Interaction of microbiota, mucosal malignancies, and immunotherapy-Mechanistic insights.

The microbiome has emerged as a crucial modulator of host-immune interactions and clearly impacts tumor development and therapy efficacy. The microbiome is a double-edged sword in cancer development and therapy as both pro-tumorigenic and anti-tumorigenic bacterial taxa have been identified. The staggering number of association-based studies in various tumor types has led to an enormous amount of data that makes it difficult to identify bacteria that promote tumor development or modulate therapy efficacy from bystander bacteria. Here we aim to comprehensively summarize the current knowledge of microbiome-host immunity interactions and cancer therapy in various mucosal tissues to find commonalities and thus identify potential functionally relevant bacterial taxa. Moreover, we also review recent studies identifying specific bacteria and mechanisms through which the microbiome modulates cancer development and therapy efficacy.

C. elegans is not a robust model organism for the magnetic sense.

Magnetoreception is defined as the ability to sense and use the Earth's magnetic field, for example to orient and direct movements. The receptors and sensory mechanisms underlying behavioral responses to magnetic fields remain unclear. A previous study described magnetoreception in the nematode Caenorhabditis elegans, which requires the activity of a single pair of sensory neurons. These results suggest C. elegans as a tractable model organism for facilitating the search for magnetoreceptors and signaling pathways. The finding is controversial, however, as an attempt to replicate the experiment in a different laboratory was unsuccessful. We here independently test the magnetic sense of C. elegans, closely replicating the assays developed in the original publication. We find that C. elegans show no directional preference in magnetic fields of both natural and higher intensity, suggesting that magnetotactic behavior in the worm is not robustly evoked in a laboratory setting. Given the lack of a robust magnetic response under controlled conditions, we conclude that C. elegans is not a suitable model organism to study the mechanism of the magnetic sense.

Cybersecurity in Power Grids: Challenges and Opportunities.

Increasing volatilities within power transmission and distribution force power grid operators to amplify their use of communication infrastructure to monitor and control their grid. The resulting increase in communication creates a larger attack surface for malicious actors. Indeed, cyber attacks on power grids have already succeeded in causing temporary, large-scale blackouts in the recent past. In this paper, we analyze the communication infrastructure of power grids to derive resulting fundamental challenges of power grids with respect to cybersecurity. Based on these challenges, we identify a broad set of resulting attack vectors and attack scenarios that threaten the security of power grids. To address these challenges, we propose to rely on a defense-in-depth strategy, which encompasses measures for (i) device and application security, (ii) network security, and (iii) physical security, as well as (iv) policies, procedures, and awareness. For each of these categories, we distill and discuss a comprehensive set of state-of-the art approaches, as well as identify further opportunities to strengthen cybersecurity in interconnected power grids.

Suicide risk after psychiatric discharge: study protocol of a naturalistic, long-term, prospective observational study.

BACKGROUND: Suicide risk of psychiatric patients has proven to be strongly increased in the months after discharge from a psychiatric hospital. Despite this high risk, there is a lack of systematic research on the causes of this elevated suicide risk as well as a lack of treatment and intervention for patients at high risk after discharge. The main objective of this pilot study is, firstly, to examine the factors contributing to the elevated suicide risk and, secondly, to investigate whether an additional setting of care starting at discharge may reduce suicidality. METHODS: In this multi-centre pilot study, treatment as usual is complemented by an additional 18-month post-discharge setting of care for psychiatric patients at high risk for suicide. Two groups of patients differing in the amount of post-discharge personal contacts will be compared. One group of patients will be offered continuous personal contacts after discharge (months 1-6: monthly contacts; months 6-18: every 2 months) while another group of patients will receive contacts only at months 6, 12, and 18 after discharge. Data on suicidality, as well as associated with other symptoms, treatment, and significant events, will be collected. In the case of health-related severe events, the setting of care allows the patient to have the opportunity to connect with the doctor or therapist treating the patient. DISCUSSION: The results of this study will contribute to identifying critical factors raising suicide risk after discharge and will demonstrate the potential influence on suicide prevention of a setting of care with regular personal contact after discharge. TRIAL REGISTRATION: ZMVI1-2517FSB135 - funded by the German Federal Ministry of Health.

