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The presence of archaeocyath-bearing clasts from Cenozoic tills and Cambrian Mount Wegener Formation reveal erosion of a hidden Cambrian carbonate platform in Shackleton Range, Antarctica. We provide microfacies, paleontological, diagenetic and tectonically induced fabric data from carbonate clasts which, in addition to available geochemical and geochronological data from Shackleton Range, allow the paleoenvironmental reconstruction of a lost CambrianSeries 2mixed siliciclastic–carbonate platform that was developed and eroded during the Ross orogeny. Carbonate production was dominated by non-skeletal grains in possibly restricted platform-interior and oolitic shoal complex settings, while open subtidal sub-environments (calcimicrobe carpets, calcimicrobe–archaeocyath patch reefs, muddy bottoms) were dominated by a diverse calcimicrobe assemblage and/or by secondary to accessory heterozoan assemblage (archaeocyaths and other sponges, chancelloriids, hyoliths, coralomorphs, trilobites, echinoderms). We describe a Botoman assemblage with 34 archaeocyathan species among 12 existing archaeocyathan genera. A new archaeocyath family Shackletoncyathidae is proposed. New species (Rotundocyathus glaciussp. nov.,Buggischicyathus microporusgen. et sp. nov.,Paragnaltacyathus hoeflei,Shackletoncyathus buggischigen. et. sp. nov.,Santelmocyathus santelmoigen. et sp. nov.,Wegenercyathus sexangulaegen. et sp. nov.) andTabulaconus kordaecoralomorph are reported from Antarctica for the first time. Archaeocyathan fauna share few species with contemporary fauna of South Australia (9) and even fewer with the Antarctic platforms of the Shackleton Limestone (2) or the Schneider Hills limestone (1). Similarity is greater with Antarctic allochthonous assemblages of Permo-Carboniferous tillites from Ellsworth Mountains (2), Cenozoic deposits from King George Island (4) or Weddell Sea (1). The Shackleton Range lost/hidden platform shows a distinct entity related with its tectonosedimentary evolution, in a possible back-arc basin on the Mozambique seaway during the E and W Gondwana amalgamation, which distinguishes it from those developed on the palaeo-Pacific margin of the E Antarctic craton.

Concerns have been raised about Renin-angiotensin system inhibitors (RASi) in patients with COVID-19. Although recent trials have proved its security, evidence regarding intrinsic differences between RASi is lacking, especially in patients with arterial hypertension. Our objective was to analyse the prognosis of hypertense patients who received angiotensin converting enzyme inhibitors (ACEi) or angiotensin-2 receptor blockers (ARBs) and were hospitalized due to COVID-19.392 consecutive patients with hypertension and COVID-19 were analyse. Incidence of the combined event (death or mechanical ventilation need) was the primary endpoint. Secondary, incidence of each event and time to event were analysed.155 received ACEi and 237 ARBs. During the hospitalization, the combined event was observed in the 31,6 % of patients. No differences were observed between those previously treated with ACEi and ARBs (33.5 vs. 30.9%; p = 0.51). In the survival analysis, no differences were observed regarding time to combined event (p = 0.91). In-hospital mortality was similar in both groups (32.3 vs. 29.1%; p = 0.51), as well as the need of mechanical ventilation (3.2 vs. 5.9%; p = 0.23).The type of RASi was not associated with in-hospital major events in patients with arterial hypertension hospitalized due to COVID-19.Han surgido dudas sobre la seguridad de los fármacos inhibidores del sistema renina-angiotensina (SRA) en pacientes con enfermedad por coronavirus 2019 (COVID-19). Aunque estudios recientes han demostrado la seguridad de este grupo de fármacos, la evidencia sobre la comparativa de los diferentes fármacos inhibidores del SRA es escasa, sobre todo en pacientes hipertensos. Nuestro objetivo fue analizar el pronóstico de los pacientes hipertensos tratados con inhibidores de la enzima convertidora de angiotensina (IECA) o antagonistas del receptor de angiotensina II (ARA II) que presentaron COVID-19.Se analizaron 582 pacientes hipertensos con COVID-19. Se registró la incidencia del evento combinado de muerte o necesidad de ventilación mecánica invasiva (VMI) durante la hospitalización. De forma secundaria, se analizó la incidencia de eventos de manera independiente y se realizó un análisis de supervivencia para analizar el tiempo hasta los eventos.155 pacientes recibían tratamiento previo con IECA y 237 con ARA II. Durante la hospitalización por COVID-19, se observó una incidencia del evento combinado del 31.6%. No se detectaron diferencias entre los pacientes que recibían tratamiento con IECA y los tratados con ARA II (33.5 vs. 30.9%; p = 0.51). En el análisis de supervivencia, no se hallaron diferencias en el tiempo hasta el evento combinado (p = 0.91). La mortalidad intrahospitalaria fue similar en ambos grupos (32.3 vs. 29.1%; p = 0.51), así como la necesidad de VMI (3.2 vs. 5.9%; p = 0.23).El tipo de inhibidor del SRA no se asoció a diferencias pronósticas significativas entre los pacientes hipertensos ingresados con COVID-19.

