Conserved G-quadruplexes regulate the immediate early promoters of human alphaherpesviruses

Human Alphaherpesviruses comprise three members, herpes simplex virus (HSV) 1 and 2 and varicella zoster virus (VZV). These viruses are characterized by a lytic cycle in epithelial cells and latency in the nervous system, with lifelong infections that may periodically reactivate and lead to serious complications, especially in immunocompromised patients. The mechanisms that regulate viral transcription have not been fully elucidated, but the master role of the immediate early (IE) genes has been established. G-quadruplexes are non-canonical nucleic-acid structures that control transcription, replication, and recombination in many organisms including viruses and that represent attractive antiviral targets. In this work, we investigate the presence, conservation, folding and activity of G-quadruplexes in the IE promoters of the Alphaherpesviruses. Our analysis shows that all IE promoters in the genome of HSV-1, HSV-2 and VZV contain fully conserved G-quadruplex forming sequences. These comprise sequences with long loops and bulges, and thus deviating from the classic G-quadruplex motifs. Moreover, their location is both on the leading and lagging strand and in some instances they contain exuberant G-tracts. Biophysical and biological analysis proved that all sequences actually fold into G-quadruplex under physiological conditions and can be further stabilized by the G-quadruplex ligand BRACO-19, with subsequent impairment of viral IE gene transcription in cells. These results help shed light on the control of viral transcription and indicate new viral targets to design drugs that impair the early steps of Alphaherpesviruses. In addition, they validate the significance of G-quadruplexes in the general regulation of viral cycles

Potencial evocado auditivo de tronco encefálico em recém-nascido: influência do sexo e da relação peso e idade gestacional

OBJECTIVE:To investigate the influence of gender and weight/gestational age ratio on the Auditory Brainstem Response (ABR) in preterm (PT) and term (T) newborns.METHODS:176 newborns were evaluated by ABR; 88 were preterm infants - 44 females (22 small and 22 appropriate for gestational age) and 44 males (22 small and 22 appropriate for gestational age). The preterm infants were compared to 88 term infants - 44 females (22 small and 22 appropriate for gestational age) and 44 males (22 small and 22 appropriate for gestational age). All newborns had bilateral presence of transient otoacoustic emissions and type A tympanometry.RESULTS:No interaural differences were found. ABR response did not differentiate newborns regarding weight/gestational age in males and females. Term newborn females showed statistically shorter absolute latencies (except on wave I) than males. This finding did not occur in preterm infants, who had longer latencies than term newborns, regardless of gender.CONCLUSIONS:Gender and gestational age influence term infants' ABR, with lower responses in females. The weight/gestational age ratio did not influence ABR response in either groups.OBJETIVO:Verificar las influencias del sexo y la relación peso/edad gestacional en las respuestas del Potencial Evocado Auditivo de Tronco Encefálico (PEATE) en recién nacidos pretérmino (PT) y a término (T).MÉTODOS:Se evaluaron a 176 recién nacidos por medio del PEATE, siendo 88 prematuros - 44 femeninos (22 pequeños y 22 adecuados para la edad gestacional) y 44 masculinos (22 pequeños y 22 adecuados para la edad gestacional). Se compararon los prematuros con 88 recién nacidos a término, 44 del sexo femenino (22 pequeños y 22 adecuados) y 44 del sexo masculino (22 pequeños y 22 adecuados). Todos los recién nacidos presentaron emisiones otoacústicas bilateralmente, por estímulo transiente y timpanometría tipo A.RESULTADOS:No se encontraron diferencias interaurales y en el desempeño de los recién nacidos en las respuestas del PEATE respecto a la clasificación peso/edad gestacional, en ambos sexos. Los recién nacidos a término del sexo femenino mostraron latencias absolutas estadísticamente más cortas (excepto onda I) que las del sexo masculino; lo mismo no pasó con los prematuros. Los neonatos pretérmino presentaron latencias más prolongadas que las de los recién nacidos a término, independiente del sexo.CONCLUSIONES:El sexo y la edad gestacional ejercen influencia relevante en el PEATE de recién nacidos a término, con respuestas menores en el sexo femenino, debiendo considerárselas en el análisis clínico. La relación peso/edad gestacional, en contrario, no interfiere en las respuestas de ese potencial.OBJETIVO:Verificar as influências do sexo e a relação peso/idade gestacional nas respostas do Potencial Evocado Auditivo de Tronco Encefálico (PEATE) em recém-nascidos pré-termo (PT) e a termo (T).MÉTODOS:Avaliaram-se 176 recém-nascidos por meio do PEATE, sendo 88 prematuros - 44 femininos (22 pequenos e 22 adequados para a idade gestacional) e 44 masculinos (22 pequenos e 22 adequados para a idade gestacional). Compararam-se os prematuros a 88 recém-nascidos a termo, 44 do sexo feminino (22 pequenos e 22 adequados) e 44 do sexo masculino (22 pequenos e 22 adequados). Todos os recém-nascidos apresentaram emissões otoacústicas bilateralmente, por estímulo transiente e timpanometria tipo A.RESULTADOS:Não se encontraram diferenças interaurais e no desempenho dos recém-nascidos nas respostas do PEATE quanto à classificação peso/idade gestacional, em ambos os sexos. Os recém-nascidos a termo do sexo feminino mostraram latências absolutas estatisticamente mais curtas (exceto onda I) do que os do masculino; o mesmo não ocorreu nos prematuros. Os neonatos pré-termo apresentaram latências mais prolongadas que as dos recém-nascidos a termo, independentemente do sexo.CONCLUSÕES O sexo e a idade gestacional exercem influência relevante no PEATE de recém-nascidos a termo, com respostas menores no sexo feminino. A relação peso/idade gestacional, ao contrário, não interfere nas respostas desse potencial.UNIFESP Hospital São PauloUniversidade de São Paulo Faculdade de MedicinaUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM)UNIFESP, Hospital São PauloUNIFESP, EPMSciEL

