Herpesviruses mimic zygotic genome activation to promote viral replication.

Zygotic genome activation (ZGA) is crucial for maternal to zygotic transition at the 2-8-cell stage in order to overcome silencing of genes and enable transcription from the zygotic genome. In humans, ZGA is induced by DUX4, a pioneer factor that drives expression of downstream germline-specific genes and retroelements. Here we show that herpesviruses from all subfamilies, papillomaviruses and Merkel cell polyomavirus actively induce DUX4 expression to promote viral transcription and replication.

Cytosolic nucleic acid sensors and interferon beta-1 activation drive radiation-induced anti-tumour immune effects in human pancreatic cancer cells.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related deaths worldwide with limited treatment options due to extensive radiation and chemotherapy resistance. Monotherapy with immune checkpoint blockade showed no survival benefit. A combination of immunomodulation and radiotherapy may offer new treatment strategies, as demonstrated for non-small cell lung cancer.

Three-dimensional radial echo-planar spectroscopic imaging for hyperpolarized C MRSI in vivo.

Purpose: To demonstrate the feasibility of 3D echo-planar spectroscopic imaging (EPSI) technique with rapid volumetric radial k-space sampling for hyperpolarized (HP) C magnetic resonance spectroscopic imaging (MRSI) in vivo.

Methods: A radial EPSI (rEPSI) was implemented on a 3 T clinical PET/MR system. To enable volumetric coverage, the sinusoidal shaped readout gradients per k-t-spoke were rotated along the three spatial dimensions in a golden-angle like manner.

A single dose of cocaine rewires the 3D genome structure of midbrain dopamine neurons.

Midbrain dopamine neurons (DNs) respond to a first exposure to addictive drugs and play key roles in chronic drug usage. As the synaptic and transcriptional changes that follow an acute cocaine exposure are mostly resolved within a few days, the molecular changes that encode the long-term cellular memory of the exposure within DNs remain unknown. To investigate whether a single cocaine exposure induces long-term changes in the 3D genome structure of DNs, we applied Genome Architecture Mapping and single nucleus transcriptomic analyses in the mouse midbrain.

A versatile look-up algorithm for mapping pH values and magnesium ion content using P MRSI.

P MRSI allows for the non-invasive mapping of pH and magnesium ion content (Mg) in vivo, by translating the chemical shifts of inorganic phosphate and adenosine-5'-triphosphate (ATP) to pH and Mg via suitable calibration equations, such as the modified Henderson-Hasselbalch equation. However, the required constants in these calibration equations are typically only determined for physiological conditions, posing a particular challenge for their application to diseased tissue, where the biochemical conditions might change manyfold. In this article, we propose a multi-parametric look-up algorithm aiming at the condition-independent determination of pH and Mg by employing multiple quantifiable P spectral properties simultaneously.

Herpesviruses mimic zygotic genome activation to promote viral replication.

DUX4 is a germline transcription factor and a master regulator of zygotic genome activation. During early embryogenesis, DUX4 is crucial for maternal to zygotic transition at the 2-8-cell stage in order to overcome silencing of genes and enable transcription from the zygotic genome. In adult somatic cells, DUX4 expression is silenced and its activation in adult muscle cells causes the genetic disorder Facioscapulohumeral Muscular Dystrophy (FSHD).

Whole-Brain Intracellular pH Mapping of Gliomas Using High-Resolution P MR Spectroscopic Imaging at 7.0 T.

Malignant tumors commonly exhibit a reversed pH gradient compared with normal tissue, with a more acidic extracellular pH and an alkaline intracellular pH (pH). In this prospective study, pH values in gliomas were quantified using high-resolution phosphorous 31 (P) spectroscopic MRI at 7.0 T and were used to correlate pH alterations with histopathologic findings.

The SPOC proteins DIDO3 and PHF3 co-regulate gene expression and neuronal differentiation.

