Some evolutionary patterns of palaeokarst developed in Pleistocene deposits (Ebro Basin, NE Spain): Improving geohazard awareness in present-day karst

Pleistocene detrital deposits in the central Ebro Basin frequently show deformation features due mainly to karstification in the underlying Neogene evaporites. In 123 cases, estimation of parameters of shape and minimum volume of materials involved was accomplished. Six of them were analysed in more detail to establish the main processes involved in their genesis and the succession of events. All the deformation features in the selected sites are synsedimentary. To achieve the objectives, intense fieldwork was made applying methods of sedimentology and structural geology. Usually, a complex evolutionary pattern was observed, with evidences of dissolution, sagging, collapse, gravity flow, suffosion, and plastic flow. In a schematic way, three main situations, independent of the age of the analysed deposits, can be distinguished: (a) slow subsidence, (b) collapse, and (c) temporal overlapping of both processes. In the first 2 scenarios, basins with smooth or abrupt borders, respectively, were generated on the land surface. In the third one, slow subsidence was followed by a collapse, located in the area of maximum flexure. These patterns are also observed in present-day dolines. Comparison of direct and indirect parameters between paleodolines and present-day dolines indicates a bigger size of the latter, probably caused by the different conditions of observation. This study helps to know the possibilities in the evolution of mantled karst features, to estimate the volume of material affected by karstification and to improve the knowledge of present-day dolines behaviour. Consequently, study of paleodolines must be considered to achieve a better urban planning in active karstic areas

The effect of visual focus on spatio-temporal and kinematic parameters of treadmill running

The characteristics of a treadmill and the environment where it is based could influence the user’s gaze and have an effect on their running kinematics and lower limb impacts. The aim of this study was to identify the effect of visual focus on spatio-temporal parameters and lower limb kinematics during treadmill running. Twenty six experienced runners ran at 3.33 m s−1 on a treadmill under two visual conditions, either looking ahead at a wall or looking down at the treadmill visual display. Spatio-temporal parameters, impact accelerations of the head and tibia, and knee and ankle kinematics were measured for the final 15 s of a 90 s bout of running under each condition. At the end of the test, participants reported their preference for the visual conditions assessed. Participants’ stride angle, flight time, knee flexion during the flight phase, and ankle eversion during contact time were increased when runners directed visual focus toward the wall compared to the treadmill display (p 0.05). However, the effect size of all biomechanical alterations was small. The Treadmill condition was the preferred condition by the participants (p < 0.001; ESw = 1.0). The results of the current study indicate that runners had a greater mass centre vertical displacement when they ran looking ahead, probably with the aim of compensating for reduced visual feedback, which resulted in larger head accelerations. Greater knee flexion during the flight phase and ankle eversion during the contact time were suggested as compensatory mechanisms for lower limb impacts

Flavonoids Of Lonchocarpus Montanus A.m.g. Azevedo And Biological Activity.

The analysis of root extracts from Lonchocarpus montanus A.M.G. Azevedo resulted in the isolation of twenty three compounds chiefly flavonoids of which five (four flavonoids and one benzophenone) are described for the first time. The molecular structures of the new compounds (1-5) were determined through spectral analysis (UV, IR, MS and NMR) as being: 2'-hydroxy-8-(alpha,alpha-dimethylallyl)-2, 2-dimethylpyrano-(5,6:3',4')-dibenzoylmethane (1), 2'-methoxy-8-(alpha,alpha-dimethylallyl)-2, 2-dimethylpyrano-(5,6:3',4')-dibenzoylmethane (2), 4'-methoxy-2,2-dimethylpyrano-(5,6:8,7)-flavone (3), 2-(1-hydroxy-1-methylethyl)-furano-(4,5:8,7)-flavone (4) and [2'-methoxy-furano-(4,5:3',4')-phenyl]-phenylmethanone (5). Additionally, fifteen fatty acids were detected through GC-MS analysis of the corresponding methyl esters [(CH3)2CH(CH2)8COOH and CH3(CH2)nCOOH (n = 6, 12-24)]. Quantitative RP-HPLC showed that the most abundant flavonoids in the petroleum ether and dichloromethane extracts were pongamol (19%) and lanceolatine B (8.0%), respectively. In the bioautography assay, the extracts, pongamol (9), lanceolatine B (10), isolonchocarpin (14), derriobtusone A (17) and medicarpine (18) were active against Staphylococcus aureus whereas 9 also against Bacillus subtilis and Cladosporium cladosporioides. Compound 1, 2,2-dimethylpyrano-(5,6:8,7)-flavone (11) and furano-(1200,1300:7,8)- 4'-methoxy flavone (12) were active against Fusarium oxysporium whereas 11 also against Rhizopus orizae. The extracts, compounds 9, 10, 17 and (E)-7-O-methoxypongamol (23) displayed high toxicity in the brine shrimp lethality assay.79351-6