Dielectric characterization of healthy and malignant colon tissues in the 0.5 18 GHz frequency band

Several reports over the last few decades have shown that the dielectric properties of healthy and malignant tissues of the same body organ usually show different values. However, no intensive dielectric studies of human colon tissue have been performed, despite colon cancer's being one of the most common types of cancer in the world. In order to provide information regarding this matter, a dielectric characterization of healthy and malignant colon tissues is presented. Measurements are performed on ex vivo surgery samples obtained from 20 patients, using an open-ended coaxial probe in the 0.5 18 GHz frequency band. Results show that the dielectric constant of colon cancerous tissue is 8.8% higher than that of healthy tissues (p = 0.002). Besides, conductivity is about 10.6% higher, but in this case measurements do not have statistical significance (p = 0.038). Performing an analysis per patient, the differences in dielectric constant between healthy and malignant tissues appear systematically. Particularized results for specific frequencies (500 MHz, 900 MHz, 2.45 GHz, 5 GHz, 8.5 GHz and 15 GHz) are also reported. The findings have potential application in early-stage cancer detection and diagnosis, and can be useful in developing new tools for hyperthermia treatments as well as creating electromagnetic models of healthy and cancerous tissues.The authors would like to thank the medical staff of the endoscopy unit of Hospital Universitari i Politecnic La Fe for their assistance in the gathering of tissue samples. This work was supported by Ministerio de Economia y Competitividad, Spain (ref. TEC2014-60258-C2-1-R, TEC2014-56469-REDT), by FEDER funds, and by a UPV-IISLaFe action (CEI-2G, 2014).Fornés Leal, A.; García Pardo, C.; Frasson, M.; Pons Beltrán, V.; Cardona Marcet, N. (2016). Dielectric characterization of healthy and malignant colon tissues in the 0.5 18 GHz frequency band. Physics in Medicine and Biology. 61(20):7334-7346. https://doi.org/10.1088/0031-9155/61/20/7334S73347346612

