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    A Novel Gemcitabine-Resistant Gallbladder Cancer Model Provides Insights into Molecular Changes Occurring during Acquired Resistance

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    Treatment options for advanced gallbladder cancer (GBC) are scarce and usually rely on cytotoxic chemotherapy, but the effectiveness of any regimen is limited and recurrence rates are high. Here, we investigated the molecular mechanisms of acquired resistance in GBC through the development and characterization of two gemcitabine-resistant GBC cell sublines (NOZ GemR and TGBC1 GemR). Morphological changes, cross-resistance, and migratory/invasive capabilities were evaluated. Then, microarray-based transcriptome profiling and quantitative SILAC-based phosphotyrosine proteomic analyses were performed to identify biological processes and signaling pathways dysregulated in gemcitabine-resistant GBC cells. The transcriptome profiling of parental and gemcitabine-resistant cells revealed the dysregulation of protein-coding genes that promote the enrichment of biological processes such as epithelial-to-mesenchymal transition and drug metabolism. On the other hand, the phosphoproteomics analysis of NOZ GemR identified aberrantly dysregulated signaling pathways in resistant cells as well as active kinases, such as ABL1, PDGFRA, and LYN, which could be novel therapeutic targets in GBC. Accordingly, NOZ GemR showed increased sensitivity toward the multikinase inhibitor dasatinib compared to parental cells. Our study describes transcriptome changes and altered signaling pathways occurring in gemcitabine-resistant GBC cells, which greatly expands our understanding of the underlying mechanisms of acquired drug resistance in GBC

    Computing the coarseness of a bicolored point set on the plane over guillotine partitions

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    The concept of coarseness measures how well blended the elements of a finite bicolored set of n points are. It is defined as the maximum bichromatic discrepancy over all partitions of the set with non-overlapping convex hulls. It is conjectured that this general computation is NP-Hard; hence several simplified lower bounds have been presented in the literature. In this work, we introduce a novel idea of this kind, considering only partitions derived from straight binary divisions of the plane. We call this the guillotine coarseness of the bicolored point set. The basic properties of this concept are studied, and a dynamic programming algorithm of {O}(n{5}) time is presented for calculating it. Finally, experimental simulations are performed to investigate a possible relationship between n and the number k of cuts used to calculate the guillotine coarseness

    Age-Dependent Behavioral and Synaptic Dysfunction Impairment Are Improved with Long-Term Andrographolide Administration in Long-Lived Female Degus (Octodon degus)

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    In Octodon degus, the aging process is not equivalent between sexes and worsens for females. To determine the beginning of detrimental features in females and the ways in which to improve them, we compared adult females (36 months old) and aged females (72 months old) treated with Andrographolide (ANDRO), the primary ingredient in Andrographis paniculata. Our behavioral data demonstrated that age does not affect recognition memory and preference for novel experiences, but ANDRO increases these at both ages. Sociability was also not affected by age; however, social recognition and long-term memory were lower in the aged females than adults but were restored with ANDRO. The synaptic physiology data from brain slices showed that adults have more basal synaptic efficiency than aged degus; however, ANDRO reduced basal activity in adults, while it increased long-term potentiation (LTP). Instead, ANDRO increased the basal synaptic activity and LTP in aged females. Age-dependent changes were also observed in synaptic proteins, where aged females have higher synaptotagmin (SYT) and lower postsynaptic density protein-95 (PSD95) levels than adults. ANDRO increased the N-methyl D-aspartate receptor subtype 2B (NR2B) at both ages and the PSD95 and Homer1 only in the aged. Thus, females exposed to long-term ANDRO administration show improved complex behaviors related to age-detrimental effects, modulating mechanisms of synaptic transmission, and proteins

    Strategies for regional modeling of surface mass balance at the Monte Sarmiento Massif, Tierra del Fuego

