18,124 research outputs found

    Ecological successions throughout the desiccation of Tirez lagoon (Spain) as an astrobiological time-analog for wet-to-dry transitions on Mars

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    Tirez was a small and seasonal endorheic athalassohaline lagoon that was located in central Spain. In recent years, the lagoon has totally dried out, offering for the first time the opportunity to analyze its desiccation process as a “time-analog” to similar events occurred in paleolakes with varying salinity during the wet-to-dry transition on early Mars. On the martian cratered highlands, an early period of water ponding within enclosed basins evolved to a complete desiccation of the lakes, leading to deposition of evaporitic sequences during the Noachian and into the Late Hesperian. As Tirez also underwent a process of desiccation, here we describe (i) the microbial ecology of Tirez when the lagoon was still active 20 years ago, with prokaryotes adapted to extreme saline conditions; (ii) the composition of the microbial community in the dried lake sediments today, in many case groups that thrive in sediments of extreme environments; and (iii) the molecular and isotopic analysis of the lipid biomarkers that can be recovered from the sediments today. We discuss the implications of these results to better understanding the ecology of possible Martian microbial communities during the wet-to-dry transition at the end of the Hesperian, and how they may inform about research strategies to search for possible biomarkers in Mars after all the water was los

    Similarity and variability of blocked weather-regime dynamics in the Atlantic–European region

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    Weather regimes govern an important part of the sub-seasonal variability of the mid-latitude circulation. Due to their role in weather extremes and atmospheric predictability, regimes that feature a blocking anticyclone are of particular interest. This study investigates the dynamics of these “blocked” regimes in the North Atlantic–European region from a year-round perspective. For a comprehensive diagnostic, wave activity concepts and a piecewise potential vorticity (PV) tendency framework are combined. The latter essentially quantifies the well-established PV perspective of mid-latitude dynamics. The four blocked regimes (namely Atlantic ridge, European blocking, Scandinavian blocking, and Greenland blocking) during the 1979–2021 period of ERA5 reanalysis are considered. Wave activity characteristics exhibit distinct differences between blocked regimes. After regime onset, Greenland blocking is associated with a suppression of wave activity flux, whereas Atlantic ridge and European blocking are associated with a northward deflection of the flux without a clear net change. During onset, the envelope of Rossby wave activity retracts upstream for Greenland blocking, whereas the envelope extends downstream for Atlantic ridge and European blocking. Scandinavian blocking exhibits intermediate wave activity characteristics. From the perspective of piecewise PV tendencies projected onto the respective regime pattern, the dynamics that govern regime onset exhibit a large degree of similarity: linear Rossby wave dynamics and nonlinear eddy PV fluxes dominate and are of approximately equal relative importance, whereas baroclinic coupling and divergent amplification make minor contributions. Most strikingly, all blocked regimes exhibit very similar (intra-regime) variability: a retrograde and an upstream pathway to regime onset. The retrograde pathway is dominated by nonlinear PV eddy fluxes, whereas the upstream pathway is dominated by linear Rossby wave dynamics. Importantly, there is a large degree of cancellation between the two pathways for some of the mechanisms before regime onset. The physical meaning of a regime-mean perspective before onset can thus be severely limited. Implications of our results for understanding predictability of blocked regimes are discussed. Further discussed are the limitations of projected tendencies in capturing the importance of moist-baroclinic growth, which tends to occur in regions where the amplitude of the regime pattern, and thus the projection onto it, is small. Finally, it is stressed that this study investigates the variability of the governing dynamics without prior empirical stratification of data by season or by type of regime transition. It is demonstrated, however, that our dynamics-centered approach does not merely reflect variability that is associated with these factors. The main modes of dynamical variability revealed herein and the large similarity of the blocked regimes in exhibiting this variability are thus significant results.</p

    Macrophages from naked mole-rat possess distinct immunometabolic signatures upon polarization

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    The naked mole-rat (NMR) is a unique long-lived rodent which is highly resistant to age-associated disorders and cancer. The immune system of NMR possesses a distinct cellular composition with the prevalence of myeloid cells. Thus, the detailed phenotypical and functional assessment of NMR myeloid cell compartment may uncover novel mechanisms of immunoregulation and healthy aging. In this study gene expression signatures, reactive nitrogen species and cytokine production, as well as metabolic activity of classically (M1) and alternatively (M2) activated NMR bone marrow-derived macrophages (BMDM) were examined. Polarization of NMR macrophages under pro-inflammatory conditions led to expected M1 phenotype characterized by increased pro-inflammatory gene expression, cytokine production and aerobic glycolysis, but paralleled by reduced production of nitric oxide (NO). Under systemic LPS-induced inflammatory conditions NO production also was not detected in NMR blood monocytes. Altogether, our results indicate that NMR macrophages are capable of transcriptional and metabolic reprogramming under polarizing stimuli, however, NMR M1 possesses species-specific signatures as compared to murine M1, implicating distinct adaptations in NMR immune system

