New Polymer Tensiometers: Measuring Matric Pressures Down to the Wilting Point

Tensiometers are commonly used for measuring soil water matric pressures. Unfortunately, the water-filled reservoir of conventional tensiometers limits their applicability to soil water matric pressures above approximately –0.085 MPa. Tensiometers filled with a polymer solution instead of water are able to measure a larger range of soil water matric pressures. We designed and constructed six prototype polymer tensiometers (previously called osmotic tensiometers) consisting of a wide-range pressure transducer with a temperature sensor, a stainless steel casing, and a ceramic plate with a membrane preventing polymer leakage. A polymer chamber (0.1–2.2 cm3) was located between the pressure transducer and the plate. We tested the polymer tensiometers for long-term operation, the effects of temperature, response times, and performance in a repacked sandy loam under laboratory conditions. Several months of continuous operation caused a gradual drop in the osmotic pressure, for which we developed a suitable correction. The osmotic potential of polymer solutions is temperature dependent, and requires calibration before installation. The response times to sudden and gradual changes in ambient temperature were found to be affected by polymer chamber height and polymer type. Practically useful response times (<0.2 d) are feasible, particularly for chambers shorter than 0.20 cm. We demonstrated the ability of the instrument to measure the range of soil water pressures in which plant roots are able to take up water (from 0 to –1.6 MPa), to regain pressure without user interference and to function properly for time periods of up to 1 yr

Measurement and interpretation of electrokinetic phenomena - (IUPAC technical report)

In this report, the status quo and recent progress in electrokinetics are reviewed. Practical rules are recommended for performing electrokinetic measurements and interpreting their results in terms of well-defined quantities, the most familiar being the ζ-potential or electrokinetic potential. This potential is a property of charged interfaces, and it should be independent of the technique used for its determination. However, often the ζ-potential is not the only property electrokinetically characterizing the electrical state of the interfacial region; the excess conductivity of the stagnant layer is an additional parameter. The requirement to obtain the ζ-potential is that electrokinetic theories be correctly used and applied within their range of validity. Basic theories and their application ranges are discussed. A thorough description of the main electrokinetic methods is given; special attention is paid to their ranges of applicability as well as to the validity of the underlying theoretical models. Electrokinetic consistency tests are proposed in order to assess the validity of the ζ-potentials obtained. The recommendations given in the report apply mainly to smooth and homogeneous solid particles and plugs in aqueous systems; some attention is paid to nonaqueous media and less ideal surfaces.Financial assistance from IUPAC is gratefully acknowledged

Polymer tensiometers with ceramic cones: direct observations of matric pressures in drying soils

Measuring soil water potentials is crucial to characterize vadose zone processes. Conventional tensiometers only measure until approximately −0.09 MPa, and indirect methods may suffer from the non-uniqueness in the relationship between matric potential and measured properties. Recently developed polymer tensiometers (POTs) are able to directly measure soil matric potentials until the theoretical wilting point (−1.6 MPa). By minimizing the volume of polymer solution inside the POT while maximizing the ceramic area in contact with that polymer solution, response times drop to acceptable ranges for laboratory and field conditions. Contact with the soil is drastically improved with the use of cone-shaped solid ceramics instead of flat ceramics. The comparison between measured potentials by polymer tensiometers and indirectly obtained potentials with time domain reflectometry highlights the risk of using the latter method at low water contents. By combining POT and time domain reflectometry readings in situ moisture retention curves can be measured over the range permitted by the measurement range of both POT and time domain reflectometry

LDL cholesterol targets rarely achieved in familial hypercholesterolemia patients: A sex and gender-specific analysis

Background and aims: Despite lipid lowering therapy (LLT), reaching LDL-C targets in patients with familial hypercholesterolemia (FH) remains challenging. Our aim was to determine attainment of LDL-C target levels and reasons for not reaching these in female and male FH patients. Methods: We performed a cross-sectional study of heterozygous FH patients in five hospitals in the Netherlands and Norway. Clinical characteristics and information about LLT, lipid levels and reasons for not being on LDL-C treatment target were retrospectively collected from electronic medical records. Results: We studied 3178 FH patients (53.9% women), median age 48.0 (IQR 34.0–59.9) years. Median LDL-C before treatment and on-treatment was higher in women compared to men (6.2 (IQR 5.1–7.3) and 6.0 (IQR 4.9–7.2) mmol/l (p=0.005) and 3.0 (IQR 2.4–3.8) and 2.8 (IQR 2.3–3.5) mmol/L (p<0.001)), respectively. A minority of women (26.9%) and men (28.9%) reached LDL-C target. In patients with CVD, 17.2% of women and 25.8% of men reached LDL-C target. Women received less often high-intensity statins and ezetimibe. Most common reported reasons for not achieving the LDL-C target were insufficient effect of maximum LLT (women 17.3%, men 24.3%) and side effects (women 15.2%, men 8.6%). Conclusions: In routine practice, only a minority of women and men with FH achieved their LDL-C treatment target. Extra efforts have to be made to provide FH patients with reliable information on the safety of statins and their long-term effects on CVD risk reduction. If statin treatment is insufficient, alternative lipid lowering therapies such as ezetimibe or PCSK9-inhibitors should be considered

