Signatures of cosmic tau-neutrinos

The importance and signatures of cosmic tau--(anti)neutrinos have been studied for upward-- and downward--going $\mu^-+\mu^+$ and hadronic shower event rates relevant for present and future underground water or ice detectors, utilizing the unique and reliable ultrasmall--$x$ predictions of the dynamical (radiative) parton model. The upward--going $\mu^- +\mu^+$ event rates calculated just from cosmic $\nu_{\mu}+\bar{\nu}_{\mu}$ fluxes are sizeably enhanced by taking into account cosmic $\nu_{\tau}+ \bar{\nu}_{\tau}$ fluxes and their associated $\tau^- +\tau^+$ fluxes as well. The coupled transport equations for the upward--going $\stackrel{(-)}{\nu}_{\tau}$ flux traversing the Earth imply an enhancement of the attenuated and regenerated $\stackrel{(-)}{\nu}_{\tau}$ flux typically around $10^4-10^5$ GeV with respect to the initial cosmic flux. This enhancement turns out to be smaller than obtained so far, in particular for flatter initial cosmic fluxes behaving like $E_{\nu}^{-1}$. Downward--going $\mu^- +\mu^+$ events and in particular the background--free and unique hadronic `double bang' and `lollipop' events allow to test downward--going cosmic $\nu_{\tau} +\bar{\nu}_{\tau}$ fluxes up to about $10^9$ GeV.Comment: 32 pages, 6 figures; Added reference

Experiences from treating seven adult 5q spinal muscular atrophy patients with Nusinersen

Background: The antisense oligonucleotide Nusinersen recently became the first approved drug against spinal muscular atrophy (SMA). It was approved for all ages, albeit the clinical trials were conducted exclusively on children. Hence, clinical data on adults being treated with Nusinersen is scarce. In this case series, we report on drug application, organizational demands, and preliminary effects during the first 10 months of treatment with Nusinersen in seven adult patients. Methods: All patients received intrathecal injections with Nusinersen. In cases with severe spinal deformities, we performed computed tomography (CT)-guided applications. We conducted a total of 40 administrations of Nusinersen. We evaluated the patients with motor, pulmonary, and laboratory assessments, and tracked patient-reported outcome. Results: Intrathecal administration of Nusinersen was successful in most patients, even though access to the lumbar intrathecal space in adults with SMA is often challenging. No severe adverse events occurred. Six of the seven patients reported stabilization of motor function or reduction in symptom severity. The changes in the assessed scores did not reach a significant level within this short time period. Conclusions: Treating adult SMA patients with Nusinersen is feasible and most patients consider it beneficial. It demands a complex organizational and interdisciplinary effort. Due to the slowly decreasing motor functions in adult SMA patients, long observation phases for this recently approved treatment are needed to allow conclusions about effectiveness of Nusinersen in adults

Reaction to Endoplasmic Reticulum Stress via ATF6 in Amyotrophic Lateral Sclerosis Deteriorates With Aging

Amyotrophic lateral sclerosis (ALS) is a multisystemic neurodegenerative disorder. Given that peripheral blood mononuclear cells (PBMCs) serve as a “window to the central nervous system” we aimed to answer whether endoplasmic reticulum (ER) stress in ALS-PBMCs is related to disease aggressiveness. We studied ER stress in the PBMCs of 49 patients with ALS and 31 age- and sex-matched healthy controls. The expression of a main ER stress marker, activating transcription factor 6 (ATF6), was significantly higher in ALS compared to controls, but did not correlate with age, disease severity, disease duration and disease progression rate. When ATF6 expression levels were plotted against relative D50 (rD50)-derived disease phases derived from the D50 ALS model, two distinct clusters of patients were observed: cluster 1, with progressively increasing ATF6 expression levels and cluster 2, which demonstrated stable ATF6 expression over the disease course. Individuals in the two clusters did not significantly differ in terms of ALS Functional Rating Scale-Revised (ALSFRS-R), disease aggressiveness, disease duration and subtype. However, patients with the increasing ATF6 level were significantly younger, indicating that aging processes might be related to ER stress in ALS. Our data suggest that the reaction to ER stress during disease course may be compromised in older patients with ALS

Natural phenolic compounds as biofilm inhibitors of multidrug-resistant Escherichia coli – the role of similar biological processes despite structural diversity