    Aflatoxins

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    The aflatoxin producing fungi Aspergillus flavus, A. parasiticus, and A. nomius, although they are also produced by other species of Aspergillus as well as by Emericella spp.(Telemorph). There are many types of aflatoxins, but the four main ones are aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1), and aflatoxin G2 (AFG2, while aflatoxin M1 (AFM1) and M2 (AFM2) are the hydroxylated metabolites of AFB1 and AFB2. Aflatoxin B1, which is a genotoxic hepatocarcinogen, which presumptively causes cancer by inducing DNA, adducts leading to genetic changes in target liver cells. Cytochrome-P450 enzymes to the reactive intermediate AFB1–8, 9 epoxide (AFBO) which binds to liver cell DNA, resulting in DNA adducts, metabolize AFB1 Ingestion of contaminated food is the main source of exposure to aflatoxins, which adversely affect the health of both humans and animals. The compounds can cause acute or chronic toxic effects of a teratogenic, mutagenic, carcinogenic, immunotoxic or hepatotoxic character. You can reduce your aflatoxin exposure by buying only major commercial brands of food and by discarding that look moldy, discolored, or shriveled

    Chromosome Abnormalities in Hematological Malignancies and Its Clinical Significance

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    The latest version of the World Health Organization guidelines focuses mainly on the genetic and cytogenetic features of hematologic neoplasms as predictors of diagnostic, treatment decision, prognostic outcome, and for treatment monitoring in hematological malignancies. There are different techniques to identify these abnormalities. Live cells are needed for chromosome preparation. The Hematological malignancies include myeloid and lymphoid neoplasms. The myeloid neoplasms include Myelodysplastic syndromes, myeloproliferative neoplasms, and acute myeloid leukemias. The Lymphoid neoplasms include acute and chronic lymphocytic leukemias, plasma cell neoplasms, myeloma, hodgkin, and non-hodgkin lymphomas. The first chromosomal abnormality discovered in connection with cancer is the Philadelphia chromosome, which is an abnormal chromosome 22, formed due to the translocation between chromosomes 9 and 22. The presence of this abnormal chromosome confirms the diagnosis of “CML”. After that, hundreds of chromosomal abnormalities have been identified in hematological malignancies in different parts of the world. In AML, specific abnormalities were identified as having a good prognosis, intermediate prognosis, and poor prognosis. In other hematological malignancies also there some specific chromosome abnormalities are associated with prognostication. Now a day’s clinicians depend mainly on genetic abnormalities for the proper treatment management of hematological malignancies, so the study of chromosomal abnormalities is essential

    Mathematical models to evaluate the impact of increasing serotype coverage in pneumococcal conjugate vaccines

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    Of over 100 serotypes of Streptococcus pneumoniae, only 7 were included in the first pneumo- coccal conjugate vaccine (PCV). While PCV reduced the disease incidence, in part because of a herd immunity effect, a replacement effect was observed whereby disease was increasingly caused by serotypes not included in the vaccine. Dynamic transmission models can account for these effects to describe post-vaccination scenarios, whereas economic evaluations can enable decision-makers to compare vaccines of increasing valency for implementation. This thesis has four aims. First, to explore the limitations and assumptions of published pneu- mococcal models and the implications for future vaccine formulation and policy. Second, to conduct a trend analysis assembling all the available evidence for serotype replacement in Europe, North America and Australia to characterise invasive pneumococcal disease (IPD) caused by vaccine-type (VT) and non-vaccine-types (NVT) serotypes. The motivation behind this is to assess the patterns of relative abundance in IPD cases pre- and post-vaccination, to examine country-level differences in relation to the vaccines employed over time since introduction, and to assess the growth of the replacement serotypes in comparison with the serotypes targeted by the vaccine. The third aim is to use a Bayesian framework to estimate serotype-specific invasiveness, i.e. the rate of invasive disease given carriage. This is useful for dynamic transmission modelling, as transmission is through carriage but a majority of serotype-specific pneumococcal data lies in active disease surveillance. This is also helpful to address whether serotype replacement reflects serotypes that are more invasive or whether serotypes in a specific location are equally more invasive than in other locations. Finally, the last aim of this thesis is to estimate the epidemiological and economic impact of increas- ing serotype coverage in PCVs using a dynamic transmission model. Together, the results highlight that though there are key parameter uncertainties that merit further exploration, divergence in serotype replacement and inconsistencies in invasiveness on a country-level may make a universal PCV suboptimal.Open Acces