SARS-CoV-2 virus requires host proteases to cleave its spike protein to bind to its ACE2 target through a two-step furin-mediated entry mechanism. Aprotinin is a broad-spectrum protease inhibitor that has been employed as antiviral drug for other human respiratory viruses. Also, it has important anti-inflammatory properties for inhibiting the innate immunity contact system.This was a multicentre, double-blind, randomized trial performed in four Spanish hospitals comparing standard treatment versus standard treatment + aprotinin for patients with COVID-19 between 20 May 2020 and 20 October 2021. The primary efficacy outcomes were length of hospital stay and ICU admission. The secondary endpoints were each of the primary efficacy outcomes and a composite of oxygen therapy, analytical parameters and death. Safety outcomes included adverse reactions to treatment during a 30-day follow-up period. Treatment was given for 11 days or till discharge.With almost identical analytical profiles, significant differences were observed in treatment time, which was 2 days lower in the aprotinin group (p = .002), and length of hospital admission, which was 5 days shorter in the aprotinin group (p = .003). The incidence of discharge was 2.19 times higher (HR: 2.188 [1.182-4.047]) in the aprotinin group than in the placebo group (p = .013). In addition, the aprotinin-treated group required less oxygen therapy and had no adverse reactions or side effects.Inhaled aprotinin may improve standard treatment and clinical outcomes in hospitalized patients with COVID-19, resulting in a shorter treatment time and hospitalization compared with the placebo group. The administration of aprotinin was safe.

Fast and selective isolation of single cells with unique spatial and morphological traits remains a technical challenge. Here, we address this by establishing high-speed image-enabled cell sorting (ICS), which records multicolor fluorescence images and sorts cells based on measurements from image data at speeds up to 15,000 events per second. We show that ICS quantifies cell morphology and localization of labeled proteins and increases the resolution of cell cycle analyses by separating mitotic stages. We combine ICS with CRISPR-pooled screens to identify regulators of the nuclear factor κB (NF-κB) pathway, enabling the completion of genome-wide image-based screens in about 9 hours of run time. By assessing complex cellular phenotypes, ICS substantially expands the phenotypic space accessible to cell-sorting applications and pooled genetic screening.

Purpose: The aim of our study is to present a series of patients in whom we have administered HIPEC therapy. Material and Methods: The treatment consists in performing cytoreductive surgery in patients diagnosed with potentially resectable pancreatic adenocarcinoma, together with the administration of HIPEC therapy with Gemcitabine. The dose of the drug is 120 mg/m2 for 30 minutes, followed by a conventional adjuvant treatment. Results: Five patients diagnosed with pancreatic adenocarcinoma have undergone surgery with a curative nature. There were no technical or hemodynamic complications during the procedure. Discussion: The use of HIPEC could achieve a decrease in the tumor progression of pancreatic cancer, improving the survival of the patient, and decreasing the recurrence of the disease. A larger number of patients will be necessary, as well as a long-term evaluation to assess the possible increase in survival in this group of patients.

The Lower Cretaceous Leza Formation is an essentially carbonate unit deposited at the northernmost active margin of the Cameros Basin (N Spain) under an extensional tectonic regime. This unit is composed of freshwater, marine-influenced, marginal-marine and hypersaline marine carbonate facies, interbedded with variable amounts of alluvial deposits, mainly derived from the erosion of the Jurassic substrate. 87Sr/86Sr, δ18O and δ13C analyses were obtained from carbonate facies of the Eastern and Western sectors of the basin. δ18O values follow the expected trend in both sectors: they are more negative (down to − 7.9‰) in freshwater carbonates and more positive (up to + 2.8‰) in marginal-marine to hypersaline facies. However, independently of the seawater or freshwater influence, in the Western Sector the 87Sr/86Sr values (0.707373–0.707801) are significantly lower and closer to the published Lower Cretaceous seawater 87Sr/86Sr ratios, than those of the Eastern Sector (0.707988–0.709033), where the overall marine influence was relatively high and the alluvial input low. These data strongly suggest that 87Sr/86Sr ratios were mainly controlled by those of the riverine freshwater arriving to the coastal and marine areas after the weathering and erosion of the Jurassic carbonates or siliciclastic rocks, in the Western and Eastern sectors, respectively. Thus, data indicate that, in coastal and shallow marine carbonates, the influence of the riverine water on the 87Sr/86Sr ratios should be systematically evaluated. This is particularly necessary in active tectonic settings, where the uplifted areas are significantly prone to weathering and erosion and where alluvial fan systems commonly developed, eventually discharging into coastal and shallow marine areas.

