Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinematics of the western Mediterranean

Summary The kinematic understanding of the relationship between relative plate motion and the structure of orogenic belts depends upon a knowledge of relative plate motion across the plate boundary system, the relative motion of small blocks and flakes within the system, an evaluation of orogenic body forces, and an understanding of the thermomechanical evolution of the upper part of the orogenic lithosphere in determining strength and detachment levels. We have built a preliminary model for the Cenozoic kinematic evolution of the western Mediterranean oceanic basins and their peripheral orogens that integrates (1) the motion of Africa relative to Europe based upon a new study of Atlantic fracture zones using SEASAT data and the Lamont-Doherty magnetic anomaly database, (2) a new interpretation of the rotation of Corsica/Sardinia and the opening of the Balearic and Tyrrhenian oceanic basins, (3) sedimentary facies sequences in the Apennines, Calabria, and Sicily, and (4) Apennine/Calabrian structure and structural sequence.
No advantage of “A β 42 -lowering” NSAIDs for prevention of AD in six pooled cohort studies

Introduction— Observational studies show reduced incidence of Alzheimer’s dementia (AD) in users of non-steroidal anti-inflammatory drugs (NSAIDs). One hypothesis holds that the subset of NSAIDs known as “selective A β 42 -lowering agents” (SALAs) is responsible for this apparent reduction in AD risk. Methods— We pooled individual-level data from six prospective studies to obtain a sufficient sample to examine AD risk in users of SALA vs . non-SALA NSAIDs. Results— Of 13,499 initially dementia-free participants (70,863 person-years), 820 developed incident AD. Users of NSAIDs (29.6%) showed reduced risk of AD (adjusted hazard ratio or aHR 0.77, 95% confidence interval or CI 0.65–0.91). The point estimates were similar for SALAs (aHR 0.87, CI 0.72–1.04) and non-SALAs (aHR 0.75, CI 0.56–1.01). Because 573 (aHR 0.78, CI 0.66–0.92). By contrast, there was no association with use of acetaminophen (aHR 0.93, CI 0.76–1.13). Conclusions— In this pooled dataset, NSAID use reduced the risk of AD. However, there was no apparent advantage in AD risk reduction for the subset of NSAIDs shown to selectively lower A β 42 , suggesting that all conventional NSAIDs including aspirin have a similar protective effect in humans.
Identification of G-Quadruplex-Binding Inhibitors of Myc Expression through Affinity Selection–Mass Spectrometry

The Myc oncogene is overexpressed in many cancers, yet targeting it for cancer therapy has remained elusive. One strategy for inhibition of Myc expression is through stabilization of the G-quadruplex (G4), a G-rich DNA secondary structure found within the Myc promoter; stabilization of G4s has been shown to halt transcription of downstream gene products. Here we used the Automated Ligand Identification System (ALIS), an affinity selection–mass spectrometry method, to identify compounds that bind to the Myc G4 out of a pool of compounds that had previously been shown to inhibit Myc expression in a reporter screen. Using an ALIS-based screen, we identified hits that bound to the Myc G4, a small subset of which bound preferentially relative to G4s from the promoters of five other genes. To determine functionality and specificity of the Myc G4-binding compounds in cell-based assays, we compared inhibition of Myc expression in cells with and without Myc G4 regulation. Several compounds inhibited Myc expression only in the Myc G4-containing line, and one compound was verified to function through Myc G4 binding. Our study demonstrates that ALIS can be used to identify selective nucleic acid-binding compounds from phenotypic screen hits, increasing the pool of drug targets beyond proteins.
Identification of Microcystis aeruginosa Peptides Responsible for Allergic Sensitization and Characterization of Functional Interactions between Cyanobacterial Toxins and Immunogenic Peptides

