Advances in Quantitative Hepcidin Measurements by Time-of-Flight Mass Spectrometry

Assays for the detection of the iron regulatory hormone hepcidin in plasma or urine have not yet been widely available, whereas quantitative comparisons between hepcidin levels in these different matrices were thus far even impossible due to technical restrictions. To circumvent these limitations, we here describe several advances in time-of flight mass spectrometry (TOF MS), the most important of which concerned spiking of a synthetic hepcidin analogue as internal standard into serum and urine samples. This serves both as a control for experimental variation, such as recovery and matrix-dependent ionization and ion suppression, and at the same time allows value assignment to the measured hepcidin peak intensities. The assay improvements were clinically evaluated using samples from various patients groups and its relevance was further underscored by the significant correlation of serum hepcidin levels with serum iron indices in healthy individuals. Most importantly, this approach allowed kinetic studies as illustrated by the paired analyses of serum and urine samples, showing that more than 97% of the freely filtered serum hepcidin can be reabsorbed in the kidney. Thus, the here reported advances in TOF MS-based hepcidin measurements represent critical steps in the accurate quantification of hepcidin in various body fluids and pave the way for clinical studies on the kinetic behavior of hepcidin in both healthy and diseased states

Stress hormones or general well-being are not altered in immune-deficient mice lacking either T- and B- lymphocytes or Interferon gamma signaling if kept under specific pathogen free housing conditions

It is controversially discussed whether immune-deficient mice experience severity in the absence of infection. Because a comprehensive analysis of the well-being of immune-deficient mice under specific pathogen free conditions is missing, we used a multi-parametric test analyzing, corticosterone, weight, nest building and facial expression over a period of 9 month to determine the well-being of two immune-deficient mouse lines (recombination activating gene 2- and interferon gamma receptor-deficient mice). We do not find evidence for severity when comparing immune-deficient mice to their heterozygous immune-competent littermates. Our data challenge the assumption that immune-deficiency per se regardless of housing conditions causes severity. Based on our study we propose to use objective non-invasive parameters determined by laboratory animal science for decisions concerning severity of immune-deficient mice

Dissolved noble gases and stable isotopes as tracers of preferential fluid flow along faults in the Lower Rhine Embayment, Germany

Groundwater in shallow unconsolidated sedimentary aquifers close to the Bornheim fault in the Lower Rhine Embayment (LRE), Germany, has relatively low δ2H and δ18O values in comparison to regional modern groundwater recharge, and 4He concentrations up to 1.7 × 10−4 cm3 (STP) g–1 ± 2.2 % which is approximately four orders of magnitude higher than expected due to solubility equilibrium with the atmosphere. Groundwater age dating based on estimated in situ production and terrigenic flux of helium provides a groundwater residence time of ∼107 years. Although fluid exchange between the deep basal aquifer system and the upper aquifer layers is generally impeded by confining clay layers and lignite, this study’s geochemical data suggest, for the first time, that deep circulating fluids penetrate shallow aquifers in the locality of fault zones, implying  that sub-vertical fluid flow occurs along faults in the LRE. However, large hydraulic-head gradients observed across many faults suggest that they act as barriers to lateral groundwater flow. Therefore, the geochemical data reported here also substantiate a conduit-barrier model of fault-zone hydrogeology in unconsolidated sedimentary deposits, as well as corroborating the concept that faults in unconsolidated aquifer systems can act as loci for hydraulic connectivity between deep and shallow aquifers. The implications of fluid flow along faults in sedimentary basins worldwide are far reaching and of particular concern for carbon capture and storage (CCS) programmes, impacts of deep shale gas recovery for shallow groundwater aquifers, and nuclear waste storage sites where fault zones could act as potential leakage pathways for hazardous fluids

Groundwater resources assessment using integrated geophysical techniques in the southwestern region of Peninsular Malaysia.