DNA replication initiates from multiple genomic locations called replication origins. In metazoa, DNA sequence elements involved in origin specification remain elusive. Here, we examine pluripotent, primary, differentiating, and immortalized human cells, and demonstrate that a class of origins, termed core origins, is shared by different cell types and host ~80% of all DNA replication initiation events in any cell population. We detect a shared G-rich DNA sequence signature that coincides with most core origins in both human and mouse genomes. Transcription and G-rich elements can independently associate with replication origin activity. Computational algorithms show that core origins can be predicted, based solely on DNA sequence patterns but not on consensus motifs. Our results demonstrate that, despite an attributed stochasticity, core origins are chosen from a limited pool of genomic regions. Immortalization through oncogenic gene expression, but not normal cellular differentiation, results in increased stochastic firing from heterochromatin and decreased origin density at TAD borders., In metazoan the DNA sequence elements characterizing origin specification are unknown. By generating and analysing 19 SNS-seq datasets from different human cell types, the authors reveal a class and features of Core origins of replication which can be predicted by an algorithm.

Measuring differences in cell cycle progression is often essential to understand cell behavior under different conditions, treatments and environmental changes. Cell synchronization is widely used for this purpose, but unfortunately, there are many cases where synchronization is not an option. Many cell lines, patient samples or primary cells cannot be synchronized, and most synchronization methods involve exposing the cells to stress, which makes the method incompatible with the study of stress responses such as DNA damage. The use of dual-pulse labelling using EdU and BrdU can potentially overcome these problems, but the need for individual sample processing may introduce a great variability in the results and their interpretation. Here, we describe a method to analyze cell proliferation and cell cycle progression by double staining with thymidine analogues in combination with fluorescent cell barcoding, which allows one to multiplex the study and reduces the variability due to individual sample staining, reducing also the cost of the experiment.

Hypertension has been associated with worse outcomes in patients with COVID-19 infection, so concerns have been raised about the possibility that inhibitors of the renin-angiotensin system (RAS) could influence the prognosis of these patients.This is an observational study of 921 consecutive patients admitted with COVID-19 respiratory infection to Hospital General Universitario Ciudad Real from March 1 to April 30, 2020. Following data were collected including patient demographic information, medical history, clinical characteristics, laboratory data, therapeutic interventions during the hospitalization and clinical outcomes.The mean age was 78 years, and 59.2% of patients had a history of hypertension. Patients with previous treatment with RAS inhibitor (42.4%) showed lower risk of the primary composite endpoint (mortality or need for invasive mechanical ventilation). Treatment with RAS inhibitor (both outpatient treatment and during hospitalization) had neither effect on mortality nor need for invasive ventilation. There were no differences in time-to-event analysis between groups.RAS inhibitor treatment prior to admission in patients with COVID-19 respiratory infection was associated with lower risk of the primary composite endpoint and did not show neither impact on mortality nor need for invasive mechanical ventilation, even if these drugs were prescribed during hospitalization.La presencia de hipertensión arterial se asocia con peor pronóstico en pacientes con COVID-19, y se ha sugerido que el uso de inhibidores del eje renina-angiotensina puede influir en el pronóstico de los pacientes.Registro observacional de 921 pacientes consecutivos ingresados por infección respiratoria COVID-19 entre el 1 de marzo y el 30 abril de 2020 en el Hospital General Universitario de Ciudad Real. Se registraron datos clínicos y analíticos, intervenciones terapéuticas y desarrollo de eventos durante el ingreso hospitalario.La mediana de edad fue de 78 años y el 59,2% tenían hipertensión arterial. Aunque el perfil clínico fue más desfavorable en el grupo de pacientes con prescripción previa de IECA o ARA2 respecto al resto, los primeros presentaron menor riesgo de desarrollo del evento primario combinado (mortalidad total o necesidad de soporte ventilatorio invasivo). Asimismo, el empleo previo al ingreso o durante el mismo de estos fármacos mostró un efecto neutro sobre la mortalidad total y sobre la necesidad de ventilación mecánica invasiva. En el análisis de supervivencia no se observó mayor riesgo de presentar más precozmente ninguno de los eventos registrados.La prescripción previa al ingreso por infección respiratoria COVID-19 de inhibidores del eje renina-angiotensina se asoció a un menor riesgo de desarrollo del evento primario combinado y a un efecto neutro sobre la mortalidad total y sobre la necesidad de ventilación mecánica invasiva.

