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"Niklas, Markus"
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Correction to: Incidence of severe sepsis and septic shock in German intensive care units: the prospective, multicentre INSEP study
The members of the SepNet Critical Care Trials Group were provided in such a way that they could not be indexed as collaborators on PubMed. The publisher apologizes for this error and is pleased to list the members of the group here:
Journal Article
Latest Knowledge on the Role of Vitamin D in Hypertension
Hypertension is the third leading cause of the global disease burden, and while populations live longer, adopt more sedentary lifestyles, and become less economically concerned, the prevalence of hypertension is expected to increase. Pathologically elevated blood pressure (BP) is the strongest risk factor for cardiovascular disease (CVD) and related disability, thus making it imperative to treat this disease. Effective standard pharmacological treatments, i.e., diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blocker (ARBs), beta-adrenergic receptor blockers (BARBs), and calcium channel blockers (CCBs), are available. Vitamin D (vitD) is known best for its role in bone and mineral homeostasis. Studies with vitamin D receptor (VDR) knockout mice show an increased renin–angiotensin–aldosterone system (RAAS) activity and increased hypertension, suggesting a key role for vitD as a potential antihypertensive agent. Similar studies in humans displayed ambiguous and mixed results. No direct antihypertensive effect was shown, nor a significant impact on the human RAAS. Interestingly, human studies supplementing vitD with other antihypertensive agents reported more promising results. VitD is considered a safe supplement, proposing its great potential as antihypertensive supplement. The aim of this review is to examine the current knowledge about vitD and its role in the treatment of hypertension.
Journal Article
Dynamics from Seconds to Hours in Hodgkin-Huxley Model with Time-Dependent Ion Concentrations and Buffer Reservoirs
The classical Hodgkin-Huxley (HH) model neglects the time-dependence of ion concentrations in spiking dynamics. The dynamics is therefore limited to a time scale of milliseconds, which is determined by the membrane capacitance multiplied by the resistance of the ion channels, and by the gating time constants. We study slow dynamics in an extended HH framework that includes time-dependent ion concentrations, pumps, and buffers. Fluxes across the neuronal membrane change intra- and extracellular ion concentrations, whereby the latter can also change through contact to reservoirs in the surroundings. Ion gain and loss of the system is identified as a bifurcation parameter whose essential importance was not realized in earlier studies. Our systematic study of the bifurcation structure and thus the phase space structure helps to understand activation and inhibition of a new excitability in ion homeostasis which emerges in such extended models. Also modulatory mechanisms that regulate the spiking rate can be explained by bifurcations. The dynamics on three distinct slow times scales is determined by the cell volume-to-surface-area ratio and the membrane permeability (seconds), the buffer time constants (tens of seconds), and the slower backward buffering (minutes to hours). The modulatory dynamics and the newly emerging excitable dynamics corresponds to pathological conditions observed in epileptiform burst activity, and spreading depression in migraine aura and stroke, respectively.
Journal Article
Higher-order mode supercontinuum generation in dispersion-engineered liquid-core fibers
Supercontinuum generation enabled a series of key technologies such as frequency comb sources, ultrashort pulse sources in the ultraviolet or the mid-infrared, as well as broadband light sources for spectroscopic methods in biophotonics. Recent advances utilizing higher-order modes have shown the potential to boost both bandwidth and modal output distribution of supercontinuum sources. However, the strive towards a breakthrough technology is hampered by the limited control over the intra- and intermodal nonlinear processes in the highly multi-modal silica fibers commonly used. Here, we investigate the ultrafast nonlinear dynamics of soliton-based supercontinuum generation and the associated mode coupling within the first three lowest-order modes of accurately dispersion-engineered liquid-core fibers. By measuring the energy-spectral evolutions and the spatial distributions of the various generated spectral features polarization-resolved, soliton fission and dispersive wave formation are identified as the origins of the nonlinear broadening. Measured results are confirmed by nonlinear simulations taking advantage of the accurate modeling capabilities of the ideal step-index geometry of our liquid-core platform. While operating in the telecommunications domain, our study allows further advances in nonlinear switching in emerging higher-order mode fiber networks as well as novel insights into the sophisticated nonlinear dynamics and broadband light generation in pre-selected polarization states.
Journal Article
Chronic hepatitis C virus infection irreversibly impacts human natural killer cell repertoire diversity
Diversity is a central requirement for the immune system’s capacity to adequately clear a variety of different infections. As such, natural killer (NK) cells represent a highly diverse population of innate lymphocytes important in the early response against viruses. Yet, the extent to which a chronic pathogen affects NK cell diversity is largely unknown. Here we study NK cell functional diversification in chronic hepatitis C virus (HCV) infection. High-dimensional flow cytometer assays combined with stochastic neighbor embedding analysis reveal that chronic HCV infection induces functional imprinting on human NK cells that is largely irreversible and persists long after successful interventional clearance of the virus. Furthermore, HCV infection increases inter-individual, but decreases intra-individual, NK cell diversity. Taken together, our results provide insights into how the history of infections affects human NK cell diversity.
Natural killer (NK) cells are important immune cells for mediating antiviral immunity. Here the authors show that chronic hepatitis C virus infection in human can imprint lasting functional phenotypes in NK cells to increase their inter-individual but decrease intra-individual diversity.
Journal Article
Women’s Empowerment in Action
We evaluate a multifaceted policy intervention attempting to jump-start adolescent women’s empowerment in Uganda by simultaneously providing them vocational training and information on sex, reproduction, and marriage. We find that four years postintervention, adolescent girls in treated communities are more likely to be self-employed. Teen pregnancy, early entry into marriage/cohabitation, and the share of girls reporting sex against their will fall sharply. The results highlight the potential of a multifaceted program that provides skills transfers as a viable and cost-effective policy intervention to improve the economic and social empowerment of adolescent girls over a four-year horizon.
Journal Article
The ALFA-tag is a highly versatile tool for nanobody-based bioscience applications
Specialized epitope tags are widely used for detecting, manipulating or purifying proteins, but often their versatility is limited. Here, we introduce the ALFA-tag, a rationally designed epitope tag that serves a remarkably broad spectrum of applications in life sciences while outperforming established tags like the HA-, FLAG®- or myc-tag. The ALFA-tag forms a small and stable α-helix that is functional irrespective of its position on the target protein in prokaryotic and eukaryotic hosts. We characterize a nanobody (NbALFA) binding ALFA-tagged proteins from native or fixed specimen with low picomolar affinity. It is ideally suited for super-resolution microscopy, immunoprecipitations and Western blotting, and also allows in vivo detection of proteins. We show the crystal structure of the complex that enabled us to design a nanobody mutant (NbALFA
PE
) that permits efficient one-step purifications of native ALFA-tagged proteins, complexes and even entire living cells using peptide elution under physiological conditions.
Epitope tags are widely used in various applications, but often lack versatility. Here, the authors introduce a small, alpha helical tag, which is recognized by a high affinity nanobody and can be used in a range of different applications, from protein purification to super-resolution imaging and in vivo detection of proteins.
Journal Article