Potassium isotopic analysis is arousing increasing interest, not only in geochemistry, but also in biomedicine. However, real-life applications are still hindered by the lack of robustness of the ...methods used. In this work, a novel and robust method for high-precision K isotopic analysis of geological and biological samples was developed, based on the use of a multicollector ICP-mass spectrometer providing a mass resolving power of 15,000 (extra-high resolution mode, XHR). After evaluation of different measurement conditions, i.e., hot vs cold plasma conditions, standard-type vs jet-type sampling cone, and high resolution (HR) vs XHR, a combination of hot plasma conditions, use of the high-transmission jet-type sampling cone, and the XHR mode allowed for high-precision and interference-free K isotopic analysis. Potassium signal monitoring was performed in the ArH+ interference-free 0.006–0.007 amu wide peak shoulder using the XHR mode. The within-run, short-term external, and long-term external precisions for the δ41K value were 0.02‰ (2se, N = 50), 0.03‰ (2SD, N = 7), and 0.06‰ (2SD, N = 163), respectively. A two-stage chromatographic procedure was developed for the isolation of K from both geological and biological samples, and potential matrix effects affecting the K isotope ratio were systematically evaluated. The method was first applied to geological reference materials (RMs) for validation purposes, and the K isotope ratio results were in good agreement with those previously reported. Subsequently, a series of biological RMs, including serum, whole blood, cerebrospinal fluid, bovine muscle, and lobster hepatopancreas, were characterized for their K isotopic composition.
Family carers are an important source of care for older people. Although several studies have reported that subjective caregiver burden is related to depressive symptoms there are no systematic ...reviews quantifying this association.
To establish the extent to which subjective caregiver burden is associated with depressive symptoms and whether this association would vary by study or care characteristics.
We searched major databases such as PubMed, CINAHL, PsycINFO, Scopus and ISI Proceedings up to March 2018, and conducted a meta-analysis of included studies. Summary estimates of the association were obtained using a random-effects model to improve generalisation of findings.
After screening of 4,688 articles, 55 studies were included providing a total of 56 independent comparisons with a total of 9,847 carers from data across 20 countries. There was a large, positive association between subjective caregiver burden and depressive symptoms (Formula: see text = 0.514; 95% CI = 0.486, 0.541), with very low heterogeneity amongst individual studies (I2 = 8.6%). Sensitivity analyses showed no differences between cross-sectional or repeated measures (Formula: see text = 0.521; 95% CI = 0.491, 0.550; 51 samples) and longitudinal studies (Formula: see text = 0.454; 95% CI = 0.398, 0.508; 6 samples). We found a higher effect size for those caring for people living with dementia compared to those caring for frail older people, and stroke survivors. Carer sex, age and kinship did not change the estimate of the effect.
Subjective caregiver burden is a significant risk factor for depressive symptoms in carers of older people and may precipitate clinical depression. Those caring for people with dementia experience greater burden. There is a need for longitudinal evaluations examining the effects of potential mediators of the association of subjective burden and depressive symptoms. Future interventions should test whether minimizing subjective burden may modify the risk of developing depression in carers of older relatives.
Peatlands of the Northern Hemisphere and Central European coniferous forests experience significant environmental change. The resultant browning of surface waters, that is, elevated concentrations of ...dissolved organic matter (DOM) and metals, is of interest in the context of the global C cycle, peatland and forest management, and water treatment. In an attempt to identify the causes of this process in the Harz Mountains (Central Germany), we studied the spatiotemporal variations in DOM molecular composition (thermally assisted hydrolysis and methylation combined with GC–MS) and metal concentrations in headwater stream samples. We found strong relationships between DOM and metals and seasonal variations in the DOM quality and tentatively DOM–metal binding mode: during summer base flow, DOM and metal concentrations are low, and all elements other than the alkali and alkaline earth metals (Ca, Mg, Sr, K, and Na) are positively correlated to DOM, whereas during spring and autumn (high discharge), only metals with strong affinity for DOM (Fe, As, Cu, Cr, Pb, and Ti), but not weakly binding ones (Al, Cd, La, Mn, Ni, Zn, and Zr), are correlated to DOM, indicative of selectivity in DOM–metal interactions. The products of polyphenols are the key ingredients of the DOM–metal complexes. We argue the importance of spruce lignin-derived vanillic acid moieties, which are involved in weak (all seasons) and strong, multidentate and/or colloidal, binding (spring and autumn) of metals. Considering the ongoing spruce forest dieback and climate change acceleration, it is tempting to conclude that spruce necromass and forest soils may release vast amounts of lignin-derived DOM and associated metals to headwater streams. This would have significant implications for forest soil C stocks and the management of connected drinking water reservoirs.