Targeting ribosomal G-quadruplexes with naphthalene-diimides as RNA polymerase I inhibitors for colorectal cancer treatment

Guanine quadruplexes (G4s) are non-canonical nucleic acid structures commonly found in regulatory genomic regions. G4 targeting has emerged as a therapeutic approach in cancer. We have screened naph thalene-diimides (NDIs), a class of G4 ligands, in a cellular model of colorectal cancer (CRC). Here, we identify the leading compound T5 with a potent and selective inhibition of cell growth by high-affinity binding to G4s in ribosomal DNA, impairing RNA polymerase I (Pol I) elongation. Consequently, T5 induces a rapid inhibition of Pol I transcription, nucleolus disruption, proteasome-dependent Pol I catalytic subunit A degradation and autophagy. Moreover, we attribute the higher selectivity of carbohydrate-conjugated T5 for tumoral cells to its preferential uptake through the overexpressed glucose transporter 1. Finally, we succinctly demon strate that T5 could be explored as a therapeutic agent in a patient cohort with CRC. Therefore, we report a mode of action for these NDIs involving ribosomal G4 targeting

Performance of QuantiFERON-TB Gold Plus assays in children and adolescents at risk of tuberculosis: a cross-sectional multicentre study

Introduction: The QuantiFERON-TB Gold Plus (QFT-Plus) assay, which features two antigen-stimulated tubes (TB1 and TB2) instead of a single tube used in previous-generation interferon-gamma release assays (IGRAs), was launched in 2016. Despite this, data regarding the assay’s performance in the paediatric setting remain scarce. This study aimed to determine the performance of QFT-Plus in a large cohort of children and adolescents at risk of tuberculosis (TB) in a low-burden setting. Methods: Cross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients <18 years who had a QFT-Plus performed between September 2016 and June 2020. Results: Of 1726 patients (52.8% male, median age: 8.4 years), 260 (15.1%) underwent testing during contact tracing, 288 (16.7%) on clinical/radiological suspicion of tuberculosis disease (TBD), 649 (37.6%) during new-entrant migrant screening and 529 (30.6%) prior to initiation of immunosuppressive treatment. Overall, the sensitivity of QFT-Plus for TBD (n=189) and for latent tuberculosis infection (LTBI, n=195) was 83.6% and 68.2%, respectively. The agreement between QFT-Plus TB1 and TB2 antigen tubes was excellent (98.9%, κ=0.961). Only five (2.5%) patients with TBD had discordance between TB1 and TB2 results (TB1+/TB2−, n=2; TB1−/TB2+, n=3). Indeterminate assay results (n=54, 3.1%) were associated with young age, lymphopenia and elevated C reactive protein concentrations. Conclusions: Our non-comparative study indicates that QFT-Plus does not have greater sensitivity than previous-generation IGRAs in children in both TBD and LTBI. In TBD, the addition of the second antigen tube, TB2, does not enhance the assay’s performance substantially

New Orchestina Simon, 1882 (Araneae: Oonopidae) From Cretaceous Ambers Of Spain And France: First Spiders Described Using Phase-Contrast X-Ray Synchrotron Microtomography

This is the publisher's version of this article. An electronic version is also available from: http://dx.doi.org/10.1111/j.1475-4983.2011.01123.x.Two new species of Orchestina (Araneae: Oonopidae) are described as O. gappi sp. nov. and O. rabagensis sp. nov. from the Cretaceous of France and Spain, respectively. Two additional specimens from Spain are placed within Orchestina but not assigned to species. These formal descriptions are the oldest for the genus and the family Oonopidae. The discovery of these older Orchestina is not surprising, as the genus is considered a basal member of the Oonopidae and one of the most diverse and long-lived spider lineages. Two of the spiders were imaged at the European Synchrotron Radiation Facility using propagation phase-contrast X-ray synchrotron microtomography, demonstrating once again the enormous potential of this technique for studying fossil inclusions in amber

Ultrasensitive multiplex optical quantification of bacteria in large samples of biofluids

Efficient treatments in bacterial infections require the fast and accurate recognition of pathogens, with concentrations as low as one per milliliter in the case of septicemia. Detecting and quantifying bacteria in such low concentrations is challenging and typically demands cultures of large samples of blood (~1 milliliter) extending over 24-72 hours. This delay seriously compromises the health of patients. Here we demonstrate a fast microorganism optical detection system for the exhaustive identification and quantification of pathogens in volumes of biofluids with clinical relevance (~1 milliliter) in minutes. We drive each type of bacteria to accumulate antibody functionalized SERS-labelled silver nanoparticles. Particle aggregation on the bacteria membranes renders dense arrays of inter-particle gaps in which the Raman signal is exponentially amplified by several orders of magnitude relative to the dispersed particles. This enables a multiplex identification of the microorganisms through the molecule-specific spectral fingerprints

