Dissecting the secondary structure of the circular RNA of a nuclear viroid in vivo: A "naked" rod-like conformation similar but not identical to that observed in vitro

[EN] With a minimal (250-400nt), non-protein-coding, circular RNA genome, viroids rely on sequence/structural motifs for replication and colonization of their host plants. These motifs are embedded in a compact secondary structure whose elucidation is crucial to understand how they function. Viroid RNA structure has been tackled in silico with algorithms searching for the conformation of minimal free energy, and in vitro by probing in solution with RNases, dimethyl sulphate and bisulphite, and with selective 2-hydroxyl acylation analyzed by primer extension (SHAPE), which interrogates the RNA backbone at single-nucleotide resolution. However, in vivo approaches at that resolution have not been assayed. Here, after confirming by 3 termodynamics-based predictions and by in vitro SHAPE that the secondary structure adopted by the infectious monomeric circular (+) RNA of potato spindle tuber viroid (PSTVd) is a rod-like conformation with double-stranded segments flanked by loops, we have probed it in vivo with a SHAPE modification. We provide direct evidence that a similar, but not identical, rod-like conformation exists in PSTVd-infected leaves of Nicotiana benthamiana, verifying the long-standing view that this RNA accumulates in planta as a naked form rather than tightly associated with protecting host proteins. However, certain nucleotides of the central conserved region, including some of the loop E involved in key functions such as replication, are more SHAPE-reactive in vitro than in vivo. This difference is most likely due to interactions with proteins mediating some of these functions, or to structural changes promoted by other factors of the in vivo habitat.This work was supported by grant BFU2014-56812-P (to R.F.) from the Ministerio de Economia y Competitividad of Spain. A.L.C. was the recipient of a predoctoral fellowship from the same organism.López-Carrasco, MA.; Flores Pedauye, R. (2017). Dissecting the secondary structure of the circular RNA of a nuclear viroid in vivo: A "naked" rod-like conformation similar but not identical to that observed in vitro. RNA Biology. 14(8):1046-1054. https://doi.org/10.1080/15476286.2016.1223005S1046105414

Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems

Urinary tract infections (UTIs) are among the most common infectious diseases worldwide but are significantly understudied. Uropathogenic E. coli (UPEC) accounts for a significant proportion of UTI, but a large number of other species can infect the urinary tract, each of which will have unique host-pathogen interactions with the bladder environment. Given the substantial economic burden of UTI and its increasing antibiotic resistance, there is an urgent need to better understand UTI pathophysiology – especially its tendency to relapse and recur. Most models developed to date use murine infection; few human-relevant models exist. Of these, the majority of in vitro UTI models have utilized cells in static culture, but UTI needs to be studied in the context of the unique aspects of the bladder’s biophysical environment (e.g., tissue architecture, urine, fluid flow, and stretch). In this review, we summarize the complexities of recurrent UTI, critically assess current infection models and discuss potential improvements. More advanced human cell-based in vitro models have the potential to enable a better understanding of the etiology of UTI disease and to provide a complementary platform alongside animals for drug screening and the search for better treatments

CAMBIO DE COBERTURA Y USO DEL SUELO EN LA CUENCA DEL RIO MOLOLOA, NAYARIT

Los cambios de cobertura y uso del suelo se han reconocido en muchos países como una de las principales causas de deterioro ambiental, por ello están ubicados en el centro de la investigación ambiental y representan un punto importante en diferentes ámbitos como medio para entender los mecanismos de este proceso de deterioro y guía para la toma razo- nable de decisiones sobre el uso del territorio. En el estado de Nayarit, la cuenca del río Mo- loloa ha proveído de un conjunto de bienes y servicios a las localidades que involucra; des- afortunadamente, esta relación ha repercutido en un deterioro acelerado de sus recursos na- turales. En este trabajo se analizan los cambios de cobertura y uso del suelo en la cuenca del río Mololoa, entre 1995 y 2005, a partir de la interpretación de ortofotos digitales y manejo de la información en un SIG. Los resultados muestran que el paisaje de la cuenca está dominado en 83.01% por la vegetación natural y tierras de cultivo. La dinámica de cambio está centrada en los tipos de cobertura “vegetación natural” y “construcciones”, la primera disminuye a una tasa de 41.67 ha/año, y la segunda, aumenta 74.86 ha/año. La tasa de deforestación de los bosques y selvas de la región fue de 0.1 y 0.36%, menor a las reportadas por diferentes autores a nivel nacional y estatal

Construyendo dominios de encuentro para problematizar acerca de las prácticas pedagógicas de profesores secundarios de Ciencias: Incorporando el modelo de Investigación-Acción como plan de formación continua