KSHV Reactivation from Latency Requires Pim-1 and Pim-3 Kinases to Inactivate the Latency-Associated Nuclear Antigen LANA

Host signal-transduction pathways are intimately involved in the switch between latency and productive infection of herpes viruses. As with other herpes viruses, infection by Kaposi's sarcoma herpesvirus (KSHV) displays these two phases. During latency only few viral genes are expressed, while in the productive infection the virus is reactivated with initiation of extensive viral DNA replication and gene expression, resulting in production of new viral particles. Viral reactivation is crucial for KSHV pathogenesis and contributes to the progression of KS. We have recently identified Pim-1 as a kinase reactivating KSHV upon over-expression. Here we show that another Pim family kinase, Pim-3, also induces viral reactivation. We demonstrate that expression of both Pim-1 and Pim-3 is induced in response to physiological and chemical reactivation in naturally KSHV-infected cells, and we show that they are required for KSHV reactivation under these conditions. Furthermore, our data indicate that Pim-1 and Pim-3 contribute to viral reactivation by phosphorylating the KSHV latency-associated nuclear antigen (LANA) on serine residues 205 and 206. This counteracts the LANA–mediated repression of the KSHV lytic gene transcription. The identification of Pim family kinases as novel cellular regulators of the gammaherpesvirus life cycle facilitates a deeper understanding of virus–host interactions during reactivation and may represent potential novel targets for therapeutic intervention

Nucleophosmin Phosphorylation by v-Cyclin-CDK6 Controls KSHV Latency

Nucleophosmin (NPM) is a multifunctional nuclear phosphoprotein and a histone chaperone implicated in chromatin organization and transcription control. Oncogenic Kaposi's sarcoma herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). In the infected host cell KSHV displays two modes of infection, the latency and productive viral replication phases, involving extensive viral DNA replication and gene expression. A sustained balance between latency and reactivation to the productive infection state is essential for viral persistence and KSHV pathogenesis. Our study demonstrates that the KSHV v-cyclin and cellular CDK6 kinase phosphorylate NPM on threonine 199 (Thr199) in de novo and naturally KSHV-infected cells and that NPM is phosphorylated to the same site in primary KS tumors. Furthermore, v-cyclin-mediated phosphorylation of NPM engages the interaction between NPM and the latency-associated nuclear antigen LANA, a KSHV-encoded repressor of viral lytic replication. Strikingly, depletion of NPM in PEL cells leads to viral reactivation, and production of new infectious virus particles. Moreover, the phosphorylation of NPM negatively correlates with the level of spontaneous viral reactivation in PEL cells. This work demonstrates that NPM is a critical regulator of KSHV latency via functional interactions with v-cyclin and LANA

Kaposi's Sarcoma Herpesvirus microRNAs Target Caspase 3 and Regulate Apoptosis

Kaposi's sarcoma herpesvirus (KSHV) encodes a cluster of twelve micro (mi)RNAs, which are abundantly expressed during both latent and lytic infection. Previous studies reported that KSHV is able to inhibit apoptosis during latent infection; we thus tested the involvement of viral miRNAs in this process. We found that both HEK293 epithelial cells and DG75 cells stably expressing KSHV miRNAs were protected from apoptosis. Potential cellular targets that were significantly down-regulated upon KSHV miRNAs expression were identified by microarray profiling. Among them, we validated by luciferase reporter assays, quantitative PCR and western blotting caspase 3 (Casp3), a critical factor for the control of apoptosis. Using site-directed mutagenesis, we found that three KSHV miRNAs, miR-K12-1, 3 and 4-3p, were responsible for the targeting of Casp3. Specific inhibition of these miRNAs in KSHV-infected cells resulted in increased expression levels of endogenous Casp3 and enhanced apoptosis. Altogether, our results suggest that KSHV miRNAs directly participate in the previously reported inhibition of apoptosis by the virus, and are thus likely to play a role in KSHV-induced oncogenesis

Oncological outcome of malignant colonic obstruction in the Dutch Stent-In 2 trial

Cellular mechanisms in basic and clinical gastroenterology and hepatolog