This study records the first occurrence of a lower Cambrian archaeocyathan fauna in limestone cobbles from Carboniferous glacigenic deposits of the Dwyka Group of the Aranos Basin in Namibia. Petrographic and microfacies analysis of 17 large, middle and standard thin sections reveals two distinctive limestone cobble facies: (a) bioclastic wackestone-packstone (hyoliths, trilobites, chancelloriids, crinoids and archaeocyaths); and (b) microbial-archaeocyathan boundstone dominated by calcimicrobes (Epiphyton and Renalcis), neomorphosed microbial crusts and crypto-fibrous calcite crusts around mainly regular archaeocyaths such as Polycoscinus scutatus, where encrusting ?sponges are accessory. The published stratigraphical and palaeocurrent data from the Dwyka Group, as well as published ages and the tectonothermal history of the underlying Nama Group, have been used in this study to establish the provenance of these lower Cambrian cobbles. The archaeocyaths from the Aranos Basin are: Favilynthus contractus, ...

Peritidal carbonate-evaporite successions, since they are developed in the transition between continental and marine realms, provide essential keys for palaeobathymetric and palaeoclimatic interpretations. As a result, several facies models have been proposed to assist on the interpretation of ancient tidal flat deposits, and peritidal successions have been extensively used for cyclicity analyses. In this study, well-exposed, Lower Cretaceous peritidal deposits (Oncala Group, Cameros Basin, N Spain) are analysed and compared with the most commonly-used present-day analogues (from Shark Bay, the Arabian Gulf and the Bahamas) and with ancient peritidal successions, providing their palaeoenvironmental and palaeoclimatic interpretation, assessing the usefulness and limitations of the facies models, and evaluating the suitability of these deposits for analysis of decimetre to metre-scale cycles. The studied peritidal deposits consist of thinly-bedded to laminated dolostones, dolomitic stromatolites, stromatolite breccias, flat-pebble and edgewise breccias, and calcite and quartz pseudomorphs after anhydrite nodules. Abundant resemblances of the peritidal deposits of the Oncala Group with those of Shark Bay, including that they are largely composed of microbialites and intraclasts, makes the peritidal deposits of the Oncala Group one of the best fossil analogues of this present-day setting. However, the presence of anhydrite nodules indicates pervasive evaporite precipitation in the supratidal zone, which is a feature that does not occur in supratidal flats of Shark Bay, but is characteristic of arid sabkhas of the Arabian Gulf. Nevertheless, the fact that carbonate-evaporite tidal flats of the Oncala Group were laterally related with siliciclastic tidal flats with large freshwater input and broadly inhabited by dinosaurs, suggests that anhydrites precipitated under less arid climates than those of the Arabian Gulf nowadays, pointing to semiarid climatic conditions during deposition. Moreover, the fact that peritidal deposits with anhydrite nodules were exclusively formed in a low-subsidence area of the Cameros Basin suggests that the rate of accommodation space creation also played an important role in their development. Regarding the comparison with other fossil peritidal sediments, the studied deposits show more abundant similarities with Proterozoic and Cambrian successions, composed mainly of stromatolites, microbial laminites, and intraclasts, than with other Mesozoic peritidal deposits, in which bioclasts and burrowing are usually more abundant. This highlights the difficulties for assigning specific features to certain geological ages. Finally, peritidal facies of the Oncala Group may change laterally and vertically to any other facies, showing a patchy lateral distribution of facies and an unsystematic vertical stacking pattern. The sedimentary features of the stromatolite, breccia and thinly-bedded to laminated dolostone facies do not allow their assignment to a unique tidal zone. Moreover, sedimentary features indicative of subaerial exposure, such as anhydrite nodules formed in the capillary zone, occur within any of the carbonate facies and show limited lateral extent. This results in a succession that cannot be clearly subdivided into subsequent shallowing-upward cycles not even by using erosive surfaces or the anhydrite nodule layers as marker horizons of the upper part of the cycles, because their limited lateral extent prevents reliable correlations. Similar composite lateral and vertical facies relationships have been documented both in the present-day analogues and in ancient successions, which suggests that this kind of facies relationships may be common in peritidal successions and highlights the caution that must be taken when trying to perform cyclicity analysis on them.

Summary In response to transcription-blocking DNA damage, cells orchestrate a multi-pronged reaction, involving transcription-coupled DNA repair, degradation of RNA polymerase II (RNAPII), and genome-wide transcription shutdown. Here, we provide insight into how these responses are connected by the finding that ubiquitylation of RNAPII itself, at a single lysine (RPB1 K1268), is the focal point for DNA-damage-response coordination. K1268 ubiquitylation affects DNA repair and signals RNAPII degradation, essential for surviving genotoxic insult. RNAPII degradation results in a shutdown of transcriptional initiation, in the absence of which cells display dramatic transcriptome alterations. Additionally, regulation of RNAPII stability is central to transcription recovery—persistent RNAPII depletion underlies the failure of this process in Cockayne syndrome B cells. These data expose regulation of global RNAPII levels as integral to the cellular DNA-damage response and open the intriguing possibility that RNAPII pool size generally affects cell-specific transcription programs in genome instability disorders and even normal cells., Graphical Abstract, Highlights • Specific RPB1 K1268 ubiquitylation targets RNAPII for UV-induced proteolysis • RPB1 K1268 ubiquitylation is required for surviving DNA damage • Control of the RNAPII pool via degradation regulates the transcriptome after UV • Lack of transcription recovery in Cockayne syndrome is caused by unstable RNAPII, Control of the pool of available RNA polymerase II shapes how cells respond to UV stress and the efficacy of the resulting damage response.