Frente a la actual crisis de la educación científica, la capacidad docente de transformar sus prácticas para mejorar el logro de aprendizajes parece ser fundamental. Los programas de formación docente continua tradicionales, generalmente prescriptivos y descontextualizados del aula, han tenido bajo impacto en los procesos de transformación de las prácticas docentes. El presente trabajo describe la primera fase de un programa de formación continua consistente en la construcción de dominios de encuentro entre el saber académico generado en la Universidad y el saber profesional de 16 profesores secundarios de Ciencias a través de un proceso de investigación-acción conjunta, basado en el trabajo colaborativo, la reflexión y la retroalimentación. Los resultados dan cuenta de la complejidad de generar significados comunes, los que una vez logrados, permiten fortalecer el razonamiento científico, la autoeficacia y conformación de una comunidad de aprendizaje que posibilita una actitud indagatoria hacia sus prácticas en Ciencias. / Considering the current scientific education crisis, teachers' capacity to transform their practice in order to improve learning achievement seems fundamental. The traditional programs of continuous professional development, generally prescriptive and uncontextualized from the classroom, have had a low impact on processes of teachers' practice transformation. This work describes the first stage of continuous development program, consisting on building encounter domains between the academic knowledge of Universities, and professional knowledge of 16 secondary science teachers, through a joint action-research process, based on collaborative work, reflection and feedback. The results show the complexity of building shared sense which, once achieved, allows strong scientific reasoning, self-efficacy and the construction of a learning community facilitating an inquiry-driven attitude towards their science teaching practice

High Plasma Levels of Betaine, a Trimethylamine N-Oxide Related Metabolite, are Associated with Severity of Cirrhosis

Background and Aims: The gut microbiome-related metabolites betaine and trimethylamine N-oxide (TMAO) affect major health issues. In cirrhosis, betaine metabolism may be diminished because of impaired hepatic betaine homocysteine methyltransferase activity, whereas TMAO generation from trimethylamine may be altered because of impaired hepatic flavin monooxygenase expression. Here, we determined plasma betaine and TMAO levels in patients with end-stage liver disease and assessed their relationships with liver disease severity. Methods: Plasma betaine and TMAO concentrations were measured by nuclear magnetic resonance spectroscopy in 129 cirrhotic patients (TransplantLines cohort study; NCT03272841) and compared with levels from 4837 participants of the PREVEND cohort study. Disease severity was assessed by Child-Pugh-Turcotte (CPT) classification and Model for End-stage Liver Disease (MELD) score. Results: Plasma betaine was on average 60% higher (p < .001), whereas TMAO was not significantly lower in cirrhotic patients vs. PREVEND population (p = .44). After liver transplantation (n = 13), betaine decreased (p = .017; p = .36 vs. PREVEND population), whereas TMAO levels tended to increase (p = .085) to higher levels than in the PREVEND population (p = .003). Betaine levels were positively associated with the CPT stage and MELD score (both p < .001). The association with the MELD score remained in the fully adjusted analysis (p < .001). The association of TMAO with the MELD score did not reach significance (p = .11). Neither betaine nor TMAO levels were associated with mortality on the waiting list for liver transplantation (adjusted p = .78 and p = .44, respectively). Conclusion: Plasma betaine levels are elevated in cirrhotic patients in parallel with disease severity and decrease after liver transplantation

Viroids: survivors from the RNA world?

[EN] Because RNA can be a carrier of genetic information and a biocatalyst, there is a consensus that it emerged before DNA and proteins, which eventually assumed these roles and relegated RNA to intermediate functions. If such a scenario¿the so-calledRNAworld¿existed,wemight hope to find its relics in our presentworld. The properties of viroids that make them candidates for being survivors of the RNA world include those expected for primitive RNA replicons: (a) small size imposed by error-prone replication, (b) high G + C content to increase replication fidelity, (c) circular structure for assuring complete replication without genomic tags, (d ) structural periodicity for modular assembly into enlarged genomes, (e) lack of protein-coding ability consistent with a ribosome-free habitat, and ( f ) replication mediated in some by ribozymes, the fingerprint of the RNA world. With the advent of DNA and proteins, those protoviroids lost some abilities and became the plant parasites we now know.R.F. has received funding by grant BFU2011-28443 from Ministerio de Economia y Competititvidad (MINECO, Spain), R.S. by grants BFU2011-25271 (MINECO) and ERC-2011-StG-281191-VIRMUT (European Research Council), and S.F.E. by grant BFU2012-30805 (MINECO). P.S. has been supported by postdoctoral contracts from Generalitat Valenciana (APOSTD/2010, program VALi+d) and MINECO (program Juan de la Cierva).Flores Pedauye, R.; Gago Zachert, SP.; Serra Alfonso, P.; Sanjuan Verdeguer, R.; Elena Fito, SF. (2014). Viroids: survivors from the RNA world?. Annual Review of Microbiology. 68:395-414. https://doi.org/10.1146/annurev-micro-091313-103416S3954146

Convex regions of stationary spacetimes and Randers spaces. Applications to lensing and asymptotic flatness

