seniors who lived in Deering House. Class of 1957 seniors residing in Deering House included in alphabetical order: Sandra Marie Adams, Linda Jane Armstrong, Joan Bancroft, Beverly Jean Bishop, Carolyn Bjorkman, Evelyn Marie Colpitts, Joyce Copeland, Mary-Josephine Digby, Margaret Ann Eustis, Josephine Anne Handley, Jeanne Langlais, Janet Teresa Lewis, Barbara Joan Meister, Cynthia Jean Nevers, Nancy Newsome, Barbara Ann Peary, Ann D. Potter, Mary Jane Proesch, Sonya D. Pulcifer, Jean Healy Quinn, Priscilla Anne Randall, Jane W. Redonnett, Judith M. Roper, Barbara Ann Sanborn, Margaret L. Sanford, Carol Bruce Shute, Ellen Sloat, Sylvia Smith, and Margaret L. Whittakerhttps://dune.une.edu/wchc_photos_students1950s/1002/thumbnail.jp

Cooperative Binding of SRSF3 to Structured 3’ss-α Exon RNA during α Exon Inclusion in the ZO-1 mRNA

ZO-1α+ and ZO-1α− proteins are expressed in hermetic and leaky tight junctions, respectively. Two cis-acting distant exonic elements partly activate the 240 nucleotide-long α exon producing the ZO-1α+ isoform. However, the elements within and around the α exon and their respective factors involved in its splicing are unknown. To study the dynamic interaction between SRSF3 and its bioinformatically predicted target sites around the 3’ss upstream of the α exon during its activation, we performed EMSA, crosslinking, and in vivo splicing assays by ZO-1 minigene expression and siRNA-mediated silencing in transfected cells. Using V1 RNase, we probed the possible formation of a hairpin RNA structure between the intronic and proximal exonic SRSF3 binding sites. The hairpin sufficed for complex formations in the EMSA. The interaction of SRSF3 with the intronic site promoted the cooperative binding of SRSF3 to the exonic site. Finally, SRSF3 restored α exon activation in SRSF3 knockdown transfectants. Altogether, our results show that SRSF3–hairpin RNA interaction is crucial in the early recognition of 3’ss for α exon activation. It remains to be explored whether SRSF3 recruits or stabilizes the binding of other factors or brings separate splice sites into proximity

Image_3_Unexplored Molecular Features of the Entamoeba histolytica RNA Lariat Debranching Enzyme Dbr1 Expression Profile.TIF

<p>The RNA lariat debranching enzyme (Dbr1) has different functions in RNA metabolism, such as hydrolyzing the 2′-5′ linkage in intron lariats, positively influencing Ty1 and HIV-1 retrotransposition, and modulating snRNP recycling during splicing reactions. It seems that Dbr1 is one of the major players in RNA turnover. It is remarkable that of all the studies carried out to date with Dbr1, to our knowledge, none of them have evaluated the expression profile of the endogenous Dbr1 gene. In this work, we describe, for the first time, that Entamoeba histolytica EhDbr1 mRNA has a very short half-life (less than 30 min) and encodes a very stable protein that is present until trophozoite cultures die. We also show that the EhDbr1 protein is present in the nuclear periphery on the cytoplasmic basal side, contrary to the localization of human Dbr1. Comparing these results with previous hypotheses and with results from different organisms suggests that Dbr1 gene expression is finely tuned and conserved across eukaryotes. Experiments describing the aspects of Dbr1 gene expression and Dbr1 mRNA turnover as well as other functions of the protein need to be performed. Particularly, a special emphasis is needed on the protozoan parasite E. histolytica, the causative agent of amoebiasis, since even though it is a unicellular organism, it is an intron-rich eukaryote whose intron lariats seem to be open to avoid intron lariat accumulation and to process them in non-coding RNAs that might be involved in its virulence.</p