Combined geophysical techniques such as multi-electrode resistivity, induced polarization, and borehole geophysical techniques were carried out on volcano-sedimentary rocks in the north of Gemas as part of the groundwater resource’s investigations. The result identifies four resistivity units: the tuffaceous mudstone, tuffaceous sandstone, the tuff bed, and the shale layer. Two types of aquifer systems in terms of storage were identified within the area: one within a fracture system (tuff), which is the leaky area through which vertical flow of groundwater occurs, and an intergranular property of the sandy material of the aquifer which includes sandstone and tuffaceous sandstone. The result also reveals that the aquifer occupies a surface area of about 3,250,555 m2 with a mean depth of 43.71 m and a net volume of 9.798 × 107 m3. From the approximate volume of the porous zone (28 %) and the total aquifer volume, a usable capacity of (274.339 ± 30.177) × 107 m3 of water in the study area can be deduced. This study provides useful information that can be used to develop a much broader understanding of the nature of groundwater potential in the area and their relationship with the local geology

Use of social networks as a CSR communication tool

The aim of this paper is to analyse the use of online social networks as a tool for Corporate Social Responsibility (CSR) communication and management. To this end, an analysis was performed of the messages posted by the 20 Spanish companies with the highest market capitalisation and the responses that they received on two of the most popular online social networks, Facebook and Twitter. The results of the analysis of these data show that the tendency has been to use social networks for the one-way communication of aspects of CSR related with the organisation. Therefore, it is necessary to change the way companies communicate their CSR issues by shifting to a two-way communication approach, as has been the case in other kinds of enterprise relations with their stakeholders.The authors received no direct funding for this research

IFNγ binding to extracellular matrix prevents fatal systemic toxicity

Interferon-γ (IFNγ) is an important mediator of cellular immune responses, but high systemic levels of this cytokine are associated with immunopathology. IFNγ binds to its receptor (IFNγR) and to extracellular matrix (ECM) via four positively charged C-terminal amino acids (KRKR), the ECM-binding domain (EBD). Across evolution, IFNγ is not well conserved, but the EBD is highly conserved, suggesting a critical function. Here, we show that IFNγ lacking the EBD (IFNγ(ΔKRKR)) does not bind to ECM but still binds to the IFNγR and retains bioactivity. Overexpression of IFNγ(ΔKRKR) in tumors reduced local ECM binding, increased systemic levels and induced sickness behavior, weight loss and toxicity. To analyze the function of the EBD during infection, we generated IFNγ(ΔKRKR) mice lacking the EBD by using CRISPR–Cas9. Infection with lymphocytic choriomeningitis virus resulted in higher systemic IFNγ(ΔKRKR) levels, enhanced sickness behavior, weight loss and fatal toxicity. We conclude that local retention of IFNγ is a pivotal mechanism to protect the organism from systemic toxicity during prolonged immune stimulation

suPAR as a prognostic biomarker in sepsis

Sepsis is the clinical syndrome derived from the host response to an infection and severe sepsis is the leading cause of death in critically ill patients. Several biomarkers have been tested for use in diagnosis and prognostication in patients with sepsis. Soluble urokinase-type plasminogen activator receptor (suPAR) levels are increased in various infectious diseases, in the blood and also in other tissues. However, the diagnostic value of suPAR in sepsis has not been well defined, especially compared to other more established biomarkers, such as C-reactive protein (CRP) and procalcitonin (PCT). On the other hand, suPAR levels have been shown to predict outcome in various kinds of bacteremia and recent data suggest they may have predictive value, similar to that of severity scores, in critically ill patients. This narrative review provides a descriptive overview of the clinical value of this biomarker in the diagnosis, prognosis and therapeutic guidance of sepsis

Complex conductivity of soils

The complex conductivity of soils remains poorly known despite the growing importance of this method in hydrogeophysics. In order to fill this gap of knowledge, we investigate the complex conductivity of 71 soils samples (including four peat samples) and one clean sand in the frequency range 0.1 Hz to 45 kHz. The soil samples are saturated with six different NaCl brines with conductivities (0.031, 0.53, 1.15, 5.7, 14.7, and 22 S m21, NaCl, 258C) in order to determine their intrinsic formation factor and surface conductivity. This data set is used to test the predictions of the dynamic Stern polarization model of porous media in terms of relationship between the quadrature conductivity and the surface conductivity. We also investigate the relationship between the normalized chargeability (the difference of in-phase conductivity between two frequencies) and the quadrature conductivity at the geometric mean frequency. This data set confirms the relationships between the surface conductivity, the quadrature conductivity, and the normalized chargeability. The normalized chargeability depends linearly on the cation exchange capacity and specific surface area while the chargeability shows no dependence on these parameters. These new data and the dynamic Stern layer polarization model are observed to be mutually consistent. Traditionally, in hydrogeophysics, surface conductivity is neglected in the analysis of resistivity data. The relationships we have developed can be used in field conditions to avoid neglecting surface conductivity in the interpretation of DC resistivity tomograms. We also investigate the effects of temperature and saturation and, here again, the dynamic Stern layer predictions and the experimental observations are mutually consistent