Summary STK19 was proposed to be a cancer driver, and recent work by Yin et al. (2019) in Cell suggested that the frequently recurring STK19 D89N substitution represents a gain-of-function change, allowing increased phosphorylation of NRAS to enhance melanocyte transformation. Here we show that the STK19 gene has been incorrectly annotated, and that the expressed protein is 110 amino acids shorter than indicated by current databases. The “cancer driving” STK19 D89N substitution is thus outside the coding region. We also fail to detect evidence of the mutation affecting STK19 expression; instead, it is a UV signature mutation, found in the promoter of other genes as well. Furthermore, STK19 is exclusively nuclear and chromatin-associated, while no evidence for it being a kinase was found. The data in this Matters Arising article raise fundamental questions about the recently proposed role for STK19 in melanoma progression via a function as an NRAS kinase, suggested by Yin et al. (2019) in Cell. See also the response by Yin et al. (2020) , published in this issue.

En la Zona Centroibérica meridional se reconoce la sucesión más completa de rocas del Ediacárico tardío que afloran en el sinclinal de la Sierra de la Zarzuela, discordantes sobre el Supergroup del Alcudiense inferior-Domo Extremeño. El objetivo de esta contribución es estudiar y redefinir un marco litoestratigráfico regional para las rocas del “Alcudiense inferior” de este área relacionada con el Grupo de Ibor.

Los clastos carbonatados de la Formación del Monte Wegener proporcionan evidencias sedimentológicas, diagenéticas y paleontológicas de la destrucción y resedimentación de un registro carbonatadoo cámbrico oculto/no conocido en aguas someras de la región de Coats Land en la Antártida. Este mosaico incompleto podría jugar un papel clave en las comparaciones y correlaciones bioestratigráficas entre el registro cámbrico de las Montañas Transantárticas, el bloque Ellsworth-Whitmore y la Península Antártica del continente antártico. Además, representa un registro clave en las futuras reconstrucciones paleobiogeográficas de Gondwana meridional basadas en asociaciones de arqueociatos.

In the Lutetian intraslope Ainsa sub-basin, small, sub-spherical, carbonate mud mounds occur associated with hemipelagic marls and mixed gravity flow deposits. The studied mud mounds consist of a mixture of allochthonous, parautochthonous and autochthonous components that show evidences of reworking, bioerosion, and accretion by different fossil assemblages at different growth stages. The crusts of microbial-lithistid sponges played an important role stabilizing the rubble of coralgal-coralline sponges and formed low-relief small benthic patches in a dominant marly soft slope environment. These accidental hard substrates turned into suitable initiation/nucleation sites for automicrite production (dense and peloidal automicrites) on which the small mud mounds dominated by opportunistic epi- and infaunal heterozoan assemblages grew. A detailed microfacies mapping and paleoenvironmental analysis reveals a multi-episodic downslope accretion history starred by demosponges (coralline and lithistid sponges), agariciid corals, calcareous red algae, putative microbial benthic communities and diverse sclerobionts from the upper slope to the middle slope. The analyzed mud mound microfacies are compared with similar fossil assemblages and growth fabrics described in many fossil mud mounds, and with recent deep-water fore reefs and cave environments.

Nascent-strand mapping of active DNA replication origins before and after gastrulation in C. elegans reveals that replication initiation is coordinated with transcriptional programs during embryonic development. Although some features underlying replication-origin activation in metazoan cells have been determined, little is known about their regulation during metazoan development. Using the nascent-strand purification method, here we identified replication origins throughout Caenorhabditis elegans embryonic development and found that the origin repertoire is thoroughly reorganized after gastrulation onset. During the pluripotent embryonic stages (pregastrula), potential cruciform structures and open chromatin are determining factors that establish replication origins. The observed enrichment of replication origins in transcription factor–binding sites and their presence in promoters of highly transcribed genes, particularly operons, suggest that transcriptional activity contributes to replication initiation before gastrulation. After the gastrula transition, when embryonic differentiation programs are set, new origins are selected at enhancers, close to CpG-island-like sequences, and at noncoding genes. Our findings suggest that origin selection coordinates replication initiation with transcriptional programs during metazoan development.