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    This study investigates strategies for calibration of surface mass balance (SMB) models in the Monte Sarmiento Massif (MSM), Tierra del Fuego, with the goal of achieving realistic simulations of the regional SMB. Applied calibration strategies range from a local single-glacier calibration to a regional calibration with the inclusion of a snowdrift parameterization. We apply four SMB models of different complexity. In this way, we examine the model transferability in space, the benefit of regional mass change observations and the advantage of increasing the complexity level regarding included processes. Measurements include ablation and ice thickness observations at Schiaparelli Glacier as well as elevation changes and flow velocity from satellite data for the entire study site. Performance of simulated SMB is validated against geodetic mass changes and stake observations of surface melting. Results show that transferring SMB models in space is a challenge, and common practices can produce distinctly biased estimates. Model performance can be significantly improved by the use of remotely sensed regional observations. Furthermore, we have shown that snowdrift does play an important role in the SMB in the Cordillera Darwin, where strong and consistent winds prevail. The massif-wide average annual SMB between 2000 and 2022 falls between -0.28 and -0.07 m w.e. yr(-1), depending on the applied model. The SMB is mainly controlled by surface melting and snowfall. The model intercomparison does not indicate one obviously best-suited model for SMB simulations in the MSM

    Characterization of alginate from Antarctic Himantothallus grandifolius (Phaeophyceae) and preparation of polyelectrolyte complexes with chitosan

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    Hydrogels are three-dimensional polymeric materials with applications in various areas such as biomedicine, tissue engineering, pollutant capture systems, and so forth. However, its application is limited due to the reproducibility of its properties. Factors such as the composition of the constituents, the type of union between the polymer chains, and the crosslinking time play a crucial role in ensuring its reproducibility. In this study, the objective is to prepare a matrix with well-defined properties that ensure controlled release processes. Treatment of Himantothallus grandifolius with Na2CO3 aqueous solution afforded in 18.9% yield alkaline extract. Hydrogels were prepared by ionic complexation of alginate from H. grandifolius, and polyguluronate enriched alginate from Desmarestia ligulata with chitosan stabilized by immersion in 0.1 M CaCl2 solution; better swelling ratio in water was found for hydrogels with low molecular weight chitosan (MW 125,000 g/mol) than those with medium molecular weight chitosan (MW450,000-500,000 g/mol). Liberation of the model drug metformin hydrochloride from alginates: chitosan complexes (3:1) at pH 1.5 was especially low for hydrogel from H. grandifolius during the first 2 h; 70% of metformin was released at pH 6.5 after 24 h. This polyelectrolyte complex constitutes a good material for potential application in biomedicine considering its cationic and anionic characteristics

    Foraminifera in temperate fjords strongly affected by glacial meltwater, Tierra del Fuego, South America

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    Chilean Patagonia is one of the few regions in the Southern Hemisphere where tidewater glaciers deliver torrential meltwater. We sampled the Beagle Channel and five tributary fjords, with and without glaciers, to explore modern foraminifera of this little studied region. Surface sediments (mud, sand, pebbles, and shell debris) were collected at 45 stations from water depths 15 to 250 m, along with four short cores. The soft bottom recovered at 35 stations was analyzed for grain size, Loss-on-ignition reflecting content of organic matter, and Rose-Bengal-stained foraminifera. The benthic fauna consisted of 86 attached and free-living species. Uvigerina bifurcata, Alveolophragmium orbiculatum, Ammobaculites americanus, Stainforthia fusiformis, Globobulimina noto-vata, and Nonionoides grateloupii were dominant. As shown by downcore distribution, U. bifurcata and A. orbiculatum occupied epifaunal and G. notovata and S. fusiformis infaunal microhabitats. Distribution of the dominant foraminifera showed no clear pattern, with the exception of S. fusiformis, which formed a monospecific assemblage in sediments enriched with organic matter. Certain subdominant species, including Cassidulinoides parkerianus, Pullenia subcarinata, and Cibicides fletcheri, showed environmental affinity to more sandy sediments, whereas the assemblage from more muddy sediments had no inherent taxa. Foraminiferal standing crop in size fraction >125 mu m was mostly 100 to 500 specimens per 10 cm3 but dropped to <1 specimen near glacier fronts, where foraminifera varied greatly between stations and did not constitute a single, unified assemblage. This patchy pattern seems to result from environmental instability caused by rapidly settling mineral fines and from random dispersal and activation of propagules. It helps to interpret records of other meltwater-dominated events

    Harnessing Diesel-Degrading Potential of an Antarctic Microalga from Greenwich Island and Its Physiological Adaptation