Multidrug-resistant gram-negative pathogens such as Escherichia coli have become increasingly difficult to treat and therefore alternative treatment options are needed. Targeting virulence factors like biofilm formation could be one such option. Inhibition of biofilm-related structures like curli and cellulose formation in E. coli has been shown for different phenolic natural compounds like epigallocatechin gallate. This study demonstrates this effect for other structurally unrelated phenolics, namely octyl gallate, scutellarein and wedelolactone. To verify whether these structurally different compounds influence identical pathways of biofilm formation in E. coli a broad comparative RNA-sequencing approach was chosen with additional RT-qPCR to gain initial insights into the pathways affected at the transcriptomic level. Bioinformatical analysis of the RNA-Seq data was performed using DESeq2, BioCyc and KEGG Mapper. The comparative bioinformatics analysis on the pathways revealed that, irrespective of their structure, all compounds mainly influenced similar biological processes. These pathways included bacterial motility, chemotaxis, biofilm formation as well as metabolic processes like arginine biosynthesis and tricarboxylic acid cycle. Overall, this work provides the first insights into the potential mechanisms of action of novel phenolic biofilm inhibitors and highlights the complex regulatory processes of biofilm formation in E. coli

The Digital MIQE Guidelines Update: Minimum Information for Publication of Quantitative Digital PCR Experiments for 2020

Digital PCR (dPCR) has developed considerably since the publication of the Minimum Information for Publication of Digital PCR Experiments (dMIQE) guidelines in 2013, with advances in instrumentation, software, applications, and our understanding of its technological potential. Yet these developments also have associated challenges; data analysis steps, including threshold setting, can be difficult and preanalytical steps required to purify, concentrate, and modify nucleic acids can lead to measurement error. To assist independent corroboration of conclusions, comprehensive disclosure of all relevant experimental details is required. To support the community and reflect the growing use of dPCR, we present an update to dMIQE, dMIQE2020, including a simplified dMIQE table format to assist researchers in providing key experimental information and understanding of the associated experimental process. Adoption of dMIQE2020 by the scientific community will assist in standardizing experimental protocols, maximize efficient utilization of resources, and further enhance the impact of this powerful technology

Microbial and Chemical Characterization of Underwater Fresh Water Springs in the Dead Sea

Due to its extreme salinity and high Mg concentration the Dead Sea is characterized by a very low density of cells most of which are Archaea. We discovered several underwater fresh to brackish water springs in the Dead Sea harboring dense microbial communities. We provide the first characterization of these communities, discuss their possible origin, hydrochemical environment, energetic resources and the putative biogeochemical pathways they are mediating. Pyrosequencing of the 16S rRNA gene and community fingerprinting methods showed that the spring community originates from the Dead Sea sediments and not from the aquifer. Furthermore, it suggested that there is a dense Archaeal community in the shoreline pore water of the lake. Sequences of bacterial sulfate reducers, nitrifiers iron oxidizers and iron reducers were identified as well. Analysis of white and green biofilms suggested that sulfide oxidation through chemolitotrophy and phototrophy is highly significant. Hyperspectral analysis showed a tight association between abundant green sulfur bacteria and cyanobacteria in the green biofilms. Together, our findings show that the Dead Sea floor harbors diverse microbial communities, part of which is not known from other hypersaline environments. Analysis of the water’s chemistry shows evidence of microbial activity along the path and suggests that the springs supply nitrogen, phosphorus and organic matter to the microbial communities in the Dead Sea. The underwater springs are a newly recognized water source for the Dead Sea. Their input of microorganisms and nutrients needs to be considered in the assessment of possible impact of dilution events of the lake surface waters, such as those that will occur in the future due to the intended establishment of the Red Sea−Dead Sea water conduit

The ScaleX campaign: scale-crossing land-surface and boundary layer processes in the TERENO-preAlpine observatory

Augmenting long-term ecosystem-atmosphere observations with multidisciplinary intensive campaigns aims at closing gaps in spatial and temporal scales of observation for energy- and biogeochemical cycling, and at stimulating collaborative research. ScaleX is a collaborative measurement campaign, co-located with a long-term environmental observatory of the German TERENO (TERrestrial ENvironmental Observatories) network in mountainous terrain of the Bavarian Prealps, Germany. The aims of both TERENO and ScaleX include the measurement and modeling of land-surface atmosphere interactions of energy, water, and greenhouse gases. ScaleX is motivated by the recognition that long-term intensive observational research over years or decades must be based on well-proven, mostly automated measurement systems, concentrated on a small number of locations