Culturable fungi associated with urban stone surfaces in Mexico City

Background: Urban surface stones in Mexico City are exposed to a temperate climate and a range of atmospheric conditions ranging from mildly impacted to heavily polluted areas. In this study, we focused on the characterization of the cultivable fungal component of selected biological patinas in the surrounding area of Chapultepec castle, a historic monument in Mexico City. Thirty four representative fungal isolates selected based on distinctive differential macroscopic characteristics out of a total of 300 fungi, were characterized using morphological and molecular approaches. Results: This identification strategy based on the combination of phenotypic- and molecular-based methodologies allowed us to discriminate the fungal community in some cases down to the species level. Conclusions: The characterization of this mycoflora revealed the presence of a complex fungal community mainly represented by filamentous fungi belonging to the genera Fusarium , Trichoderma , Aspergillus , Cladosporium , Alternaria , Mucor , Penicillium , Pestalotiopsis , and the dimorphic fungus Aureobasidium , along with the yeast Rhodotorula . A specific distribution of fungi could be observed based on the type of biological patina analyzed

DHX9 Helicase promotes R-loop formation in cells with impaired RNA splicing

Unresolved R-loops can represent a threat to genome stability. Here the authors reveal that DHX9 helicase can promote R-loop formation in the absence of splicing factors SFPQ and SF3B3

Beta decay of the Tz=-2 nucleus 64Se and its descendants

International audience; The beta decay of the Tz=-2 nucleus 64Se has been studied in a fragmentation reaction at RIKEN-Nishina Center. 64Se is the heavies Tz=-2 nucleus that decays to bound states in the daughter nucleus and the heaviest case where the mirror reaction 64Zn(3He,t)64Ga on the Tz=+2 64Zn stable target exists and can be compared. Beta-delayed gamma and proton radiation is reported for the 64Se and 64As cases. New levels have been observed in 64As, 64Ge (N=Z), 63Ge and 63Ga. The associated T1/2 values have been obtained

The intracellular domain of β-dystroglycan mediates the nucleolar stress response by suppressing UBF transcriptional activity

β-dystroglycan (β-DG) is a key component of multiprotein complexes in the plasma membrane and nuclear envelope. In addition, β-DG undergoes two successive proteolytic cleavages that result in the liberation of its intracellular domain (ICD) into the cytosol and nucleus. However, stimuli-inducing ICD cleavage and the physiological relevance of this proteolytic fragment are largely unknown. In this study we show for the first time that β-DG ICD is targeted to the nucleolus where it interacts with the nuclear proteins B23 and UBF (central factor of Pol I-mediated rRNA gene transcription) and binds to rDNA promoter regions. Interestingly DG silencing results in reduced B23 and UBF levels and aberrant nucleolar morphology. Furthermore, β-DG ICD cleavage is induced by different nucleolar stressors, including oxidative stress, acidosis, and UV irradiation, which implies its participation in the response to nucleolar stress. Consistent with this idea, overexpression of β-DG elicited mislocalization and decreased levels of UBF and suppression of rRNA expression, which in turn provoked altered ribosome profiling and decreased cell growth. Collectively our data reveal that β-DG ICD acts as negative regulator of rDNA transcription by impeding the transcriptional activity of UBF, as a part of the protective mechanism activated in response to nucleolar stress

Amazonian Amphibian Diversity Is Primarily Derived from Late Miocene Andean Lineages

The Neotropics contains half of remaining rainforests and Earth's largest reservoir of amphibian biodiversity. However, determinants of Neotropical biodiversity (i.e., vicariance, dispersals, extinctions, and radiations) earlier than the Quaternary are largely unstudied. Using a novel method of ancestral area reconstruction and relaxed Bayesian clock analyses, we reconstructed the biogeography of the poison frog clade (Dendrobatidae). We rejected an Amazonian center-of-origin in favor of a complex connectivity model expanding over the Neotropics. We inferred 14 dispersals into and 18 out of Amazonia to adjacent regions; the Andes were the major source of dispersals into Amazonia. We found three episodes of lineage dispersal with two interleaved periods of vicariant events between South and Central America. During the late Miocene, Amazonian, and Central American-Chocoan lineages significantly increased their diversity compared to the Andean and Guianan-Venezuelan-Brazilian Shield counterparts. Significant percentage of dendrobatid diversity in Amazonia and Chocó resulted from repeated immigrations, with radiations at <10.0 million years ago (MYA), rather than in situ diversification. In contrast, the Andes, Venezuelan Highlands, and Guiana Shield have undergone extended in situ diversification at near constant rate since the Oligocene. The effects of Miocene paleogeographic events on Neotropical diversification dynamics provided the framework under which Quaternary patterns of endemism evolved

Adaptación cultural al español del instrumento de evaluación de funcionalidad física en Unidad de Paciente Crítico: “The Chelsea Critical Care Physical Assessment Tool (CPAx)”