Age-related increase of VGF-expression in T lymphocytes.

VGF is a protein expressed by neurons and processed into several peptides. It plays a role in energy homeostasis and promotes growth and survival. Recently, VGF mRNA was detected in peripheral leukocytes. Since it is known that aging is associated with a decrease in the development and function of neuronal as well as immune cells, we addressed the question whether a peripheral expression of VGF by CD3+ T cells and CD56+ NK cells is correlated with age. Therefore, the frequency of VGF+CD3+ and VGF+CD56+ cells was determined in mentally healthy volunteers aged between 22 and 88. We found an age-dependent increase in the number of VGF+CD3+ T cells that correlated with HbA1c and the body mass index (BMI). VGF-expression by NK cells was age-independent. Blockade of VGF reduced proliferation and secretion of cytokines such as IL-2, IL-17A, IL-1ß, IL-10 and TNF by CD3+ T cells and PBMCs. Rapamycin-mediated T cell blockade significantly reduced the frequency of VGF-expressing T cells. We conclude that VGF contributes to survival and function of peripheral T cells. The age-dependent increase in VGF-expression could serve as mechanism that counterregulates the decrease in functionality of T lymphocytes.

Risk factors for suicide--an alternative view.

During the past years suicide statistics in Germany showed a dramatic decrease of suicide rates. Such a reduction in a comparatively short time period is not explainable by an altered frequency of major psychiatric disorders or certain neurobiological conditions that may underlie suicide; other factors causing or leading to suicide and their modification have to be considered. This overview illustrates various risk factors for suicide different from neurobiology. Epidemiological aspects and the effect of political, social and economic contributions to suicide rates are exemplified. With regard to the incidence of major psychiatric disorders the paper focuses on physical illnesses and their risk of suicide. Finally the significance of changes in the accessibility of suicide methods is discussed.

Precision velocity measurements of pulsed supersonic jets.

We introduce a straightforward experimental approach for determining the mean flow velocity of a supersonic jet with very high precision. While time measurements easily can achieve accuracies of Δt/t ≤ 10(-4), typically the absolute flight distances are much less well-defined. This causes significantly increased errors in calculations of the mean flow velocity and mean kinetic energy. The basic concept to improve on this situation is changing the flight distance in vacuo by precisely defined increments employing a linear translation stage. We demonstrate the performance of this method with a flight path that can be varied by approximately 15% with a tolerance of setting of 50 µm. In doing so, an unprecedented accurate value for the mean flow velocity of Δv/ < 3 × 10(-4) has been obtained without prior knowledge of the total distance. This very high precision in source pressure, temperature, and particle speed facilitates an improved energetic analysis of condensation processes in supersonic jet expansions. The technique is also of broad interest to other fields employing the strong adiabatic cooling of supersonic beams, in particular, molecular spectroscopy. In the presented case study, a thorough analysis of arrival time spectra of neutral helium implies cluster formation even at elevated temperatures.

Precise thermodynamic control of high pressure jet expansions.

We describe an experimental setup for supersonic jet expansions of supercritical fluids. It is characterized by well-defined thermodynamic values to allow systematic investigations of pressure and temperature effects on molecular beam parameters. The design permits stagnation temperatures T(0)=225-425 K with a thermal stability DeltaT(0)<30 mK and stagnation pressures p(0)=0.2-12 MPa that are measured with 0.05% precision. For optimum stability, gas reservoir, pressure transducer, and gauge amplifier are temperature-controlled, and a feedback loop permits active pressure stabilization using a pulseless syringe pump. With this approach stagnation pressures can be reproduced and kept constant to Deltap(0)<2.9 kPa. As a result, flow velocity and kinetic energy of molecular beams can be controlled with maximum accuracy.