Client applications and Server Side docker for management of RNASeq and/or VariantSeq workflows and pipelines of the GPRO Suite

The GPRO suite is an in-progress bioinformatic project for -omic data analyses. As part of the continued growth of this project, we introduce a client side & server side solution for comparative transcriptomics and analysis of variants. The client side consists of two Java applications called "RNASeq" and "VariantSeq" to manage workflows for RNA-seq and Variant-seq analysis, respectively, based on the most common command line interface tools for each topic. Both applications are coupled with a Linux server infrastructure (named GPRO Server Side) that hosts all dependencies of each application (scripts, databases, and command line interface tools). Implementation of the server side requires a Linux operating system, PHP, SQL, Python, bash scripting, and third-party software. The GPRO Server Side can be deployed via a Docker container that can be installed in the user's PC using any operating system or on remote servers as a cloud solution. The two applications are available as desktop and cloud applications and provide two execution modes: a Step-by-Step mode enables each step of a workflow to be executed independently and a Pipeline mode allows all steps to be run sequentially. The two applications also feature an experimental support system called GENIE that consists of a virtual chatbot/assistant and a pipeline jobs panel coupled with an expert system. The chatbot can troubleshoot issues with the usage of each tool, the pipeline job panel provides information about the status of each task executed in the GPRO Server Side, and the expert provides the user with a potential recommendation to identify or fix failed analyses. The two applications and the GPRO Server Side combine the user-friendliness and security of client software with the efficiency of front-end & back-end solutions to manage command line interface software for RNA-seq and variant-seq analysis via interface environments

Clinical characteristics and outcome of drug-induced liver injury in the older patients: from the young-old to the oldest-old

Old patients with hepatotoxicity have been scarcely studied in idiosyncratic drug-induced liver injury (DILI) cohorts. We sought for the distinctive characteristics of DILI in older patients across age groups. A total of 882 DILI patients included in the Spanish DILI Registry (33% ≥65 years) were categorized according to age: “young” (<65y); “young-old” (65-74y); “middle-old” (75-84y); and “oldest-old” (≥85y). All elderly groups had increasingly higher comorbidity burden (p<0.001) and polypharmacy (p<0.001). There was a relationship between jaundice and hospitalization (p<0.001), and both were more prevalent in the elderly age groups, especially in the oldest-old (88% and 69%, respectively) and the DILI episode was more severe (p=0.029). The proportion of females decreased across age groups from the young to the middle-old, yet in the oldest-old there was a distinct female predominance. Pattern of liver injury shifted towards cholestatic with increasing age among top culprit drugs amoxicillin- clavulanate, atorvastatin, levofloxacin, ibuprofen, and ticlopidine. The best cut-off point for increased odds of cholestatic DILI was 65y. Older patients had increased non-liver related mortality (p=0.030) as shown by the predictive capacity of MELD (OR=1.116; p<0.001), and comorbidity burden (OR=4.188; p=0.001) in the 6-month mortality. Older patients with DILI exhibited an increasingly predominant cholestatic phenotype across a range of culprit drugs other that amoxicillin-clavulanate, with increased non-liver related mortality and require a different approach to predict outcome. The oldest DILI patients exhibited a particular phenotype with more severe DILI episodes and need to be considered when stratifying older DILI populations.The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional - FEDER (contract numbers: PI 18/01804; PT17/0017/0020) and Agencia Española del Medicamento. SCReN and CIBERehd are funded by ISCIII. JSC holds a Rio Hortega (CM17/00243) and MR a “Joan Rodes” (JR16/00015) research contract from the National Health System, ISCIII. RAW held a University of Málaga visiting scientist scholarship

Podocalyxin Is a Novel Polysialylated Neural Adhesion Protein with Multiple Roles in Neural Development and Synapse Formation

Neural development and plasticity are regulated by neural adhesion proteins, including the polysialylated form of NCAM (PSA-NCAM). Podocalyxin (PC) is a renal PSA-containing protein that has been reported to function as an anti-adhesin in kidney podocytes. Here we show that PC is widely expressed in neurons during neural development. Neural PC interacts with the ERM protein family, and with NHERF1/2 and RhoA/G. Experiments in vitro and phenotypic analyses of podxl-deficient mice indicate that PC is involved in neurite growth, branching and axonal fasciculation, and that PC loss-offunction reduces the number of synapses in the CNS and in the neuromuscular system. We also show that whereas some of the brain PC functions require PSA, others depend on PC per se. Our results show that PC, the second highly sialylated neural adhesion protein, plays multiple roles in neural development