Surgical management of complex ileocolonic Crohn’s disease: a survey of IBD colorectal surgeons to assess variability in operative strategy

Cirurgia colorectal; Malaltia de Crohn; Resecció ileocecalCirugía colorrectal; Enfermedad de Crohn; Resección ileocecalColorectal surgery; Crohn’s disease; Ileocaecal resectionIntroduction To explore the reported variability in the surgical management of ileocolonic Crohn’ s disease and identify areas of standard practice, we present this study which aims to assess how different colorectal surgeons with a subspecialty interest in inflammatory bowel disease (IBD) surgery may act in different clinical scenarios of ileocolonic Crohn’s disease. Methods Anonymous videos demonstrating the small bowel walkthrough and anonymised patients’ clinical data, imaging and pathological findings were distributed to the surgeons using an electronic tool. Surgeons answered on operative strategy, bowel resections, management of small bowel mesentery, type of anastomosis and use of stomas. Results Eight small bowel walkthrough videos were registered and 12 assessors completed the survey with a questionnaire completion rate of 87.5%. There was 87.7% agreement in the need to perform an ileocolonic resection. However, the agreement for the need to perform associated surgical procedures such as strictureplasties or further bowel resections was only 57.4%. When an anastomosis was fashioned, the side to side configuration was the most commonly used. The preferred management of the mesentery was dissection close to the bowel. Conclusions The decision on the main procedure to be performed had a high agreement amongst the different assessors, but the treatment of multifocal disease was highly controversial, with low agreement on the need for associated procedures to treat internal fistulae and the use of strictureplasties. At the same time, there was significant heterogeneity in the decision on when to anastomose and when to fashion an ileostomy

High-quality draft genome sequence of Pseudomonas reidholzensis strain CCOS 865T

We have sequenced and assembled the genome of Pseudomonas reidholzensis CCOS 865T, which was isolated in 2014 from forest soil. Members of the genus Pseudomonas play important roles in environmental systems and are utilized in many biotechnological processes. The genome of this species may provide an important resource for the discovery of novel enzyme activities

Ecotoxicity variation through parabens degradation by single and catalytic ozonation using volcanic rock

Parabens are widely used as antimicrobial and preservative ingredients in pharmaceutical and personal care products. Nevertheless, these compounds have been increasingly seen as emerging contaminants that can be toxic to a wide range of species. In this study, the toxic effect of a mixture of parabens (10 mg/L of each paraben: methyl-, ethyl-, propyl-, benzyl- and butylparaben) and its degradation products through single and catalytic ozonation (using volcanic rock as low-cost catalyst) was investigated over several non-target species: cladocerans, microalgae, clams, macrophytes and cress. The analysis of the toxicity of parabens mixture is relevant since usually these compounds are used as blends rather than individually. While parabens were totally removed both by single and catalytic ozonation the toxicity of the samples resulting from both treatments was generally high. This toxicity was still compared to the one obtained for several dilutions of the initial parabens mixture and it was concluded that the by-products formed are more toxic than the most diluted parabens mixture sample (0.625 mg/L). While catalytic ozonation allows reducing the amount of ozone (about 3-fold) required for total removal of parabens, the resulting treated solution was more toxic than the sample taken at the endpoint of the single ozonation treatment. This suggests that the highest amount of ozone used for single ozonation allowed the elimination of toxic by-products such as hydroquinone and 1,4-benzoquinone. Still, the effect of by-products and parabens interaction depends on the species analyzed due to their different tolerances to potentially toxic products.publishe

Complete genome sequence of the cyanogenic phosphate-solubilizing Pseudomonas sp. strain CCOS 191 : a close relative of Pseudomonas mosseli

We sequenced the complete genome of the isolate Pseudomonas sp. CCOS 191. This strain is able to dissolve phosphate minerals and form cyanide. The genome sequence is used to establish the phylogenetic relationship of this species