Background Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is the best operative treatment currently available for patients with peritoneal carcinomatosis of ovarian origin. The open abdomen technique is the classic technique for hyperthermic intraperitoneal chemotherapy. We developed a closed abdomen model that improves temperature control and increases exposure of peritoneal surfaces to the drug by recirculating the perfusate. Methods We used a porcine model with 12 female, Large White pigs—4 in the open technique group and 8 in the closed technique CO2 group. We performed cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for 60 minutes using paclitaxel (175 mg/m2) at an input temperature of 42°C. Perfusate recirculation was performed under controlled pressure (range, 12–15 mmHg). The infusion of 0.7 L of CO2 via a separate intraperitoneal infusion catheter mixed the perfusate within the peritoneal cavity. Intra-abdominal temperature was assessed using 6 intra-abdominal temperature probes and 2 temperature probes in the inflow and outflow circuits. Drug distribution was assessed using methylene blue staining. Results Intra-abdominal temperatures remained constant and homogeneous in all intra-abdominal quadrants with a constant input temperature of 42°C and a minimum output temperature of 41.4°C. The infused CO2 caused the fluid to bubble and created agitation inside the abdominal cavity to facilitate a homogeneous distribution of the drug-containing perfusate. Conclusion The closed recirculation hyperthermia with intraperitoneal chemotherapy technique developed in this study is safe and feasible, and may provide a more homogeneous delivery of heated chemotherapy to the peritoneal cavity in patients with peritoneal malignancies.

The Cambrian Pedroche Formation comprises a mixed siliciclastic–carbonate succession recording subtidal deposition on a marine platform. Carbonate carbon isotope chemostratigraphy confirms previous biostratigraphic assignment of the Pedroche Formation to the Atdabanian regional stage of Siberia, correlative to Cambrian Series 2. At the outcrop scale, thrombolitic facies comprise ~ 60% of carbonate-normalized stratigraphy and coated-grains another ~ 10%. Petrographic point counts reveal that skeletons contribute at most 20% to thrombolitic inter-reef and reef-flank lithologies; on average, archaeocyath clasts make up 68% of skeletal materials. In contrast, petrographic point counts show that skeletons comprise a negligible volume of biohermal and biostromal thrombolite, associated nodular carbonate facies, and ooid, oncoid and peloid grainstone facies. As such, archaeocyathan reefal bioconstructions represent a specific and limited locus of skeletal carbonate production and deposition. Consistent with data from coeval, globally dispersed lower Cambrian successions, our analysis of the Pedroche Formation supports the view that lower Cambrian carbonates have more in common with earlier, Neoproterozoic deposits than with younger carbonates dominated by skeletal production and accumulation.

A fine-grained stromatolite bed, laterally continuous on the kilometer scale and with small synoptic relief, crops out in the Munecas Formation in the Northern Iberian Ranges. The Munecas Fm. was deposited during the late Turonian on a shallow water platform in the Upper Cretaceous intracratonic Iberian basin. The stromatolite bed has a tabular to domed biostromal macrostructure. Its internal mesostructure consists of planar, wavy to hemispherical stromatoids that display a broad spectrum of microstructures, including dense micrite, bahamite peloids, peloidal to clotted microfabrics, irregular micritic-wall tubes, which are suggestive of algae and filamentous microframeworks, which are suggestive of filamentous cyanobacteria. Various stromatolite growth stages have been linked to the dominance of different accretion processes. The accretion of the entire fine-grained stromatolite involves a complex mosaic of processes: trapping and binding of quartz-silt grains and bahamites, which form the agglutinated parts of some laminae, and microbially induced precipitation, which forms spongiostromic and micritic laminae. Tubiform and filamentous microframeworks resembling porostromatate or skeletal stromatolitic growth were also recognized. Laser ICP-MS measurements of Al, Si, Mg, Mn, Sr, S and Fe were analyzed to detect the influence of siliciclastic inputs and major trends during stromatolite accretion. Carbon and oxygen isotopic compositions from the stromatolite and associated facies were used to identify possible microbial signatures. These data describes a unique and well-preserved example of a shallow marine Upper Turonian fine-grained stromatolite.

The Upper Visean outcrops from the Guadiato Valley (Cordoba, SW Spain) provide a well-preserved record of the mud mound factory, which was developed in a mainly siliciclastic synorogenic foreland basin during the oblique sinistral collision of two terranes (Ossa Morena and Central Iberian blocks). The first onset of mud mound development has been recorded as microbial mud mound-derived boulders in polymictic megabreccias as result of strong tectonic activity. The Upper Visean record from the Mississippian central band at Guadiato Valley starts with lower heterolithic units (up to 180 m thick) and shows two major tectonically-controlled cycles: a fining upwards interval (FU) followed by a coarsening upwards interval (CU). These cycles are linked to two active margins with gravelly fan delta development and different source areas. Mud mound-derived boulders occur in the CU interval and are formed by peloidal primary and secondary (reworked) automicrites and allomicrites, showing a diverse faunal and floral assemblage, although never as the main skeletal framebuilders. However, the observed coeval richness in sponges (lyssacinose hexactinellids and non-lithistid demosponges) and the diverse calcareous algae assemblage in mud mound derived boulders are not common in other Visean buildups. The growth cavities display changes in the geopetal relationships between fillings and the secondary cavities containing sand to gravel fillings reflecting a complex pre-boulder and mud mound derived boulder history. Detailed mapping, sampling, stratigraphic and microfacial analyses have allowed the reconstruction of the mud mounds sedimentary environment prior to the collapse, transport and emplacement as boulders with polymictic gravels.

