Application of Raman Microspectroscopic and Raman imaging techniques for cell biological studies

Raman spectroscopy is being used to study biological molecules for some three decades now. Thanks to continuing advances in instrumentation more and more applications have become feasible in which molecules are studied in situ, and this has enabled Raman spectroscopy to enter the realms of biomedicine and cell biology [1-5].\ud Here we will describe some of the recent work carried out in our laboratory, concerning studies of human white blood cells and further instrumentational developments

The Vector Meson Form Factor Analysis in Light-Front Dynamics

We study the form factors of vector mesons using a covariant fermion field theory model in $(3+1)$ dimensions. Performing a light-front calculation in the $q^+ =0$ frame in parallel with a manifestly covariant calculation, we note the existence of a nonvanishing zero-mode contribution to the light-front current $J^+$ and find a way of avoiding the zero-mode in the form factor calculations. Upon choosing the light-front gauge (\ep^+_{h=\pm}=0) with circular polarization and with spin projection $h=\uparrow\downarrow=\pm$, only the helicity zero to zero matrix element of the plus current receives zero-mode contributions. Therefore, one can obtain the exact light-front solution of the form factors using only the valence contribution if only the helicity components, $(h'h)=(++),(+-)$, and $(+0)$, are used. We also compare our results obtained from the light-front gauge in the light-front helicity basis (i.e. $h=\pm,0$) with those obtained from the non-LF gauge in the instant form linear polarization basis (i.e. $h=x,y,z$) where the zero-mode contributions to the form factors are unavoidable.Comment: 33 pages; typo in Eq.(15) is corrected; comment on Ref.[9] is corrected; version to appear in Phys. Rev.

Salt marsh accretion with and without deep soil subsidence as a proxy for sea-level rise

The relation between salt marsh accretion and flooding regime was quantified by statistical analysis of a unique dataset of accretion measurements using sedimentation-erosion bars, on three barrier islands in the Dutch Wadden Sea over a period of c. 15 years. On one of the islands, natural gas extraction caused deep soil subsidence, which resulted in gradually increasing flooding frequency, duration, and depth, and can thus be seen as a proxy for sea-level rise. Special attention was paid to effects of small-scale variation e.g., in distance to tidal creeks or marsh edges, elevation of the marsh surface, and presence of livestock. Overall mean accretion rate was 0.44 ± 0.0005 cm year−1, which significantly exceeded the local rate of sea-level rise of 0.25 ± 0.009 cm year−1. A multiple regression approach was used to detect the combined effect of flooding regime and the local environment. The most important flooding-related factors that enhance accretion are mean water depth during flooding and overall mean water depth, but local accretion strongly decreases with increasing distance to the nearest creek or to the salt marsh edge. Mean water depth during flooding can be seen as an indicator for storm intensity, while overall mean water depth is a better indicator for storm frequency. The regression parameters were used to run a simple model simulating the effect of various sea-level scenarios on accretion and show that, even under extreme scenarios of sea-level rise, these salt marshes can probably persist for the next 100 years, although the higher parts may experience more frequent inundation

Public exhibit for demonstrating the quantum of electrical conductance

We present a new robust setup that explains and demonstrates the quantum of electrical conductance for a general audience and which is continuously available in a public space. The setup allows users to manually thin a gold wire of several atoms in diameter while monitoring its conductance in real time. During the experiment, a characteristic step-like conductance decrease due to rearrangements of atoms in the cross-section of the wire is observed. Just before the wire breaks, a contact consisting of a single atom with a characteristic conductance close to the quantum of conductance can be maintained up to several seconds. The setup is operated full-time, needs practically no maintenance and is used on different educational levels

Pyruvate Dehydrogenase Kinase Inhibition by Dichloroacetate in Melanoma Cells Unveils Metabolic Vulnerabilities

Melanoma is characterized by high glucose uptake, partially mediated through elevated pyruvate dehydrogenase kinase (PDK), making PDK a potential treatment target in melanoma. We aimed to reduce glucose uptake in melanoma cell lines through PDK inhibitors dichloroacetate (DCA) and AZD7545 and through PDK knockdown, to inhibit cell growth and potentially unveil metabolic co-vulnerabilities resulting from PDK inhibition. MeWo cells were most sensitive to DCA, while SK-MEL-2 was the least sensitive, with IC50 values ranging from 13.3 to 27.0 mM. DCA strongly reduced PDH phosphorylation and increased the oxygen consumption rate:extracellular acidification rate (OCR:ECAR) ratio up to 6-fold. Knockdown of single PDK isoforms had similar effects on PDH phosphorylation and OCR:ECAR ratio as DCA but did not influence sensitivity to DCA. Growth inhibition by DCA was synergistic with the glutaminase inhibitor CB-839 (2-to 5-fold sensitization) and with diclofenac, known to inhibit monocarboxylate transporters (MCTs) (3-to 8-fold sensitization). CB-839 did not affect the OCR:ECAR response to DCA, whereas diclofenac strongly inhibited ECAR and further increased the OCR:ECAR ratio. We conclude that in melanoma cell lines, DCA reduces proliferation through reprogramming of cellular metabolism and synergizes with other metabolically targeted drugs

Pre-Transplant Plasma Potassium as a Potential Risk Factor for the Need of Early Hyperkalaemia Treatment after Kidney Transplantation:A Cohort Study

INTRODUCTION: Plasma potassium (K+) abnormalities are common among patients with chronic kidney disease and are associated with higher rates of death, major adverse cardiac events, and hospitalization in this population. Currently, no guidelines exist on how to handle pre-transplant plasma K+ in renal transplant recipients (RTR). OBJECTIVE: The aim of this study is to examine the relation between pre-transplant plasma K+ and interventions to resolve hyperkalaemia within 48 h after kidney transplantation. METHODS: In a single-centre cohort study, we addressed the association between the last available plasma K+ level before transplantation and the post-transplant need for dialysis or use of K+-lowering medication to resolve hyperkalaemia within 48 h after renal transplantation using multivariate logistic regression analysis. RESULTS: 151 RTR were included, of whom 51 (33.8%) patients received one or more K+ interventions within 48 h after transplantation. Multivariate regression analysis revealed that a higher pre-transplant plasma K+ was associated with an increased risk of post-transplant intervention (odds ratio 2.2 [95% CI: 1.1-4.4]), independent of donor type (deceased or living) and use of K+-lowering medication within 24 h prior to transplantation). CONCLUSIONS: This study indicates that a higher pre-transplant plasma K+ is associated with a higher risk of interventions necessary to resolve hyperkalaemia within 48 h after renal transplantation. Further research is recommended to determine a cutoff level for pre-transplant plasma K+ that can be used in practice

Osteoclast-like Cells in Early Zebrafish Embryos

Animal science