Background The cyanobacterium species Microcystis aeruginosa produces microcystin and an array of diverse metabolites believed responsible for their toxicity and/or immunogenicity. Previously, chronic rhinitis patients were demonstrated to elicit a specific IgE response to nontoxic strains of M. aeruginosa by skin-prick testing, indicating that cyanobacteria allergenicity resides in a non-toxin–producing component of the organism. Objectives We sought to identify and characterize M. aeruginosa peptide(s) responsible for allergic sensitization in susceptible individuals, and we investigated the functional interactions between cyanobacterial toxins and their coexpressed immunogenic peptides. Methods Sera from patients and extracts from M. aeruginosa toxic [MC(+)] and nontoxic [MC(–)] strains were used to test IgE-specific reactivity by direct and indirect ELISAs; 2D gel electrophoresis, followed by immunoblots and mass spectrometry (MS), was performed to identify the relevant sensitizing peptides. Cytotoxicity and mediator release assays were performed using the MC(+) and MC(–) lysates. Results We found specific IgE to be increased more in response to the MC(–) strain than the MC(+) strain. This response was inhibited by preincubation of MC(–) lysate with increasing concentrations of microcystin. MS revealed that phycocyanin and the core-membrane linker peptide are the responsible allergens, and MC(–) extracts containing these proteins induced β-hexosaminidase release in rat basophil leukemia cells. Conclusions Phycobiliprotein complexes in M. aeruginosa have been identified as the relevant sensitizing proteins. Our finding that allergenicity is inhibited in a dose-dependent manner by microcystin toxin suggests that further investigation is warranted to understand the interplay between immunogenicity and toxicity of cyanobacteria under diverse environmental conditions. Citation Geh EN, Ghosh D, McKell M, de la Cruz AA, Stelma G, Bernstein JA. 2015. Identification of Microcystis aeruginosa peptides responsible for allergic sensitization and characterization of functional interactions between cyanobacterial toxins and immunogenic peptides. Environ Health Perspect 123:1159–1166; http://dx.doi. org/10.1289/ehp.1409065
Chronic Antidepressant Administration Increases the Expression of Camp-specific Phosphodiesterase 4a and 4b Isoforms

The influence of chronic antidepressant administration on expression of the three major phosphodiesterase (PDE) 4 sub-types found in brain (PDE4A, PDE4B, and PDE4D) was examined. The treatments tested included representatives of four major classes of antidepressants: selective reuptake inhibitors of serotonin (sertraline and fluoxetine) or norepinephrine (desi-pramine), a monoamine oxidase inhibitor (tranylcypromine), and electroconvulsive seizure. Expression of PDE4A and PDE4B, but not PDE4D, mRNA and immunoreactivity were significantly increased in rat frontal cortex by chronic administration of each of the four classes of antidepressants. We also found that antidepressant administration significantly increased the expression of PDE4B mRNA in the nucleus accumbens, a brain region thought to mediate pleasure and reward that could also contribute to the anhedonia often observed in depressed patients. In contrast, expression of PDE4A and PDE4B were not influenced by short-term treatment (1 or 7 d) and were not influenced by chronic administration of nonantidepressant psy-chotropic drugs (cocaine or haloperidol), demonstrating the time dependence and pharmacological specificity of these effects. Upregulation of PDE4A and PDE4B may represent a compensatory response to antidepressant treatment and activation of the cAMP system. The possibility that targeted inhibition of these PDE4 subtypes may produce an antidepressant effect is discussed. Although antidepressant drugs are widely prescribed for a variety of affective illnesses, the molecular and cellular adaptations that underlie the therapeutic action of these treatments have remained obscure. Moreover, the targets for development of therapeutic agents have remained primarily unchanged over the past 40 years (i.e., inhibition of monoamine reuptake and metabolism). Recent studies have demonstrated adaptations at several levels of the cAMP signal transduction cascade in response to antidepressant treatments, including increased coupling of stimulatory G-protein and adenylyl cyclase (Ozawa and Rasenick, 1991), increased levels of cAM P-dependent protein kinase (Nestler et al., 1989; Perez et al., 1989, 1991), and increased expression and f unction of the cAM P response element binding protein (CREB) (Nibuya et al., 1996). These findings support the hypothesis that the action of antidepressant treatment is mediated, in part, by increased function of the cAM P signal transduction cascade (Duman et al., 1997). The possibility that the cAM P system is involved in the mechanism of action of antidepressants is supported by basic and clinical studies of inhibitors of phosphodiesterase (PDE), the enzyme responsible for metabolism of cAM P. Preclinical studies demonstrate that PDE inhibitors have antidepressant-like effects Treatment with papaverine, a non-specific PDE inhibitor, was also …
Chondrichthyans from a Cenomanian (Late Cretaceous) bonebed, Saskatchewan, Canada