Las Unidades de Cuidados Intensivos (UCI), presentan una sobrevida cada vez mayor de los pacientes que ingresan a ellas, donde se ven enfrentados a una nueva entidad fisiopatológica llamada Debilidad Muscular Adquirida en UCI (DAUCI). Algunos test desarrollados para la evaluación de función motriz, que permiten objetivar la progresión del paciente, son la escala de fuerza muscular del Medical Research Council (MRC), el Functional status score for the intensive care unit (FSS-ICU) y el “Chelsea Critical Care Physical Assessment Tool (CPAx). La ventaja del CPAx radica en que este test incluye mayor información asociada al funcionamiento humano como recomienda la OMS, incorporando tanto el componente ventilatorio (que también se ve deteriorado por DAUCI) como neuromuscular lo que permite al profesional kinesiólogo tener una herramienta objetiva más completa del nivel funcional del paciente. Para que sea confiable, todo test debe ser validado en el país donde quiere aplicarse, pero antes de esto debe ser adaptado culturalmente. El objetivo de este trabajo fue efectuar la adaptación transcultural (AT) al español del test de funcionalidad física de aplicación kinésica CPAx. Se utilizó el proceso establecido por Beaton y cols que incluye la formación de un comité de expertos multidisciplinario que da una visión integral a la adaptación y una prueba piloto en que kinesiólogos de UCI sin capacitación previa del test lo lean, posteriormente lo apliquen y entreguen sus observaciones. Conclusiones: Realizar la AT permite dimensionar la importancia que tiene cada una de las etapas de este proceso. El test es el mismo, equivalente al original, pero contiene nuestras características culturales y condiciones técnicas, que lo hace ser comprensible y aplicable en nuestro país. Esta adaptación transcultural también es útil a nivel latinoamericano; para los países de habla hispana que quieran validarlo tenerlo adaptado al español, hace el proceso menos complejo. Palabras clave: Evaluación funcional, Unidad de cuidados intensivos, CPAx, adaptación transcultural

XRN2 Links Transcription Termination to DNA Damage and Replication Stress

We thank the Proteomics Core Facility. We thank Dr. Robert J. Crouch for providing us with GFP- and GFP-RNase H expression plasmids. We also thank Dr. Stephen H. Leppla for providing us with antibodies directed against RNA:DNA hybrids (R loops) (S9.6). We thank Novus Biologicals for generously providing XRN2 and Rrp45 antibodies. We also thank the members of the Boothman lab for critical reading of this manuscript.Author Summary Genomic instability is one of the primary causes of disease states, in particular cancer. One major cause of genomic instability is the formation of DNA double strand breaks (DSBs), which are one of the most dangerous types of DNA lesions the cell can encounter. If not repaired in a timely manner, one DSB can lead not only to cell death. If misrepaired, one DSB can lead to a hazardous chromosomal aberration, such as a translocation, that can eventually lead to cancer. The cell encounters and repairs DSBs that arise from naturally occurring cellular processes on a daily basis. A number of studies have demonstrated that aberrant structures that form during transcription under certain circumstances, in particular RNA:DNA hybrids (R loops), can lead to DSB formation and genomic instability, especially during DNA synthesis. Thus, it is important to understand how the cell responds and repairs transcription-mediated DNA damage in general and R loop-related DNA damage in particular. This paper both demonstrates that the XRN transcription termination factor links transcription and DNA damage, but also provides a better understanding of how the cell prevents transcription-related DNA damage.Yeshttp://www.plosgenetics.org/static/editorial#pee

Safety and effectiveness of CIMAvax-EGF administered in community polyclinics

In spite of the advances in immunotherapy and targeted therapies, lung cancer continues to be the leading cause of cancer-related death. The epidermal growth factor receptor is an established target for non-small cell lung cancer (NSCLC), and its overactivation by the ligands can induce accelerated proliferation, angiogenesis, and metastasis as well as proinflammatory or immunosuppressive signals. CIMAvax-EGF is an epidermal growth factor (EGF)-depleting immunotherapy that is approved for the treatment of NSCLC patients in Cuba. The study was designed as a phase IV trial to characterize the safety and effectiveness of CIMAvax-EGF in advanced NSCLC patients treated in 119 community polyclinics and 24 hospitals. CIMAvax-EGF treatment consisted of four bi-weekly doses followed by monthly boosters. Overall, 741 NSCLC patients ineligible for further cancer-specific treatment were enrolled. CIMAvax-EGF was safe, and the most common adverse events consisted of mild-to-moderate injection site reactions, fever, chills, tremors, and headache. For patients completing the loading doses, the median survival was 9.9 months. For individuals achieving at least stable disease to the frontline and completing vaccination induction, the median survival was 12 months. Most of the functional activities and symptoms evaluated through the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire improved over time. In conclusion, this real-world trial demonstrated that CIMAvax-EGF was safe and effective in patients who were vaccinated in the maintenance scenario. A larger effect was seen in subjects with poor prognosis like those with squamous tumors and high EGF levels. Remarkably, this community-based intervention was very important because it demonstrated the feasibility of treating advanced lung cancer patients with active immunotherapy in primary care institutions. In addition to CIMAvax-EGF, patients received supportive care at the community clinic. Vaccine administration by the family doctors at the polyclinics reduced the patients’ burden on the medical oncology services that continued providing chemotherapy and other complex therapies. We conclude that community polyclinics constitute the optimal scenario for administering those cancer vaccines that are safe and require prolonged maintenance in patients with advanced cancer, despite the continuous deterioration of their general condition.Clinical trial registrationhttps://rpcec.sld.cu/trials/RPCEC00000205-En, identifier RPCEC00000205