Scientific research plays a vital role for society, but carries a significant environmental footprint, involving intensive use of energy and resources. Scientists are well placed to understand the ...unfolding climate and ecological crises, but may not appreciate how heavily their research, and other work-related activities, contribute to emissions and pollution. With the consequences of climate change and ecological breakdown playing out in real time, scientists now have an important, urgent role to play in catalyzing solutions. Here, we explore how research organizations can reduce their environmental impact, share useful resources and encourage the global community to engage in making science more sustainable.
Working in tandem: Highly functionalized pyrroles and pyrazoles can be synthesized from a domino Cu‐catalyzed CN coupling/hydroamidation sequence. The scope and the generality of the method is ...noteworthy as a wide variety of substituents, either in the alkene or alkyne counterparts, are well tolerated.
•High-precision isotopic analysis of Ca, Cu, Fe and Zn reveals clinically relevant information.•Isotope ratio variability among organs, biofluids, tissues and bone.•As a first stage, factors ...affecting isotope ratios were studied in controls.•Isotope ratio data show diagnostic and prognostic capabilities.
High-precision isotopic analysis of essential mineral elements, mainly Ca, Cu, Fe and Zn, provides relevant biomedical information. For this application, multi-collector ICP-mass spectrometry is the preferred technique. Variation in the isotopic signature of these elements is governed by alterations in their uptake, metabolism and/or excretion. Therefore, diseases that affect mineral metal metabolism, such as hemochromatosis, cancer, liver cirrhosis and Wilson's disease, affect the isotopic composition of these elements in some body compartments. This review discusses how natural isotope ratio variations in biofluids can potentially be exploited as alternative approaches for the diagnosis of diseases that can otherwise only be established at a later stage or via a more invasive method and/or for prognostic purposes. This discussion also includes an evaluation of the isotopic variability in biofluids for apparently healthy individuals and in biofluids, soft tissues and bone of experimentally controlled animals. Physiological and lifestyle factors were also paid attention to.
Mantle cell lymphoma (MCL) is an incurable B-cell neoplasm characterized by an aggressive behavior, short responses to conventional therapies and SOX11 overexpression, which is associated with ...aggressive disease features and inferior clinical outcome of patients. Oxidative stress is known to induce tumorigenesis and tumor progression, whereas high expression levels of antioxidant genes have been associated with chemoresistance in different cancers. However, the role of oxidative stress in MCL pathogenesis and the involvement of SOX11 regulating redox homeostasis in MCL cells are largely unknown. Here, by integrating gene set enrichment analysis of two independent series of MCL, we observed that SOX11+ MCL had higher reactive oxygen species (ROS) levels compared to SOX11- MCL primary tumors and increased expression of Peredoxine2 (PRDX2), which upregulation significantly correlated with SOX11 overexpression, higher ROS production and worse overall survival of patients. SOX11 knockout (SOX11KO) significantly reduced PRDX2 expression, and SOX11KO and PRDX2 knockdown (PRDX2KD) had increased ROS levels and ROS-mediated tumor cell death upon treatment with drugs, compared to control MCL cell lines. Our results suggest an aberrant redox homeostasis associated with chemoresistance in aggressive MCL through SOX11-mediated PRDX2 upregulation, highlighting PRDX2 as promising target for new therapeutic strategies to overcome chemoresistance in aggressive MCLs.
All elements with two or more isotopes show natural variation in their isotopic composition as a result of the isotope fractionation that accompanies (bio)chemical reactions and (bio)physical ...processes. Multicollector inductively coupled plasma‐mass spectrometry (MC‐ICP‐MS) offers the precision required to reveal and quantify the differences in isotope ratios thus caused, although they are often of sub‐permil magnitude only. Using MC‐ICP‐MS, it has been shown that (a) in different body compartments, essential mineral elements may display different isotopic compositions, and (b) disease conditions may alter the isotopic composition of an essential mineral element in a biofluid and/or tissue. As a result, high‐precision isotopic analysis of these elements is a powerful way to unravel the actual role these essential mineral elements play in specific biochemical processes. Moreover, isotope ratio shifts also show promise as a diagnostic or prognostic tool. Despite the intensive sample pretreatment preceding MC‐ICP‐MS isotopic analysis and the high purchase and running costs of the instrumentation, this approach may be valuable, especially for diseases that can otherwise only be established at a later stage and/or via a more invasive approach. This review paper describes the basics of “biomedical isotopic analysis” and uses selected cases from the literature to sketch the state‐of‐art and illustrate in which context isotope ratio markers could be exploited in a clinical context.