Abstract: Acid preparation of samples of a bonebed from the Cenomanian of central Canada yielded several thousand well‐preserved chondrichthyan teeth, in addition to numerous other vertebrate remains. Teeth and other remains of one species of chimaeroid, one species of hybodont shark, three species of Ptychodus, 10 species of neoselachian sharks and two species of batoid were recorded. The family Archaeolamnidae fam. nov., genera Meristodonoides gen. nov. and Telodontaspis gen. nov. and species Ptychodus rhombodus sp. nov., Telodontaspis agassizensis gen et sp. nov., Eostriatolamia paucicorrugata sp. nov., Roulletia canadensis sp. nov., Cretorectolobus robustus sp. nov. and Orectoloboides angulatus sp. nov. are described. Status of the genus Palaeoanacorax and the species Cretoxyrhina denticulata, Squalicorax curvatus and ‘Rhinobatos’incertus are discussed, and reconstructed dentitions of Archaeolamna and Roulletia presented. The fauna is of low diversity and dominated by active hunters, with many species apparently endemic to the northern Western Interior Seaway.
pChem: a modification-centric assessment tool for the performance of chemoproteomic probes

We report a modification-centric, blind-search tool termed pChem to provide a streamlined pipeline for unbiased assessing of the performance of chemoproteomic probes. The pipeline starts with an experimental setting for isotopically coding probe-derived modifications that can be automatically recognized, accurately calculated and precisely localized by pChem with neither prior knowledge nor manual inspection. Further, pChem exports on-demand reports by scoring the profiling efficiency, modification-homogeneity and proteome-wide residue selectivity of a tested probe. The performance and robustness of pChem were benchmarked by applying it to various bioorthogonal probes, including 15 activity-based protein profiling (ABPP) probes and 3 metabolic labeling probes. Together, pChem is a user-friendly computational tool for probe developers, even those with no experience in informatics, and aims to facilitate the development and optimization of probes for the ever-growing field of chemoproteomics.
US FDA Breast Implant Postapproval Studies Long-term Outcomes in 99,993 Patients

Objective: To analyze the long-term safety and efficacy outcomes of patients with breast implants. Summary Background Data: Research is ongoing regarding the safety of silicone breast implants. Despite the number of patients with breast implants followed by United States Food and Drug Administration large postapproval studies (LPAS), this database has not been thoroughly analyzed or reported. Methods: This is a multicentered, cohort study. LPAS prospectively monitor long-term implant-related outcomes and systemic harms for silicone/saline implants from 2 manufacturers (Allergan and Mentor) placed for primary/ revision augmentation/reconstruction. Systemic harms, self-harm, and repro- ductive outcomes are compared with normative data. Implant-related com-plicationsare analyzedbyimplantcompositionand operative indicationinthe short and long terms. Results: LPAS data includes 99,993 patients, 56% of implants were silicone for primary augmentation. Long-term magnetic resonance imaging surveillance is under 5%. Compared with normative data, silicone implants are associated with higher rates of Sjogren syndrome (Standardized incidence ratio [SIR]8.14), scleroderma (SIR 7.00), rheumatoid arthritis (SIR5.96), stillbirth (SIR4.50), and melanoma (SIR3.71). One case of BI-ALCL is reported. There is no association with suicide. In the short term, rupture is higher for saline (2.5% vs. 0.5%, P < 0.001), and capsular contracture higher for silicone (5.0% vs. 2.8%, P < 0.001). At 7 years, reoperation rate is 11.7% for primary augmentation, and 25% for primary/revision reconstruction. Capsular contracture (III/IV) occurs in 7.2% of primary augmentations, 12.7% primary reconstructions, and is the most common reason for reoperation among augmentations. Conclusions: This is the largest study of breast implant outcomes. Silicone implants are associated with an increased risk of certain rare harms; asso- ciations need to be further analyzed with patient-level data to provide conclusive evidence. Long-term safety and implant-related outcomes should inform patient and surgeon decision-making when selecting implants.
Remote sensing of vertically structured phytoplankton pigments