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    Phytoremediation is a plant-based approach to extract, stabilise, eliminate, or render pollutants into less harmful form. The study highlights the use of a native polar microalga as a means of phytoremediation in Antarctica where imported microbes are prohibited. Since 1959, Antarctica has been a protected region to preserve its dynamic ecosystems, but it is increasingly vulnerable to climate change and pollution. One of the anthropogenic disturbances in the continent is diesel spillage. Due to the extreme polar environment, natural attenuation of spilled diesel is severely hindered; hence, the problem calls for an effective and sustainable solution. This laboratory study proved that Antarctic microalga was capable of removing diesel (57.6%) through biodegradation and biosorption in the span of nine days. Meanwhile, mixotrophic cultivation triggered the vacuolar activities and potentially stimulated lipid assimilation in the cells. The microalgal-based process offers a cheap alternative in water decontamination while bearing the economic potential through the secretion of valuable products, such as biolipids. Abstract: Microalgae are well known for their metal sorption capacities, but their potential in the remediation of hydrophobic organic compounds has received little attention in polar regions. We evaluated in the laboratory the ability of an Antarctic microalga to remediate diesel hydrocarbons and also investigated physiological changes consequent upon diesel exposure. Using a polyphasic taxonomic approach, the microalgal isolate, WCY_AQ5_1, originally sampled from Greenwich Island (South Shetland Islands, maritime Antarctica) was identified as Tritostichococcus sp. (OQ225631), a recently erected lineage within the redefined Stichococcus clade. Over a nine-day experimental incubation, 57.6% of diesel (similar to 3.47 g/L) was removed via biosorption and biodegradation, demonstrating the strain's potential for phytoremediation. Fourier transform infrared spectroscopy confirmed the adsorption of oil in accordance with its hydrophobic characteristics. Overall, degradation predominated over sorption of diesel. Chromatographic analysis confirmed that the strain efficiently metabolised medium-chain length n-alkanes (C-7 to C-21), particularly n-heneicosane. Mixotrophic cultivation using diesel as the organic carbon source under a constant light regime altered the car/chl-a ratio and triggered vacuolar activities. A small number of intracellular lipid droplets were observed on the seventh day of cultivation in transmission electron microscopic imaging. This is the first confirmation of diesel remediation ability in an Antarctic green microalga

    Multi-salinity core flooding study in clay-bearing sandstones, a contribution to geothermal reservoir characterisation

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    Porosity and permeability measurements aid the characterisation of geothermal reservoirs as they improve understanding of the impact of rock-fluid interactions during the life cycle of wells. Core flooding experiments can help us comprehend the rock-brine electrochemical system as critical parameters like salinity, pH, temperature, or pressure change. If the clay mineral content is significant it can reduce permeability and porosity since these particles can block the pore throat network connectivity through clay migration or swelling. A multi-salinity experiment was conducted in three tight clay-bearing (kaolinite, chlorite, and glauconite) sandstones to study the impact of clay on their petrophysical properties. The experiment consisted of core-flooding brines with salinities of 75 000-200 000 and 0-50 000 ppm NaCl at very low flow rates. Electrical resistivity, the differential pressure across the sample, outlet brine electrical conductivity, and brine permeability were measured. Pore size distribution was acquired by measuring nuclear magnetic resonance (NMR) T-2 relaxation time. Cation-exchange capacity (CEC) was derived using the Waxman and Smits (1968) approach. The derived CECs were 71.5, 4.7, and 3.6 meq per 100 g for the kaolinite, chlorite, and glauconite sandstones, respectively. Kaolinite was the least water-sensitive as its permeability decreased uniformly. Chlorite and glauconite were more water-sensitive as in the low salinity range; their permeability increased, and both displayed a bimodal NMR T-2 distribution and pore size rearrangement towards the mesoporosity and macroporosity range, indicating that the cation-exchange site prevailed within the pore space. This investigation highlights the importance of ensuring that appropriate fluid chemistry is used on brines flowing in clay-bearing geothermal reservoirs

    Mountain social-ecological resilience requires transdisciplinarity with Indigenous and local worldviews

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    Addressing the shocks of global crises requires that scientists, pol-icymakers, and Indigenous Peo-ples and Local Communities work together to enable communities to withstand and adapt to distur-bances. On the basis of our experi-ences in the Andes, we propose the '10-step cycle of transdisciplinarity' for designing projects to build social-ecologi cal resilience in mountains

    On a remarkable teratological case in Lygaeus analis Dallas, 1852 (Hemiptera: Heteroptera: Lygaeidae)

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    Se describe el primer caso teratológico para Lygaeus analis, correspondiente a una hemiatrofia cefálica izquierda con reducción ocular, en base a un ejemplar proveniente de México. Se discuten y analizan las posibles causas de la malformación

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