Disease conditions may alter the isotopic composition of an essential mineral element in a biofluid and/or tissue. Multicollector inductively coupled plasma‐mass spectrometry enables such changes in isotopic composition to be revealed and quantified. This approach is a novel way to unravel the actual role these essential mineral elements play in specific biochemical processes and shows promise for diagnostic and/or prognostic purposes. This review paper describes the basics of “biomedical isotopic analysis” and uses selected cases from the literature to illustrate how isotope ratio markers could be exploited in a clinical context.
SOX11 overexpression in mantle cell lymphoma (MCL) has been associated with more aggressive behavior and worse outcome. However, SOX11 oncogenic pathways driving MCL tumor progression are poorly ...understood. Here, we demonstrate that SOX11 binds to regulatory regions of 2 important genes for microenvironment signals in cancer: (C-X-C motif) chemokine receptor 4 (CXCR4) and PTK2 (encoding for focal adhesion kinase FAK). Moreover, SOX11+ xenograft and human primary MCL tumors overexpress cell migration and stromal stimulation gene signatures compared with their SOX11− counterparts. We show that SOX11 directly upregulates CXCR4 and FAK expression, activating PI3K/AKT and ERK1/2 FAK-downstream pathways in MCL. Concordantly, SOX11+ MCL cells have higher cell migration, transmigration through endothelial cells, adhesion to stromal cells, and cell proliferation and display an increased resistance to conventional drug therapies compared with SOX11− MCL cells. Specific FAK inhibition blocks downstream PI3K/AKT- and ERK1/2-mediated phosphorylation. Additionally, specific FAK and PI3K inhibitors reduce SOX11-enhanced MCL cell migration and stromal interactions and revert cell adhesion–mediated drug resistance (CAM-DR) to the same levels as SOX11− MCL cells. In intravenous MCL xenograft models, SOX11+ MCL cells display higher cell migration, invasion, and growth compared with SOX11-knockdown cells, and specific FAK and CXCR4 inhibitors impair SOX11-enhanced MCL engraftment in bone marrow. Overall, our results suggest that SOX11 promotes MCL homing and invasion and increases CAM-DR through the direct regulation of CXCR4 and FAK expression and FAK/PI3K/AKT pathway activation, contributing to a more aggressive phenotype. Inhibition of this pathway may represent an efficient strategy to overcome stromal-mediated chemotherapy refractoriness in aggressive MCL.
•SOX11 regulates MCL homing and invasion via direct regulation of CXCR4 and FAK expression and PI3K/AKT and ERK1/2 signaling activation.•SOX11 expression increases CAM-DR, contributing to a more aggressive MCL phenotype.
Understanding the role of catchment sensitivity to dissolved carbon export to aquatic systems is crucial to predict future changes in carbon fluxes under changing climatic conditions. We present ...1-year variations in dissolved organic (DOC) and inorganic carbon (DIC) concentrations and fluxes in eight river catchments differing in size (3–300 km
2
), morphology (steep to flat), and vegetation cover (grassland, forest and peatland) along a precipitation gradient in southern Patagonia, Chile. The results show large differences between catchments in terms of river DOC (2–47 mg L
−1
; 1–44 tons km
−2
year
−1
) and DIC (0.1–38 mg L
−1
; 1–5 tons km
−2
year
−1
) concentrations and fluxes in response to changes in discharge. Small and
s
teep catchments hosting organic rich forest soils and peatlands were the most sensitive and showed the highest and fastest DOC release if evaluated on a per unit area basis. Here, rain events caused a rapid exponential increase in DOC release, while DIC export decreased exponentially. A negative correlation between DOC and DIC reveals the minor importance of DIC production through mineralization of DOC in most catchments. Catchments hosting large peatlands had low sensitivity to discharged controlled DOC release attributed to their high hydrological buffer capacity. Similarly, flat and relatively dry Patagonian steppe catchments have comparatively low sensitivity but have short-term high release of DOC accumulated during dry periods. In conclusion, morphology, rather than catchment size or vegetation cover, was found to show the major influence on sensitivity to DOC release.
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