Satellites data can be used to estimate the phytoplankton pigment concentration averaged over the upper few meters of the water column, the penetration depth, whereas the depth at which photosynthetic activity takes place, the euphotic depth, is about four times larger. This limitation, intrinsic to optical remote sensing, can lead to serious misinterpretations of satellite data. Vertical profiles of phytoplankton very often show a non-homogeneous distribution, which can result in errors in the satellite-derived estimation of the depth of the euphotic zone and its phytoplankton biomass. For this study the pigment concentration as would be measured by a satellite was calculated numerically using a Gaussian representation of the vertical distribution. A new understanding of the satellite estimation has been obtained. This new approach provides a physical interpretation of the satellite estimation as an increasing function of the maximum pigment concentration within the vertical distribution. The relationship is expressed as the linear function Cf = m Chlm + b, where Cfthe satellite observation and Chlm is the maximum pigment concentration. The slope m and offset b are expressed as functions of the other features of the vertical distribution, namely the depth where the maximum concentration is located, the spread of the increased concentration and a background concentration.
Incidence and clearance of anal HPV-16 and HPV-18 infection, and their determinants, among HIV-infected men who have sex with men in France

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Incidence and clearance of anal HPV-16 and HPV-18 infection, and their determinants, among HIV-infected men who have sex with men in France Catharina J Alberts, Isabelle Heard, Ana Canestri, Lucie Marchand, Jean-François Fléjou, Lionel Piroth, Tristan Ferry, Jean-Michel Didelot, Laurent Siproudhis, Sebastien Henno, et al.
Asociaciones de fósiles y hiatos en el Supracretácico-Neogeno de Patagonia: una perspectiva estratigraficosecuencial

The Maastrichtian through Miocene series in the midplate San Jorge Basin contains rich and comprehensively studied vertebrate and invertebrate fossil assemblages. These strata reflect a depositional seuing featuring a shallow to deeper epicontinental shelf, framed by a paralic tract with shallow neritic to estuarine-lagoonal belts and a variably wide coastal plain dominated by low energy alluviation and aeolian processes. Gradual facies changes and evidences of stratigraphic condensation, both at the proximal subaerial and distal marine domains where paleosoil stacks and glauconitic concentrations have been found, reveal an accumulation regime controlled by mild depositional gradient and meager sediment supply. Observations near the Atlantic coast at Comodoro Rivadavia (46° S) and data from outcrops, oil wells, and seismic sections scattered across the patagonian hinterland, demonstrate massive late Cretaceous epicontinental flooding and episodic Danian through Eocene marine retreat, leading to the development of an aelian-fed (Loessic) coastal plain superimposed on Mesozoic basins and arches that separate them. Deposition resumed after a widespread late Eocene-early Oligocene gap, following a pattern that altemated phases of shelfal flooding and coastal aggradation, with periods of shelfal emersion and degradational incision of the coastal plain. By middle and late Miocene the region was finally dominated by easterly directed progradation, possibly after roughly linear coastal accretion of the chenier-plain type. Sequence analysis ofthe 850-450 m thick Maastrichtian-Miocene coastal wedge dernonstrates the presence of, at least, thirteen unconfonnity bound stratal packages with basin-wide persistence. Sequence boundaries occur as complex surfaces irregularly shaped after subaerial incision, coastal abrasion, and marine scouring. The coastal plain members of most of the sequences contain characteristic fossil mammal assemblages (distinct Land Mammal Ages). The present sequence stratigraphic examination supports previous work pointing out that faunal changes take place mostly at stratigraphic breaks, that we now attribute to base level fluctuations. Considering the chronology of these stratal discontinuities and region allocation at the back of a mature passive margin dominated by mild and steady subsidence, we suggest that the discontinuities in the Central Patagonian mammal succesion developed in phase with accomodation changes linked to global eustatism.
Combination of Ad-SGE-REIC and bevacizumab modulates glioma progression by suppressing tumor invasion and angiogenesis

Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and its overexpression has been shown to exert anti-tumor effects as a therapeutic target gene in many human cancers. Recently, we demonstrated the anti-glioma effects of an adenoviral vector carrying REIC/Dkk-3 with the super gene expression system (Ad-SGE-REIC). Anti-vascular endothelial growth factor treatments such as bevacizumab have demonstrated convincing therapeutic advantage in patients with glioblastoma. However, bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. In this study, we examined the effects of Ad-SGE-REIC on glioma treated with bevacizumab. Ad-SGE-REIC treatment resulted in a significant reduction in the number of invasion cells treated with bevacizumab. Western blot analyses revealed the increased expression of several endoplasmic reticulum stress markers in cells treated with both bevacizumab and Ad-SGE-REIC, as well as decreased β-catenin protein levels. In malignant glioma mouse models, overall survival was extended in the combination therapy group. These results suggest that the combination therapy of Ad-SGE-REIC and bevacizumab exerts anti-glioma effects by suppressing the angiogenesis and invasion of tumors. Combined Ad-SGE-REIC and bevacizumab might be a promising strategy for the treatment of malignant glioma.
RESPIRATORY AND DEHYDROGENASE ACTIVITIES IN THE SOIL UNDER MAIZE GROWTH IN THE CONDITIONS OF IRRIGATED AND NONIRRIGATED FIELDS

The aim of the study was to ascertain the impact of irrigation or its absence on respiratory and dehydrogenase activities in soils under maize growth. Investigations were carried out in years 2007-2009 at six times of analysis during the maize growth season. The experiment included experimental plots on which maize of Clarica hybrid (FAO 220, Pioneer) intended for CCM was grown. The experimental plots were irrigated with the use of semi-permanent sprinkling machines. Dehydrogenase activity in the soil was determined colorimetrically, and soil respiratory activity was determined with the titration method. Soil respiratory activity did not exhibit significant variability during the growth season with the exception of 2009 at the second time of analysis (at the 2-3 maize leaf stage), when the highest average values in the season were recorded. In the third year of the analysis (2009), practically speaking, no significant differences were observed in the activity of the examined enzymes between irrigated and nonirrigated plots. The comparison of the dates of the analyses showed that the highest activity of the investigated enzymes occurred in the spring before sowing and in the summer. Mean values of the respiratory activity did not show large differences in the individual seasons.
Using the Paleorecord to Evaluate Climate and Fire Interactions in Australia

AbstractBurning has been a near-continuous feature of the Australian environment but has become progressively more important since the mid-Tertiary, associated with the development of the characteristic sclerophyll vegetation. In the Quaternary, the extent of burning has varied temporally and regionally with glacial-interglacial cyclicity. Burning during glacial periods was reduced in drier areas, presumably because of a critical reduction in fuel availability, but increased in relatively wetter areas where fuel levels were high. On both glacial and Holocene timescales, peaks in charcoal often accompany transitions between fire-insensitive vegetation types, suggesting that burning is facilitated during periods of climate change and environmental instability. This suggestion has been supported by the demonstration of close relationships between fire and El Nino activity. Burning has also increased progressively over the past few hundred thousand years with major accelerations around the time of first human.
Predicting and understanding collagen remodeling in human native heart valves during early development

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