Transcription is regulated by a multitude of activators and repressors, which bind to the RNA polymerase II (Pol II) machinery and modulate its progression. Death-inducer obliterator 3 (DIDO3) and PHD finger protein 3 (PHF3) are paralogue proteins that regulate transcription elongation by docking onto phosphorylated serine-2 in the C-terminal domain (CTD) of Pol II through their SPOC domains. Here, we show that DIDO3 and PHF3 form a complex that bridges the Pol II elongation machinery with chromatin and RNA processing factors and tethers Pol II in a phase-separated microenvironment.

First implementation of dynamic oxygen-17 (O) magnetic resonance imaging at 7 Tesla during neuronal stimulation in the human brain.

Objective: First implementation of dynamic oxygen-17 (O) MRI at 7 Tesla (T) during neuronal stimulation in the human brain.

Methods: Five healthy volunteers underwent a three-phase O gas (O) inhalation experiment. Combined right-side visual stimulus and right-hand finger tapping were used to achieve neuronal stimulation in the left cerebral hemisphere.

The SPOC domain is a phosphoserine binding module that bridges transcription machinery with co- and post-transcriptional regulators.

The heptad repeats of the C-terminal domain (CTD) of RNA polymerase II (Pol II) are extensively modified throughout the transcription cycle. The CTD coordinates RNA synthesis and processing by recruiting transcription regulators as well as RNA capping, splicing and 3'end processing factors. The SPOC domain of PHF3 was recently identified as a CTD reader domain specifically binding to phosphorylated serine-2 residues in adjacent CTD repeats.

Talimogene laherparepvec monotherapy for head and neck melanoma patients.

Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus, type 1, intralesionally administered in patients with stage IIIB/C-IVM1a unresectable melanoma. When surgery is not a treatment option in the head and neck region, T-VEC can be an elegant alternative to systemic immunotherapy. Ten patients with metastatic melanoma in the head and neck region started treatment with T-VEC monotherapy at the Netherlands Cancer Institute.

Multi-Omics Alleviates the Limitations of Panel Sequencing for Cancer Drug Response Prediction.

Comprehensive genomic profiling using cancer gene panels has been shown to improve treatment options for a variety of cancer types. However, genomic aberrations detected via such gene panels do not necessarily serve as strong predictors of drug sensitivity. In this study, using pharmacogenomics datasets of cell lines, patient-derived xenografts, and ex vivo treated fresh tumor specimens, we demonstrate that utilizing the transcriptome on top of gene panel features substantially improves drug response prediction performance in cancer.

Complement Regulation in Immortalized Fibroblast-like Synoviocytes and Primary Human Endothelial Cells in Response to SARS-CoV-2 Nucleocapsid Protein and Pro-Inflammatory Cytokine TNFα.

: Case reports are available showing that patients develop symptoms of acute arthritis during or after recovery from SARS-CoV-2 infection. Since the interrelation is still unknown, our aim was to study the impact of the SARS-CoV-2 nucleocapsid protein (NP) on human fibroblast-like synoviocytes and human endothelial cells (hEC) in terms of complement and cytokine regulation. : Non-arthritic (K4IM) synoviocyte, arthritic (HSE) synoviocyte cell lines and primary hEC were stimulated with recombinant NP and/or TNFα.

SARS-CoV-2 infection dynamics revealed by wastewater sequencing analysis and deconvolution.

The use of RNA sequencing from wastewater samples is a valuable way for estimating infection dynamics and circulating lineages of SARS-CoV-2. This approach is independent from testing individuals and can therefore become the key tool to monitor this and potentially other viruses. However, it is equally important to develop easily accessible and scalable tools which can highlight critical changes in infection rates and dynamics over time across different locations given sequencing data from wastewater.

[The situation of physicians in acute hospitals during the second wave of the SARS-CoV-2 pandemic: An online survey].

Background: The SARS-CoV-2 pandemic has an impact on the wellbeing of health care workers. The influence of a work-related sense of coherence as well as perceived organizational support on the level of burnout and the intention to leave the job is largely unknown, especially for physicians in German hospitals.

Method: In December 2020 and January 2021, physicians of 81 hospitals in Hessian (Germany) participated in an online survey using the BAT (Burnout Assessment Tool), Work-SoC (Work-related Sense of Coherence), the POS-s (Perceived Organizational SUPPORT - short version) and literature-based items based.