    Quantification and role of innate lymphoid cell subsets in Chronic Obstructive Pulmonary Disease

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    Objectives Innate lymphoid cells (ILCs) secrete cytokines, such as IFN-γ, IL-13 and IL-17, which are linked to chronic obstructive pulmonary disease (COPD). Here, we investigated the role of pulmonary ILCs in COPD pathogenesis. Methods Lung ILC subsets in COPD and control subjects were quantified using flow cytometry and associated with clinical parameters. Tissue localisation of ILC and T-cell subsets was determined by immunohistochemistry. Mice were exposed to air or cigarette smoke (CS) for 1, 4 or 24 weeks to investigate whether pulmonary ILC numbers and activation are altered and whether they contribute to CS-induced innate inflammatory responses. Results Quantification of lung ILC subsets demonstrated that ILC1 frequency in the total ILC population was elevated in COPD and was associated with smoking and severity of respiratory symptoms (COPD Assessment Test [CAT] score). All three ILC subsets localised near lymphoid aggregates in COPD. In the COPD mouse model, CS exposure in C57BL/6J mice increased ILC numbers at all time points, with relative increases in ILC1 in bronchoalveolar lavage (BAL) fluid. Importantly, CS exposure induced increases in neutrophils, monocytes and dendritic cells that remained elevated in Rag2/Il2rg-deficient mice that lack adaptive immune cells and ILCs. However, CS-induced CXCL1, IL-6, TNF-α and IFN-γ levels were reduced by ILC deficiency. Conclusion The ILC1 subset is increased in COPD patients and correlates with smoking and severity of respiratory symptoms. ILCs also increase upon CS exposure in C57BL/6J mice. In the absence of adaptive immunity, ILCs contribute to CS-induced pro-inflammatory mediator release, but are redundant in CS-induced innate inflammation

    Characterising the role of the Amyloid Precursor Protein and Glucagon-like peptide-1 analogues in Age-Related Macular Degeneration

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    Age-related macular degeneration (AMD) is a progressive retinal neurodegenerative disorder characterised, in some forms of the disease, by the loss of photoreceptors and the underlying retinal pigment epithelium (RPE) in the macula due to the accumulation of extracellular deposits known as “drusen”. A major component of drusen deposits is the Alzheimer’s disease (AD)-related amyloid beta (Aβ)-peptide, a 4kDa peptide derived from the larger amyloid precursor protein (APP) through sequential cleavage by enzymes known as β- and γ-secretases. Alternatively, in the ‘non-amyloidogenic’ pathway, APP can be processed by a third enzyme, α-secretase, which cleaves within the Aβ region of the protein thereby preventing the production of toxic peptides as well as producing a larger soluble fragment, sAPPα, known for its neuroprotective and neurotrophic properties. The current project aims to characterise the role played by APP and its proteolytic fragments in AMD using human retinal pigment epithelial cells (ARPE-19) and UV-A light (a known AMD risk factor) as the stressor. In addition, a group of diabetes drugs known as Glucagon Like Peptide-1 (GLP-1) analogues that have previously been purported to reduce neuronal death in AD and Parkinson’s Disease (PD) have been tested for their ability to protect ARPE-19 cells against stress-inducing reagents relative to AMD (UV-A light, hydrogen peroxide and Aβ-peptides). The results of the current study demonstrate that endogenous cell-associated full-length APP expression was depleted in ARPE-19 cells following UV-A irradiation. Furthermore, β-secretase but not α-secretase processing of the protein was reduced. Small interfering RNA-mediated depletion of endogenous APP or γ-secretase (but not α- or β-secretase) inhibition ablated the detrimental effect of UV-A on cell viability. In contrast, α-secretase and, possibly, γ-secretase but not β-secretase activity appeared to promote the longer-term proliferation of ARPE-19 cells in the absence of UV-A irradiation. Furthermore, two of the GLP-1 analogues tested, liraglutide and lixisenatide, were able to restore cell viability after UV-A exposure. Collectively, these data indicate clear links between the expression/proteolysis of APP and the proliferation and resistance of ARPE-19 cells to UV-A irradiation. Whilst these effects are clearly differential, the data warrant further investigation of the role played by APP in AMD. Furthermore, the protective effects against UV-A shown by liraglutide and lixisenatide warrant further investigation of the molecular mechanisms involved with a view to identifying new drug targets for the prevention or treatment of retinal neurodegenerative diseases such as AMD
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