The origin of pancreatic cancer has been identified as a population of malignant pancreatic stem cells CD133+ CXCR4+ immunophenotype. These cells have high capacity for early locoregional invasion, being responsible for early recurrence and high mortality rates of pancreatic cancer. We propose a study for decreasing tumor progression of pancreatic cancer by reducing the volume and neoplastic subpopulation of pancreatic cancer stem cells CD133+ CXCR4+. Therefore, we develop a new therapeutic model, characterized by the application of HIPEC (Hyperthermic Intraperitoneal Chemotherapy) with gemcitabine.Pancreatic tumor cell line: human cell line BxPC-3. The animal model involved 18 immunosuppressed rats 5 weeks weighing 150-200 gr. The implantation of 13 × 10(6) cells/mL was performed with homogeneous distribution in the 13 abdominopelvic quadrants according to the peritoneal carcinomatosis index (PCI) and were randomized into three treatment groups. Group I (4 rats) received intravenous saline. Group II (6 rats) received intravenous gemcitabine. Group III (8 rats) received HIPEC at 41 °C for 30 min with gemcitabine + gemcitabine IV. A histological study confirmed pancreatic cancer and immunohistochemical quantification of pancreatic cancer stem cells CD133+ CXCR4+ tumor cells.There was a population decline of pancreatic cancer stem cells CD133+ CXCR4+ in the HIPEC group with respect to the other two groups (p 0.001). There was a decrease in PCI between treatment groups (p 0.05).The initial results are encouraging since there is a declining population of cancer stem cells CD133+ CXCR4+ in the HIPEC group and decreased tumor volume compared to the other two treatment groups. All the conclusions are only valid for BxPC3 cell line, and the effects HIPEC on Kras-driven pancreatic tumors remain to be determined.

In all living organisms, genome replication is essential for their development and maintenance. In the genome of simple organisms, such as bacteria and small eukaryotic deoxyribonucleic acid (DNA) viruses, DNA replication starts from a well-characterised single origin. In complex eukaryotes, such as metazoans, DNA replication starts from dozens of thousands of origins spread along the different chromosomes. This high number of origins, together with the technical problems encountered in finding reliable methods for their large-scale mapping, made difficult their characterisation. However, owing to the new genome-wide approaches developed in the past few years, we have now a better understanding of how replication origins are established in higher eukaryotes. These studies have shown an intrinsic correlation between replication origins and other genome features, such as gene transcription and epigenetic regulation, and revealed an amazing flexibility in their usage. Key Concepts: Replication origins are defined by specific DNA sequences in bacteria, viruses and Saccharomyces cerevisiae, but not in Schizosaccharomyces pombe and metazoans. DNA replication origins are activated in a defined temporal order, called timing of DNA replication. DNA replication origins are flexible: only a subset of them is activated at each cell cycle. DNA replication takes place at specific subnuclear structures, called replication foci. The number and position of replication origins to be activated may vary according to the developmental or growing conditions. Keywords: DNA replication; chromatin; epigenetic; transcription; development

Recent palaeontological and microfacies studies carried out on the Láncara Formation (early Cambrian) provide evidence for an interesting, previously undescribed association of archaeocyaths (Salce locality) and microbialites (Salce and Barrios de Luna localities). The archaeocyathan assemblage consists of Archaeocyathus laqueus (Vologdin, 1932) and Pycnoidocyathus erbiensis (Zhurav leva, 1955), indicating an early Bilbilian age (Stage 4, Series 2, Cambrian) for these materials. The analysis of the upper part of the lower member has allowed differentiation of eleven carbonate facies that have been grouped into: i) non-skeletal grain packstone-grainstone, ii) fenestral mudstone-packstone, iii) heterolithic stylonodular facies, iv) microbialites, v) bioclast-intraclast packstone-grainstone. Archaeocyaths occur reworked in stylonodular facies as well as forming small archaeocyaths-thrombolitic patches (centimetre-scale). The archaeocyath-rich thrombolitic microbialites from Salce were developed in very shallow subtidal conditions surrounded by other microbialites and small lenticular intertidal bars in the inner ramp. Toyonian biostratigraphic and paleobiogeographic analyses have also been carried out. After the comparison with Toyonian archaeocyathan rich facies from Gondwana, it has become evident that the early Cambrian record from the Cantabrian Mountains provides the richest generic assemblage from Gondwana for Toyonian time., Departamento de Paleontología, Universidad Complutense de Madrid, España, Geologisch-Paläontologisches Institut, Ruprecht –Karls Universität, Alemania, Museo Geominero, Instituto Geológico y Minero de España, España, Departamento de Estratigrafía, Universidad Complutense de Madrid, España