By using Stationary-to-Randers correspondence (SRC), a characterization of light and time-convexity of the boundary of a region of a standard stationary (n+1)-spacetime is obtained, in terms of the convexity of the boundary of a domain in a Finsler n or (n+1)-space of Randers type. The latter convexity is analyzed in depth and, as a consequence, the causal simplicity and the existence of causal geodesics confined in the region and connecting a point to a stationary line are characterized. Applications to asymptotically flat spacetimes include the light-convexity of stationary hypersurfaces which project in a spacelike section of an end onto a sphere of large radius, as well as the characterization of their time-convexity with natural physical interpretations. The lens effect of both light rays and freely falling massive particles with a finite lifetime, (i.e. the multiplicity of such connecting curves) is characterized in terms of the focalization of the geodesics in the underlying Randers manifolds.Comment: AMSLaTex, 41 pages. v2 is a major revision: new discussions on physical applicability of the results, especially to asymptotically flat spacetimes; references adde

Mammal-Like Organization of the Avian Midbrain Central Gray and a Reappraisal of the Intercollicular Nucleus

In mammals, rostrocaudal columns of the midbrain periaqueductal gray (PAG) regulate diverse behavioral and physiological functions, including sexual and fight-or-flight behavior, but homologous columns have not been identified in non-mammalian species. In contrast to mammals, in which the PAG lies ventral to the superior colliculus and surrounds the cerebral aqueduct, birds exhibit a hypertrophied tectum that is displaced laterally, and thus the midbrain central gray (CG) extends mediolaterally rather than dorsoventrally as in mammals. We therefore hypothesized that the avian CG is organized much like a folded open PAG. To address this hypothesis, we conducted immunohistochemical comparisons of the midbrains of mice and finches, as well as Fos studies of aggressive dominance, subordinance, non-social defense and sexual behavior in territorial and gregarious finch species. We obtained excellent support for our predictions based on the folded open model of the PAG and further showed that birds possess functional and anatomical zones that form longitudinal columns similar to those in mammals. However, distinguishing characteristics of the dorsal/dorsolateral PAG, such as a dense peptidergic innervation, a longitudinal column of neuronal nitric oxide synthase neurons, and aggression-induced Fos responses, do not lie within the classical avian CG, but in the laterally adjacent intercollicular nucleus (ICo), suggesting that much of the ICo is homologous to the dorsal PAG

Common Variants of TLR1 Associate with Organ Dysfunction and Sustained Pro-Inflammatory Responses during Sepsis

Background: Toll-like receptors (TLRs) are critical components for host pathogen recognition and variants in genes participating in this response influence susceptibility to infections. Recently, TLR1 gene polymorphisms have been found correlated with whole blood hyper-inflammatory responses to pathogen-associated molecules and associated with sepsis-associated multiorgan dysfunction and acute lung injury (ALI). We examined the association of common variants of TLR1 gene with sepsis-derived complications in an independent study and with serum levels for four inflammatory biomarker among septic patients. Methodology/Principal Findings: Seven tagging single nucleotide polymorphisms of the TLR1 gene were genotyped in samples from a prospective multicenter case-only study of patients with severe sepsis admitted into a network of intensive care units followed for disease severity. Interleukin (IL)-1 b, IL-6, IL-10, and C-reactive protein (CRP) serum levels were measured at study entry, at 48 h and at 7th day. Alleles -7202G and 248Ser, and the 248Ser-602Ile haplotype were associated with circulatory dysfunction among severe septic patients (0.001<=p <= 0.022), and with reduced IL-10 (0.012<= p <=0.047) and elevated CRP (0.011<= p <=0.036) serum levels during the first week of sepsis development. Additionally, the -7202GG genotype was found to be associated with hospital mortality (p =0.017) and ALI (p =0.050) in a combined analysis with European Americans, suggesting common risk effects among studies Conclusions/Significance: These results partially replicate and extend previous findings, supporting that variants of TLR1 gene are determinants of severe complications during sepsis

Extragalactic Results from the Infrared Space Observatory

More than a decade ago the IRAS satellite opened the realm of external galaxies for studies in the 10 to 100 micron band and discovered emission from tens of thousands of normal and active galaxies. With the 1995-1998 mission of the Infrared Space Observatory the next major steps in extragalactic infrared astronomy became possible: detailed imaging, spectroscopy and spectro-photometry of many galaxies detected by IRAS, as well as deep surveys in the mid- and far- IR. The spectroscopic data reveal a wealth of detail about the nature of the energy source(s) and about the physical conditions in galaxies. ISO's surveys for the first time explore the infrared emission of distant, high-redshift galaxies. ISO's main theme in extragalactic astronomy is the role of star formation in the activity and evolution of galaxies.Comment: 106 pages, including 17 figures. Ann.Rev.Astron.Astrophys. (in press), a gzip'd pdf file (667kB) is also available at http://www.mpe.mpg.de/www_ir/preprint/annrev2000.pdf.g