Neoadjuvant nivolumab + T-VEC combination therapy for resectable early stage or metastatic (IIIB-IVM1a) melanoma with injectable disease: study protocol of the NIVEC trial.

Background: Trials investigating neoadjuvant treatment with immune checkpoint inhibitors (ICI) in patients with melanoma have shown high clinical and pathologic response rates. Treatment with talimogene laherparepvec (T-VEC), a modified herpes simplex virus type-1 (HSV-1), is approved for patients with unresectable stage IIIB-IVM1a melanoma and has the potential to make tumors more susceptible for ICI. Combination ICI and intralesional T-VEC has already been investigated in patients with unresectable stage IIIB-IV disease, however, no data is available yet on the potential benefit of this combination therapy in neoadjuvant setting.

Cleidocervical muscle: a mini literature survey of a human muscle variation.

Cleidocervical muscles (CCM) or levator claviculae muscles in humans can be found as supernumerary unilaterally or bilaterally on the neck attached proximally to the clavicle and distally to the transverse process of cervical vertebrae at various levels. Altogether 20 case reports from year 1994 till present including 25 subjects related to CCM were found and analysed where parameters such as cervical insertion level, clavicular insertion at the middle vs. lateral third, unilateral vs.

Identifying tumor cells at the single-cell level using machine learning.

Tumors are complex tissues of cancerous cells surrounded by a heterogeneous cellular microenvironment with which they interact. Single-cell sequencing enables molecular characterization of single cells within the tumor. However, cell annotation-the assignment of cell type or cell state to each sequenced cell-is a challenge, especially identifying tumor cells within single-cell or spatial sequencing experiments.

Re-introduction of T-VEC Monotherapy in Recurrent Melanoma is Effective.

Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus type 1, which can be administered intralesionally in patients with stage IIIB/C-IVM1a (American Joint Committee of Cancer; AJCC 7th edition) unresectable melanoma. In the case of disease recurrence, T-VEC can be re-introduced for the same category of patients. Five patients with recurrent disease after a prior achieved complete response (CR) recommenced treatment with T-VEC monotherapy at the Netherlands Cancer Institute.

Rapid Inflammasome Activation Is Attenuated in Post-Myocardial Infarction Monocytes.

Inflammasomes are crucial gatekeepers of the immune response, but their maladaptive activation associates with inflammatory pathologies. Besides canonical activation, monocytes can trigger non-transcriptional or rapid inflammasome activation that has not been well defined in the context of acute myocardial infarction (AMI). Rapid transcription-independent inflammasome activation induced by simultaneous TLR priming and triggering stimulus was measured by caspase-1 (CASP1) activity and interleukin release.

P MRSI at 7 T enables high-resolution volumetric mapping of the intracellular magnesium ion content in human lower leg muscles.

Purpose: The non-invasive determination of the free magnesium ion concentration ([Mg ]) using P MRSI in vivo is of interest in research on various pathologies, e.g. diabetes.

Mapping an Extended Metabolic Profile of Gliomas Using High-Resolution P MRSI at 7T.

Phosphorus magnetic resonance spectroscopic imaging (P MRSI) is of particular interest for investigations of patients with brain tumors as it enables to non-invasively assess altered energy and phospholipid metabolism . However, the limited sensitivity of P MRSI hampers its broader application at clinical field strengths. This study aimed to identify the additional value of P MRSI in patients with glioma at ultra-high = 7T, where the increase in signal-to-noise ratio may foster its applicability for clinical research.

Mapping intracellular pH in tumors using amide and guanidyl CEST-MRI at 9.4 T.

Purpose: In principle, non-invasive mapping of the intracellular pH (pH ) in vivo is possible using endogenous chemical exchange saturation transfer (CEST)-MRI of the amide and guanidyl signals. However, the application for cancer imaging is still impeded, as current state-of-the-art approaches do not allow for simultaneous compensation of concomitant effects that vary within tumors. In this study, we present a novel method for absolute pH mapping using endogenous CEST-MRI, which simultaneously compensates for concentration changes, superimposing CEST signals, magnetization transfer contrast, and spillover dilution.