Foraminifera are the most abundant sessile organisms found on ferromanganese crusts and nodules (Greenslate 1974; Wendt 1974; Dugolinsky et al. 1977; Riemann 1983; von Stackelberg 1984; Mullineaux 1987, 1988; Verlaan 1992; Resig and Glenn 1997; Toscano and Raspini 2005). In fact, actual ferromanganesecrusts and nodules share numerous similarities with their fossil counterparts.

Los estromatolitos adquieren una relevante importancia ya que constituyen una de las primeras pruebas del origen de la vida. En este trabajo, con objeto de facilitar la compresión y el conocimiento de los estromatolitos, como rocas bioconstruidas por la actividad de microorganismos, se reseña de forma didáctica la génesis, los componentes, los ambientes donde se desarrollan y la distribución en el tiempo geológico. Al final del texto se adjuntan cuatro anexos en formato de paneles expositivos donde se sintetiza toda la información y una ficha didáctica para valorar la compresión de estos paneles.

[ES] En la Sierra de la Estrella (Área del Guadiato, Córdoba) se localiza una sucesión del Viseense superior, principalmente carbonatada, con desarrollo de montículos tipo mud-mound. En esta zona predominan calizas bioclásticas, brechoideas y bioconstruidas, aunque también se localizan niveles de areniscas y conglomerados. Se han identificado un total de 7 litofacies que agrupan a su vez a 9 microfacies tipo: 1.–Mudstonewackestone con cavidades estromatactoideas y fábricas fenestrales, 2.–Wackestonepackstone con algas y bioclastos, 3.1.–Packstone de pseudopeloides, 3.2.–Packstone con algas, pseudopeloides y litoclastos, 4.1.–Packstone de briozoos y crinoideos, 4.2.–Packstone con algas y espículas, 5.–Packstone-rudstone de litoclastos, 6.–Grainstone de cortoides y litoclastos, 7.–Arenitas híbridas. El ambiente de sedimentación se interpreta como una zona de transición entre rampa interna y externa carbonática con influencia de terrígenos y desarrollo de montículos microbianos., [EN] Late Viséan calcareous rocks containing buildups occur in the Sierra de la Estrella, Guadiato Valley. Bioclastic, breccioid and biohermal limestones as well as sandstones and conglomerates occur. Lithofacies analysis allow to identify 7 types, with 9 characteristic microfacies: 1.–Micropeloidal mudstone-wackestone with stromatactoid cavities and fenestral fabrics, 2.–Algal-bioclastic wackestone-packstone, 3.1.–Pseudopeloidal packstone, 3.2.–Packstone with algae, pseudopeloids and lithoclast, 4.1.–Bryozoal-crinoidal packstone, 4.2.–Packstone with algae and sponge spiculae, 5.–Packstone-rudstone with lithoclasts, 6.–Cortoid-lithoclasts grainstone, 7.–Hybrid sandstones. Sediments are attributed to a inner to outer carbonate ramp with sporadic terrigenous influence. Some microbial mounds developed in such environment., Este trabajo se enmarca en el proyecto PB 96-0842 de la DGICYT.

Currently, the different roles of peloidal micrites are not well understood in matrix-supported bioconstructions such as mud mounds. Upper Viséan outcrops from Guadiato Valley, Cordoba Province, SW Spain provide well-preserved peloidal-dominated mud mounds. Microstructual analysis of these mud mounds has allowed us to establish 13 microfabrics. Although peloids are conspicuous constituents in the microfabrics, they have been differentiated into seven peloidal-dominated types, grouped into three categories: (a) homogeneous fine peloidal types (3 subtypes); (b) homogeneous coarse peloidal types (2 subtypes); and (c) heterogeneous coarse peloidal types (two subtypes). Fast cm-scale microfabric changes were mapped directly onto thin sections. This methodology allows the researcher to recognize the micro-framework of these mud mounds as a complex, multiepisodic organization of microframes and intermicroframes that are formed by primary and secondary automicrites (non-reworked and reworked automicrites, respectively), autochthonous internal sediment, and allomicrite and marine fibrous cements. The thin-section mapping was also used to estimate the automicrite-allomicrite relationship, which is crucial in separating the microbial and biodetrital mud mounds. peerReviewed